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Bio

Academic Appointments

Administrative Appointments

  • Director of Hematology-Oncology Outpatient Clinic, Lucile Packard Children's Hospital (2000 - 2016)
  • Director, Pediatric Hematology-Oncology Fellowship Program, Stanford University (2000 - 2008)
  • Associate Chief of Clinical Affairs, Pediatric Hematology-Oncology, Lucile Packard Children's Hospital (2006 - 2011)
  • Oncology Section Chief, Stanford University, Division of Pediatric Hematology-Oncology (2013 - 2017)

Honors & Awards

  • Magna Cum Laude-Antoine Lavoiser Chemistry Award, University of PR, Mayaguez Campus (1979)
  • Phi Kappa Phi Honor Society, Phi Kappa Phi (1979)
  • Alfa Omega Alfa Honor Society, Alfa Omega Alfa (1982)

Boards, Advisory Committees, Professional Organizations

  • Pediatric Oncology Specialty Steering Board, Epic (2014 - 2016)
  • Editorial Advisory Board Member, PDQ Pediatric Treatment (2010 - 2017)
  • External Advisory Board, CPRIT Baylor Osteosarcoma Grant (2016 - 2017)

Professional Education

  • MS, Stanford University, Epidemiology (2011)
  • Fellowship, St. Jude Children's Hospital, Pediatric Hematology-Oncology (1989)
  • Residency, University of PR, Pediatrics (1986)
  • MD, University of PR, Medicine (1983)
  • BS, University of PR, Mayaguez, Chemistry (1979)

Contact

Research & Scholarship

Current Research and Scholarly Interests

The main focus of my research is the development of new treatment strategies for patients with bone sarcoma.

Clinical Trials

  • Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma Recruiting

    This research trial studies biomarkers in tumor tissue samples from patients with newly diagnosed neuroblastoma or ganglioneuroblastoma. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.

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  • Childhood Cancer Survivor Study Recruiting

    The Childhood Cancer Survivor Study (CCSS) will investigate the long-term effects of cancer and its associated therapies. A retrospective cohort study will be conducted through a multi-institutional collaboration, which will involve the identification and active follow-up of a cohort of approximately 50,000 survivors of cancer, diagnosed before 21 years of age, between 1970 and 1999 and 10,000 sibling controls. This project will study children and young adults exposed to specific therapeutic modalities, including radiation, chemotherapy, and/or surgery, who are at increased risk of late-occurring adverse health outcomes. A group of sibling controls will be identified and data collected for comparison purposes.

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  • Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma Recruiting

    This randomized phase III trial studies how well combination chemotherapy (vincristine sulfate, dactinomycin, cyclophosphamide alternated with vincristine sulfate and irinotecan hydrochloride or vinorelbine) works compared to combination chemotherapy plus temsirolimus in treating patients with rhabdomyosarcoma (cancer that forms in the soft tissues, such as muscle), and has an intermediate chance of coming back after treatment (intermediate risk). Drugs used work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combination chemotherapy and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether chemotherapy plus temsirolimus is more effective than chemotherapy alone in treating patients with intermediate-risk rhabdomyosarcoma.

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  • Development of Radiation Free Whole Body Magnetic Resonance (MR) Imaging Technique for Staging Children With Cancer Recruiting

    A research study on the diagnosis of spread of disease for children who have been diagnosed with solid tumors using a new whole body imaging technique and a new MR contrast agent (ferumoxytol). Standard tests that are used to determine the extent and possible spread of a child's disease include magnetic resonance (MR) imaging, computed tomography (CT), Positron Emission Tomography (PET) as well as bone scanning, and metaiodobenzylguanidine (MIBG) scanning. The purpose of this study is to determine if newer imaging tests referred to as whole body diffusion-weighted MR and whole body PET/MR can detect the extent and spread of the disease as accurately or even better as the standard tests (CT, MR and/or PET/CT). The advantage of the new imaging test is that it is associated with no or significantly reduced radiation exposure compared to standard CT and PET/CT imaging tests. The results of whole body MR and PET/MR will be compared with that of the conventional, standard imaging studies for tumor detecting.

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  • Differentiation of Bone Sarcomas and Osteomyelitis With Ferumoxytol-Enhanced MRI Recruiting

    This pilot trial studies the differentiation of bone sarcomas and osteomyelitis with ferumoxytol-enhanced magnetic resonance imaging (MRI). Imaging procedures that allow doctors to more accurately differentiate between malignant bone sarcomas and osteomyelitis may help in diagnosing patients correctly and may result in more timely treatment.

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  • Dinutuximab in Combination With Sargramostim in Treating Patients With Recurrent Osteosarcoma Recruiting

    This phase II trial studies how well dinutuximab works when given with sargramostim in treating patients with osteosarcoma that has come back after treatment (recurrent). Monoclonal antibodies, such as dinutuximab, may find tumor cells and help kill them. Sargramostim may help the body increase the amount of white blood cells it produces, which help the body fight off infections. Giving dinutuximab with sargramostim may work better and kill more cancer cells.

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  • Genetic Analysis in Identifying Late-Occurring Complications in Childhood Cancer Survivors Recruiting

    This clinical trial studies cancer survivors to identify those who are at increased risk of developing late-occurring complications after undergoing treatment for childhood cancer. A patient's genes may affect the risk of developing complications, such as congestive heart failure, avascular necrosis, stroke, and second cancer, years after undergoing cancer treatment. Genetic studies may help doctors identify survivors of childhood cancer who are more likely to develop late complications.

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  • Long-Term Follow-Up of Patients Who Have Participated in Children's Oncology Group Studies Recruiting

    This clinical trial keeps track of and collects follow-up information from patients who are currently enrolled on or have participated in a Children's Oncology Group study. Developing a way to keep track of patients who have participated in Children's Oncology Group studies may allow doctors learn more about the long-term effects of cancer treatment and help them reduce problems related to treatment and improve patient quality of life.

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  • Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma Recruiting

    This partially randomized phase III trial is studying maintenance chemotherapy to see how well it works compared to observation following induction chemotherapy and radiation therapy in treating young patients with newly diagnosed ependymoma. Drugs used in chemotherapy, such as vincristine sulfate, carboplatin, cyclophosphamide, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.

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  • Neuroblastoma Biology Study Recruiting

    Medical scientists want to find better ways to treat neuroblastoma and to find ways to prevent the tumor from growing back. To do this, they need more information about the characteristics of neuroblastoma cells. Therefore, they want to study samples of neuroblastoma tissues and neuroblastoma and normal cells in the blood and bone marrow that may be related to the growth of neuroblastoma cells. Doctors and other medical scientists also want to find better ways to detect and measure neuroblastoma to improve the ability to follow the response of tumor cells to therapy.

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  • Neuropsychological and Behavioral Testing in Younger Patients With Cancer Recruiting

    This research trial studies neuropsychological (learning, remembering or thinking) and behavioral outcomes in children and adolescents with cancer by collecting information over time from a series of tests.

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  • Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas Recruiting

    This phase I/II trial studies the side effects and best dose of nivolumab when given with or without ipilimumab to see how well they work in treating younger patients with solid tumors or sarcomas that have come back (recurrent) or do not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better alone or with ipilimumab in treating patients with recurrent or refractory solid tumors or sarcomas.

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  • Study of Kidney Tumors in Younger Patients Recruiting

    This research trial studies kidney tumors in younger patients. Collecting and storing samples of tumor tissue, blood, and urine from patients with cancer to study in the laboratory may help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer.

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  • 131I-MIBG Alone VS. 131I-MIBG With Vincristine and Irinotecan VS131I-MIBG With Vorinistat Not Recruiting

    This study will compare three treatment regimens containing metaiodobenzylguanidine (MIBG) and compare their effects on tumor response and associated side effects, to determine if one therapy is better than the other for people diagnosed with relapsed or persistent neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-726-4281.

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  • A Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung Not Recruiting

    The purpose of this study is to determine how long patients who undergo complete surgical removal of recurrent osteosarcoma in the lung will remain free of cancer after taking Saracatinib compared to patients taking placebo (a sugar pill).

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 725 - 1662.

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  • A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias. Not Recruiting

    Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted. The purpose of the phase 1 portion of this study was to determine if clofarabine added to a combination of etoposide and cyclophosphamide is safe in children with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). The purpose of the phase 2 portion of the study was to measure the effectiveness of the combination therapy in children with ALL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • A Study of Lenalidomide in Pediatric Subjects With Relapsed or Refractory Acute Myeloid Leukemia Not Recruiting

    To determine the activity of lenalidomide in the treatment of pediatric subjects with relapsed/refractory acute myeloid leukemia (AML) (with second or greater relapse or refractory to at least 2 prior induction attempts) measured by morphological complete response defined as either a CR or CRi within the first 4 cycles of treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Study of Pemetrexed in Children With Recurrent Cancer Not Recruiting

    To determine the response rate of pemetrexed given every 21 days for the treatment of children with relapsed or refractory osteosarcoma, Ewing's sarcoma/peripheral primitive neuroectodermal tumors (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET or non-brain stem high-grade glioma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • A Study of R1507 in Participants With Recurrent or Refractory Sarcoma Not Recruiting

    The study was primarily designed to determine objective response, progression-free survival (PFS), and the safety and tolerability of R1507 in participants with recurrent or refractory Ewing's sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas including alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Ahern, (650) 725 - 6413.

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  • ABT-751 in Treating Children With Neuroblastoma That Has Relapsed or Not Responded to Previous Treatment Not Recruiting

    This phase II trial is studying how well ABT-751 works in treating children with neuroblastoma that has relapsed or not responded to previous treatment. Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa Marina, (650) 723 - 5535.

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  • Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia Not Recruiting

    This phase II trial is studying the side effects of and how well alisertib works in treating young patients with relapsed or refractory solid tumors or leukemia. Alisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, 650497881.

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  • Bevacizumab and Lapatinib in Children With Recurrent or Refractory Ependymoma Not Recruiting

    The goal of this clinical research study is to learn if the combination of Avastin (bevacizumab) and Tykerb (lapatinib) can help to control ependymoma in pediatric patients. The safety of this drug combination will also be studied.

    Stanford is currently not accepting patients for this trial. For more information, please contact Carissa Bailey, (650) 725 - 4708.

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  • Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia Not Recruiting

    This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia.

    Stanford is currently not accepting patients for this trial.

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  • Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma Not Recruiting

    This pilot, phase II trial studies the side effects of giving bortezomib together with combination chemotherapy and to see how well it works in treating young patients with relapsed acute lymphoblastic leukemia or lymphoblastic lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia Not Recruiting

    This phase II trial is studying the side effects and best dose of bortezomib and to see how well it works when given together with combination chemotherapy in treating younger patients with recurrent, refractory, or secondary acute myeloid leukemia (AML). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin, cytarabine, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells

    Stanford is currently not accepting patients for this trial. For more information, please contact Lan Wang, (650) 725 - 4708.

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  • Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Not Recruiting

    This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds/Hem Onc CRAs, (650) 497-8953.

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  • Bortezomib, Ifosfamide, and Vinorelbine Tartrate in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy Not Recruiting

    This phase II trial studies the side effects and efficacy of bortezomib with ifosfamide and vinorelbine in children and young adults with Hodgkin's lymphoma that was recurrent or did not respond to previous therapy. Bortezomib is an inhibitor of protein degradation. Bortezomib degrades short-lived regulatory proteins in the cell, and has been reported to increase the tumor cells. Bortezomib may increase the effectiveness of ifosfamide and vinorelbine (two standard drugs given to children with Hodgkin Lymphoma that has come back after initial treatment) by making cancer cells more sensitive to effectiveness of standard chemotherapy by preventing anti-death responses in these drugs. Giving bortezomib together with ifosfamide and vinorelbine tartrate should kill more cancer cells than are killed with ifosfamide and vinorelbine alone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa Marina, (650) 723 - 5535.

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  • Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia Not Recruiting

    This clinical trial is looking at brain function in young patients receiving methotrexate for acute lymphoblastic leukemia. Learning about the long-term effects of methotrexate on brain function may help doctors plan cancer treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma Not Recruiting

    This phase I/II trial studies the side effects and the best dose of brentuximab vedotin when given together with gemcitabine hydrochloride and to see how well they work in treating younger patients with Hodgkin lymphoma that has returned or does not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may find cancer cells and help kill them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin together with gemcitabine hydrochloride may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-736-4281.

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  • Brentuximab Vedotin or Crizotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II-IV Anaplastic Large Cell Lymphoma Not Recruiting

    This partially randomized phase II trial studies how well brentuximab vedotin or crizotinib and combination chemotherapy works in treating patients with newly diagnosed stage II-IV anaplastic large cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in targeted way and delivers vedotin to kill them. Crizotinib and methotrexate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether brentuximab vedotin and combination chemotherapy is more effective than crizotinib and combination chemotherapy in treating anaplastic large cell lymphoma.

    Stanford is currently not accepting patients for this trial.

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  • Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Not Recruiting

    This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed neuroblastoma that is likely to come back or spread. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-736-4281.

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  • Calaspargase Pegol or Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia Not Recruiting

    This randomized clinical trial is studying giving calaspargase pegol together with combination chemotherapy to see how well it works compared with giving pegaspargase together with combination chemotherapy in treating younger patients with newly diagnosed high-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL) Not Recruiting

    This Phase II trial is studying how well giving epratuzumab together with an established chemotherapy platform works in treating young patients with relapsed acute lymphoblastic leukemia. Monoclonal antibodies, such as epratuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing them or by stopping them from dividing. Giving monoclonal antibody therapy in combination chemotherapy may kill cancer cells more effectively.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET Not Recruiting

    This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Carissa Bailey, (650) 725 - 4708.

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  • Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors Not Recruiting

    This phase II trial studies how well chemotherapy followed by radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors that have not spread to other parts of the brain, spinal canal, or body (localized). Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x rays to kill tumor cells. Giving chemotherapy followed by radiation therapy may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-497-8953.

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  • Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease Not Recruiting

    This randomized phase III trial is studying different chemotherapy regimens given with or without radiation therapy to compare how well they work in treating children with newly diagnosed Hodgkin's disease. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known if chemotherapy is more effective with or without additional chemotherapy and/or radiation therapy in treating Hodgkin's disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy Not Recruiting

    This phase II trial studies how well cilengitide works in treating younger patients with recurrent or progressive high-grade glioma that has not responded to standard therapy. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor Not Recruiting

    This phase III clinical trial is studying how well cisplatin-based chemotherapy and/or surgery works in treating young patients with stage I, stage II, stage III or stage IV adrenocortical cancer. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pediatric Hematology/Oncology, (650) 497 - 8953.

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  • Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma Not Recruiting

    This phase II trial studies how well cixutumumab and temsirolimus work in treating patients with recurrent or refractory sarcoma. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab and temsirolimus together may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Amie Denisova, (650) 497 - 8966.

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  • Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors Not Recruiting

    This phase II trial is studying the side effects and how well cixutumumab works in treating patients with relapsed or refractory solid tumors. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Collecting and Storing Biological Samples From Patients With Ewing Sarcoma Not Recruiting

    This research study is collecting and storing samples of tumor tissue, bone marrow, and blood from patients with Ewing sarcoma. Collecting and storing samples of tumor tissue, bone marrow, and blood from patients with cancer to test in the laboratory may help the study of cancer in the future.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem Onc CRAs, 650-723-5535.

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  • Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer Not Recruiting

    This study is collecting and storing malignant, borderline malignant neoplasms, and related biological samples from young patients with cancer. Collecting and storing samples of tumor tissue, blood, and bone marrow from patients with cancer to study in the laboratory may help the study of cancer in the future.

    Stanford is currently not accepting patients for this trial.

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  • Collecting and Storing Samples of Blood and Tumor Tissue From Patients With Osteosarcoma Not Recruiting

    The purpose of this study is to collect and store samples of blood and tumor tissue from patients with osteosarcoma. Collecting and storing samples of tumor tissue and blood from patients to test in the laboratory may help the study of cancer in the future.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-726-4281.

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  • Collecting and Storing Samples of Bone Marrow and Blood From Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma Not Recruiting

    This research study is collecting and storing samples of bone marrow and blood from patients with relapsed acute lymphoblastic leukemia or relapsed non-Hodgkin lymphoma. Collecting and storing samples of bone marrow and blood from patients with cancer to study in the laboratory may help doctors learn more about cancer and help predict the recurrence of cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-726-4281.

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  • Collecting and Storing Tissue Samples From Patients With Rare or Cutaneous Non-Hodgkin Lymphoma Not Recruiting

    This research study is collecting and storing tissue samples from patients with rare or cutaneous non-Hodgkin lymphoma. Collecting and storing samples of tissue from patients with cancer to test in the laboratory may help the study of cancer in the future.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-723-5535.

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  • Collecting and Storing Tissue, Blood, and Bone Marrow Samples From Patients With Rhabdomyosarcoma or Other Soft Tissue Sarcoma Not Recruiting

    The purpose of this study is to collect and store tumor tissue, blood, and bone marrow samples from patients with soft tissue sarcoma that will be tested in the laboratory. Collecting and storing samples of tumor tissue, blood, and bone marrow from patients to test in the laboratory may help the study of cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-726-4281.

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  • Combination Chemotherapy and Radiation Therapy in Treating Patients With Acute Lymphoblastic Leukemia That Has Relapsed in the CNS or Testes Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells. PURPOSE: This clinical trial is studying how well giving chemotherapy together with radiation therapy works in treating patients with acute lymphoblastic leukemia that has relapsed in the CNS and/or testes.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 725 - 1662.

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  • Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma Not Recruiting

    This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with radiation therapy in treating patients with rhabdomyosarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor Not Recruiting

    This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-497-8953.

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  • Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, and doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Isotretinoin may help neuroblastoma cells become more like normal cells, and grow and spread more slowly. Giving combination chemotherapy before surgery may make the tumor smaller and make it more likely that the tumor can be surgically removed. It is not yet known what is the minimal amount of chemotherapy needed to achieve sufficient tumor shrinkage to control intermediate risk neuroblastoma and prevent tumor recurrence or metastases. PURPOSE: This phase III trial is designed to reduce therapy for patients with favorable biology intermediate risk neuroblastoma by decreasing the number of chemotherapy cycles administered and by allowing for up to 50% residual tumor volume for patients with localized disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Enas Mohamed, (650) 725 - 1662.

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  • Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effect on the body of combining cyclophosphamide with cisplatin, etoposide, and bleomycin in treating children who have newly diagnosed malignant germ cell tumors that are not in the brain and gonads.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma Not Recruiting

    This randomized phase III trial studies combination chemotherapy to see how well it works compared to combination chemotherapy with topotecan hydrochloride in treating patients with extracranial Ewing sarcoma that has not spread from the primary site to other places in the body. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, etoposide, and topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective with topotecan hydrochloride in treating Ewing sarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem Onc CRAs, 650-723-5535.

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  • Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes Not Recruiting

    This phase III trial is studying how well combination chemotherapy works in treating young patients with Down syndrome and acute myeloid leukemia or myelodysplastic syndromes. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Dechant, (650) 724 - 3063.

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  • Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Not Recruiting

    This randomized phase III trial is studying different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact LPCH New Patient Coordinator, (650) 725 - 1072.

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  • Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia Not Recruiting

    This phase III trial is studying combination chemotherapy to see how well it works in treating young patients with newly diagnosed acute promyelocytic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations Not Recruiting

    This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-736-4281.

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  • Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma Not Recruiting

    This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. After a common induction therapy, patients were risk assigned and eligible for one or both post-induction randomizations: Escalating dose Methotrexate versus High Dose Methotrexate in Interim Maintenance therapy, No Nelarabine versus Nelarabine in Consolidation therapy. T-ALL patients are risk assigned as Low Risk, Intermediate Risk or High Risk. Low Risk patients are not eligible for the Nelarabine randomization, Patients with CNS disease at diagnosis were assgined to receive High Dose Methotrexate, patients who failed induction therapy were assigned to receive Nelarabine and High Dose Methotrexate. T-LLy patients were all assigned to escalating dose Methotrexate and were risk assigned as Standard Risk, High Risk and induction failures. Standard risk patients did not receive nelarabine, High risk T-LLy patients were randomized to No Nelarabine versus Nelarabine, and Induction failures were assigned to receive Nelarabine.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pediatric Hematology/Oncology, (650) 497 - 8953.

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  • Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors Not Recruiting

    This phase II trial is studying how well giving combination chemotherapy works in treating young patients with recurrent or resistant malignant germ cell tumors. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma Not Recruiting

    This randomized phase III trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa M. Marina, 650-498-7061.

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  • Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma Not Recruiting

    This randomized phase III trial studies how well combination chemotherapy with or without ganitumab works in treating patients with newly diagnosed Ewing sarcoma that has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as ganitumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether combination chemotherapy is more effective with or without ganitumab in treating patients with newly diagnosed Ewing sarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa M. Marina, 650-498-7061.

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  • Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Not Recruiting

    This phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Combination Chemotherapy With or Without Peripheral Stem Cell Transplantation, Radiation Therapy, and/or Surgery in Treating Patients With Ewing's Sarcoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more tumor cells. It is not yet known if combination chemotherapy is more effective with or without radiation therapy and/or surgery in treating Ewing's sarcoma. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to see how well they work when given with or without peripheral stem cell transplantation, radiation therapy, and/or surgery in treating patients with Ewing's sarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Favorable-Risk Hodgkin Lymphoma Not Recruiting

    This phase II trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with favorable-risk Hodgkin lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, mechlorethamine hydrochloride, vincristine sulfate, bleomycin, etoposide, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells for those patients that still had residual cancer at the end of chemotherapy. Giving combination chemotherapy with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650-726-4281.

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  • Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Newly Diagnosed Stage III or Stage IV Wilms' Tumor Not Recruiting

    This phase III trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with newly diagnosed stage III or stage IV Favorable Histology Wilms' tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 725 - 1662.

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  • Combination Chemotherapy, Autologous Stem Cell Transplant, and/or Radiation Therapy in Treating Young Patients With Extraocular Retinoblastoma Not Recruiting

    This phase III trial is studying the side effects and how well giving combination chemotherapy together with autologous stem cell transplant and/or radiation therapy works in treating young patients with extraocular retinoblastoma. Giving chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient?s blood and/or bone marrow and stored. More chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Radiation therapy uses high energy x-rays to kill tumor cells. Giving radiation therapy after combination chemotherapy and/or autologous stem cell transplant may kill any remaining tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lan Wang, (650) 723 - 5535.

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  • Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma Not Recruiting

    This randomized phase III trial is studying combination chemotherapy followed by surgery and two different combination chemotherapy regimens with or without PEG-interferon alfa-2b to compare how well they work in treating patients with osteosarcoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Biological therapies, such as PEG-interferon alfa-2b, may interfere with the growth of tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so it can be removed. Giving combination chemotherapy together with PEG-interferon alfa-2b after surgery may kill any remaining tumor cells. It is not yet known whether giving combination therapy together with PEG-interferon alfa-2b is more effective than two different combination chemotherapy regimens alone after surgery in treating osteosarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors Not Recruiting

    This phase II trial is studying how well combination chemotherapy, radiation therapy, and/or surgery work in treating patients with high-risk kidney tumors. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Combination Chemotx in Treating Children or Adolescents With Newly Diagnosed Stg III or Stg IV Lymphoblastic Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which regimen of combination chemotherapy is most effective for lymphoblastic lymphoma. PURPOSE: This randomized phase III trial is studying different regimens of combination chemotherapy to compare how well they work in treating children or adolescents with newly diagnosed stage III or stage IV lymphoblastic lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma Not Recruiting

    This randomized phase III trial compares two different high-dose chemotherapy regimens followed by a stem cell transplant in treating younger patients with high-risk neuroblastoma. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments before a peripheral blood stem cell transplant helps kill any tumor cells that are in the body and helps make room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. High-dose chemotherapy and radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the high- chemotherapy. It is not yet known which regimen of high-dose chemotherapy is more effective for patients with high-risk neuroblastoma undergoing a peripheral blood stem cell transplant.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem mukhtar, (650) 725 - 1662.

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  • Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma Not Recruiting

    This randomized phase III trial is studying how well standard-dose radiation therapy works compared to reduced-dose radiation therapy in children 3-7 years of age AND how well standard volume boost radiation therapy works compared to smaller volume boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy is more effective than reduced-dose radiation therapy when given together with chemotherapy after surgery in treating young patients with medulloblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Consent for Obtaining Additional Bone Marrow Specimens at Time of Diagnostic Bone Marrow Procedure Not Recruiting

    The purpose of this study is to collect bone marrow samples for experimental studies.

    Stanford is currently not accepting patients for this trial.

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  • Consent for Obtaining Additional Tissue at the Time of a Diagnostic Biopsy Not Recruiting

    This study is designed to collect tissue samples that may aid in the treatment and learning about various oncology diagnosis.

    Stanford is currently not accepting patients for this trial.

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  • Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma Not Recruiting

    This randomized phase III trial is studying cyclophosphamide, prednisone, and immunoglobulin to see how well they work compared to cyclophosphamide and prednisone alone in treating patients with abnormal eye and trunk muscle movements (known as opsoclonus myoclonus ataxia) associated with neuroblastoma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Steroid therapy decreases inflammation. Combining chemotherapy and steroid therapy with immunoglobulin may be effective in treating abnormal muscle movement associated with neuroblastoma. Chemotherapy(cyclophosphamide), prednisone and intravenous gamma globulin all suppress the immune system which may be helpful in treating opsoclonus-myoclonus-ataxia (OMA).

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa Marina, (650) 723 - 5535.

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  • Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation Not Recruiting

    RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, prednisone, and methylprednisolone use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining cyclophosphamide and either prednisone or methylprednisolone with rituximab may be effective in treating lymphoproliferative disease following organ transplantation. PURPOSE: Phase II trial to study the effectiveness of combining cyclophosphamide and either prednisone or methylprednisolone with rituximab in treating patients who have Epstein-Barr virus-positive lymphoproliferative disease following organ transplantation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Cytarabine in Treating Young Patients With Recurrent or Refractory Ewing's Sarcoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well cytarabine works in treating young patients with recurrent or refractory Ewing's sarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Not Recruiting

    This phase II/III trial is studying the side effects and how well giving dasatinib together with combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia (ALL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with combination chemotherapy may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle DeChant, (650) 724 - 3063.

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  • Dasatinib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate Not Recruiting

    This phase I trial is studying the side effects and best dose of dasatinib in treating young patients with recurrent or refractory solid tumors or Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myelogenous leukemia that did not respond to imatinib mesylate. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa Marina, (650) 723 - 5535.

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  • Dexamethasone Compared With Prednisone During Induction Therapy and MTX With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as dexamethasone, prednisone, methotrexate, and leucovorin calcium (LCV), work in different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia. PURPOSE: This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy. This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma Not Recruiting

    Diagnostic trial to study genetic differences in patients who have Ewing's sarcoma. Genetic testing may help predict how cancer will respond to treatment and allow doctors to plan more effective therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Enrollment on the Childhood Cancer Research Network (CCRN) of the Children s Oncology Group Not Recruiting

    Background: - The Children s Oncology Group has established a research network, the Childhood Cancer Research Network (CCRN), to collect information about children with cancer and other conditions that are benign but involve abnormal cell growth in order to help doctors and scientists better understand childhood cancer. The CCRN's goal is to collect clinical information about every child diagnosed with cancer and similar conditions in the United States and Canada, to allow researchers to study patterns, characteristics, and causes of childhood cancer. The information can also help researchers study the causes of childhood cancer. To expand the CCRN, parents of children who have been diagnosed with cancer will be asked to provide information about themselves and their child for research purposes. Objectives: - To obtain informed consent from parents (and the child, when appropriate) of infants, children, adolescents, and young adults newly diagnosed with cancer to enter their names and certain information concerning their child into the Childhood Cancer Research Network. - To obtain informed consent from parents (and the child, when appropriate) of infants, children, adolescents, and young adults newly diagnosed with cancer for permission to be contacted in the future to consider participating in non-therapeutic and prevention research studies involving the parents and/or the child. Eligibility: - Parents of children who have been seen at or treated by a hospital that is a member of the Children s Oncology Group. Design: - Parents will provide permission to have personal information sent from their child s hospital to the CCRN, including the child and parents' names; child's gender, birth date, race, and ethnicity; information about the disease; and the treating institution. - Parents will also give permission for CCRN to contact the diagnostic laboratory to obtain specific information about the tumor or cancer cells. - Parents will be asked if they are willing to be contacted in the future to consider participating in CCRN research studies, and will provide contact information (name, home address, and telephone number) to be entered in the CCRN. - Parents or patients who change their minds about having information available in the CCRN can ask the treatment institution to restrict access to the identifying information. Parents or patients who refuse to have information included in the CCRN or be contacted in the future will still be able to enter clinical cancer research studies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-723-5535.

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  • Erlotinib Versus Oral Etoposide in Patients With Recurrent or Refractory Pediatric Ependymoma Not Recruiting

    This is a phase 2 study to evaluate the efficacy of single-agent erlotinib versus oral etoposide in patients with recurrent or refractory pediatric ependymoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Carissa Bailey, (650) 725 - 4708.

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  • Erwinase Master Treatment Protocol Not Recruiting

    The purpose of this study is to make Erwinase available to patients with acute lymphoblastic leukemia (ALL) who have had previous allergic reactions to certain formulations of L-asparaginase.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 725 - 1662.

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  • Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia Not Recruiting

    This clinical trial is studying the side effects of Erwinia asparaginase and what happens to the drug in the body in treating young patients with acute lymphoblastic leukemia who are allergic to PEG-asparaginase. Drugs used in chemotherapy, such as Erwinia asparaginase, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Etanercept in Treating Young Patients With Idiopathic Pneumonia Syndrome After Undergoing a Donor Stem Cell Transplant Not Recruiting

    This phase II trial is studying how well etanercept works in treating young patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant. Etanercept may be effective in treating patients with idiopathic pneumonia syndrome after undergoing a donor stem cell transplant.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Fragmin for the Treatment of Acute VTE in Pediatric Cancer Patients Not Recruiting

    Three month treatment of acute VTE with Fragmin in pediatric cancer patients

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 725 - 1662.

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  • Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia Not Recruiting

    This phase I/II clinical trial is studying the side effects and best dose of gamma-secretase inhibitor RO4929097 and to see how well it works in treating young patients with relapsed or refractory solid tumors, CNS tumors, lymphoma, or T-cell leukemia. Gamma-secretase inhibitor RO4929097 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Genomic Analysis of Pediatric Bone Tumors Not Recruiting

    To determine whether gene expression analysis of primary tumor samples before and after chemotherapy are predictive of long-term survival in pediatric patients with bone sarcomas (Ewings sarcoma (ES) and Osteosarcoma(OS)).

    Stanford is currently not accepting patients for this trial. For more information, please contact Alejandro Sweet-Cordero, 650-725-5901.

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  • High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as vincristine, irinotecan, ifosfamide, etoposide, doxorubicin, cyclophosphamide, and dactinomycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving high-dose combination chemotherapy together with radiation therapy may kill more tumor cells. PURPOSE: This phase III trial is studying how well giving high-dose combination chemotherapy together with radiation therapy works in treating patients with newly diagnosed metastatic rhabdomyosarcoma or ectomesenchymoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • hu14.18-Interleukin-2 Fusion Protein in Treating Young Patients With Recurrent or Refractory Neuroblastoma Not Recruiting

    RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein work in different ways to stimulate the immune system and stop tumor cells from growing. PURPOSE: This phase II trial is studying how well hu14.18-interleukin-2 fusion protein works in treating young patients with recurrent or refractory neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact LPCH New Patient Coordinator, (650) 725 - 1072.

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  • Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) Recurrence of Osteosarcoma Not Recruiting

    RATIONALE: Inhaling aerosolized sargramostim before and after surgery may interfere with the growth of tumor cells and shrink the tumor so that it can be removed during surgery. Sargramostim may then kill any tumor cells remaining after surgery. This may be an effective treatment for osteosarcoma that has spread to the lung. PURPOSE: This phase II trial is studying how well inhaled sargramostim works in treating patients who are undergoing surgery for the first recurrence of osteosarcoma that has spread to the lung.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Intergroup Trial for Children or Adolescents With Primary Mediastinal Large B-Cell Lymphoma: DA-EPOCH-Rituximab Evaluation Not Recruiting

    Phase II trial to determine the efficacy of Dose Adjusted-EPOCH-Rituximab regimen in children and adolescent with primary mediastinal large B cell lymphoma in terms of event free survival.

    Stanford is currently not accepting patients for this trial.

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  • Irinotecan Hydrochloride and Temozolomide With Temsirolimus or Dinutuximab in Treating Younger Patients With Refractory or Relapsed Neuroblastoma Not Recruiting

    This randomized phase II trial studies how well irinotecan hydrochloride and temozolomide with temsirolimus or dinutuximab work in treating younger patients with neuroblastoma that has returned or does not respond to treatment. Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as dinutuximab, may find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving irinotecan hydrochloride and temozolomide together with temsirolimus or dinutuximab is more effective in treating neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa M. Marina, 650-498-7061.

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  • Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma Not Recruiting

    This partially randomized phase III trial studies isotretinoin with dinutuximab, aldesleukin, and sargramostim to see how well it works compared to isotretinoin alone following stem cell transplant in treating patients with neuroblastoma. Drugs used in chemotherapy, such as isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as dinutuximab, may block tumor growth in different ways by targeting certain cells. Aldesleukin and sargramostim may stimulate a person's white blood cells to kill cancer cells. It is not yet known if chemotherapy is more effective with or without dinutuximab, aldesleukin, and sargramostim following stem cell transplant in treating neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Ixabepilone in Treating Young Patients With Refractory Solid Tumors Not Recruiting

    This phase II trial is studying how well ixabepilone works in treating young patients with refractory solid tumors. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Norman Lacayo, (650) 723 - 5535.

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  • Lenalidomide and Dinutuximab With or Without Isotretinoin in Treating Younger Patients With Refractory or Recurrent Neuroblastoma Not Recruiting

    This phase I trial studies the side effects and best dose of lenalidomide when given together with dinutuximab with or without isotretinoin in treating younger patients with neuroblastoma that does not respond to treatment or that has come back. Drugs used in chemotherapy, such as lenalidomide and isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as dinutuximab, may interfere with the ability of tumor cells to grow and spread. Giving more than one drug (combination chemotherapy) together with dinutuximab therapy may kill more tumor cells.

    Stanford is currently not accepting patients for this trial.

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  • Lenalidomide in Treating Young Patients With Relapsed or Refractory Solid Tumors or Myelodysplastic Syndromes Not Recruiting

    This phase I trial is studying the side effects and best dose of lenalidomide in treating young patients with relapsed or refractory solid tumors or myelodysplastic syndromes. Lenalidomide may stop the growth of solid tumors or myelodysplastic syndromes by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing.

    Stanford is currently not accepting patients for this trial. For more information, please contact LPCH New Patient Coordinator, (650) 725 - 1072.

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  • Linsitinib in Treating Patients With Gastrointestinal Stromal Tumors Not Recruiting

    This phase II trial studies how well linsitinib works in treating younger and adult patients with gastrointestinal stromal tumors. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Ahern, 650-725-6413.

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  • Long-Term Effects of Treatment in Patients Previously Treated for Childhood Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Assessing the long-term effects of cancer treatment in cancer survivors may help improve the ability to plan effective treatment and follow-up care. PURPOSE: This clinical trial is studying the long-term effects of treatment in patients who were previously treated for childhood Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma Not Recruiting

    This randomized phase II trial studies how well low-dose lenalidomide works compared with high-dose lenalidomide in treating younger patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas that have come back (recurrent), have not responded to treatment (refractory), or are growing, spreading, or getting worse (progressive). Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether low-dose lenalidomide is more or less effective than high-dose lenalidomide in treating patients with juvenile pilocytic astrocytomas or optic nerve pathway gliomas.

    Stanford is currently not accepting patients for this trial. For more information, please contact Carissa Bailey, 650-725-4708.

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  • Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia Not Recruiting

    This randomized phase III trial is studying low-dose vincristine to see how well it works compared with high-dose vincristine when given together with different combination chemotherapy regimens in treating young patients with intermediate-risk relapsed B-cell acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different ways and different doses may kill more cancer cells..

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Modafinil in Treating Children With Memory and Attention Problems Caused by Cancer Treatment for a Brain Tumor Not Recruiting

    RATIONALE: Modafinil may help improve memory, attention, and fatigue caused by cancer treatment. PURPOSE: This phase II randomized trial studies how well modafinil works in treating children with memory and attention problems caused by cancer treatment for a brain tumor.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-723-5535.

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  • Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma Not Recruiting

    This phase III trial is studying the side effects of giving monoclonal antibody Ch14.18 together with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant in treating patients with neuroblastoma. Monoclonal antibodies, such as Ch14.18, may find tumor cells and help kill them. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white blood cells to kill tumor cells. Isotretinoin may help neuroblastoma cells become more like normal cells, and to grow and spread more slowly. Giving monoclonal antibody Ch14.18 with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant may be an effective treatment for neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • N2004-06: Irinotecan and Vincristine With 131I-MIBG Therapy for Resistant/Relapsed High-Risk Neuroblastoma Not Recruiting

    RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine (MIGB), may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as irinotecan and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving iodine I 131 MIGB together with irinotecan and vincristine may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of iodine I 131 MIGB when given together with irinotecan and vincristine in treating young patients with resistant or relapsed high-risk neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Natural History Study of Infants With Adrenal Masses Found on Prenatal and/or Neonatal Imaging Not Recruiting

    This natural history study is collecting health information about infants with adrenal masses found on prenatal and/or neonatal imaging. Gathering information over time from imaging and laboratory tests of infants with adrenal masses may help doctors learn more about the disease and plan the best treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa Marina, (650) 723 - 5535.

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  • Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it is no longer present by conventional imaging and tumor markers from serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill more tumor cells. PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without surgery and with or without high dose chemotherapy and peripheral stem cell transplantation, can increase response rates prior to radiation therapy and increase progression free and overall surviving patients with newly diagnosed intracranial germ cell tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Observation or Radiation Therapy and/or Chemotherapy and Second Surgery in Treating Children Who Have Undergone Surgery for Ependymoma Not Recruiting

    RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Phase II trial to determine the effectiveness of specialized radiation therapy either alone or after chemotherapy and second surgery in treating children who have undergone surgery for localized ependymoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma Not Recruiting

    This phase III trial is studying observation to see how well a risk based treatment strategy works in patients with soft tissue sarcoma. In the study, patients are assigned to receive surgery +/- radiotherapy +/- chemotherapy depending on their risk of recurrence. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 725 - 1662.

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  • Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients. Not Recruiting

    To evaluate the safety, efficacy and pharmacokinetics of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to <18 years).

    Stanford is currently not accepting patients for this trial. For more information, please contact Contact, 650-723-5117.

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  • Pazopanib Paediatric Phase II Trial Children's Oncology Group (COG) in Solid Tumors Not Recruiting

    The study design was an open-label Phase II pediatric clinical study. The purpose of Study X2203 was to identify any efficacy signal in subjects with the disease subtypes under study, when treated with pazopanib monotherapy. Furthermore, it was to define the toxicities of pazopanib in children, as well as examine biological markers, e.g. cytokines and angiogenic factors, that could help further characterize any response of pazopanib in children. Pazopanib was administered as monotherapy in tablet and powder suspension formulations at daily doses of 450 mg/m2/dose or 225 mg/m2/dose, respectively. The first 6 enrolled subjects receiving oral suspension formulation were assessed for tolerability and extended PK sampling; and, only if pazopanib was tolerated, subsequent subjects were enrolled at the same starting dose with the suspension. Dose escalation was not permitted. For the tablet, a dosing nomogram was used based on the subject's BSA. Dose reduction was dependent upon the toxicity of pazopanib and disease status of the infants, toddlers, children, adolescents, and young adults. Subjects could be as young as 1 year-old infants to screen for enrollment. Subjects were assessed for initial response after 8 weeks of treatment prior to Cycle 3. A cycle was defined as 28 days of pazopanib treatment with no rest period between cycles. Treatment was administered continuously once daily. Treatment was to be discontinued if there was evidence of disease progression, unacceptable treatment-related toxicity, pregnancy. Histological classification was an important diagnostic inclusion in these subjects with a wide variety of refractory solid tumors, i.e. 7 different tumor types and each being a cohort.

    Stanford is currently not accepting patients for this trial.

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  • Pediatric Philadelphia Positive Acute Lymphoblastic Leukemia Not Recruiting

    The purpose of this study is to determine whether Dasatinib when added to standard chemotherapy is effective and safe in the treatment of pediatric philadelphia chromosome positive acute lymphoblastic leukemia

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson Falwell, 650736428.

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  • Pharmacokinetics of Daunorubicin in Young Patients With Cancer Not Recruiting

    This laboratory study is looking at the pharmacokinetics of daunorubicin in young patients with cancer. Collecting and storing samples of blood from patients with cancer to study in the laboratory may help doctors learn more about how patients respond to treatment with certain chemotherapy drugs.

    Stanford is currently not accepting patients for this trial. For more information, please contact Alyson A. Falwell, 650-736-4281.

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  • Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma Not Recruiting

    To establish whether treatment with Inhaled Lipid Cisplatin (ILC) is effective in delaying/preventing pulmonary relapse in osteosarcoma patients in complete surgical remission following one or two prior pulmonary relapses.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-497-8953.

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  • Phase I Rindopepimut After Conventional Radiation in Children w/ Diffuse Intrinsic Pontine Gliomas Not Recruiting

    This is a research study of patients with diffuse intrinsic pontine gliomas. We hope to learn about the safety and efficacy of treating pediatric diffuse intrinsic pontine glioma patients with the EGFRvIII peptide vaccine after conventional radiation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christina Huang, 650-723-0574.

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  • Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy alone is as effective as chemotherapy plus radiation therapy in treating germ cell tumor. PURPOSE: This randomized phase III trial is studying radiation therapy alone to see how well it works compared to chemotherapy and radiation therapy in treating patients with newly diagnosed primary CNS germ cell tumor.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery Not Recruiting

    This randomized phase II/III trial studies how well pazopanib, when combined with chemotherapy and radiation therapy or radiation therapy alone, work in the treatment of patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can eventually be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether these therapies can be safely combined and if they work better when given together in treating patients with non-rhabdomyosarcoma soft tissue sarcomas.

    Stanford is currently not accepting patients for this trial. For more information, please contact Neyssa M. Marina, 650-498-7061.

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  • Radiation Therapy, Amifostine, and Chemotherapy in Treating Young Patients With Newly Diagnosed Nasopharyngeal Cancer Not Recruiting

    This phase III trial is studying how well radiation therapy, amifostine, and chemotherapy work in treating young patients with newly diagnosed nasopharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as amifostine, may protect normal cells from the side effects of radiation therapy. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with amifostine and chemotherapy may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jenniver Lew, (650) 725 - 4318.

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  • Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas Not Recruiting

    RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells. PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma Not Recruiting

    This phase III trial studies how well response and biology-based risk factor-guided therapy works in treating younger patients with non-high risk neuroblastoma. Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Measuring biomarkers in tumor cells may help plan when effective treatment is necessary and what the best treatment is. Response and biology-based risk factor-guided therapy may be effective in treating patients with non-high risk neuroblastoma and may help to avoid some of the risks and side effects related to standard treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-498-7061.

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  • Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma Not Recruiting

    This partially randomized phase III trial studies the side effects of different combinations of risk-adapted chemotherapy regimens and how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia or B-lineage lymphoblastic lymphoma that is found only in the tissue or organ where it began (localized). Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem Onc CRAs, 650-723-5535.

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  • Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma Not Recruiting

    RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat brain tumors in young children. Using chemotherapy gives the brain more time to develop before radiation is given. The chemotherapy in this study includes the drug methotrexate. This drug was an important part of the two clinical trials which resulted in the best survival results for children less than 3 years of age with medulloblastoma. Most patients treated on this trial will also receive radiation which is carefully targeted to the area of the tumor. This type of radiation (focal conformal or proton beam radiotherapy) may result in fewer problems with thinking and learning than radiation to the whole brain and spinal cord. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem Onc CRAs, 650-723-5535.

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  • Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Not Recruiting

    This research trial studies a risk-based classification system for patients with newly diagnosed acute lymphoblastic leukemia. Gathering health information about patients with acute lymphoblastic leukemia may help doctors learn more about the disease and plan the best treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem Onc CRAs, 650-723-5535.

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  • Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer Not Recruiting

    This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver cancer. Surgery, chemotherapy drugs (cancer fighting medicines), and when necessary, liver transplant, are the main current treatments for hepatoblastoma. The stage of the cancer is one factor used to decide the best treatment. Treating patients according to the risk group they are in may help get rid of the cancer, keep it from coming back, and decrease the side effects of chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem Onc CRAs, 650-723-5535.

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  • Risk-Group Classification of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Not Recruiting

    This clinical trial is studying risk-group classification of patients with newly diagnosed acute lymphoblastic leukemia. Developing a risk-group classification guide may help doctors assign patients with newly diagnosed acute lymphoblastic leukemia to treatment clinical trials.

    Stanford is currently not accepting patients for this trial. For more information, please contact LPCH New Patient Coordinator, (650) 725 - 1072.

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  • Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205 Not Recruiting

    Participants that were assigned to the oral etoposide treatment arm in protocol OSI-774-205 and either progressed while on study or discontinued due to unacceptable toxicity related to etoposide were allowed to participate in this study to assess the safety profile of single-agent erlotinib in participants with recurrent or refractory pediatric ependymoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Carissa Bailey, (650) 725 - 4708.

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  • Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy Not Recruiting

    RATIONALE: Sodium thiosulfate may reduce or prevent hearing loss in young patients receiving cisplatin for cancer. It is not yet known whether sodium thiosulfate is more effective than no additional treatment in preventing hearing loss. PURPOSE: This randomized phase III trial is studying sodium thiosulfate to see how well it works in preventing hearing loss in young patients receiving cisplatin for newly diagnosed germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or other malignancy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Sorafenib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia Not Recruiting

    This phase I/II trial is studying the side effects and best dose of sorafenib in treating young patients with relapsed or refractory solid tumors or leukemia. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Study of Blood Samples From Newborns With Down Syndrome Not Recruiting

    This research study is looking at blood samples from newborns with Down syndrome. Studying the genes expressed in samples of blood from patients with Down syndrome may help doctors identify biomarkers related to cancer.

    Stanford is currently not accepting patients for this trial.

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  • Sulindac and Tamoxifen in Treating Patients With Desmoid Tumor Not Recruiting

    This phase II trial is studying how well giving sulindac together with tamoxifen works in treating patients with desmoid tumor. Sulindac may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Hormone therapy using tamoxifen may fight cancer by blocking the use of estrogen. Combining sulindac with tamoxifen may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Sunitinib Malate in Treating Younger Patients With Recurrent, Refractory, or Progressive Malignant Glioma or Ependymoma Not Recruiting

    This phase II trial studies how well sunitinib malate works in treating younger patients with recurrent, refractory, or progressive malignant glioma or ependymoma. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christina Huang, 650-723-0574.

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  • Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors Not Recruiting

    This phase III trial is studying surgery followed by combination chemotherapy to see how well it works in treating children with germ cell tumors that are not located in the head. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is effective in decreasing the recurrence of childhood germ cell tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Surgery and/or Chemotherapy in Treating Children With Infantile, Congenital, or Childhood Fibrosarcoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed. Giving combination chemotherapy after surgery may kill any remaining tumor cells. PURPOSE: This phase II trial is studying how well surgery and/or combination chemotherapy work in treating children with fibrosarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Symptom Assessment With Patient Surveys Not Recruiting

    The primary purpose of the proposed research is to explore methods of obtaining symptom assessments from pediatric oncology patients and/or their caregivers in hopes of improving the accuracy and thoroughness of these reports. Additionally the researchers hope to simply staff efforts in obtaining detailed medical histories from pediatric oncology patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christina Baggott, (650) 497 - 8815.

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  • Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors Not Recruiting

    This randomized phase II trial studies how well giving temozolomide and irinotecan hydrochloride together with or without bevacizumab works in treating young patients with recurrent or refractory medulloblastoma or central nervous system (CNS) primitive neuroectodermal tumors. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide and irinotecan hydrochloride are more effective with or without bevacizumab in treating medulloblastoma or CNS primitive neuroectodermal tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-497-8953.

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  • Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma Not Recruiting

    This randomized pilot clinical trial is studying the side effects and how well giving temozolomide and cixutumumab together with combination chemotherapy works in treating patients with metastatic rhabdomyosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving temozolomide and cixutumumab together with combination chemotherapy may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Muktar Nadeem, (650) 497 - 8815.

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  • Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as temozolomide, vincristine, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with temozolomide and vincristine in treating young patients with refractory solid tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Topotecan, G-CSF, and Radiation Therapy in Treating Young Patients With Newly Diagnosed Brain Stem Glioma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Topotecan may make tumor cells more sensitive to radiation therapy . Giving topotecan and G-CSF together with radiation therapy may be an effective treatment for brain stem glioma. PURPOSE: This phase I/II trial is studying the side effects and best dose of topotecan when given together with G-CSF and radiation therapy and to see how well they work in treating young patients with newly diagnosed brain stem glioma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors Not Recruiting

    This phase II trial is studying how well trabectedin works in treating young patients with recurrent or refractory soft tissue sarcoma or Ewing's family of tumors. Drugs used in chemotherapy such as trabectedin use different ways to stop tumor cells from dividing so they stop growing or die.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia Not Recruiting

    This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly diagnosed acute promyelocytic leukemia. Standard treatment for acute promyelocytic leukemia involves high doses of a common class of chemotherapy drugs called anthracyclines, which are known to cause long-term side effects, especially to the heart. Tretinoin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Arsenic trioxide may stop the growth of cancer cells by either killing the cells, by stopping them from dividing, or by stopping them from spreading. Completely removing or reducing the amount of anthracycline chemotherapy and giving tretinoin together with arsenic trioxide may be an effective treatment for acute promyelocytic leukemia and may reduce some of the long-term side effects.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Two Regimens of Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed Localized Ewing Sarcoma Family of Tumors Not Recruiting

    This clinical trial is studying the side effects of combination chemotherapy and to see how well they work in treating patients with newly diagnosed localized Ewing sarcoma family of tumors. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different ways may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Valproic Acid in Treating Young Patients With Recurrent or Refractory Solid Tumors or CNS Tumors Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as valproic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Valproic acid may also stop the growth of solid tumors or CNS tumors by blocking blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and best dose of valproic acid in treating patients with recurrent or refractory solid tumors or CNS tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact LPCH New Patient Coordinator, (650) 725 - 1072.

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  • Vincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide With or Without Bevacizumab in Treating Young Patients With Refractory or First Recurrent Extracranial Ewing Sarcoma Not Recruiting

    This phase II trial study has a 6-patient feasibility portion studying the tolerability of chemotherapy with vincristine sulfate together with topotecan hydrochloride, cyclophosphamide, and bevacizumab in treating young patients with refractory or first recurrent extracranial Ewing's sarcoma. If the therapy is considered tolerable, this feasibility run-in will be followed by a randomized phase II portion studying giving vincristine sulfate together with topotecan hydrochloride, and cyclophosphamide to see how well it works compared with giving vincristine sulfate together with topotecan hydrochloride, cyclophosphamide, and bevacizumab in treating young patients with refractory or first recurrent extracranial Ewing's sarcoma. Drugs used in chemotherapy, such as vincristine sulfate, topotecan hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop tumor growth by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Vincristine, Carboplatin, and Etoposide or Observation Only in Treating Patients Who Have Undergone Surgery for Newly Diagnosed Retinoblastoma Not Recruiting

    This phase III trial is studying vincristine, carboplatin, and etoposide to see how well they work compared to observation only in treating patients who have undergone surgery for newly diagnosed retinoblastoma. Drugs used in chemotherapy, such as vincristine, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, no additional treatment is needed for the tumor until it progresses. In this case, observation may be sufficient.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Vincristine, Dactinomycin, and Cyclophosphamide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma Not Recruiting

    This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine, dactinomycin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective in treating low-risk rhabdomyosarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor Not Recruiting

    This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lan Wang, (650) 725 - 4708.

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  • Vinorelbine Tartrate and Cyclophosphamide in Combination With Bevacizumab or Temsirolimus in Treating Patients With Recurrent or Refractory Rhabdomyosarcoma Not Recruiting

    This randomized phase II trial studies how well vinorelbine tartrate and cyclophosphamide work in combination with bevacizumab or temsirolimus in treating patients with recurrent or refractory rhabdomyosarcoma. Drugs used in chemotherapy, such as vinorelbine tartrate and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of rhabdomyosarcoma by blocking blood flow to the tumor. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective when given together with bevacizumab or temsirolimus in treating rhabdomyosarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Vorinostat and Isotretinoin in Treating Patients With High-Risk Refractory or Recurrent Neuroblastoma Not Recruiting

    This phase I trial is studying the side effects and the best dose of vorinostat when given together with isotretinoin to see how well it works in treating patients with high-risk refractory or recurrent neuroblastoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may help vorinostat work better by making tumor cells more sensitive to the drug. Giving vorinostat together with isotretinoin may be an effective treatment for neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mario DeSouza, (650) 724 - 3063.

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  • Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia Not Recruiting

    This phase I trial is studying the side effects and best dose of vorinostat when given together with isotretinoin in treating young patients with recurrent or refractory solid tumors, lymphoma, or leukemia. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Isotretinoin may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may be an effective treatment for cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 736 - 4281.

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  • Vorinostat, Temozolomide, or Bevacizumab in Combination With Radiation Therapy Followed by Bevacizumab and Temozolomide in Young Patients With Newly Diagnosed High-Grade Glioma Not Recruiting

    This randomized phase II/III trial is studying vorinostat, temozolomide, or bevacizumab to see how well they work compared with each other when given together with radiation therapy followed by bevacizumab and temozolomide in treating young patients with newly diagnosed high-grade glioma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving vorinostat is more effective then temozolomide or bevacizumab when given together with radiation therapy in treating glioma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Peds Hem/Onc CRAs, 650-497-8953.

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  • Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This clinical trial is studying the side effects and best dose of zoledronic acid when given together with combination chemotherapy in treating patients with newly diagnosed metastatic osteosarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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Teaching

2020-21 Courses

Publications

All Publications

  • Phase 1a/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors. Sachdev, J. C., Bauer, T., Chawla, S. P., Pant, S., Patnaik, A., Wainberg, Z. A., Inamdar, S. P., Marina, N., Sun, S., Schmidt, M., Xiang, H., LoRusso, P. AMER SOC CLINICAL ONCOLOGY. 2019

    View details for DOI 10.1200/JCO.2019.37.15_suppl.2529

    View details for Web of Science ID 000487345804480

  • Genomic analysis of osteosarcoma reveals opportunities for targeted therapy Sayles, L., Breese, M., Koehne, A., Straessler, K., Leung, S., Spillinger, A., Hawkins, D., Dubois, S., Lee, A., Tanasa, B., Miok, K., Shah, A., Spunt, S., Marina, N., Hazard, K., Sweet-Cordero, A. AMER ASSOC CANCER RESEARCH. 2018

    View details for DOI 10.1158/1538-7445.PEDCA17-PR05

    View details for Web of Science ID 000468803500087

  • Genome-Informed Targeted Therapy for Osteosarcoma. Cancer discovery Sayles, L. C., Breese, M. R., Koehne, A. L., Leung, S. G., Lee, A. G., Liu, H., Spillinger, A., Shah, A. T., Tanasa, B., Straessler, K., Hazard, F. K., Spunt, S. L., Marina, N., Kim, G. E., Cho, S., Avedian, R. S., Mohler, D. G., Kim, M., Dubois, S. G., Hawkins, D. S., Sweet-Cordero, E. A. 2018

    Abstract

    Osteosarcoma (OS) is a highly aggressive cancer for which treatment has remained essentially unchanged for over 30 years. OS is characterized by widespread and recurrent somatic copy-number alterations (SCNAs) and structural rearrangements. In contrast, few recurrent point mutations in protein-coding genes have been identified, suggesting that genes within SCNAs are key oncogenic drivers in this disease. SCNAs and structural rearrangements are highly heterogeneous across OS cases, suggesting the need for a genome-informed approach to targeted therapy. To identify patient-specific candidate drivers, we used a simple heuristic based on degree and rank order of copy number amplification (identified by Whole Genome Sequencing) and changes in gene expression as identified by RNAseq. Using patient-derived tumor xenografts, we demonstrate that targeting of patient-specific somatic copy number alterations leads to significant decrease in tumor burden, providing a roadmap for genome-informed treatment of OS.

    View details for PubMedID 30266815

  • Second Malignancies in Ewing Sarcoma Survivors Reply CANCER Marina, N. M., Liu, Q., Donaldson, S. S., Sklar, C. A., Armstrong, G. T., Oeffinger, K. C., Leisenring, W. M., Ginsberg, J. P., Henderson, T. O., Neglia, J. P., Stovall, M. A., Yasui, Y., Randall, R., Geller, D. S., Robison, L. L., Ness, K. K. 2017; 123 (20): 4075?76

    View details for PubMedID 28837220

    View details for PubMedCentralID PMC5626614

  • Longitudinal follow-up of adult survivors of Ewing sarcoma: A report from the Childhood Cancer Survivor Study. Cancer Marina, N. M., Liu, Q., Donaldson, S. S., Sklar, C. A., Armstrong, G. T., Oeffinger, K. C., Leisenring, W. M., Ginsberg, J. P., Henderson, T. O., Neglia, J. P., Stovall, M. A., Yasui, Y., Randall, R. L., Geller, D. S., Robison, L. L., Ness, K. K. 2017

    Abstract

    Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown.This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03).Among 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively.With extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017. © 2017 American Cancer Society.

    View details for DOI 10.1002/cncr.30627

    View details for PubMedID 28222219

  • How to Provide Gadolinium-Free PET/MR Cancer Staging of Children and Young Adults in Less than 1 h: the Stanford Approach. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Muehe, A. M., Theruvath, A. J., Lai, L., Aghighi, M., Quon, A., Holdsworth, S. J., Wang, J., Luna-Fineman, S., Marina, N., Advani, R., Rosenberg, J., Daldrup-Link, H. E. 2017

    Abstract

    To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h.In this prospective clinical trial, 20 children and young adults (11-30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [(18)F]FDG (2-3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher's exact tests.Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol "off label" as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [(18)F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %).Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.

    View details for PubMedID 28721605

  • Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial. The Lancet. Oncology Marina, N. M., Smeland, S., Bielack, S. S., Bernstein, M., Jovic, G., Krailo, M. D., Hook, J. M., Arndt, C., van den Berg, H., Brennan, B., Brichard, B., Brown, K. L., Butterfass-Bahloul, T., Calaminus, G., Daldrup-Link, H. E., Eriksson, M., Gebhardt, M. C., Gelderblom, H., Gerss, J., Goldsby, R., Goorin, A., Gorlick, R., Grier, H. E., Hale, J. P., Hall, K. S., Hardes, J., Hawkins, D. S., Helmke, K., Hogendoorn, P. C., Isakoff, M. S., Janeway, K. A., Jürgens, H., Kager, L., Kühne, T., Lau, C. C., Leavey, P. J., Lessnick, S. L., Mascarenhas, L., Meyers, P. A., Mottl, H., Nathrath, M., Papai, Z., Randall, R. L., Reichardt, P., Renard, M., Safwat, A. A., Schwartz, C. L., Stevens, M. C., Strauss, S. J., Teot, L., Werner, M., Sydes, M. R., Whelan, J. S. 2016; 17 (10): 1396-1408

    Abstract

    We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (?10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma.EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m(2), doxorubicin 37·5 mg/m(2) per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m(2) over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m(2)) at 2·8 g/m(2) per day with equidose mesna uroprotection, followed by etoposide 100 mg/m(2) per day over 1 h on days 1-5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030.Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6-76·6); 62·3 months (IQR 46·9-77·1) for the MAP group and 61·1 months (IQR 46·5-75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78-1·23]); hazards were non-proportional (p=0·0003). The most common grade 3-4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate.EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting.UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.

    View details for DOI 10.1016/S1470-2045(16)30214-5

    View details for PubMedID 27569442

  • Assessing the Prognostic Significance of Histologic Response in Osteosarcoma: A Comparison of Outcomes on CCG-782 and INT0133-A Report From the Children's Oncology Group Bone Tumor Committee. Pediatric blood & cancer Bishop, M. W., Chang, Y., Krailo, M. D., Meyers, P. A., Provisor, A. J., Schwartz, C. L., Marina, N. M., Teot, L. A., Gebhardt, M. C., Gorlick, R., Janeway, K. A., Chou, A. J. 2016; 63 (10): 1737-1743

    Abstract

    The prognostic value of histologic response for osteosarcoma may have changed with induction chemotherapy schedules over time. We hypothesized that the increased intensity of induction therapy provided on INT0133 compared to the Children's Cancer Group study CCG-782 would diminish the impact of histologic response on the risk of events after definitive surgery.Retrospective analysis was performed for patients aged <22 with newly diagnosed nonmetastatic osteosarcoma enrolled on CCG-782 and INT0133. Clinical factors were evaluated for association with response and outcome. Good response was defined as <5% viable tumor at resection. Associations of response, study, and postdefinitive surgery event-free survival (EFS-DS) were determined using Cox proportional hazard models. EFS-DS was estimated by Kaplan-Meier methodology.Data were available for 814 patients (206 CCG-782, 608 INT0133). For good responders, 10-year EFS-DS (±SE) was 75.4% ± 7.7% for CCG-782 and 70.8% ± 3.1% for INT0133. For poor responders, 10-year EFS-DS was 39.9% ± 4.9% for CCG-782 and 58.4% ± 3.1% for INT0133. Histologic response predicted outcome across studies (P < 0.0001). Significant interaction between study and histologic response was observed for EFS-DS (P = 0.011). Using proportional hazards regression, INT0133 poor responders had less risk of events compared to CCG-782 poor responders (relative hazard ratio (RHR) = 0.6:1), but good responders on INT0133 had a greater risk of events compared to CCG-782 good responders (RHR = 1.53:1).We observed an inverse relationship between the predictive value of tumor necrosis and intensity of induction therapy, raising questions about the true prognostic value of histologic response. This highlights the need for novel markers to develop strategies for treatment in future trials.

    View details for DOI 10.1002/pbc.26034

    View details for PubMedID 27128693

  • Comparison of clinical features and outcomes in patients with extraskeletal versus skeletal localized Ewing sarcoma: A report from the Children's Oncology Group. Pediatric blood & cancer Cash, T., McIlvaine, E., Krailo, M. D., Lessnick, S. L., Lawlor, E. R., Laack, N., Sorger, J., Marina, N., Grier, H. E., Granowetter, L., Womer, R. B., DuBois, S. G. 2016; 63 (10): 1771-1779

    Abstract

    The prognostic significance of having extraskeletal (EES) versus skeletal Ewing sarcoma (ES) in the setting of modern chemotherapy protocols is unknown. The purpose of this study was to compare the clinical characteristics, biologic features, and outcomes for patients with EES and skeletal ES.Patients had localized ES and were treated on two consecutive protocols using five-drug chemotherapy (INT-0154 and AEWS0031). Patients were analyzed based on having an extraskeletal (n = 213) or skeletal (n = 826) site of tumor origin. Event-free survival (EFS) was estimated using the Kaplan-Meier method, compared using the log-rank test, and modeled using Cox multivariate regression.Patients with extraskeletal ES (EES) were more likely to have axial tumors (72% vs. 55%; P < 0.001), less likely to have tumors >8 cm (9% vs. 17%; P < 0.01), and less likely to be white (81% vs. 87%; P < 0.001) compared to patients with skeletal ES. There was no difference in key genomic features (type of EWSR1 translocation, TP53 mutation, CDKN2A mutation/loss) between groups. After controlling for age, race, and primary site, EES was associated with superior EFS (hazard ratio = 0.69; 95% confidence interval: 0.50-0.95; P = 0.02). Among patients with EES, age ?18, nonwhite race, and elevated baseline erythrocyte sedimentation rate were independently associated with inferior EFS.Clinical characteristics, but not key tumor genomic features, differ between EES and skeletal ES. Extraskeletal origin is a favorable prognostic factor, independent of age, race, and primary site.

    View details for DOI 10.1002/pbc.26096

    View details for PubMedID 27297500

  • Local Control Modality and Outcome for Ewing Sarcoma of the Femur: A Report From the Children's Oncology Group. Annals of surgical oncology Daw, N. C., Laack, N. N., McIlvaine, E. J., Krailo, M., Womer, R. B., Granowetter, L., Grier, H. E., Marina, N. M., Bernstein, M. L., Gebhardt, M. C., Marcus, K. J., Advani, S. M., Healey, J. H., Letson, G. D., Gorlick, R. G., Randall, R. L. 2016; 23 (11): 3541-3547

    Abstract

    The choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes.The study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression.The median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (<8 vs ?8 cm). The findings showed no statistically significant differences in EFS, OS, cumulative incidence of local failure, or cumulative incidence of distant failure according to LC modality (surgery, surgery plus radiation, or radiation).The LC modality did not significantly affect disease outcome for EWS of the femur. Further study of treatment complications and functional outcome may help to define the optimal LC modality.

    View details for DOI 10.1245/s10434-016-5269-1

    View details for PubMedID 27216741

  • Three-dimensional Radiologic Assessment of Chemotherapy Response in Ewing Sarcoma Can Be Used to Predict Clinical Outcome. Radiology Aghighi, M., Boe, J., Rosenberg, J., von Eyben, R., Gawande, R. S., Petit, P., Sethi, T. K., Sharib, J., Marina, N. M., DuBois, S. G., Daldrup-Link, H. E. 2016; 280 (3): 905-915

    Abstract

    Purpose To compare the agreement of three-dimensional (3D) tumor measurements for therapeutic response assessment of Ewing sarcoma according to the Children's Oncology Group (COG) criteria, one-dimensional (1D) Response Evaluation Criteria in Solid Tumors (RECIST), and two-dimensional (2D) measurements defined by the World Health Organization (WHO) with tumor volume measurements as the standard of reference and to determine which method correlates best with clinical outcomes. Materials and Methods This retrospective study was approved by the institutional review board of three institutions. Seventy-four patients (mean age ± standard deviation, 14.5 years ± 6.5) with newly diagnosed Ewing sarcoma treated at three medical centers were evaluated. Primary tumor size was assessed on pre- and posttreatment magnetic resonance images according to 1D RECIST, 2D WHO, and 3D COG measurements. Tumor responses were compared with the standard of reference (tumor volume) on the basis of RECIST, COG, and WHO therapeutic response thresholds. Agreement between the percentage reduction measurements of the methods was assessed with concordance correlation, Bland-Altman analysis, and Spearman rank correlation. Agreement between therapeutic responses was assessed with Kendall tau and unweighted ? statistics. Tumor responses were compared with patient survival by using the log-rank test, Kaplan-Meier plots, and Cox regression. Results Agreement with the reference standard was significantly better for 3D measurement than for 1D and 2D measurements on the basis of RECIST and COG therapeutic response thresholds (concordance correlation of 0.41, 0.72, and 0.84 for 1D, 2D, and 3D measurements, respectively; P < .0001). Comparison of overall survival of responders and nonresponders demonstrated P values of .4133, .0112, .0032, and .0027 for 1D, 2D, 3D, and volume measurements, respectively, indicating that higher dimensional measurements were significantly better predictors of overall survival. Conclusion The 3D tumor measurements according to COG are better predictors of therapeutic response of Ewing sarcoma than 1D RECIST or 2D WHO measurements and show a significantly higher correlation with clinical outcomes. (©) RSNA, 2016 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2016151301

    View details for PubMedID 26982677

  • Assessment of extent of surgical resection of primary high-grade osteosarcoma by treating institutions: A report from the Children's Oncology Group JOURNAL OF SURGICAL ONCOLOGY Morris, C. D., Teot, L. A., Bernstein, M. L., Marina, N., Krailo, M. D., Villaluna, D., Janeway, K. A., DuBois, S. G., Gorlick, R. G., Randall, R. L. 2016; 113 (4): 351-354

    Abstract

    Complete surgical resection of primary tumors is critical for long-term control of high-grade osteosarcoma. Uniform assessment of the extent of surgical resection is important in clinical trials, though the accuracy of this reporting has been poorly studied.We conducted a retrospective cohort study of patients 5-40 years of age with newly diagnosed high-grade resectable osteosarcoma treated as part of the AOST0331 clinical trial at Children's Oncology Group institutions. The extent of surgical resection of the primary tumor was graded as wide or radical by the treating institution. Central assessment of the extent of resection by two orthopedic oncologists was compared with institutional assessment by reviewing pathology and operative reports.We included 956 patients who had data available for central review. The extent of resection reported by treating institutions was 536/956 (56%) radical and 420/956 (44%) wide. The extent of resection assessed by central review was 162/956 (17%) radical and 794/956 (83%) wide. The overall discordance rate for the cohort was 43%.Institutional reports of radical resection in high-grade osteosarcoma significantly over-estimate the proportion of patients undergoing radical resection. This highlights the need for centralized review and improved accuracy of reporting of the extent of resection. J. Surg. Oncol. 2016;113:351-354. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jso.24145

    View details for Web of Science ID 000374711400001

    View details for PubMedID 26776342

  • Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group. Pediatric blood & cancer Mascarenhas, L., Felgenhauer, J. L., Bond, M. C., Villaluna, D., Femino, J. D., Laack, N. N., Ranganathan, S., Meyer, J., Womer, R. B., Gorlick, R., Krailo, M. D., Marina, N. 2016; 63 (3): 493-498

    Abstract

    The combination of topotecan and cyclophosphamide is active in relapsed Ewing sarcoma family of tumors (ESFT). The feasibility of adding these agents combined with vincristine (vincristine-topotecan-cyclophosphamide [VTc]) to standard five-drug chemotherapy with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) administered in an interval-compressed (2-week instead of 3-week intervals) schedule was investigated.Newly diagnosed patients with localized ESFT < 31 years, with good performance status and adequate organ function were eligible. Seventeen alternating cycles of chemotherapy with VTc, VDC, and IE were administered at 2-week intervals. Local control (LC) of the primary tumor occurred following six cycles. Primary endpoints were the ability to deliver chemotherapy in an interval-compressed schedule, and the rate of grade 3 or greater nonhematologic toxicity and grade 4 hematologic toxicity, which delayed chemotherapy by ?2 weeks. Secondary endpoints were event-free survival (EFS) and overall survival (OS).Thirty-five patients with a median age of 11 years were enrolled. The mean time to last dose of chemotherapy prior to LC was 12.6 ± 1.4 weeks and 45.5% of patients received intended chemotherapy without any delay prior to LC. There were no toxic deaths or unexpected toxicities. Five-year EFS was 79.6% (95% confidence interval [CI]: 61.8-89.7%) and 5-year OS was 88% (95% CI: 71.4-95.3%).The addition of VTc to standard therapy was tolerable with sufficient interval compression compared to historical standard 3-week cycles.

    View details for DOI 10.1002/pbc.25837

    View details for PubMedID 26579879

    View details for PubMedCentralID PMC4860347

  • Identification of Discrete Prognostic Groups in Ewing Sarcoma PEDIATRIC BLOOD & CANCER Karski, E. E., McIlvaine, E., Segal, M. R., Krailo, M., Grier, H. E., Granowetter, L., Womer, R. B., Meyers, P. A., Felgenhauer, J., Marina, N., DuBois, S. G. 2016; 63 (1): 47-53

    Abstract

    Although multiple prognostic variables have been proposed for Ewing sarcoma (EWS), little work has been done to further categorize these variables into prognostic groups for risk classification.We derived initial prognostic groups from 2,124 patients with EWS in the SEER database. We constructed a multivariable recursive partitioning model of overall survival using the following covariates: age; stage; race/ethnicity; sex; axial primary; pelvic primary; and bone or soft tissue primary. Based on this model, we identified risk groups and estimated 5-year overall survival for each group using Kaplan-Meier methods. We then applied these groups to 1,680 patients enrolled on COG clinical trials.A multivariable model identified five prognostic groups with significantly different overall survival: (i) localized, age <18 years, non-pelvic primary; (ii) localized, age <18, pelvic primary or localized, age ?18, white, non-Hispanic; (iii) localized, age ?18, all races/ethnicities other than white, non-Hispanic; (iv) metastatic, age <18; and (v) metastatic, age ?18. These five groups were applied to the COG dataset and showed significantly different overall and event-free survival based upon this classification system (P?

    View details for DOI 10.1002/pbc.25709

    View details for Web of Science ID 000367097800008

    View details for PubMedID 26257296

    View details for PubMedCentralID PMC5011751

  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Sampson, J. N., Wheeler, W. A., Yeager, M., Panagiotou, O., Wang, Z., Berndt, S. I., Lan, Q., Abnet, C. C., Amundadottir, L. T., Figueroa, J. D., Landi, M. T., Mirabello, L., Savage, S. A., Taylor, P. R., De Vivo, I., McGlynn, K. A., Purdue, M. P., Rajaraman, P., Adami, H., Ahlbom, A., Albanes, D., Amary, M. F., An, S., Andersson, U., Andriole, G., Andrulis, I. L., Angelucci, E., Ansell, S. M., Arici, C., Armstrong, B. K., Arslan, A. A., Austin, M. A., Baris, D., Barkauskas, D. A., Bassig, B. A., Becker, N., Benavente, Y., Benhamou, S., Berg, C., Van Den Berg, D., Bernstein, L., Bertrand, K. A., Birmann, B. M., Black, A., Boeing, H., Boffetta, P., Boutron-Ruault, M., Bracci, P. M., Brinton, L., Brooks-Wilson, A. R., Bueno-de-Mesquita, H. B., Burdett, L., Buring, J., Butler, M. A., Cai, Q., Cancel-Tassin, G., Canzian, F., Carrato, A., Carreon, T., Carta, A., Chan, J. K., Chang, E. T., Chang, G., Chang, I., Chang, J., Chang-Claude, J., Chen, C., Chen, C., Chen, C., Chen, C., Chen, C., Chen, H., Chen, K., Chen, K., Chen, K., Chen, Y., Chen, Y., Chen, Y., Chen, Y., Chien, L., Chirlaque, M., Choi, J. E., Choi, Y. Y., Chow, W., Chung, C. C., Clavel, J., Clavel-Chapelon, F., Cocco, P., Colt, J. S., Comperat, E., Conde, L., Connors, J. M., Conti, D., Cortessis, V. K., Cotterchio, M., Cozen, W., Crouch, S., Crous-Bou, M., Cussenot, O., Davis, F. G., Ding, T., Diver, W. R., Dorronsoro, M., Dossus, L., Duell, E. J., Ennas, M. G., Erickson, R. L., Feychting, M., Flanagan, A. M., Foretova, L., Fraumeni, J. F., Freedman, N. D., Freeman, L. E., Fuchs, C., Gago-Dominguez, M., Gallinger, S., Gao, Y., Gapstur, S. M., Garcia-Closas, M., Garcia-Closas, R., Gascoyne, R. D., Gastier-Foster, J., Gaudet, M. M., Gaziano, J. M., Giffen, C., Giles, G. G., Giovannucci, E., Glimelius, B., Goggins, M., Gokgoz, N., Goldstein, A. M., Gorlick, R., Gross, M., Grubb, R., Gu, J., Guan, P., Gunter, M., Guo, H., Habermann, T. M., Haiman, C. A., Halai, D., Hallmans, G., Hassan, M., Hattinger, C., He, Q., He, X., Helzlsouer, K., Henderson, B., Henriksson, R., Hjalgrim, H., Hoffman-Bolton, J., Hohensee, C., Holford, T. R., Holly, E. A., Hong, Y., Hoover, R. N., Horn-Ross, P. L., Hosain, G. M., Hosgood, H. D., Hsiao, C., Hu, N., Hu, W., Hu, Z., Huang, M., Huerta, J., Hung, J., Hutchinson, A., Inskip, P. D., Jackson, R. D., Jacobs, E. J., Jenab, M., Jeon, H., Ji, B., Jin, G., Jin, L., Johansen, C., Johnson, A., Jung, Y. J., Kaaks, R., Kamineni, A., Kane, E., Kang, C. H., Karagas, M. R., Kelly, R. S., Khaw, K., Kim, C., Kim, H. N., Kim, J. H., Kim, J. S., Kim, Y. H., Kim, Y. T., Kim, Y., Kitahara, C. M., Klein, A. P., Klein, R. J., Kogevinas, M., Kohno, T., Kolonel, L. N., Kooperberg, C., Kricker, A., Krogh, V., Kunitoh, H., Kurtz, R. C., Kweon, S., LaCroix, A., Lawrence, C., Lecanda, F., Lee, V. H., Li, D., Li, H., Li, J., Li, Y., Li, Y., Liao, L. M., Liebow, M., Lightfoot, T., Lim, W., Lin, C., Lin, D., Lindstrom, S., Linet, M. S., Link, B. K., Liu, C., Liu, J., Liu, L., Ljungberg, B., Lloreta, J., di Lollo, S., Lu, D., Lund, E., Malats, N., Mannisto, S., Le Marchand, L., Marina, N., Masala, G., Mastrangelo, G., Matsuo, K., Maynadie, M., McKay, J., McKean-Cowdin, R., Melbye, M., Melin, B. S., Michaud, D. S., Mitsudomi, T., Monnereau, A., Montalvan, R., Moore, L. E., Mortensen, L. M., Nieters, A., North, K. E., Novak, A. J., Oberg, A. L., Offit, K., Oh, I., Olson, S. H., Palli, D., Pao, W., Park, I. K., Park, J. Y., Park, K. H., Patino-Garcia, A., Pavanello, S., Peeters, P. H., Perng, R., Peters, U., Petersen, G. M., Picci, P., Pike, M. C., Porru, S., Prescott, J., Prokunina-Olsson, L., Qian, B., Qiao, Y., Rais, M., Riboli, E., Riby, J., Risch, H. A., Rizzato, C., Rodabough, R., Roman, E., Roupret, M., Ruder, A. M., de Sanjose, S., Scelo, G., Schned, A., Schumacher, F., Schwartz, K., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H. D., Setiawan, V. W., Severi, G., Severson, R. K., Shanafelt, T. D., Shen, H., Shen, W., Shin, M., Shiraishi, K., Shu, X., Siddiq, A., Sierrasesumaga, L., Sihoe, A. D., Skibola, C. F., Smith, A., Smith, M. T., Southey, M. C., Spinelli, J. J., Staines, A., Stampfer, M., Stern, M. C., Stevens, V. L., Stolzenberg-Solomon, R. S., Su, J., Su, W., Sund, M., Sung, J. S., Sung, S. W., Tan, W., Tang, W., Tardon, A., Thomas, D., Thompson, C. A., Tinker, L. F., Tirabosco, R., Tjonneland, A., Travis, R. C., Trichopoulos, D., Tsai, F., Tsai, Y., Tucker, M., Turner, J., Vajdic, C. M., Vermeulen, R. C., Villano, D. J., Vineis, P., Virtamo, J., Visvanathan, K., Wactawski-Wende, J., Wang, C., Wang, C., Wang, J., Wang, J., Wei, F., Weiderpass, E., Weiner, G. J., Weinstein, S., Wentzensen, N., White, E., Witzig, T. E., Wolpin, B. M., Wong, M. P., Wu, C., Wu, G., Wu, J., Wu, T., Wu, W., Wu, X., Wu, Y., Wunder, J. S., Xiang, Y., Xu, J., Xu, P., Yang, P., Yang, T., Ye, Y., Yin, Z., Yokota, J., Yoon, H., Yu, C., Yu, H., Yu, K., Yuan, J., Zelenetz, A., Zeleniuch-Jacquotte, A., Zhang, X., Zhang, Y., Zhao, X., Zhao, Z., Zheng, H., Zheng, T., Zheng, W., Zhou, B., Zhu, M., Zucca, M., Boca, S. M., Cerhan, J. R., Ferri, G. M., Hartge, P., Hsiung, C. A., Magnani, C., Miligi, L., Morton, L. M., Smedby, K. E., Teras, L. R., Vijai, J., Wang, S. S., Brennan, P., Caporaso, N. E., Hunter, D. J., Kraft, P., Rothman, N., Silverman, D. T., Slager, S. L., Chanock, S. J., Chatterjee, N. 2015; 107 (12)

    Abstract

    Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (? = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (? = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (? = 0.51, SE =0.18), and bladder and lung (? = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

    View details for DOI 10.1093/jnci/djv279

    View details for Web of Science ID 000366970900015

    View details for PubMedID 26464424

    View details for PubMedCentralID PMC4806328

  • Mifepristone Treatment of Cushing's Syndrome in a Pediatric Patient PEDIATRICS Banerjee, R. R., Marina, N., Katznelson, L., Feldman, B. J. 2015; 136 (5): E1377-E1381

    Abstract

    Cushing's syndrome (CS) in the pediatric population is challenging to diagnose and treat. Although next-generation medical therapies are emerging for adults with CS, none are currently approved or used in children. Here we describe the first use of mifepristone, a glucocorticoid receptor antagonist, to treat CS in a pediatric subject. The patient, a 14-year-old girl with an 18-month history of metastatic neuroendocrine carcinoma, suffered from fatigue, profound myopathy, irritability, and depression. She was found to have hypertension, hypokalemia, and worsening control of her preexisting type 1 diabetes. In this report, we detail our clinical evaluation that confirmed CS caused by an ectopic adrenocorticotropic hormone secreting tumor. Surgical and radiation therapies were not pursued because of her poor functional status and limited life expectancy, and medical treatment of CS was indicated for symptom relief. Mifepristone treatment provided rapid improvement in glycemic control, insulin resistance, and hypertension as well as significant diminishment of her myopathy and fatigue. Hypokalemia was managed with an oral potassium replacement and dose escalation of spironolactone; no other significant adverse effects were observed. Despite successful palliation of Cushing's signs and symptoms, the patient died of progression of her cancer. This case demonstrates the safety and efficacy of mifepristone treatment in a pediatric patient with symptomatic, ectopic CS. We conclude that, in appropriate pediatric patients with CS, glucocorticoid receptor antagonism with mifepristone should be considered to control the effects of hypercortisolism and to improve quality of life.

    View details for DOI 10.1542/peds.2015-0684

    View details for Web of Science ID 000363969600027

    View details for PubMedID 26459648

  • Racial/ethnic and socioeconomic disparities in survival among children with acute lymphoblastic leukemia in California, 1988-2011: A population-based observational study PEDIATRIC BLOOD & CANCER Abrahao, R., Lichtensztajn, D. Y., Ribeiro, R. C., Marina, N. M., Keogh, R. H., Marcos-Gragera, R., Glaser, S. L., Keegan, T. H. 2015; 62 (10): 1819-1825

    Abstract

    Despite advances in treatment, survival from acute lymphoblastic leukemia (ALL) remains lower among non-White children than White children in the US. We investigated the association of race/ethnicity and socioeconomic status (SES) with survival.We analyzed 9,295 Californian children (3,251 Whites, 4,890 Hispanics, 796 Asians, and 358 Blacks) aged ?19 years diagnosed with a first primary ALL during 1988-2011. We used the Kaplan-Meier method to estimate survival at 1, 5, and 10 years after diagnosis for three calendar periods. Hazard ratios of death for race/ethnicity, SES, and clinical factors were estimated by Cox regression models.Median follow-up time was 7.4 years (range 0-25 years). Over time, survival after ALL improved steadily, but inequalities persisted across races/ethnicities. Five-year survival (95% confidence interval) was 85.0% (83.6-86.2) for White, 81.4% (78.3-84.0) for Asian, 79.0% (77.8-80.2) for Hispanic, and 74.4% (69.4-78.8) for Black children. In multivariable-adjusted models, the hazard of death was increased by 57% among Black, 38% among Hispanic, and 33% among Asian children compared with White children. Patients residing in the lowest SES neighborhoods at diagnosis had a 39% increased risk of death relative to those living in higher SES neighborhoods.Despite significant improvements in survival, non-White children and children residing in low SES neighborhoods experienced worse survival even after adjusting for potential confounders. Our findings highlight the need to capture specific information on disease biology, treatment, and treatment adherence to better understand the predictors of lower survival in minority and low SES groups. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

    View details for DOI 10.1002/pbc.25544

    View details for Web of Science ID 000360228000021

  • Racial/ethnic and socioeconomic disparities in survival among children with acute lymphoblastic leukemia in California, 1988-2011: A population-based observational study. Pediatric blood & cancer Abrahăo, R., Lichtensztajn, D. Y., Ribeiro, R. C., Marina, N. M., Keogh, R. H., Marcos-Gragera, R., Glaser, S. L., Keegan, T. H. 2015; 62 (10): 1819-1825

    Abstract

    Despite advances in treatment, survival from acute lymphoblastic leukemia (ALL) remains lower among non-White children than White children in the US. We investigated the association of race/ethnicity and socioeconomic status (SES) with survival.We analyzed 9,295 Californian children (3,251 Whites, 4,890 Hispanics, 796 Asians, and 358 Blacks) aged ?19 years diagnosed with a first primary ALL during 1988-2011. We used the Kaplan-Meier method to estimate survival at 1, 5, and 10 years after diagnosis for three calendar periods. Hazard ratios of death for race/ethnicity, SES, and clinical factors were estimated by Cox regression models.Median follow-up time was 7.4 years (range 0-25 years). Over time, survival after ALL improved steadily, but inequalities persisted across races/ethnicities. Five-year survival (95% confidence interval) was 85.0% (83.6-86.2) for White, 81.4% (78.3-84.0) for Asian, 79.0% (77.8-80.2) for Hispanic, and 74.4% (69.4-78.8) for Black children. In multivariable-adjusted models, the hazard of death was increased by 57% among Black, 38% among Hispanic, and 33% among Asian children compared with White children. Patients residing in the lowest SES neighborhoods at diagnosis had a 39% increased risk of death relative to those living in higher SES neighborhoods.Despite significant improvements in survival, non-White children and children residing in low SES neighborhoods experienced worse survival even after adjusting for potential confounders. Our findings highlight the need to capture specific information on disease biology, treatment, and treatment adherence to better understand the predictors of lower survival in minority and low SES groups. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

    View details for DOI 10.1002/pbc.25544

    View details for PubMedID 25894846

  • A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma. Cancer discovery Mirabello, L., Koster, R., Moriarity, B. S., Spector, L. G., Meltzer, P. S., Gary, J., Machiela, M. J., Pankratz, N., Panagiotou, O. A., Largaespada, D., Wang, Z., Gastier-Foster, J. M., Gorlick, R., Khanna, C., de Toledo, S. R., Petrilli, A. S., Patiño-Garcia, A., Sierrasesúmaga, L., Lecanda, F., Andrulis, I. L., Wunder, J. S., Gokgoz, N., Serra, M., Hattinger, C., Picci, P., Scotlandi, K., Flanagan, A. M., Tirabosco, R., Amary, M. F., Halai, D., Ballinger, M. L., Thomas, D. M., Davis, S., Barkauskas, D. A., Marina, N., Helman, L., Otto, G. M., Becklin, K. L., Wolf, N. K., Weg, M. T., Tucker, M., Wacholder, S., Fraumeni, J. F., Caporaso, N. E., Boland, J. F., Hicks, B. D., Vogt, A., Burdett, L., Yeager, M., Hoover, R. N., Chanock, S. J., Savage, S. A. 2015; 5 (9): 920-931

    Abstract

    Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.2 × 10(-9); OR, 2.43; 95% confidence interval, 1.83-3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene.Metastasis at diagnosis in osteosarcoma is the leading cause of death in these patients. Here we show data that are supportive for the NFIB locus as associated with metastatic potential in osteosarcoma.

    View details for DOI 10.1158/2159-8290.CD-15-0125

    View details for PubMedID 26084801

  • Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial. Journal of clinical oncology Bielack, S. S., Smeland, S., Whelan, J. S., Marina, N., Jovic, G., Hook, J. M., Krailo, M. D., Gebhardt, M., Pápai, Z., Meyer, J., Nadel, H., Randall, R. L., Deffenbaugh, C., Nagarajan, R., Brennan, B., Letson, G. D., Teot, L. A., Goorin, A., Baumhoer, D., Kager, L., Werner, M., Lau, C. C., Sundby Hall, K., Gelderblom, H., Meyers, P., Gorlick, R., Windhager, R., Helmke, K., Eriksson, M., Hoogerbrugge, P. M., Schomberg, P., Tunn, P., Kühne, T., Jürgens, H., van den Berg, H., Böhling, T., Picton, S., Renard, M., Reichardt, P., Gerss, J., Butterfass-Bahloul, T., Morris, C., Hogendoorn, P. C., Seddon, B., Calaminus, G., Michelagnoli, M., Dhooge, C., Sydes, M. R., Bernstein, M. 2015; 33 (20): 2279-2287

    Abstract

    EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-?-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy.At diagnosis, patients age ? 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ? two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-?-2b (0.5 to 1.0 ?g/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary).Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-?-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-?-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-?-2b and for stopping prematurely, respectively. Median IFN-?-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-?-2b and provided toxicity information reported grade ? 3 toxicity during IFN-?-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-?-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model.At the preplanned analysis time, MAP plus IFN-?-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-?-2b or stopped prematurely. Long-term follow-up for events and survival continues.

    View details for DOI 10.1200/JCO.2014.60.0734

    View details for PubMedID 26033801

  • Tumoral TP53 and/or CDKN2A Alterations Are Not Reliable Prognostic Biomarkers in Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group PEDIATRIC BLOOD & CANCER Lerman, D. M., Monument, M. J., McIlvaine, E., Liu, X., Huang, D., Monovich, L., Beeler, N., Gorlick, R. G., Marina, N. M., Womer, R. B., Bridge, J. A., Krailo, M. D., Randall, R. L., Lessnick, S. L. 2015; 62 (5): 759-765

    Abstract

    A growing collection of retrospective studies have suggested that TP53 mutations and/or CDKN2A deletions have prognostic significance in Ewing sarcoma. We sought to evaluate these variables in patients with localized disease treated prospectively on a single Children's Oncology Group protocol.Of the 568 patients enrolled on Children's Oncology Group protocol AEWS0031 (NCT00006734), 112 had tumor specimens of sufficient quality and quantity to allow for analysis of TP53 mutations status by DNA sequencing, and CDKN2A deletion by dual color fluorescent in situ hybridization.Eight of 93 cases (8.6%) were found to have TP53 point mutations and 12 of 107 cases (11.2%) demonstrated homozygous CDKN2A deletion. Two cases were found to have an alteration in both genes. There was no significant difference in event-free survival of patients with TP53 mutations and/or CDKN2A deletions compared to patients with normal TP53/CDKN2A gene status, as demonstrated by log rank test (p = 0.58).Although previous retrospective studies suggest their significance, TP53 mutation and/or CDKN2A deletion are not reliable prognostic biomarkers in localized Ewing sarcoma. Pediatr Blood Cancer 2015;62:759-765. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/pbc.25340

    View details for Web of Science ID 000351680400006

    View details for PubMedID 25464386

    View details for PubMedCentralID PMC4376595

  • A summary of the osteosarcoma banking efforts: A report from the Children's Oncology Group and the QuadW Foundation. Pediatric blood & cancer Glover, J., Krailo, M., Tello, T., Marina, N., Janeway, K., Barkauskas, D., Fan, T. M., Gorlick, R., Khanna, C. 2015; 62 (3): 450-455

    Abstract

    Survival rates of patients with osteosarcoma have remained stagnant over the last thirty years. Better understanding of biology, new therapeutics, and improved biomarkers are needed. The Children's Oncology Group (COG) addressed this need by developing one of the largest osteosarcoma biorepositories ever, containing over 15,000 tumor and tissue samples from over 1,500 patients.The biology study P9851 and the banking study AOST06B1 has enrolled 1,787 patients (as of September, 2013). Clinical information was lacking on 510 patients on P9851, who were not enrolled on a concurrent therapeutic trial. The value of these specimens was diminished. The lack of statistical support available for biology projects slowed the analysis of several critical studies. The QuadW Foundation, CureSearch, and the COG formed the Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) to provide the infrastructure and address these needs by linking clinically annotated patient data to archived tissue samples and to develop biostatistical support for childhood sarcoma research.Originally 5.3% of samples from the 510 patients on P9851 not enrolled on a therapeutic study had full clinical annotation. The efforts of the CSBAO have linked clinical annotation to 90.8% of those specimens and provided statistical analyses to several studies that had used COG samples. As a result, 24 biology studies in osteosarcoma have been completed and published in peer-reviewed journals.These samples and in-silico data are available to the research community for basic and translational science projects to improve the biological understanding and treatment of patients affected by osteosarcoma. Pediatr Blood Cancer 2015;62:450-455. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/pbc.25346

    View details for PubMedID 25611047

    View details for PubMedCentralID PMC4304398

  • Comparative evaluation of local control strategies in localized Ewing sarcoma of bone: A report from the Children's Oncology Group. Cancer DuBois, S. G., Krailo, M. D., Gebhardt, M. C., Donaldson, S. S., Marcus, K. J., Dormans, J., Shamberger, R. C., Sailer, S., Nicholas, R. W., Healey, J. H., Tarbell, N. J., Randall, R. L., Devidas, M., Meyer, J. S., Granowetter, L., Womer, R. B., Bernstein, M., Marina, N., Grier, H. E. 2015; 121 (3): 467-475

    Abstract

    Patients with Ewing sarcoma require local primary tumor control with surgery, radiation, or both. The optimal choice of local control for overall and local disease control remains unclear.Patients with localized Ewing sarcoma of bone who were treated on 3 consecutive protocols with standard-dose, 5-drug chemotherapy every 3 weeks were included (n=465). Propensity scores were used to control for differences between local control groups by constructing multivariate models to assess the impact of local control type on clinical endpoints (event-free survival [EFS], overall survival, local failure, and distant failure) independent of differences in their propensity to receive each local control type.Patients who underwent surgery were younger (P=.02) and had more appendicular tumors (P<.001). Compared with surgery, radiation had higher unadjusted risks of any event (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.18-2.44), death (HR, 1.84; 95% CI, 1.18-2.85), and local failure (HR, 2.57; 95% CI, 1.37-4.83). On multivariate analysis, compared with surgery, radiation had a higher risk of local failure (HR, 2.41; 95% CI, 1.24-4.68), although there were no significant differences in EFS (HR, 1.42; 95% CI, 0.94-2.14), overall survival (HR, 1.37; 95% CI, 0.83-2.26), or distant failure (HR, 1.13; 95% CI, 0.70-1.84) between local control groups.In this large group of similarly treated patients, choice of the mode of local control was not related significantly to EFS, overall survival, or distant failure, although the risk of local failure was greater for radiation compared with surgery. These data support surgical resection when appropriate, whereas radiotherapy remains a reasonable alternative in selected patients. Cancer 2015;121:467-475. © 2014 American Cancer Society.

    View details for DOI 10.1002/cncr.29065

    View details for PubMedID 25251206

    View details for PubMedCentralID PMC4305012

  • EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment?. Annals of oncology Whelan, J. S., Bielack, S. S., Marina, N., Smeland, S., Jovic, G., Hook, J. M., Krailo, M., Anninga, J., Butterfass-Bahloul, T., Böhling, T., Calaminus, G., Capra, M., Deffenbaugh, C., Dhooge, C., Eriksson, M., Flanagan, A. M., Gelderblom, H., Goorin, A., Gorlick, R., Gosheger, G., Grimer, R. J., Hall, K. S., Helmke, K., Hogendoorn, P. C., Jundt, G., Kager, L., Kuehne, T., Lau, C. C., Letson, G. D., Meyer, J., Meyers, P. A., Morris, C., Mottl, H., Nadel, H., Nagarajan, R., Randall, R. L., Schomberg, P., Schwarz, R., Teot, L. A., Sydes, M. R., Bernstein, M. 2015; 26 (2): 407-414

    Abstract

    Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.Patients with resectable osteosarcoma aged ?40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ?10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken.Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen.New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

    View details for DOI 10.1093/annonc/mdu526

    View details for PubMedID 25421877

  • Imaging Tumor Necrosis with Ferumoxytol. PloS one Aghighi, M., Golovko, D., Ansari, C., Marina, N. M., Pisani, L., Kurlander, L., Klenk, C., Bhaumik, S., Wendland, M., Daldrup-Link, H. E. 2015; 10 (11)

    View details for DOI 10.1371/journal.pone.0142665

    View details for PubMedID 26569397

  • Age, Tumor Characteristics, and Treatment Regimen as Event Predictors in Ewing: A Children's Oncology Group Report. Sarcoma Marina, N., Granowetter, L., Grier, H. E., Womer, R. B., Randall, R. L., Marcus, K. J., McIlvaine, E., Krailo, M. 2015; 2015: 927123-?

    Abstract

    Purpose. To associate baseline patient characteristics and relapse across consecutive COG studies. Methods. We analyzed risk factors for LESFT patients in three randomized COG trials. We evaluated age at enrollment, primary site, gender, tumor size, and treatment (as randomized). We estimated event-free survival (EFS, Kaplan-Meier) and compared risk across groups (log-rank test). Characteristics were assessed by proportional hazards regression with the characteristic of interest as the only component. Confidence intervals (CI) for RR were derived. Factors related to outcome at level 0.05 were included in a multivariate regression model. Results. Between 12/1988 and 8/2005, 1444 patients were enrolled and data current to 2001, 2004, or 2008 were used. Patients were with a median age of 12 years (0-45), 55% male and 88% Caucasian. The 5-year EFS was 68.3% ± 1.3%. In univariate analysis age, treatment, and tumor location were identified for inclusion in the multivariate model, and all remained significant (p < 0.01). Since tumor size was not collected in the last study, the other two were reanalyzed. This model identified age, treatment, tumor location, and tumor size as significant predictors. Conclusion. Age > 18 years, pelvic tumor, size > 8?cms, and chemotherapy without ifosfamide/etoposide significantly predict worse outcome. AEWS0031 is NCT00006734, INT0091 and INT0054 designed before 1993 (unregistered).

    View details for DOI 10.1155/2015/927123

    View details for PubMedID 26508901

    View details for PubMedCentralID PMC4609872

  • Congenital peribronchial myofibroblastic tumor: case report of an asymptomatic infant with a rapidly enlarging pulmonary mass and review of the literature. Annals of clinical and laboratory science Brock, K. E., Wall, J., Esquivel, M., Newman, B., Marina, N., Albanese, C., Hazard, F. K. 2015; 45 (1): 83-89

    Abstract

    Congenital peribronchial myofibroblastic tumor (CPMT) is a rare, benign lung tumor of infants, with only 19 reported cases worldwide. It is often diagnosed by prenatal imaging or in the immediate postnatal period due to co-morbidities like polyhydramnios, fetal hydrops, respiratory distress, and heart failure.We report the oldest known infant (8 weeks old) diagnosed with CPMT, and present his clinical course including the relevant radiographic and histopathologic findings.CPMT is a rare tumor that should be considered among other primary lung tumors of infancy (developmental, benign, and malignant) even if not detected prenatally or in the immediate postnatal period.

    View details for PubMedID 25696016

  • Imaging Tumor Necrosis with Ferumoxytol. PloS one Aghighi, M., Golovko, D., Ansari, C., Marina, N. M., Pisani, L., Kurlander, L., Klenk, C., Bhaumik, S., Wendland, M., Daldrup-Link, H. E. 2015; 10 (11)

    Abstract

    Ultra-small superparamagnetic iron oxide nanoparticles (USPIO) are promising contrast agents for magnetic resonance imaging (MRI). USPIO mediated proton relaxation rate enhancement is strongly dependent on compartmentalization of the agent and can vary depending on their intracellular or extracellular location in the tumor microenvironment. We compared the T1- and T2-enhancement pattern of intracellular and extracellular USPIO in mouse models of cancer and pilot data from patients. A better understanding of these MR signal effects will enable non-invasive characterizations of the composition of the tumor microenvironment.Six 4T1 and six MMTV-PyMT mammary tumors were grown in mice and imaged with ferumoxytol-enhanced MRI. R1 relaxation rates were calculated for different tumor types and different tumor areas and compared with histology. The transendothelial leakage rate of ferumoxytol was obtained by our measured relaxivity of ferumoxytol and compared between different tumor types, using a t-test. Additionally, 3 patients with malignant sarcomas were imaged with ferumoxytol-enhanced MRI. T1- and T2-enhancement patterns were compared with histopathology in a descriptive manner as a proof of concept for clinical translation of our observations.4T1 tumors showed central areas of high signal on T1 and low signal on T2 weighted MR images, which corresponded to extracellular nanoparticles in a necrotic core on histopathology. MMTV-PyMT tumors showed little change on T1 but decreased signal on T2 weighted images, which correlated to compartmentalized nanoparticles in tumor associated macrophages. Only 4T1 tumors demonstrated significantly increased R1 relaxation rates of the tumor core compared to the tumor periphery (p<0.001). Transendothelial USPIO leakage was significantly higher for 4T1 tumors (3.4±0.9x10-3 mL/min/100cm3) compared to MMTV-PyMT tumors (1.0±0.9x10-3 mL/min/100 cm3). Likewise, ferumoxytol imaging in patients showed similar findings with high T1 signal in areas of tumor necrosis and low signal in areas of intracellularly compartmentalized iron.Differential T1- and T2-enhancement patterns of USPIO in tumors enable conclusions about their intracellular and extracellular location. This information can be used to characterize the composition of the tumor microenvironment.

    View details for DOI 10.1371/journal.pone.0142665

    View details for PubMedID 26569397

  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. Human molecular genetics Wang, Z., Zhu, B., Zhang, M., Parikh, H., Jia, J., Chung, C. C., Sampson, J. N., Hoskins, J. W., Hutchinson, A., Burdette, L., Ibrahim, A., Hautman, C., Raj, P. S., Abnet, C. C., Adjei, A. A., Ahlbom, A., Albanes, D., Allen, N. E., Ambrosone, C. B., Aldrich, M., Amiano, P., Amos, C., Andersson, U., Andriole, G., Andrulis, I. L., Arici, C., Arslan, A. A., Austin, M. A., Baris, D., Barkauskas, D. A., Bassig, B. A., Beane Freeman, L. E., Berg, C. D., Berndt, S. I., Bertazzi, P. A., Biritwum, R. B., Black, A., Blot, W., Boeing, H., Boffetta, P., Bolton, K., Boutron-Ruault, M., Bracci, P. M., Brennan, P., Brinton, L. A., Brotzman, M., Bueno-de-Mesquita, H. B., Buring, J. E., Butler, M. A., Cai, Q., Cancel-Tassin, G., Canzian, F., Cao, G., Caporaso, N. E., Carrato, A., Carreon, T., Carta, A., Chang, G., Chang, I., Chang-Claude, J., Che, X., Chen, C., Chen, C., Chen, C., Chen, C., Chen, K., Chen, Y., Chokkalingam, A. P., Chu, L. W., Clavel-Chapelon, F., Colditz, G. A., Colt, J. S., Conti, D., Cook, M. B., Cortessis, V. K., Crawford, E. D., Cussenot, O., Davis, F. G., De Vivo, I., Deng, X., Ding, T., Dinney, C. P., Di Stefano, A. L., Diver, W. R., Duell, E. J., Elena, J. W., Fan, J., Feigelson, H. S., Feychting, M., Figueroa, J. D., Flanagan, A. M., Fraumeni, J. F., Freedman, N. D., Fridley, B. L., Fuchs, C. S., Gago-Dominguez, M., Gallinger, S., Gao, Y., Gapstur, S. M., Garcia-Closas, M., Garcia-Closas, R., Gastier-Foster, J. M., Gaziano, J. M., Gerhard, D. S., Giffen, C. A., Giles, G. G., Gillanders, E. M., Giovannucci, E. L., Goggins, M., Gokgoz, N., Goldstein, A. M., Gonzalez, C., Gorlick, R., Greene, M. H., Gross, M., Grossman, H. B., Grubb, R., Gu, J., Guan, P., Haiman, C. A., Hallmans, G., Hankinson, S. E., Harris, C. C., Hartge, P., Hattinger, C., Hayes, R. B., He, Q., Helman, L., Henderson, B. E., Henriksson, R., Hoffman-Bolton, J., Hohensee, C., Holly, E. A., Hong, Y., Hoover, R. N., Hosgood, H. D., Hsiao, C., Hsing, A. W., Hsiung, C. A., Hu, N., Hu, W., Hu, Z., Huang, M., Hunter, D. J., Inskip, P. D., Ito, H., Jacobs, E. J., Jacobs, K. B., Jenab, M., Ji, B., Johansen, C., Johansson, M., Johnson, A., Kaaks, R., Kamat, A. M., Kamineni, A., Karagas, M., Khanna, C., Khaw, K., Kim, C., Kim, I., Kim, J. H., Kim, Y. H., Kim, Y., Kim, Y. T., Kang, C. H., Jung, Y. J., Kitahara, C. M., Klein, A. P., Klein, R., Kogevinas, M., Koh, W., Kohno, T., Kolonel, L. N., Kooperberg, C., Kratz, C. P., Krogh, V., Kunitoh, H., Kurtz, R. C., Kurucu, N., Lan, Q., Lathrop, M., Lau, C. C., Lecanda, F., Lee, K., Lee, M. P., Le Marchand, L., Lerner, S. P., Li, D., Liao, L. M., Lim, W., Lin, D., Lin, J., Lindstrom, S., Linet, M. S., Lissowska, J., Liu, J., Ljungberg, B., Lloreta, J., Lu, D., Ma, J., Malats, N., Mannisto, S., Marina, N., Mastrangelo, G., Matsuo, K., McGlynn, K. A., McKean-Cowdin, R., McNeill, L. H., Mcwilliams, R. R., Melin, B. S., Meltzer, P. S., Mensah, J. E., Miao, X., Michaud, D. S., Mondul, A. M., Moore, L. E., Muir, K., Niwa, S., Olson, S. H., Orr, N., Panico, S., Park, J. Y., Patel, A. V., Patino-Garcia, A., Pavanello, S., Peeters, P. H., Peplonska, B., Peters, U., Petersen, G. M., Picci, P., Pike, M. C., Porru, S., Prescott, J., Pu, X., Purdue, M. P., Qiao, Y., Rajaraman, P., Riboli, E., Risch, H. A., Rodabough, R. J., Rothman, N., Ruder, A. M., Ryu, J., Sanson, M., Schned, A., Schumacher, F. R., Schwartz, A. G., Schwartz, K. L., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H. D., Severi, G., Shen, H., Shen, M., Shete, S., Shiraishi, K., Shu, X., Siddiq, A., Sierrasesumaga, L., Sierri, S., Loon Sihoe, A. D., Silverman, D. T., Simon, M., Southey, M. C., Spector, L., Spitz, M., Stampfer, M., Stattin, P., Stern, M. C., Stevens, V. L., Stolzenberg-Solomon, R. Z., Stram, D. O., Strom, S. S., Su, W., Sund, M., Sung, S. W., Swerdlow, A., Tan, W., Tanaka, H., Tang, W., Tang, Z., Tardon, A., Tay, E., Taylor, P. R., Tettey, Y., Thomas, D. M., Tirabosco, R., Tjonneland, A., Tobias, G. S., Toro, J. R., Travis, R. C., Trichopoulos, D., Troisi, R., Truelove, A., Tsai, Y., Tucker, M. A., Tumino, R., Van Den Berg, D., Van Den Eeden, S. K., Vermeulen, R., Vineis, P., Visvanathan, K., Vogel, U., Wang, C., Wang, C., Wang, J., Wang, S. S., Weiderpass, E., Weinstein, S. J., Wentzensen, N., Wheeler, W., White, E., Wiencke, J. K., Wolk, A., Wolpin, B. M., Wong, M. P., Wrensch, M., Wu, C., Wu, T., Wu, X., Wu, Y., Wunder, J. S., Xiang, Y., Xu, J., Yang, H. P., Yang, P., Yatabe, Y., Ye, Y., Yeboah, E. D., Yin, Z., Ying, C., Yu, C., Yu, K., Yuan, J., Zanetti, K. A., Zeleniuch-Jacquotte, A., Zheng, W., Zhou, B., Mirabello, L., Savage, S. A., Kraft, P., Chanock, S. J., Yeager, M., Landi, M. T., Shi, J., Chatterjee, N., Amundadottir, L. T. 2014; 23 (24): 6616-6633

    Abstract

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

    View details for DOI 10.1093/hmg/ddu363

    View details for PubMedID 25027329

  • HER-2 expression is not prognostic in osteosarcoma; a Children's Oncology Group prospective biology study. Pediatric blood & cancer Gorlick, S., Barkauskas, D. A., Krailo, M., Piperdi, S., Sowers, R., Gill, J., Geller, D., Randall, R. L., Janeway, K., Schwartz, C., Grier, H., Meyers, P. A., Gorlick, R., Bernstein, M., Marina, N. 2014; 61 (9): 1558-1564

    Abstract

    Since the initial reports of human epidermal growth factor receptor 2 (HER-2) expression as being prognostic in osteosarcoma, numerous small studies varying in the interpretation of the immunohistochemical (IHC) staining patterns have produced conflicting results. The Children's Oncology Group therefore embarked on a prospective biology study in a larger sample of patients to define in osteosarcoma the prognostic value of HER-2 expression using the methodology employed in the initial North American study describing an association between HER-2 expression and outcome.The analytic patient population was comprised of 149 patients with newly diagnosed osteosarcoma, 135 with localized disease and 14 with metastatic disease, all of whom had follow up clinical data. Paraffin embedded material from the diagnostic biopsy was stained with CB11 antibody and scored by two independent observers. Correlation of HER-2 IHC score and demographic variables was analyzed using a Fisher's exact test and correlation with survival using a Kaplan-Meier analysis.No association was found with HER-2 status and any of the demographic variables tested including the presence or absence of metastatic disease at diagnosis. No association was found between HER-2 status and either event free survival or overall survival in the patients with localized disease.HER-2 expression is not prognostic in osteosarcoma in the context of this large prospective study. HER-2 expression cannot be used as a basis for stratification of therapy. Identification of potential prognostic factors should occur in the context of large multi-institutional biology studies. Pediatr Blood Cancer 2014;61:1558-1564. © 2014 Wiley Periodicals, Inc.

    View details for DOI 10.1002/pbc.25074

    View details for PubMedID 24753182

  • A Phase 2 Trial of R1507, a Monoclonal Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R), in Patients With Recurrent or Refractory Rhabdomyosarcoma, Osteosarcoma, Synovial Sarcoma, and Other Soft Tissue Sarcomas Results of a Sarcoma Alliance for Research Through Collaboration Study CANCER Pappo, A. S., Vassal, G., Crowley, J. J., Bolejack, V., Hogendoorn, P. C., Chugh, R., Ladanyi, M., Grippo, J. F., Dall, G., Staddon, A. P., Chawla, S. P., Maki, R. G., Araujo, D. M., Geoerger, B., Ganjoo, K., Marina, N., Blay, J., Schuetze, S. M., Chow, W. A., Helman, L. J. 2014; 120 (16): 2448-2456

    Abstract

    Insulin-like growth factor-1 receptor (IGF-1R) is implicated in the pathogenesis of rhabdomyosarcoma (RMS), osteosarcoma (OS), and synovial sarcoma (SS). The authors conducted a multi-institutional phase 2 trial of the monoclonal antibody R1507 in patients with various subtypes of recurrent or refractory sarcomas.Eligibility criteria included age ? 2 years and a diagnosis of recurrent or refractory RMS, OS, SS, and other soft tissue sarcomas. Patients received a weekly dose of 9 mg/kg R1507 intravenously. The primary endpoint was the best objective response rate using World Health Organization criteria. Tumor imaging was performed every 6 weeks × 4 and every 12 weeks thereafter.From December 2007 through August 2009, 163 eligible patients from 33 institutions were enrolled. The median patient age was 31 years (range, 7-85 years). Histologic diagnoses included OS (n = 38), RMS (n = 36), SS (n = 23), and other sarcomas (n = 66). The overall objective response rate was 2.5% (95% confidence interval, 0.7%-6.2%). Partial responses were observed in 4 patients, including 2 patients with OS, 1 patient with RMS, and 1 patient with alveolar soft part sarcoma. Four additional patients (3 with RMS and 1 with myxoid liposarcoma) had a ? 50% decrease in tumor size that lasted for <4 weeks. The median progression-free survival was 5.7 weeks, and the median overall survival was 11 months. The most common grade 3/4 toxicities were metabolic (12%), hematologic (6%), gastrointestinal (4%), and general constitutional symptoms (8%).R1507 is safe and well tolerated but has limited activity in patients with recurrent or refractory bone and soft tissue sarcomas. Additional studies to help identify the predictive factors associated with clinical benefit in selected histologies such as RMS appear to be warranted.

    View details for DOI 10.1002/cncr.28728

    View details for Web of Science ID 000340464100011

    View details for PubMedID 24797726

  • Symptom Assessment in Pediatric Oncology How Should Concordance Between Children's and Parents' Reports Be Evaluated? CANCER NURSING Baggott, C., Cooper, B. A., Marina, N., Matthay, K. K., Miaskowski, C. 2014; 37 (4): 252-262

    Abstract

    Clinical evaluations in pediatric oncology are often triadic, involving children or adolescents, parents, and clinicians. However, few studies have evaluated the concordance between children's and parents' reports of symptom occurrence.The purposes of this study were to evaluate the concordance between children's and parents' symptom reports during the week of chemotherapy administration using 5 statistical approaches and determine which factors are associated with higher levels of dyadic concordance.Independent assessments of symptom occurrence were obtained from children and adolescents with cancer (n = 107) and their parents using the Memorial Symptom Assessment Scale 10-18. Concordance was assessed using (1) percentage of overall agreement, (2) Cohen ? coefficients, (3) McNemar tests, (4) positive percentage agreement, and (5) negative percentage agreement.For each dyad, an average of 20 of the 31 symptom reports were concordant. Using children's reports as the "gold standard," parents rarely underestimated the children's symptoms. However, compared with children's reports, parents overestimated 7 symptoms. Advantages and disadvantages of each of the statistical approaches used to evaluate concordance are described in this article.A variety of statistical approaches are needed to obtain a thorough evaluation of the concordance between symptom reports. Discordance was most common for symptoms that children refuted, particularly psychosocial symptoms.Clinicians need to interview children and adolescents along with their parents about the occurrence of symptoms and evaluate discrepant reports. Effective approaches are needed to improve communication between children and parents to improve symptom assessment and management.

    View details for DOI 10.1097/NCC.0000000000000111

    View details for Web of Science ID 000338724700007

  • Symptom assessment in pediatric oncology: how should concordance between children's and parents' reports be evaluated? Cancer nursing Baggott, C., Cooper, B. A., Marina, N., Matthay, K. K., Miaskowski, C. 2014; 37 (4): 252-262

    Abstract

    Clinical evaluations in pediatric oncology are often triadic, involving children or adolescents, parents, and clinicians. However, few studies have evaluated the concordance between children's and parents' reports of symptom occurrence.The purposes of this study were to evaluate the concordance between children's and parents' symptom reports during the week of chemotherapy administration using 5 statistical approaches and determine which factors are associated with higher levels of dyadic concordance.Independent assessments of symptom occurrence were obtained from children and adolescents with cancer (n = 107) and their parents using the Memorial Symptom Assessment Scale 10-18. Concordance was assessed using (1) percentage of overall agreement, (2) Cohen ? coefficients, (3) McNemar tests, (4) positive percentage agreement, and (5) negative percentage agreement.For each dyad, an average of 20 of the 31 symptom reports were concordant. Using children's reports as the "gold standard," parents rarely underestimated the children's symptoms. However, compared with children's reports, parents overestimated 7 symptoms. Advantages and disadvantages of each of the statistical approaches used to evaluate concordance are described in this article.A variety of statistical approaches are needed to obtain a thorough evaluation of the concordance between symptom reports. Discordance was most common for symptoms that children refuted, particularly psychosocial symptoms.Clinicians need to interview children and adolescents along with their parents about the occurrence of symptoms and evaluate discrepant reports. Effective approaches are needed to improve communication between children and parents to improve symptom assessment and management.

    View details for DOI 10.1097/NCC.0000000000000111

    View details for PubMedID 24936750

  • Comparison of Latino and Non-Latino Patients With Ewing Sarcoma PEDIATRIC BLOOD & CANCER Sharib, J., Horvai, A., Hazard, F. K., Daldrup-Link, H., Goldsby, R., Marina, N., DuBois, S. G. 2014; 61 (2): 233-237

    Abstract

    Ewing sarcoma (ES) is a malignancy of bone and soft tissue in children and adults. Previous registry-based studies indicate that Latino patients with ES have inferior outcomes compared to non-Latino patients, though an etiology for this difference could not be identified. To explore possible differences that might underlie this disparity, we conducted a retrospective study to compare clinical characteristics, tumor features, healthcare access, and treatment outcomes between Latino and non-Latino patients with ES.Primary data for 218 ES patients treated at two academic medical centers between 1980 and 2010 were collected. Categorical data were compared using Fisher exact tests; Wilcoxon rank-sum tests were used for continuous variables. Survival was estimated using Kaplan-Meier analysis and compared using log-rank testing.Latino patients were diagnosed at a younger age (P = 0.014). All other clinical and histological data were similar between groups, including radiologic and histologic response to neoadjuvant chemotherapy. Latino patients had lower socioeconomic status (P = 0.001), were less likely to have insurance (P = 0.001), and were more likely to present to the emergency room at onset of symptoms (P = 0.031) rather than to primary care physicians. Five-year event free survival (EFS) and overall survival (OS) were similar between Latino and non-Latino patients (EFS: 60.5% vs. 50.9% P = 0.37; OS: 77.6% vs. 68.6% P = 0.54).Latino patients with ES present at a younger age, and have evidence of impaired access to healthcare. Response to initial therapy appears similar between Latino and non-Latino patients.

    View details for DOI 10.1002/pbc.24745

    View details for Web of Science ID 000328694300016

    View details for PubMedID 23970433

  • Pilot study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high risk germ cell tumors: A report of the children's oncology group (COG) PEDIATRIC BLOOD & CANCER Malogolowkin, M. H., Krailo, M., Marina, N., Olson, T., Frazier, A. L. 2013; 60 (10): 1602-1605

    Abstract

    BACKGROUND: To establish the maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide with cisplatin, etoposide, and bleomycin (C-PEB) in children with high-risk malignant germ cell tumors (HR-MGCT). PROCEDURE: Eligibility criteria included untreated patients???21 years of age with stage III/IV extragonadal, extra cranial MGCT. Patients received four cycles (repeated every 3 weeks) of cisplatin (20?mg/m(2) /day?×?5 days), etoposide (100?mg/m(2) /day?×?5 days), and bleomycin (15?mg/m(2) on Day 1) with escalating doses of cyclophosphamide on Day 1, assigned at the time of enrollment (1.2, 1.8, or 2.4?g/m(2) ). Patients with complete response had therapy discontinued. Patients with residual disease underwent second-look surgery, those with pathologic evidence of residual MGCT or whose markers had not normalized received two more cycles. All other patients had protocol therapy stopped. RESULTS: Nineteen patients were enrolled between July 2004 and August 2007. Three patients were non-evaluable. Sixteen patients completed four cycles. Eleven had complete response, one had progressive disease and four had partial response. All four with partial response underwent second look surgery followed by two more cycles. Only one patient, on dose 1.8?g/m(2) , experienced dose-limiting toxicity (DLT) during the first cycle of therapy (grade 3 hyperglycemia). The 4-year EFS and OS (± standard deviation) were 74?±?7% and 89?±?10%, respectively. CONCLUSION: The addition of cyclophosphamide to the standard PEB regimen (cisplatin, etoposide, and bleomycin) is feasible and well-tolerated at all dose levels used on this study. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

    View details for DOI 10.1002/pbc.24601

    View details for Web of Science ID 000322885200016

    View details for PubMedID 23703725

  • Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: A report from the Children's Oncology Group. European journal of cancer Goldsby, R. E., Fan, T. M., Villaluna, D., Wagner, L. M., Isakoff, M. S., Meyer, J., Lor Randall, R., Lee, S., Kim, G., Bernstein, M., Gorlick, R., Krailo, M., Marina, N. 2013; 49 (10): 2384-2391

    Abstract

    Patients with metastatic osteosarcoma (OS) have a poor outcome with conventional therapies. Zoledronic acid (ZA) is a third-generation bisphosphonate that reduces skeletal-related events in many adult cancers, and pre-clinical data suggest a possible benefit in OS. This study assessed the maximum tolerated dose (MTD) and the feasibility of ZA when combined with chemotherapy in patients with metastatic OS.Patients with a histological diagnosis of OS were eligible if they were <40years of age, had initially metastatic disease and met organ function requirements. Treatment combined surgery and a conventional chemotherapy regimen. ZA was given concurrent with chemotherapy for a total of eight doses over 36weeks. Three dose levels of ZA were tested: 1.2mg/m(2) [max 2mg], 2.3mg/m(2) [max 4mg] and 3.5mg/m(2) [max 6mg]. The MTD was determined during induction. Six patients were to be treated at each dose level, with an additional six patients treated with the MTD to help assess post-induction feasibility.Twenty-four patients (median age 13.5years [range, 7-22]; 16 females) were treated. Five patients experienced dose-limiting toxicities (DLTs) during induction, including three patients treated with 3.5mg/m(2). DLTs included hypophosphatemia, hypokalemia, hyponatremia, mucositis, limb pain and limb oedema. There were no reports of excessive renal toxicity or osteonecrosis of the jaw. The MTD was defined as 2.3mg/m(2) (max 4mg).ZA can be safely combined with conventional chemotherapy with an MTD of 2.3mg/m(2) (max 4mg) for patients with metastatic osteosarcoma.

    View details for DOI 10.1016/j.ejca.2013.03.018

    View details for PubMedID 23664013

  • Genome-wide association study identifies two susceptibility loci for osteosarcoma NATURE GENETICS Savage, S. A., Mirabello, L., Wang, Z., Gastier-Foster, J. M., Gorlick, R., Khanna, C., Flanagan, A. M., Tirabosco, R., Andrulis, I. L., Wunder, J. S., Gokgoz, N., Patino-Garcia, A., Sierrasesumaga, L., Lecanda, F., Kurucu, N., Ilhan, I. E., Sari, N., Serra, M., Hattinger, C., Picci, P., Spector, L. G., Barkauskas, D. A., Marina, N., Caminada de Toledo, S. R., Petrilli, A. S., Amary, M. F., Halai, D., Thomas, D. M., Douglass, C., Meltzer, P. S., Jacobs, K., Chung, C. C., Berndt, S. I., Purdue, M. P., Caporaso, N. E., Tucker, M., Rothman, N., Landi, M. T., Silverman, D. T., Kraft, P., Hunter, D. J., Malats, N., Kogevinas, M., Wacholder, S., Troisi, R., Helman, L., Fraumeni, J. F., Yeager, M., Hoover, R. N., Chanock, S. J. 2013; 45 (7): 799-?

    Abstract

    Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10(-9)) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10(-8) and 2.9 × 10(-7), respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.

    View details for DOI 10.1038/ng.2645

    View details for Web of Science ID 000321005200015

  • Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nature genetics Savage, S. A., Mirabello, L., Wang, Z., Gastier-Foster, J. M., Gorlick, R., Khanna, C., Flanagan, A. M., Tirabosco, R., Andrulis, I. L., Wunder, J. S., Gokgoz, N., Patiño-Garcia, A., Sierrasesúmaga, L., Lecanda, F., Kurucu, N., Ilhan, I. E., Sari, N., Serra, M., Hattinger, C., Picci, P., Spector, L. G., Barkauskas, D. A., Marina, N., de Toledo, S. R., Petrilli, A. S., Amary, M. F., Halai, D., Thomas, D. M., Douglass, C., Meltzer, P. S., Jacobs, K., Chung, C. C., Berndt, S. I., Purdue, M. P., Caporaso, N. E., Tucker, M., Rothman, N., Landi, M. T., Silverman, D. T., Kraft, P., Hunter, D. J., Malats, N., Kogevinas, M., Wacholder, S., Troisi, R., Helman, L., Fraumeni, J. F., Yeager, M., Hoover, R. N., Chanock, S. J. 2013; 45 (7): 799-803

    Abstract

    Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10(-9)) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10(-8) and 2.9 × 10(-7), respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.

    View details for DOI 10.1038/ng.2645

    View details for PubMedID 23727862

  • Children's Oncology Group's 2013 blueprint for research: Bone tumors. Pediatric blood & cancer Gorlick, R., Janeway, K., Lessnick, S., Randall, R. L., Marina, N. 2013; 60 (6): 1009-1015

    Abstract

    In the US, approximately 650 children are diagnosed with osteosarcoma and Ewing sarcoma (ES) each year. Five-year survival ranges from 65% to 75% for localized disease and <30% for patients with metastases. Recent findings include interval-compressed five drug chemotherapy improves survival with localized ES. In osteosarcoma a large international trial investigating the addition of ifosfamide/etoposide or interferon to standard therapy has completed accrual. For ES an ongoing trial explores the addition of cyclophosphamide/topotecan to interval-compressed chemotherapy. Trials planned by the Children's Oncology Group will investigate new target(s) including IGF-1R and mTOR in ES, and RANKL and GD2 in osteosarcoma.

    View details for DOI 10.1002/pbc.24429

    View details for PubMedID 23255238

  • Changes in health status among aging survivors of pediatric upper and lower extremity sarcoma: a report from the childhood cancer survivor study. Archives of physical medicine and rehabilitation Marina, N., Hudson, M. M., Jones, K. E., Mulrooney, D. A., Avedian, R., Donaldson, S. S., Popat, R., West, D. W., Fisher, P., Leisenring, W., Stovall, M., Robison, L. L., Ness, K. K. 2013; 94 (6): 1062-1073

    Abstract

    To evaluate health status and participation restrictions in survivors of childhood extremity sarcomas.Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003, or 2007 were included.Cohort study of survivors of extremity sarcomas.Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5% white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986.Not applicable.Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age.In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation.Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age.

    View details for DOI 10.1016/j.apmr.2013.01.013

    View details for PubMedID 23380347

  • Pediatric Acute Myeloid Leukemia as Classified Using 2008 WHO Criteria: A Single-Center Experience. American journal of clinical pathology Davis, K. L., Marina, N., Arber, D. A., Ma, L., Cherry, A., Dahl, G. V., Heerema-McKenney, A. 2013; 139 (6): 818-825

    Abstract

    The classification of acute myeloid leukemia (AML) has evolved to the most recent World Health Organization (WHO) schema, which integrates genetic, morphologic, and prognostic data into a single system. However, this system was devised using adult data and how this system applies to a pediatric cohort is unknown. Performing a retrospective chart review, we examined our single-center experience with AML in 115 children and classified their leukemia using the WHO 2008 schema. We examined patient samples for mutations of FLT3, NPM1, and CEBPA. Overall survival was calculated within categories. In our pediatric population, most cases of AML had recurrent genetic abnormalities of favorable prognosis. More than 10% of patients in our series were categorized as AML, with myelodysplasia-related changes, an entity not well-described in pediatric patients. In addition, a large proportion of patients were categorized with secondary, therapy-related AML. To our knowledge, this is the first application of the WHO 2008 classification to a pediatric cohort. In comparison to adult studies, AML in the pediatric population shows a distinct distribution within the WHO 2008 classification.

    View details for DOI 10.1309/AJCP59WKRZVNHETN

    View details for PubMedID 23690127

  • A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893 PEDIATRIC BLOOD & CANCER Felgenhauer, J. L., Nieder, M. L., Krailo, M. D., Bernstein, M. L., Henry, D. W., Malkin, D., Baruchel, S., Chuba, P. J., Sailer, S. L., Brown, K., Ranganathan, S., Marina, N. 2013; 60 (3): 409-414

    Abstract

    The aims of this study were to determine the feasibility of the combination of low dose, anti-angiogenic chemotherapy with standard therapy for patients with metastatic Ewing sarcoma (ES), and to obtain preliminary outcome data.Patients with metastatic ES were eligible. Therapy consisted of alternating cycles of ifosfamide-etoposide, and vincristine, doxorubicin, cyclophosphamide. Vinblastine and celecoxib were concomitantly administered. Surgical, radiotherapeutic, or combination local control therapy was given per institutional preference.Thirty-five eligible patients were enrolled. Ninety percent received at least 75% of planned vinblastine/celecoxib doses. There was no excess of neurologic, infectious, hemorrhagic, or cardiovascular toxicities. However, 7 of 21 patients who received pulmonary irradiation prior to experiencing pulmonary toxicity did develop grade 2 or greater pulmonary toxicity, including two deaths of apparent radiation pneumonitis. Fourteen of 16 patients with pelvic disease received local irradiation. Hemorrhagic cystitis developed in six patients, five of whom had received pelvic irradiation. The overall 24-month event free survival was 35% (19-51%); 71% (26-92%) for the seven with isolated pulmonary metastases, 26% (10-45%) for all others.The combination of vinblastine/celecoxib metronomic therapy with standard ES treatment was feasible according to the protocol definitions. However, excess toxicity in irradiated areas was noted and limits the usefulness of this protocol. The 24-month EFS for those with isolated pulmonary metastases is better than historical controls, although the number of patient number is small, follow up short and we are lacking contemporaneous controls.

    View details for DOI 10.1002/pbc.24328

    View details for Web of Science ID 000313727000011

    View details for PubMedID 23065953

  • Predictors of acute chemotherapy-associated toxicity in patients with Ewing sarcoma PEDIATRIC BLOOD & CANCER Sharib, J. M., Cyrus, J., Horvai, A., Hazard, F. K., Neuhaus, J., Matthay, K. K., Goldsby, R., Marina, N., DuBois, S. G. 2012; 59 (4): 611-616

    Abstract

    Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue of children and young adults. Patients with ES are treated with intensive chemotherapy regimens. We describe predictors of acute chemotherapy-associated toxicity in this population.In this retrospective cohort study, records of ES patients treated at two academic medical centers between 1980 and 2010 were reviewed. Grade 3 and 4 non-hematologic chemotherapy-associated toxicities during frontline therapy were recorded for each patient, along with potential clinical and demographic predictors of toxicity. Bivariate analyses were performed using the Fisher exact test. Multivariate analysis was performed using logistic regression.The cohort included 142 patients with ES and toxicity data. In bivariate analyses, age <12 years at diagnosis, Latino ethnicity, low family income, and treatment on a clinical trial were associated with higher incidence of toxicity (P < 0.01). Tumor size, site, stage, mode of local control, body mass index, overall chemotherapy exposure and dose-intensity were not associated with toxicity. In multivariate analysis, low income (odds ratio (OR) 4.97, 95% confidence interval (CI) 1.9-13.1), clinical trial enrollment (OR 3.67, 95% CI 1.2-10.9), pelvic tumor site (OR 3.88, 95% CI 1.17-12.88), and age <12 years (OR 2.8, 95% CI 1.0-7.5) were independent predictors of toxicity.ES patients who are younger, of Latino ethnicity, have pelvic tumors or low income have higher rates of toxicity that may require increased supportive care. Treatment on a clinical trial was also associated with higher rates of toxicity, though this finding may reflect better reporting in these patients.

    View details for DOI 10.1002/pbc.24031

    View details for Web of Science ID 000307386300004

    View details for PubMedID 22180320

    View details for PubMedCentralID PMC3310949

  • Lack of trial participation and lack of centralization for young adults with osteosarcoma: Experience from the European and American Osteosarcoma Study, EURAMOS-1 Bielack, S., Hook, J., Jovic, G., Marina, N., Reichardt, P., Smeland, S., Sydes, M. R., Whelan, J., Wilhelm, M., Zils, K., Bernstein, M. KARGER. 2012: 250?250

    View details for Web of Science ID 000310766700660

  • Outcome for adolescent and young adult patients with osteosarcoma: a report from the Children's Oncology Group. Cancer Janeway, K. A., Barkauskas, D. A., Krailo, M. D., Meyers, P. A., Schwartz, C. L., Ebb, D. H., Seibel, N. L., Grier, H. E., Gorlick, R., Marina, N. 2012; 118 (18): 4597-4605

    Abstract

    There are conflicting data regarding age as a prognostic factor in osteosarcoma. The authors conducted a study evaluating the impact of age on prognosis in children and young adults with osteosarcoma enrolled on North American cooperative group trials.Patients with high-grade osteosarcoma of any site enrolled on North American cooperative group trials CCG-7943, POG-9754, INT-0133, and AOST0121 were included in this study. Primary tumor site, age, sex, ethnicity, histologic response, and presence of metastatic disease at diagnosis were evaluated for their impact on overall survival (OS) and event-free survival (EFS).A total of 1054 patients were eligible and had complete data available for the study. Age was not significantly associated with any other presenting covariate analyzed except sex. Age 18 or older was associated with a statistically significant poorer EFS (P = .019) and OS (P = .043). The 10-year EFS and OS in patients <10, 10 to 17, and ?18 years old were 55%, 55%, 37% and 68%, 60%, 41%, respectively. The poorer EFS in patients ?18 years old was because of an increased rate of relapse. Presence of metastatic disease at diagnosis, poor histologic response, and pelvic tumor site were also associated with a poorer prognosis. In multivariate analysis, age continued to be associated with poorer EFS (P = .019) and OS (P = .049).In osteosarcoma, age 18 to 30 years is associated with a statistically significant poorer outcome because of an increased rate of relapse. Poorer outcome in adolescent and young adult patients is not explained by tumor location, histologic response, or metastatic disease at presentation.

    View details for DOI 10.1002/cncr.27414

    View details for PubMedID 22252521

  • Outcome for adolescent and young adult patients with osteosarcoma CANCER Janeway, K. A., Barkauskas, D. A., Krailo, M. D., Meyers, P. A., Schwartz, C. L., Ebb, D. H., Seibel, N. L., Grier, H. E., Gorlick, R., Marina, N. 2012; 118 (18): 4597-4605

    Abstract

    There are conflicting data regarding age as a prognostic factor in osteosarcoma. The authors conducted a study evaluating the impact of age on prognosis in children and young adults with osteosarcoma enrolled on North American cooperative group trials.Patients with high-grade osteosarcoma of any site enrolled on North American cooperative group trials CCG-7943, POG-9754, INT-0133, and AOST0121 were included in this study. Primary tumor site, age, sex, ethnicity, histologic response, and presence of metastatic disease at diagnosis were evaluated for their impact on overall survival (OS) and event-free survival (EFS).A total of 1054 patients were eligible and had complete data available for the study. Age was not significantly associated with any other presenting covariate analyzed except sex. Age 18 or older was associated with a statistically significant poorer EFS (P = .019) and OS (P = .043). The 10-year EFS and OS in patients <10, 10 to 17, and ?18 years old were 55%, 55%, 37% and 68%, 60%, 41%, respectively. The poorer EFS in patients ?18 years old was because of an increased rate of relapse. Presence of metastatic disease at diagnosis, poor histologic response, and pelvic tumor site were also associated with a poorer prognosis. In multivariate analysis, age continued to be associated with poorer EFS (P = .019) and OS (P = .049).In osteosarcoma, age 18 to 30 years is associated with a statistically significant poorer outcome because of an increased rate of relapse. Poorer outcome in adolescent and young adult patients is not explained by tumor location, histologic response, or metastatic disease at presentation.

    View details for DOI 10.1002/cncr.27414

    View details for Web of Science ID 000308404100032

  • Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group JOURNAL OF CLINICAL ONCOLOGY Ebb, D., Meyers, P., Grier, H., Bernstein, M., Gorlick, R., Lipshultz, S. E., Krailo, M., Devidas, M., Barkauskas, D. A., Siegal, G. P., Ferguson, W. S., Letson, G. D., Marcus, K., Goorin, A., Beardsley, P., Marina, N. 2012; 30 (20): 2545-2551

    Abstract

    Despite efforts to intensify chemotherapy, survival for patients with metastatic osteosarcoma remains poor. Overexpression of human epidermal growth factor receptor 2 (HER2) in osteosarcoma has been shown to predict poor therapeutic response and decreased survival. This study tests the safety and feasibility of delivering biologically targeted therapy by combining trastuzumab with standard chemotherapy in patients with metastatic osteosarcoma and HER2 overexpression.Among 96 evaluable patients with newly diagnosed metastatic osteosarcoma, 41 had tumors that were HER2-positive by immunohistochemistry. All patients received chemotherapy with cisplatin, doxorubicin, methotrexate, ifosfamide, and etoposide. Dexrazoxane was administered with doxorubicin to minimize the risk of cardiotoxicity from treatment with trastuzumab and anthracycline. Only patients with HER2 overexpression received concurrent therapy with trastuzumab given for 34 consecutive weeks.The 30-month event-free and overall survival rates for patients with HER2 overexpression treated with chemotherapy and trastuzumab were 32% and 59%, respectively. For patients without HER2 overexpression, treated with chemotherapy alone, the 30-month event-free and overall survival rates were 32% and 50%, respectively. There was no clinically significant short-term cardiotoxicity in patients treated with trastuzumab and doxorubicin.Despite intensive chemotherapy plus trastuzumab for patients with HER2-positive disease, the outcome for all patients was poor, with no significant difference between the HER2-positive and HER2-negative groups. Although our findings suggest that trastuzumab can be safely delivered in combination with anthracycline-based chemotherapy and dexrazoxane, its therapeutic benefit remains uncertain. Definitive assessment of trastuzumab's potential role in treating osteosarcoma would require a randomized study of patients with HER2-positive disease.

    View details for DOI 10.1200/JCO.2011.37.4546

    View details for Web of Science ID 000306244300022

    View details for PubMedID 22665540

    View details for PubMedCentralID PMC3397787

  • Evaluation of local control strategies in patients with localized Ewing sarcoma of bone: A report from the Children's Oncology Group. 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) DuBois, S. G., Krailo, M. D., Gebhardt, M. C., Donaldson, S. S., Marcus, K. C., Dormans, J. P., Shamberger, R. C., Sailer, S. L., Nicholas, R. W., Healey, J. H., Tarbell, N., Devidas, M., Meyer, J. S., Granowetter, L., Womer, R., Bernstein, M. L., Marina, N., Grier, H. E. AMER SOC CLINICAL ONCOLOGY. 2012

    View details for Web of Science ID 000318009802115

  • EURAMOS-1 study: Recruitment, characteristics, and initial treatment of more than 2,000 patients (pts) with high-grade osteosarcoma 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Whelan, J., Hook, J., Bielack, S. S., Marina, N., Smeland, S., Jovic, G., Krailo, M. D., Kuehne, T., Eriksson, M., Butterfass-Bahloul, T., Teot, L. A., Kager, L., Gelderblom, H., Hall, K. S., Hogendoorn, P. C., Sydes, M. R., Bernstein, M. L. AMER SOC CLINICAL ONCOLOGY. 2012

    View details for Web of Science ID 000318009800793

  • The effects of dexrazoxane on cardiac status and second malignant neoplasms (SMN) in doxorubicin-treated patients with osteosarcoma (OS) 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Kopp, L. M., Bernstein, M. L., Schwartz, C. L., Ebb, D., Krailo, M. D., Grier, H. E., Meyers, P. A., Wexler, L. H., Marina, N., Womer, R., Janeway, K. A., Gorlick, R. G., Lipshultz, S. E. AMER SOC CLINICAL ONCOLOGY. 2012

    View details for Web of Science ID 000318009800049

  • Symptom Cluster Analyses Based on Symptom Occurrence and Severity Ratings Among Pediatric Oncology Patients During Myelosuppressive Chemotherapy CANCER NURSING Baggott, C., Cooper, B. A., Marina, N., Matthay, K. K., Miaskowski, C. 2012; 35 (1): 19-28

    Abstract

    Symptom cluster research is an emerging field in symptom management. The ability to identify symptom clusters that are specific to pediatric oncology patients may lead to improved understanding of symptoms' underlying mechanisms among patients of all ages.The purpose of this study, in a sample of children and adolescents with cancer who underwent a cycle of myelosuppressive chemotherapy, was to compare the number and types of symptom clusters identified using patients' ratings of symptom occurrence and symptom severity.Children and adolescents with cancer (10-18 years of age; N = 131) completed the Memorial Symptom Assessment Scale 10-18 on the day they started a cycle of myelosuppressive chemotherapy, using a 1-week recall of experiences. Symptom data based on occurrence and severity ratings were examined using exploratory factor analysis. The defined measurement model suggested by the best exploratory factor analysis model was then examined with a latent variable analysis.Three clusters were identified when symptom occurrence ratings were evaluated, which were classified as a chemotherapy sequela cluster, mood disturbance cluster, and a neuropsychological discomfort cluster. Analysis of symptom severity ratings yielded similar cluster configurations.Cluster configurations remained relatively stable between symptom occurrence and severity ratings. The evaluation of patients at a common point in the chemotherapy cycle may have contributed to these findings.Additional uniformity in symptom clusters investigations is needed to allow appropriate comparisons among studies. The dissemination of symptom cluster research methodology through publication and presentation may promote uniformity in this field.

    View details for DOI 10.1097/NCC.0b013e31822909fd

    View details for Web of Science ID 000298150000009

    View details for PubMedID 21921793

    View details for PubMedCentralID PMC3237960

  • Body Mass Index (BMI) at Diagnosis Is Associated With Surgical Wound Complications in Patients With Localized Osteosarcoma: A Report From the Children's Oncology Group PEDIATRIC BLOOD & CANCER Hingorani, P., Seidel, K., Krailo, M., Mascarenhas, L., Meyers, P., Marina, N., Conrad, E. U., Hawkins, D. S. 2011; 57 (6): 939-942

    Abstract

    Malnutrition is common at diagnosis and during treatment for sarcoma patients. Poor nutritional status is associated with increased risk of complications, particularly infections. We investigated the role of body mass index (BMI) on the incidence of surgical wound complications in patients with localized osteosarcoma treated on the Children's Oncology Group (COG) legacy trial, INT-0133.Patients considered in this report had localized osteosarcoma, enrolled on COG trial INT-0133, remained on protocol therapy to have definitive surgery 6-16 weeks after study entry, and had adequate height, weight, and surgical complication data for analysis. By protocol design, definitive surgical resection was planned for 10 weeks after induction chemotherapy. Wound complications within 30 days after definitive surgery were considered post-operative. BMI was calculated at the start of neoadjuvant chemotherapy and expressed as age- and gender-adjusted percentile. The incidence of wound complications was evaluated by logistic regression or Fisher's exact test.A total of 498 patients met criteria for analysis. Low BMI (?10th percentile) was seen in 73 (14.7%), middle BMI (11th-94th percentile) in 382 (76.7%), and high BMI (?95th percentile) in 43 (8.6%) patients. Wound infection or slough was seen in low BMI patients (OR = 2.0, P = 0.07) although the results did not reach statistical significance. Arterial thrombosis was more common in high BMI patients (OR = 9.4, P = 0.03).Abnormal BMI at the start of treatment for localized osteosarcoma is associated with increased risk of post-operative wound complications such as arterial thrombosis. Future studies should evaluate whether maintenance of age-appropriate BMI reduces the risk of surgical complications.

    View details for DOI 10.1002/pbc.23129

    View details for Web of Science ID 000295257700009

    View details for PubMedID 21480474

    View details for PubMedCentralID PMC3135763

  • FEASIBILITY AND DOSE DISCOVERY ANALYSIS OF ZOLEDRONIC ACID WITH CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED METASTATIC OSTEOSARCOMA; A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP Goldshy, R., Krailo, M., Wagner, L., Krasin, M., Randall, R. L., Lee, S., Powell, C. L., Kim, G., Gorlick, R., Marina, N., Vilaluna, D., Meyer, J. WILEY-BLACKWELL. 2011: 716?16

    View details for Web of Science ID 000295239600037

  • LACK OF CENTRALIZATION AND UNDER-RECRUITING OF YOUNG-ADULTS: LESSONS FROM EURAMOS-1/AOST0331 (NCT00134030) Zils, K., Marina, N., Bielack, S., Jovic, G., Pickering, J., Sydes, M. R., Smeland, S., Whelan, J., Bernstein, M. WILEY-BLACKWELL. 2011: 779?79

    View details for Web of Science ID 000295239600290

  • High-Intensity Focused Ultrasound (HIFU) Is Not Indicated for Treatment of Primary Bone Sarcomas CANCER Bielack, S. S., Marina, N., Bernstein, M. 2011; 117 (12): 2822-2822

    View details for DOI 10.1002/cncr.25881

    View details for Web of Science ID 000291450100033

    View details for PubMedID 21656761

  • An evaluation of the factors that affect the health-related quality of life of children following myelosuppressive chemotherapy SUPPORTIVE CARE IN CANCER Baggott, C. R., Dodd, M., Kennedy, C., Marina, N., Matthay, K. K., Cooper, B., Miaskowski, C. 2011; 19 (3): 353-361

    Abstract

    The purposes of this study, in children who were assessed 1 week after the administration of myelosuppressive chemotherapy were: to compare the total and subscale scores on a generic measure of health-related quality of life (HRQOL) to normative data from healthy children and describe the relationships between demographic, clinical, and symptom characteristics of children with cancer and generic and disease-specific dimensions of HRQOL.Patients (n =?61) were predominantly male (52.5%), minority (63.9%), and 14.7 years of age. Children completed the Memorial Symptom Assessment Scale for 10- to 18-year olds, the PedsQL? Generic and Cancer Modules, and the Karnofsky Performance Status (KPS) scale 1 week after the start of a chemotherapy cycle.The mean number of symptoms per patient was 10.6. Compared with the normative sample, children with cancer reported significantly lower scores for the total scale and all of the subscales except emotional and social functioning. No significant differences were found between any demographic characteristics and total or subscale scores on the generic or disease-specific measures of HRQOL. Lower KPS scores were associated with poorer generic and disease-specific HRQOL scores. In addition, a higher number of symptoms was associated with poorer generic and disease-specific HRQOL scores. Finally, higher symptom distress scores were associated with poorer generic and disease-specific HRQOL scores.Among the demographic, clinical, and symptom characteristics studied, poorer functional status and higher symptom burden were associated with significant decreases in HRQOL in children who received myelosuppressive chemotherapy.

    View details for DOI 10.1007/s00520-010-0824-y

    View details for Web of Science ID 000287851500005

    View details for PubMedID 20157746

    View details for PubMedCentralID PMC2909452

  • Twenty Years of Follow-Up of Survivors of Childhood Osteosarcoma CANCER Nagarajan, R., Kamruzzaman, A., Ness, K. K., Marchese, V. G., Sklar, C., Mertens, A., Yasui, Y., Robison, L. L., Marina, N. 2011; 117 (3): 625-634

    Abstract

    Osteosarcoma survivors have received significant chemotherapy and have undergone substantial surgeries. Their very long-term outcomes (20 year) are reported here.The authors assessed the long-term outcomes of 733 5-year survivors of childhood osteosarcoma diagnosed from 1970 to 1986 to provide a comprehensive evaluation of medical and psychosocial outcomes for survivors enrolled in the Childhood Cancer Survivor Study (CCSS). Outcomes evaluated included overall survival, second malignant neoplasms (SMNs), recurrent osteosarcoma, chronic health conditions, health status (general and mental health and functional limitations), and psychosocial factors. Outcomes of osteosarcoma survivors were compared with general-population statistics, other CCSS survivors, and CCSS siblings.Survivors had a mean follow-up of 21.6 years. The overall survival of children diagnosed with osteosarcoma who survived 5 years at 20 years from original diagnosis was 88.6% (95% confidence interval [CI], 86.6%-90.5%). The cumulative incidence of SMNs at 25 years was 5.4%, with a standardized incidence ratio of 4.79 (95% CI, 3.54-6.33; P<.01). Overall, 86.9% of osteosarcoma survivors experienced at least 1 chronic medical condition, and >50% experienced ?2 conditions. Compared with survivors of other cancers, osteosarcoma survivors did not differ in their reported general health status (odds ratio [OR], 0.9; 95% CI, 0.7-1.2), but were more likely to report an adverse health status in at least 1 domain (OR, 1.9; 95% CI, 1.6-2.2), with activity limitations (29.1%) being the most common.Childhood osteosarcoma survivors in this cohort did relatively well, considering their extensive treatment, but are at risk of experiencing chronic medical conditions and adverse health status. Survivors warrant life-long follow-up.

    View details for DOI 10.1002/cncr.25446

    View details for Web of Science ID 000286433300028

    View details for PubMedID 20922787

    View details for PubMedCentralID PMC3025070

  • Changes in Children's Reports of Symptom Occurrence and Severity During a Course of Myelosuppressive Chemotherapy JOURNAL OF PEDIATRIC ONCOLOGY NURSING Baggott, C., Dodd, M., Kennedy, C., Marina, N., Matthay, K. K., Cooper, B. A., Miaskowski, C. 2010; 27 (6): 307-315

    Abstract

    The purposes of this study in children who underwent a cycle of myelosuppressive chemotherapy were to describe changes in symptom occurrence and severity during the chemotherapy cycle. Patients (N = 66) 10 to 18 years of age completed the Memorial Symptom Assessment Scale for 10- to 18-year-olds (MSAS 10-18) at the start of a chemotherapy cycle (T1) and weekly for the next 2 weeks (T2 and T3). More than 30% of children reported 10 or more symptoms at all 3 time points. Symptom occurrence trajectories were tested with multilevel logistic regression. In all, 6 symptoms (ie, fatigue, sadness, irritability, worrying, weight loss, sweating) showed a decreasing linear trend. Significant quadratic patterns of change were found for feeling drowsy, nausea, and vomiting. Changes in symptom severity over time were evaluated with multilevel negative binomial regression. No significant differences over time were found in any of the symptom severity scores on the MSAS. Children experienced a high number of symptoms at the initiation of a chemotherapy cycle that persisted over the subsequent 2 weeks.

    View details for DOI 10.1177/1043454210377619

    View details for Web of Science ID 000283296300001

    View details for PubMedID 20739586

  • Inhaled Granulocyte-Macrophage Colony Stimulating Factor for First Pulmonary Recurrence of Osteosarcoma: Effects on Disease-Free Survival and Immunomodulation. A Report From the Children's Oncology Group CLINICAL CANCER RESEARCH Arndt, C. A., Koshkina, N. V., Inwards, C. Y., Hawkins, D. S., Krailo, M. D., Villaluna, D., Anderson, P. M., Goorin, A. M., Blakely, M. L., Bernstein, M., Bell, S. A., Ray, K., Grendahl, D. C., Marina, N., Kleinerman, E. S. 2010; 16 (15): 4024-4030

    Abstract

    Osteosarcoma most commonly recurs in the lung. Based on preliminary data on the antitumor effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in animal models, and promising phase I trials, we embarked on a feasibility study of inhaled GM-CSF in patients with first isolated pulmonary recurrence of osteosarcoma.Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 microg twice daily on alternate weeks. Following two cycles, patients underwent thoracotomy to resect tumor and analyze pulmonary nodules for expression of Fas/Fas ligand (Fas/FasL), and the presence of dendritic cells by immunostaining for CD1a, clusterin, and S100. Following surgery, patients received 12 additional cycles of therapy on alternating weeks or until progression. Event-free survival and survival, and feasibility of therapy delivery were evaluated.Dose escalation to 1,750 microg twice daily was feasible with no dose-limiting toxicity. Mean scores for Fas/FasL in nodules from patients with bilateral recurrence who underwent unilateral thoracotomy pretreatment (using a scoring system of 0-3) were 1.3 and 0.88, respectively, compared with 0.78 and 0.62 in nodules resected following two cycles of therapy. Only 11 of 30 nodules postinhalation were positive for CD1a, 4 of 30 for S100, and 6 of 30 for clusterin. Event-free and overall survival at 3 years were 7.8% and 35.4%, respectively.Inhalation of GM-CSF at doses from 250 to 1,750 microg twice daily on alternate weeks was feasible with low toxicity. However, no detectable immunostimulatory effect in pulmonary metastases or improved outcome postrelapse was seen.

    View details for DOI 10.1158/1078-0432.CCR-10-0662

    View details for Web of Science ID 000280530300023

    View details for PubMedID 20576718

    View details for PubMedCentralID PMC2989183

  • Current Treatment Protocols Have Eliminated the Prognostic Advantage of Type 1 Fusions in Ewing Sarcoma: A Report From the Children's Oncology Group JOURNAL OF CLINICAL ONCOLOGY van Doorninck, J. A., Ji, L., Schaub, B., Shimada, H., Wing, M. R., Krailo, M. D., Lessnick, S. L., Marina, N., Triche, T. J., Sposto, R., Womer, R. B., Lawlor, E. R. 2010; 28 (12): 1989-1994

    Abstract

    PURPOSE Ewing sarcoma family tumors (ESFTs) exhibit chromosomal translocations that lead to the creation of chimeric fusion oncogenes. Combinatorial diversity among chromosomal breakpoints produces varying fusions. The type 1 EWS-FLI1 transcript is created as a result of fusion between exons 7 of EWS and 6 of FLI1, and retrospective studies have reported that type 1 tumors are associated with an improved outcome. We have re-examined this association in a prospective cohort of patients with ESFT treated according to current Children's Oncology Group (COG) treatment protocols. METHODS Frozen tumor tissue was prospectively obtained from patients diagnosed with ESFT, and reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine translocation status. Analysis was confined to patients with localized tumors who were diagnosed after 1994 and treated according to COG protocols. Translocation status was correlated with disease characteristics, event-free survival (EFS), and overall survival (OS). Results RT-PCR identified chimeric fusion oncogenes in 119 of 132 ESFTs. Eighty-nine percent of identified transcripts were EWS-FLI1, and of these, 58.8% were type 1. Five-year EFS and OS rates for patients with type 1 and non-type 1 fusions diagnosed between 2001 and 2005 were equivalent (type 1: EFS, 63% +/- 7%; OS, 83% +/- 6%; non-type 1: EFS, 71% +/- 9%; OS, 79% +/- 8%). CONCLUSION Current intensive treatment protocols for localized ESFT have erased the clinical disadvantage that was formerly observed in patients with non-type 1 EWS-FLI1 fusions.

    View details for DOI 10.1200/JCO.2009.24.5845

    View details for Web of Science ID 000276764000006

    View details for PubMedID 20308669

    View details for PubMedCentralID PMC2860404

  • The Role of Interferons in the Treatment of Osteosarcoma PEDIATRIC BLOOD & CANCER Whelan, J., Patterson, D., Perisoglou, M., Bielack, S., Marina, N., Smeland, S., Bernstein, M. 2010; 54 (3): 350-354

    Abstract

    Interferons, a group of cytokines with antiangiogenic, direct antitumour and immunostimulating properties, have shown significant activity against osteosarcoma in vitro and in xenograft models. They have also been used in osteosarcoma clinical trials as a single adjuvant to surgery, with an apparent increase in relapse-free survival. In the ongoing EURAMOS 1 clinical trial, interferon alpha-2b is evaluated as an adjuvant treatment in osteosarcoma. This article reviews the rationale for the use of interferon in cancer with special reference to the treatment of osteosarcoma, including all published data of clinical efficacy in this disease.

    View details for DOI 10.1002/pbc.22136

    View details for Web of Science ID 000274421400005

    View details for PubMedID 19902521

  • Knowledge of Hepatitis C Virus Screening in Long-Term Pediatric Cancer Survivors A Report From the Childhood Cancer Survivor Study CANCER Lansdale, M., Castellino, S., Marina, N., Goodman, P., Hudson, M. M., Mertens, A. C., Smith, S. M., Leisenring, W., Robison, L. L., Oeffinger, K. C. 2010; 116 (4): 974-982

    Abstract

    Pediatric cancer survivors who were treated before routine hepatitis C virus (HCV) screening of blood donors in 1992 have an elevated risk of transfusion-acquired HCV.To assess long-term pediatric cancer survivors' knowledge of HCV testing and blood transfusion history, a questionnaire was administered to 9242 participants in the Childhood Cancer Survivor Study who are at risk for transfusion-acquired HCV after cancer therapy from 1970 to 1986.More than 70% of survivors reported either no prior HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting prior testing. One half recalled having a treatment-related blood transfusion; those who recalled a transfusion were more likely to report HCV testing (39%) than those who did not (18%) or were unsure (20%). In multivariate models, survivors who reported no prior HCV testing were more likely to be older (odds ratio [OR] per 5-year increase, 1.1; 95% confidence interval [CI], 1.0-1.1) and to report no care at a cancer center within the past 2 years (OR, 1.2; 95% CI, 1.0-1.4), no cancer treatment summary (OR, 1.3; 95% CI, 1.2-1.5), and no transfusions (OR, 2.6; 95% CI, 2.3-3.0) or uncertainty about transfusions (OR, 2.2; 95% CI, 1.9-2.6), and less likely to be racial/ethnic minorities (OR, 0.9; 95% CI, 0.8-1.0) or survivors of acute myeloid leukemia (OR, 0.7; 95% CI, 0.5-1.0).Many pediatric cancer survivors at risk for transfusion-acquired HCV are unaware of their transfusion history and prior testing for HCV and would benefit from programs to increase HCV knowledge and screening.

    View details for DOI 10.1002/cncr.24810

    View details for Web of Science ID 000274315800027

    View details for PubMedID 20041485

    View details for PubMedCentralID PMC2819650

  • Angiogenesis and Vascular Targeting in Ewing Sarcoma A Review of Preclinical and Clinical Data CANCER DuBois, S. G., Marina, N., Glade-Bender, J. 2010; 116 (3): 749-757

    Abstract

    Ewing sarcoma is the second most common type of bone cancer in children and young adults. In recent years, the mechanisms by which these tumors develop and maintain their vascular supply have been elucidated. Additional work has demonstrated that inhibition of angiogenic pathways or disruption of established vasculature can attenuate the growth of Ewing sarcoma mouse xenografts. Early clinical data suggest that these results also may extend to patients with Ewing sarcoma who are treated with antiangiogenic or antivascular therapies. For the current review, the authors summarized the available data supporting this approach.

    View details for DOI 10.1002/cncr.24844

    View details for Web of Science ID 000274169200023

    View details for PubMedID 20029966

    View details for PubMedCentralID PMC2815027

  • Multiple Symptoms in Pediatric Oncology Patients: A Systematic Review JOURNAL OF PEDIATRIC ONCOLOGY NURSING Baggott, C., Dodd, M., Kennedy, C., Marina, N., Miaskowski, C. 2009; 26 (6): 325-339

    Abstract

    Clinical experience suggests that children with cancer experience multiple symptoms as a result of their disease and/ or its treatment. These symptoms may have a negative impact on children's ability to function and on their quality of life. No systematic review has summarized the findings from studies that assessed multiple symptoms in these patients. The purposes of this article are to summarize the findings from the studies of multiple symptoms in pediatric oncology patients and to describe directions for future research. Although there has been a recent increase in the studies of the multiple symptoms in pediatric cancer patients, only 9 studies were found that met the inclusion criteria for this review. Thus, little is known about the relationships between demographic and clinical characteristics and the occurrence of multiple symptoms. Additional research is warranted on the prevalence and impact of multiple symptoms, particularly among homogeneous samples of patients. Future directions for symptom studies in pediatric oncology include symptom cluster research and the search for biological bases for the untoward effects of cancer treatment.

    View details for DOI 10.1177/1043454209340324

    View details for Web of Science ID 000271236500001

    View details for PubMedID 19687466

  • Dose-Intensified Compared With Standard Chemotherapy for Nonmetastatic Ewing Sarcoma Family of Tumors: A Children's Oncology Group Study JOURNAL OF CLINICAL ONCOLOGY Granowetter, L., Womer, R., Devidas, M., Krailo, M., Wang, C., Bernstein, M., Marina, N., Leavey, P., Gebhardt, M., Healey, J., Shamberger, R. C., Goorin, A., Miser, J., Meyer, J., Arndt, C. A., Sailer, S., Marcus, K., Perlman, E., Dickman, P., Grier, H. E. 2009; 27 (15): 2536-2541

    Abstract

    The Ewing sarcoma family of tumors (ESFT) is a group of malignant tumors of soft tissue and bone sharing a chromosomal translocation affecting the EWS locus. The Intergroup INT-0091 demonstrated the superiority of a regimen of vincristine, cyclophosphamide, doxorubicin (VDC), and dactinomycin alternating with ifosfamide and etoposide (IE) over VDC for patients with nonmetastatic ESFT of bone. The goal of this study was to determine whether a dose-intensified regimen of VDC alternating with IE would further improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.Patients with previously untreated, nonmetastatic ESFT of bone or soft tissue were eligible. They were randomly assigned to receive standard doses of VDC/IE over 48 weeks or a dose-intensified regimen of VDC/IE over 30 weeks.Four hundred seventy-eight patients met eligibility requirements: 231 patients received the standard regimen; 247 patients received the intensified regimen. The 5-year event-free survival (EFS) and overall survival rates for all eligible patients were 71.1% (95% CI, 67.7% to 75.0%) and 78.6% (95% CI, 74.6% to 82.1%), respectively. There was no significant difference (P = .57) in EFS between patients treated with the standard (5-year EFS, 72.1%; 95% CI, 65.8% to 77.5%) or intensified regimen (5-year EFS, 70.1%; 63.9% to 75%). Patients with soft tissue tumors accounted for 20% of the study population; there was no difference in outcome between patients with soft tissue and bone primary sites.Dose escalation of alkylating agents as tested in this trial did not improve the outcome for patients with nonmetastatic ESFT of bone or soft tissue.

    View details for DOI 10.1200/JCO.2008.19.1478

    View details for Web of Science ID 000266195400021

    View details for PubMedID 19349548

    View details for PubMedCentralID PMC2684856

  • Immune approaches to treating osteosarcoma CANCER BIOLOGY & THERAPY Marina, N., Gorlick, R. 2009; 8 (10): 981-983

    View details for Web of Science ID 000268393300018

    View details for PubMedID 19395866

  • Physical Performance Limitations in the Childhood Cancer Survivor Study Cohort 43rd Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Ness, K. K., Hudson, M. M., Ginsberg, J. P., Nagarajan, R., Kaste, S. C., Marina, N., Whitton, J., Robison, L. L., Gurney, J. G. AMER SOC CLINICAL ONCOLOGY. 2009: 2382?89

    Abstract

    Physical performance limitations are one of the potential long-term consequences following diagnosis and treatment for childhood cancer. The purpose of this review is to describe the risk factors for and the participation restrictions that result from physical performance limitations among childhood cancer survivors who participated in the Childhood Cancer Survivor Study (CCSS). Articles previously published from the CCSS cohort related to physical performance limitations were reviewed and the results summarized. Our review showed that physical performance limitations are prevalent among childhood cancer survivors and may increase as they age. Host-based risk factors for physical disability include an original diagnosis of bone tumor, brain tumor, or Hodgkin's disease; female sex; and an income less than $20,000 per year. Treatment-based risk factors include radiation and treatment with a combination of alkylating agents and anthracyclines. Musculoskeletal, neurologic, cardiac, pulmonary, sensory, and endocrine organ system dysfunction also increase the risk of developing a physical performance limitation. In summary, monitoring of physical performance limitations in an aging cohort of childhood cancer survivors is important and will help determine the impact of physical performance limitations on morbidity, mortality, and caregiver burden. In addition, in developing restorative and preventive interventions for childhood cancer survivors, we must take into account the special needs of survivors with physical disability to optimize their health and enhance participation in daily living activities.

    View details for DOI 10.1200/JCO.2008.21.1482

    View details for Web of Science ID 000266195200009

    View details for PubMedID 19332713

    View details for PubMedCentralID PMC2738647

  • Phase II Study of Intermediate-Dose Cytarabine in Patients With Relapsed or Refractory Ewing Sarcoma: A Report From the Children's Oncology Group PEDIATRIC BLOOD & CANCER DuBois, S. G., Krailo, M. D., Lessnick, S. L., Smith, R., Chen, Z., Marina, N., Grier, H. E., Stegmaier, K. 2009; 52 (3): 324-327

    Abstract

    Patients with relapsed or refractory Ewing sarcoma have a poor outcome with conventional therapies. Cytarabine decreases EWS/FLI1 protein levels in Ewing sarcoma cells and has demonstrated preclinical activity against Ewing sarcoma in vitro and in vivo. The purpose of this phase II clinical trial was to estimate the response rate of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma.Patients with a histologic diagnosis of Ewing sarcoma were eligible if they were <30 years of age, had relapsed or refractory measurable disease, and met standard organ function requirements. Patients received cytarabine 500 mg/m(2)/dose intravenously over 2 hr every 12 hr for 10 doses with cycles repeated every 21 days. Response was assessed according to RECIST criteria.Ten patients (median age 20 years; 7 males) were treated. Only five patients had documented EWS/FLI1 translocated tumors. No objective responses were seen. One patient had stable disease for 5 cycles before developing progressive disease. All patients evaluable for hematologic toxicity developed grade 4 neutropenia and thrombocytopenia during protocol therapy. Patients were not able to receive therapy according to the planned 21-day cycles, with a median interval of 26.5 days.Cytarabine at the dose and schedule utilized in this trial resulted in hematologic toxicity that limited delivery of this therapy. This regimen also had minimal activity in this patient population.

    View details for DOI 10.1002/pbc.21822

    View details for Web of Science ID 000262603900007

    View details for PubMedID 18989890

    View details for PubMedCentralID PMC2791370

  • International Collaboration is Feasible in Trials for Rare Conditions: The EURAMOS Experience Symposium on Pediatric and Adolescent Osteosarcoma Marina, N., Bielack, S., Whelan, J., Smeland, S., Krailo, M., Sydes, M. R., Butterfass-Bahloul, T., Calaminus, G., Bernstein, M. SPRINGER. 2009: 339?353

    Abstract

    The introduction of multi-agent chemotherapy dramatically improved the outcome for patients with osteosarcoma. However, we appear to have reached a plateau in outcome with a long-term event-free survival of 60-70%. Therefore, detection of further improvements will likely require larger numbers of patients. This goal is best achieved via randomized clinical trials (RCTs) requiring large-scale cooperation and collaboration. With this background, four multinational groups agreed on the merits of collaboration: Children's Oncology Group (COG), Cooperative Osteosarcoma Study Group (COSS), European Osteosarcoma Intergroup (EOI) and Scandinavian Sarcoma Group (SSG); they designed a study to determine whether altering postoperative therapy based on histological response improved the outcome. The study design includes a backbone of 10 weeks of preoperative therapy using MAP (methotrexate, Adriamycin and cisplatin). Following surgery, patients are stratified according to histological response. Patients classified as "good responders" (>or=90% necrosis) are randomized to continue MAP or to receive MAP followed by maintenance pegylated interferon, while "poor responders" (<90% necrosis) are randomized to either continue MAP or to receive MAPIE (MAP+ifosfamide, etoposide). The design includes the registration of 1,400 patients over 4 years as well as the evaluation of quality of life using two different instruments. The group has established an efficient infrastructure to ensure successful implementation of the trial. This has included the EURAMOS Intergroup Safety Desk, which has established an international system for SAE, SAR and SUSAR reporting to the relevant competent authorities and ethics committees for each participating country. The group has also developed trial site monitoring and data center audits with funding from the European Science Foundation (ESF). The ESF has also funded three training courses to familiarize institutional staff with the requirements of multinational GCP trials. We have established a successful collaboration, and as of February 2008, 901 patients have been enrolled (COG 448; COSS 226; EOI 181; SSG 46) from 249 institutions in 16 different countries. As expected, 80% of the patients are <18 years of age, and accrual into the Quality of Life sub-study is proceeding as planned with 90% of the subjects agreeing to participate. International awareness is increasing and procedures for applicant countries wishing to join the collaboration have been implemented. Details about EURAMOS can be found at www.euramos.org. International trials in rare diseases are practicable with appropriate funding, planning and support. Although the implementation of such trials is difficult and time consuming, it is a worthwhile effort to rapidly complete RCTs and identify interventions that will improve the outcome of all osteosarcoma patients.EURAMOS-1 is the fastest accruing osteosarcoma trial and is already the largest osteosarcoma study conducted.

    View details for Web of Science ID 000273510800018

    View details for PubMedID 20213400

  • Renal function after ifosfamide, carboplatin and etoposide (ICE) chemotherapy, nephrectomy and radiotherapy in children with wilms tumour EUROPEAN JOURNAL OF CANCER Daw, N. C., Gregornik, D., Rodman, J., Marina, N., Wu, J., Kun, L. E., Jenkins, J. J., McPherson, V., Wilimas, J., Jones, D. P. 2009; 45 (1): 99-106

    Abstract

    We prospectively evaluated tumour response and renal function in 12 newly diagnosed children with high-risk Wilms tumour receiving ifosfamide, carboplatin and etoposide (ICE) chemotherapy. Two cycles of ICE were followed by 5 weeks of vincristine, dactinomycin and doxorubicin (Adriamycin) (VDA), and nephrectomy, radiotherapy, additional VDA, and a third ICE cycle. Carboplatin dosage was based on glomerular filtration rate (GFR) to achieve targeted systemic exposure (6mg/ml min). Mean GFR (measured by technetium 99m-DTPA clearance) declined by 7% after 2 cycles of ICE and by 38% after nephrectomy; the mean carboplatin dose was reduced 32% after nephrectomy. Mean GFR remained stable after the third ICE cycle. Although urinary beta(2)-microglobulin excretion increased during therapy, no patient had clinically significant renal tubular dysfunction at the end of treatment. Treatment with ICE, nephrectomy and radiotherapy significantly reduces GFR, largely as the result of nephrectomy. Adjustment of carboplatin dosage on the basis of GFR and careful monitoring of renal function may alleviate nephrotoxicity.

    View details for DOI 10.1016/j.ejca.2008.09.017

    View details for Web of Science ID 000262735900019

    View details for PubMedID 18996004

  • Anti-insulin growth factor receptor therapy in Ewing sarcoma. F1000 medicine reports Isakoff, M. S., Marina, N. 2009; 1

    Abstract

    The insulin-like growth factor (IGF) signal transduction pathway appears to play a key role in the development and proliferation of the Ewing sarcoma family of tumors. Integration of anti-IGF-1 receptor therapy into the standard treatment for these patients is a novel approach that will likely be incorporated into future treatment to determine whether such agents will improve the outcome for patients with this malignancy.

    View details for DOI 10.3410/M1-62

    View details for PubMedID 20948718

  • Second Solid Malignancies Among Children, Adolescents, and Young Adults Diagnosed With Malignant Bone Tumors After 1976 Follow-Up of a Children's Oncology Group Cohort CANCER Goldsby, R., Burke, C., Nagarajan, R., Zhou, T., Chen, Z., Marina, N., Friedman, D., Neglia, J., Chuba, P., Bhatia, S. 2008; 113 (9): 2597-2604

    Abstract

    The growing number of individuals surviving childhood cancer has increased the awareness of adverse long-term sequelae. One of the most worrisome complications after cancer therapy is the development of second malignant neoplasms (SMNs).The authors describe the incidence of solid organ SMN in survivors of pediatric malignant bone tumors who were treated on legacy Children's Cancer Group/Pediatric Oncology Group protocols from 1976 to 2005. This retrospective cohort study included 2842 patients: 1686 who were treated for osteosarcoma (OS) and 1156 who were treated for Ewing sarcoma (ES).The cohort included 56% boys/young men and 44% girls/young women, and the median age at primary diagnosis was 13 years. The median length of follow-up was 6.1 years (range, 0-20.9 years). In this analysis, 64% of patients were alive. Seventeen patients with solid organ SMN were identified. The standardized incidence ratio was 2.9 (95% confidence interval [CI], 1.4-5.4) for patients who were treated for OS and 5.0 (95% CI, 2.6-9.4) for patients who were treated for ES. The median time from diagnosis to development of solid SMN was 7 years (range, 1-13 years). The 10-year cumulative incidence of solid organ SMN for the entire cohort was 1.4% (95%CI 0.6%-2%).The magnitude of risk of solid SMNs was modest after treatment for malignant bone tumors. However, radiation-related solid SMNs will increase with longer follow-up. Because nearly 33% of patients die from their disease, recurrence remains the most significant problem. The development of improved therapies with fewer long-term consequences is paramount. Follow-up should focus on monitoring for both recurrence of primary malignancies and development of SMNs.

    View details for DOI 10.1002/cncr.23860

    View details for Web of Science ID 000260405100029

    View details for PubMedID 18823030

    View details for PubMedCentralID PMC2765980

  • Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence following multi-modality therapy: A report from the Children's Oncology Group PEDIATRIC BLOOD & CANCER Leavey, P. J., Mascarenhas, L., Marina, N., Chen, Z., Krailo, M., Miser, J., Brown, K., Tarbell, N., Bernstein, M. L., Granowetter, L., Gebhardt, M., Grier, H. E. 2008; 51 (3): 334-338

    Abstract

    The prognosis for patients with recurrent Ewing sarcoma (EWS) is very poor with 5-year survival of 13%.To evaluate prognostic factors for these patients we studied patients initially treated on the multi-institutional study INT0091.Two hundred sixty-two patients experienced disease recurrence. The median time to first recurrence was 1.3 years (0-7.4 years), 1.4 years (0-7.4 years) for patients with initially localized disease and 1 year (0-6 years) for patients with initially metastatic disease. Time to first recurrence from date of initial diagnosis was a predictor of post-recurrence survival (P < 0.0001). Twenty-one percent of patients, with recurrent or progressive disease >or=2 years from initial diagnosis, had an estimated 5-year survival of 30% (vs. 7% estimated 5-year survival with an earlier recurrence). No statistical difference was detected between patients whose disease recurred <1 year and between 1 and 2 years from initial diagnosis. A stepwise relative risk model and backwards stepwise regression was used to explore factors significantly associated with risk for post-recurrence death. Significant risk factors for death after recurrence included recurrence at combined local and distant sites, elevated LDH at initial diagnosis and initial recurrence less than 2 years after diagnosis. Isolated pulmonary recurrence was not predictive of survival after recurrence.Patients with a longer disease control interval represent the subset of patients most likely to survive following recurrence of EWS. All patients with recurrence would benefit from collaborative trials to investigate new therapeutic options.

    View details for DOI 10.1002/pbc.21618

    View details for Web of Science ID 000257907300005

    View details for PubMedID 18506764

    View details for PubMedCentralID PMC2728357

  • Imaging guidelines for children with Ewing sarcoma and osteosarcoma: A report from the Children's Oncology Group Bone Tumor Committee PEDIATRIC BLOOD & CANCER Meyer, J. S., Nadel, H. R., Marina, N., Womer, R. B., Brown, K. L., Eary, J. F., Gorlick, R., Grier, H. E., Randall, R. L., Lawlor, E. R., Lessnick, S. L., Schomberg, P. J., Kailo, M. D. 2008; 51 (2): 163-170

    Abstract

    The Children's Oncology Group (COG) is a multi-institutional cooperative group dedicated to childhood cancer research that has helped to increase the survival of children with cancer through clinical trials. These clinical trials include a standardized regimen of imaging examinations performed prior to, during, and following therapy. This article presents imaging guidelines developed by a multidisciplinary group from the COG Bone Tumor Committee. These guidelines provide both required and recommended studies. Recommended examinations may become required in the future. These guidelines should be considered a work in progress that will evolve with advances in imaging and childhood cancer research.

    View details for DOI 10.1002/pbc.21596

    View details for Web of Science ID 000256871800004

    View details for PubMedID 18454470

  • Osteosarcoma: The same old drugs or more? JOURNAL OF CLINICAL ONCOLOGY Bielack, S. S., Marina, N., Ferrari, S., Helman, L. J., Smeland, S., Whelan, J. S., Reaman, G. H. 2008; 26 (18): 3102-3103

    View details for DOI 10.1200/JCO.2008.17.1108

    View details for Web of Science ID 000256879700039

    View details for PubMedID 18565904

  • Application of the adult International Germ Cell Classification system to pediatric malignant non-seminomatous germ cell tumors: A report from the children's oncology group PEDIATRIC BLOOD & CANCER Frazier, A. L., Rumcheva, P., Olson, T., Giller, R., Cushing, B., Cullen, J., Marina, N., London, W. B. 2008; 50 (4): 746-751

    Abstract

    The purpose of this analysis is to explore whether the International Germ Cell Classification Consensus (IGCCC) tumor marker criteria, developed for adult males with metastatic malignant germ cell tumors (MGCT), are prognostic among pediatric patients and whether tumor marker data may be relevant in pediatric risk stratification.The IGCCC was applied to 436 pediatric germ cell patients treated on Pediatric Intergroup Studies from 1990 to 1996. Multivariable Cox proportional hazards model identified prognostic variables; survival rates among IGCCC risk groups were compared using the log-rank test. Concordance and relative performance of IGCCC versus COG risk stratification was evaluated.Applying the IGCCC, 21% of pediatric patients were good risk (GR), 35% intermediate risk (IR), and 44% poor risk (PR). Only modest concordance between IGCCC and COG stratification systems was noted (49%). Nonetheless, the IGCCC identified a group of PR patients who had significantly worse event-free survival (EFS) versus GR/IR patients (6-year EFS 80% vs. 91%), which was similar to the difference observed using the COG system (6-year EFS 77% vs. 90%). The IGCCC performed well within subgroups for which the IGCCC is not intended (prepubertal, female, and non-metastatic patients).Applying the IGCCC system to pediatric patients produces a different stratification than does the application of the COG system, although both are prognostic. Development of a de novo pediatric prognostic classification is warranted.

    View details for DOI 10.1002/pbc.21304

    View details for Web of Science ID 000253661200004

    View details for PubMedID 18085675

  • Monitoring for cardiovascular disease in survivors of childhood cancer: Report from the cardiovascular disease task force of the children's oncology group PEDIATRICS Shankar, S. M., Marina, N., Hudson, M. M., Hodgson, D. C., Adams, M. J., Landier, W., Bhatia, S., Meeske, K., Chen, M. H., Kinahan, K. E., Steinberger, J., Rosenthal, D. 2008; 121 (2): E387-E396

    Abstract

    Curative therapy for childhood cancer has improved significantly in the last 2 decades such that, at present, approximately 80% of all children with cancer are likely to survive > or = 5 years after diagnosis. Prevention, early diagnosis, and treatment of long-term sequelae of therapy have become increasingly more significant as survival rates continue to improve. Cardiovascular disease is a well-recognized cause of increased late morbidity and mortality among survivors of childhood cancer. The Children's Oncology Group Late Effects Committee and Nursing Discipline and Patient Advocacy Committee have recently developed guidelines for follow-up of long-term survivors of pediatric cancer. A multidisciplinary task force critically reviewed the existing literature to evaluate the evidence for the cardiovascular screening recommended by the Children's Oncology Group guidelines. In this review we outline the clinical manifestations of late cardiovascular toxicities, suggest modalities and frequency of monitoring, and address some of the controversial and unresolved issues regarding cardiovascular disease in childhood cancer survivors.

    View details for DOI 10.1542/peds.2007-0575

    View details for Web of Science ID 000252877600058

    View details for PubMedID 18187811

  • Complementary and alternative therapy use in adult survivors of childhood cancer: A report from the childhood cancer survivor study PEDIATRIC BLOOD & CANCER Mertens, A. C., Sencer, S., Myers, C. D., Recklitis, C., Kadan-Lottick, N., Whitton, J., Marina, N., Robison, L. L., Zeltzer, L. 2008; 50 (1): 90-97

    Abstract

    Little information is available on the use of complementary and alternative medicine (CAM) in long-term survivors of childhood and adolescent cancer.The Childhood Cancer Survivor Study (CCSS) is a resource evaluating the long-term effects of cancer and associated therapies in 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986 before the age of 21 years. A survey of CAM use during the previous year was distributed in 2000-2001 and completed by 9,984 survivors and 2,474 sibling controls.CAM use reporting was similar in cases (39.4%) and siblings (41.1%). Compared to female siblings, female survivors were more likely to use biofeedback (odds ratio (OR) = 3.3; 95% CI = 1.0-10.8) and hypnosis/guided imagery (OR = 3.2; 95% CI = 1.6-6.8); male survivors were more likely than male siblings to use herbal remedies (OR = 1.3; 95% CI = 1.1-1.6). Factors associated with CAM use in survivors included elevated scores on the brief symptom inventory (BSI)-18 (OR = 1.6; 95% CI = 1.3-1.9), prolonged pain (OR = 1.5; 95% CI = 1.3-1.7), and having seen a physician in the past 2 years (OR = 1.6; 95% CI = 1.4-1.8). Survivors reporting low alcohol intake and excellent or good general health reported lower levels of CAM use (OR = 0.7; 95% CI = 0.7-0.8 and OR = 0.8; 95% CI = 0.7-0.9, respectively).Survivors have a similar reported use of CAM compared to a sibling cohort. However, our data suggest that survivors turn to CAM for specific symptoms related to previous diagnosis and treatment. Future research is needed to determine whether CAM use reflects unmet health needs in this population.

    View details for DOI 10.1002/pbc.21177

    View details for Web of Science ID 000251410400016

    View details for PubMedID 17366533

  • Challenges in the recruitment of adolescents and young adults to cancer clinical trials CANCER Burke, M. E., Albritton, K., Marina, N. 2007; 110 (11): 2385-2393

    Abstract

    The adolescent and young adult (AYA) oncology population has seen inferior progress in cancer survival compared with younger children and older adults over the past 25 years. Previously, AYAs had the best survival rates due to the prevalence of highly curable diseases including Hodgkin lymphoma and germ cell tumors, yet today AYAs have inferior survival rates to children and some adult cohorts. Survival rates are particularly poor for AYA-specific diseases such as sarcomas. Research involving children and adults diagnosed with common malignancies such as acute lymphoblastic leukemia has resulted in improved survival rates. However, AYAs have not directly benefited from such research due to low rates of access to and accrual on clinical trials. AYAs are less likely to have insurance or access to healthcare, are more likely to see providers who are not part of research institutions, and are less likely to be referred to or to join clinical trials, all of which may contribute to worse outcomes. Few clinical trials target AYA-specific diseases, leading to little information regarding how these diseases behave and what role the host plays. Tumor samples for this population are underrepresented in national tumor banks. Coupled with the need for more clinical trials that focus on AYA-specific cancers, better collaboration between adult and pediatric cooperative groups as well as increased education among community oncologists and primary care providers will be needed to enhance participation in clinical trials with the goal to increase survival and improve quality of that survival.

    View details for DOI 10.1002/cncr.23060

    View details for Web of Science ID 000251209100004

    View details for PubMedID 17918260

  • Successful pan-European and trans-Atlantic collaboration in a randomised controlled trial in osteosarcoma: EURAMOS1 (ISRCTN67613327; a trial conducted as part of ECT-EUROCORES) 14th European Cancer Conference (ECCO 14) Whelan, J., Smeland, S., Marina, N., Bernstein, M., Sydes, M. R., May, B., Butterfass-Bahloui, T., Perisoglou, M., CARRLE, D., Bielack, S. PERGAMON-ELSEVIER SCIENCE LTD. 2007: 408?9

    View details for Web of Science ID 000250204001349

  • Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors JOURNAL OF CLINICAL ONCOLOGY Hudson, M. M., Rai, S. N., Nunez, C., Merchant, T. E., Marina, N. M., Zalamea, N., Cox, C., Phipps, S., Pompeu, R., Rosenthal, D. 2007; 25 (24): 3635-3643

    Abstract

    PURPOSEl: Childhood cancer survivors treated with anthracyclines and cardiac radiation are at risk for late-onset cardiotoxicity. The purpose of this study was to delineate the relationship between clinical factors and abnormalities of noninvasive cardiac testing (NICT).Participants were recruited from a long-term follow-up clinic. Study measures comprised physical examination, laboratory evaluation, echocardiogram, and ECG. Mean fractional shortening (FS) and afterload were compared for survivors who did (at risk [AR]) and did not (no risk [NR]) receive potentially cardiotoxic modalities, and with values expected for comparable age- and sex-matched controls.The 278 study participants (mean age, 18.1 years; median age, 16.8 years; range, 7.5 to 39.7 years) included 223 survivors AR for cardiotoxicity after treatment with anthracyclines (median dose +/- standard deviation [SD], 202 +/- 109 mg/m(2)) and/or cardiac radiation. Mean FS (+/- SD) was lower for AR (0.33 +/- 0.06) compared with NR survivors (0.36 +/- 0.05; P = .004) and normative controls (0.36 +/- 0.04; P < .001). Mean afterload (+/- SD) was higher for AR (58 +/- 21 g/cm(2)) compared with NR survivors (46 +/- 15 g/cm(2); P < .001) and normative controls (48 +/- 13 g/cm(2); P < .001). The distribution of FS and afterload among NR survivors did not differ from that of controls. After adjustment for age group at diagnosis and time since completion of therapy, anthracycline dose predicted decline in distribution of FS (P < .001) and increase in distribution of afterload (P < .001). Treatment with anthracycline doses >or= 100 mg/m(2) increased the risk of abnormal NICT; survivors who received >or= 270 mg/m(2) had a 4.5-fold excess risk of abnormal NICT (95% CI, 2.1 to 9.6) compared with controls.Childhood cancer survivors treated with anthracycline doses >or= 270 mg/m(2) are at greatest risk for abnormalities of FS and afterload.

    View details for DOI 10.1200/JCO.2006.09.7451

    View details for Web of Science ID 000249415900015

    View details for PubMedID 17704413

  • The euramos osteosarcoma study Bernstein, M. L., Marina, N. WILEY PERIODICALS, INC. 2007: 610?10

    View details for Web of Science ID 000246013900040

  • Chronic health conditions in adult survivors of childhood cancer NEW ENGLAND JOURNAL OF MEDICINE Oeffinger, K. C., Mertens, A. C., Sklar, C. A., Kawashima, T., Hudson, M. M., Meadows, A. T., Friedman, D. L., Marina, N., Hobbie, W., Kadan-Lottick, N. S., Schwartz, C. L., Leisenring, W., Robison, L. L. 2006; 355 (15): 1572-1582

    Abstract

    Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors.The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition.Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition.Survivors of childhood cancer have a high rate of illness owing to chronic health conditions.

    View details for Web of Science ID 000241160400008

    View details for PubMedID 17035650

  • Prognostic factors in children with extragonadal malignant germ cell tumors: A pediatric intergroup study 33rd Meeting of the International-Society-for-Paediatric-Oncology Marina, N., London, W. B., Frazier, A. L., Lauer, S., Rescorla, F., Cushing, B., Malogolowkin, M. H., Castleberry, R. P., Womer, R. B., Olson, T. AMER SOC CLINICAL ONCOLOGY. 2006: 2544?48

    Abstract

    To investigate prognostic factors for pediatric extragonadal malignant germ cell tumors (PEMGCT).Between 1990 and 1996, patients with stage I through IV PEMGCT were eligible for a trial of cisplatin dose intensity. We retrospectively investigated prognostic factors for PEMGCT, including age, stage, primary site, treatment, and elevated alfa fetoprotein by univariate and multivariate analysis.The 165 patients had a median age of 1.9 years (range, 3 days to 18.5 years); 109 were female; and 99 had alfa fetoprotein > or = 10,000. There were 30 stage I/II, 61 stage III, and 74 stage IV tumors; primary sites included 88 sacrococcygeal, 39 thoracic, and 38 others. The 5-year overall survival (OS) and event-free survival (EFS) rates with standard deviations were 83.4% +/- 3.7% and 79.0% +/- 4.1%, respectively. Univariate analysis identified age > or = 12 years as a highly significant prognostic factor for EFS (5-year EFS, 48.9% +/- 15.6% v 84.1% +/- 3.9%; P < .0001) and for OS (5-year OS, 53.7% +/- 14.9% v 88.5% +/- 3.4%; P < .0001), whereas treatment was of borderline significance (P = .0777). Multivariate Cox proportional hazards regression identified only age > or = 12 years as a significant prognostic factor for EFS (P = .0002). In multivariate Cox regression for OS, the combination of age and primary site was highly significant (P < .0001). Patients > or = 12 years of age with thoracic tumors had six times the risk of death compared with patients younger than 12 years with other primaries.Age is the most predictive factor of EFS in PEMGCT. There is a significant interaction between age and primary site, suggesting that patients > or = 12 years of age with thoracic tumors are a biologically distinct group.

    View details for DOI 10.1200/JCO.2005.04.1251

    View details for Web of Science ID 000237940900023

    View details for PubMedID 16735707

  • Amifostine does not protect against the ototoxicity of high-dose cisplatin combined with etoposide and bleomycin in pediatric germ-cell tumors - A children's Oncology Group study CANCER Marina, N., Chang, K. W., Malogolowkin, M., London, W. B., Frazier, A. L., Womer, R. B., Rescorla, F., Billmire, D. F., DAVIS, M. M., Perlman, E. J., Giller, R., Lauer, S. J., Olson, T. A. 2005; 104 (4): 841-847

    Abstract

    High-dose cisplatin combined with etoposide and bleomycin (HDPEB) improves event-free survival (EFS) in advanced pediatric germ-cell tumors (PGCT), but has significant ototoxicity. Amifostine appears to protect against toxicity. The authors combined amifostine with HDPEB and evaluated the efficacy and toxicity, specifically whether ototoxicity decreased.Eligibility criteria included age < 15 years and unresectable Stage III/IV extracranial, extragonadal PGCT. Patients received bleomycin 15 IU/m(2) on Day 1, then etoposide 100 mg/m(2) per day, amifostine 825 mg/m(2) per day, and cisplatin 40 mg/m(2)per day on Days 1-5, intravenously. The cycles were repeated every 3-4 weeks with imaging evaluation after 4 cycles. Patients with residual radiographic abnormalities underwent resection. Patients with residual tumor received two additional HDPEB cycles. Hearing evaluations were required at diagnosis and after two and four cycles. Audiologic results were reviewed and compared with historical controls treated with HDPEB.Twenty-five eligible patients were enrolled between April 2000 and April 2002. Their median age was 1.6 years (range, 0.64-13.9 years), 17 patients were female, 11 had metastases, and 24 had a yolk sac carcinoma component histologically. Primary sites included sacrococcygeal area/pelvis (n = 15), vagina (n = 5), and other (n = 5). Two-year EFS and overall survival were 83.5% +/- 12.8% and 85.6% +/- 12.3%, respectively. Eight patients were removed from the study (four had progressive disease/disease recurrence and four had ototoxicity). Grade 3/4 toxicities included neutropenia (n = 20), thrombocytopenia (n = 14), electrolyte imbalances (n = 14), and gastrointestinal toxicity (n = 12). Twenty-four of 25 patients received hearing evaluations, and 75% had significant hearing loss.Amifostine did not protect against HDPEB-associated ototoxicity.

    View details for DOI 10.1002/cncr.21218

    View details for PubMedID 15999362

  • High-dose therapy and stem-cell rescue for Ewing's family of tumors in second remission JOURNAL OF CLINICAL ONCOLOGY Marina, N., Meyers, P. A. 2005; 23 (19): 4262-4264

    View details for DOI 10.1200/JCO.2005.12.915

    View details for Web of Science ID 000230332800006

    View details for PubMedID 15781877

  • Low levels of Her2/neu expressed by Ewing's family tumor cell lines can redirect cytokine-induced killer cells CLINICAL CANCER RESEARCH Verneris, M. R., Arshi, A., Edinger, M., Kornacker, M., Natkunam, Y., Karami, M., Cao, Y. A., Marina, N., Contag, C. H., Negrin, R. S. 2005; 11 (12): 4561-4570

    Abstract

    To identify novel treatments for pediatric solid tumors and/or for malignancies with low-level Her2/neu expression.Using fluorescence-activated cell sorting and immunohistochemistry, Her2/neu expression was determined on cell lines derived vfrom Ewing's family tumors (EFT) and neuroblastoma. Sensitivity to trastuzumab treatment was investigated using an in vitro proliferation assay. Cytotoxicity against EFT cell lines was done with either freshly isolated or ex vivo activated and expanded T cells (cytokine-induced killer cells, CIK cells), with or without addition of a CD3xHer2/neu bispecific antibody. The effects of either trastuzumab, CIK cells alone, or CD3xHer2/neu bispecific antibody redirected CIK cells was determined using a SCID/hu model of EFTs and serial, noninvasive bioluminescent imaging.EFT cell lines express 5- to 10-fold lower levels of her2/neu than either breast (BT-474) or ovarian (SK-OV-3) cell lines. Treatment of EFT cell lines with trastuzumab did not induce growth inhibition either in vitro or in vivo. In contrast, Her2/neu could be used to redirect CIK cell to mediate cytotoxicity against EFTs both in vitro and in vivo (using two different treatment schemas).CD3xHer2/neu bispecific antibody and CIK cells may be a suitable approach to treat malignancies with low-level Her2/neu expression not responsive to trastuzumab.

    View details for Web of Science ID 000229725900037

    View details for PubMedID 15958642

  • Development of risk-based guidelines for pediatric cancer survivors: The Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline JOURNAL OF CLINICAL ONCOLOGY Landier, W., Bhatia, S., Eshelman, D. A., Forte, K. J., Sweeney, T., Hester, A. L., Darling, L., Armstrong, E. D., Blatt, J., Constine, L. S., Freeman, C. R., Friedman, D. L., Green, D. M., Marina, N., Meadows, A. T., Neglia, J. P., Oeffinger, K. C., Robison, L. L., Ruccione, K. S., Sklar, C. A., Hudson, M. M. 2004; 22 (24): 4979-4990

    Abstract

    The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers are risk-based, exposure-related clinical practice guidelines intended to promote earlier detection of and intervention for complications that may potentially arise as a result of treatment for pediatric malignancies. Developed through the collaborative efforts of the Children's Oncology Group Late Effects Committee, Nursing Discipline, and Patient Advocacy Committee, these guidelines represent a statement of consensus from a multidisciplinary panel of experts in the late effects of pediatric cancer treatment. The guidelines are both evidence-based (utilizing established associations between therapeutic exposures and late effects to identify high-risk categories) and grounded in the collective clinical experience of experts (matching the magnitude of risk with the intensity of screening recommendations). They are intended for use beginning 2 or more years following the completion of cancer therapy; however, they are not intended to provide guidance for follow-up of the survivor's primary disease. A complementary set of patient education materials ("Health Links") was developed to enhance follow-up care and broaden the application of the guidelines. The information provided in these guidelines is important for health care providers in the fields of pediatrics, oncology, internal medicine, family practice, and gynecology, as well as subspecialists in many fields. Implementation of these guidelines is intended to increase awareness of potential late effects and to standardize and enhance follow-up care provided to survivors of pediatric cancer throughout the lifespan. The Guidelines, and related Health Links, can be downloaded in their entirety at www.survivorshipguidelines.org.

    View details for DOI 10.1200/JCO.2004.11.032

    View details for Web of Science ID 000226238900018

    View details for PubMedID 15576413

  • Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A pediatric intergroup study - Pediatric oncology group 9048 and children's cancer group 8891 39th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Rogers, P. C., Olson, T. A., Cullen, J. W., Billmire, D. F., Marina, N., Rescorla, F., DAVIS, M. M., London, W. B., Lauer, S. J., Giller, R. H., Cushing, B. AMER SOC CLINICAL ONCOLOGY. 2004: 3563?69

    Abstract

    To determine whether children with localized gonadal malignant germ cell tumors (MGCT) stage II testicular and stages I and II ovarian treated with four cycles of standard-dose cisplatin combined with etoposide and low-dose bleomycin (PEB) have an event-free survival (EFS) of at least 85% without significant toxicity.Between May 1990 and July 1995, eligible pediatric patients with stage II or recurrent from stage I (as a stage II) testicular MGCT and stages I and II ovarian MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. PEB chemotherapy consisted of bleomycin 15 U/m2 on day 1, cisplatin 20 mg/m2/d on days 1 to 5, and etoposide 100 mg/m2/d on days 1 to 5. Patients received four cycles of therapy at 21-day intervals.Seventy-four patients with a median age of 10.5 years (range, 8.7 months to 16.7 years) were enrolled. Primary sites included: stage II testicular (n = 17), stage I ovarian (n = 41), and stage II ovarian MGCT (n = 16). Treatment with standard PEB resulted in 6-year EFS of 95% and overall survival (OS) of 95.7%. EFS and OS by primary site were as follows: stage II testicular, 100% and 100%; stage I ovarian, 95.1% and 95.1%; and stage II ovarian, 87.5% and 93.8%, respectively. Two patients died from recurrent disease, and one patient died of secondary acute myelocytic leukemia. Infrequent grade 3 to 4 hematologic toxicity was reported. No grade 3 to 4 renal, pulmonary, or ototoxicity was observed.Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT.

    View details for DOI 10.1200/JCO.2004.01.006

    View details for Web of Science ID 000223711300019

    View details for PubMedID 15337806

  • Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: A pediatric intergroup study - Pediatric Oncology Group 9049 and Children's Cancer Group 8882 34th Annual Meeting of the American-Society-of-Clinical-Oncology Cushing, B., Giller, R., Cullen, J. W., Marina, N. M., Lauer, S. J., Olson, T. A., Rogers, P. C., Colombani, P., Rescorla, F., Billmire, D. F., Vinocur, C. D., Hawkins, E. P., DAVIS, M. M., Perlman, E. J., Castleberry, R. P. AMER SOC CLINICAL ONCOLOGY. 2004: 2691?2700

    Abstract

    To determine in a randomized comparison whether combination chemotherapy with high-dose cisplatin (HDPEB) improves the event-free (EFS) and overall (OS) survival of children and adolescents with high-risk malignant germ cell tumors (MGCT) as compared with standard-dose cisplatin (PEB) and to compare the regimens' toxicity.Between March 1990 and February 1996, 299 eligible patients with stage III and IV gonadal and extragonadal (all stages) MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. Chemotherapy included bleomycin 15 units/m(2) on day 1, etoposide 100 mg/m(2) on days 1 through 5, and either high-dose cisplatin 40 mg/m(2) on days 1 through 5 (HDPEB; n = 149) or standard-dose cisplatin 20 mg/m(2) on days 1 through 5 (PEB; n = 150). Patients were evaluated after four cycles of therapy, and those with residual disease underwent surgery. Those with malignant disease in resected specimen received two additional cycles of their assigned regimen.One hundred thirty-four eligible patients with advanced testicular (n = 60) or ovarian (n = 74) tumors and 165 with stage I to IV extragonadal tumors were enrolled. HDPEB treatment resulted in significantly improved 6-year EFS rate +/- SE (89.6% +/- 3.6% v 80.5% +/- 4.8% for PEB; P =.0284). There was no significant difference in OS (HDPEB 91.7% +/- 3.3% v PEB 86.0% +/- 4.1%). Tumor-related deaths were more common after PEB (14 deaths v two deaths). Toxic deaths were more common with HDPEB (six deaths v one death). Other treatment-related toxicities were more common with HDPEB.Combination chemotherapy with HDPEB significantly improves EFS for children with high-risk MGCT. The OS is similar in both regimens, and the significant toxicity associated with HDPEB limits its use.

    View details for DOI 10.1200/JCO.2004.08.015

    View details for Web of Science ID 000222408400023

    View details for PubMedID 15226336

  • Biology and therapeutic advances for pediatric osteosarcoma ONCOLOGIST Marina, N., Gebhardt, M., Teot, L., Gorlick, R. 2004; 9 (4): 422-441

    Abstract

    Osteosarcoma is the most common malignant bone tumor in children and adolescents. Survival for these patients was poor with the use of surgery and/or radiotherapy. The introduction of multi-agent chemotherapy dramatically improved the outcome for these patients and the majority of modern series report 3-year disease-free survival of 60%-70%. This paper describes current strategies for treating patients with osteosarcoma as well as review of the clinical features, radiologic and diagnostic work-up, and pathology. The authors review the state of the art management for patients with osteosarcoma in North America and Europe including the use of limb-salvage procedures and reconstruction as well as discuss the etiologic and biologic factors associated with tumor development. Therapy-related sequelae and future directions in the biology and therapy for these patients are also discussed.

    View details for Web of Science ID 000223067300008

    View details for PubMedID 15266096

  • Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: Meeting summary CLINICAL CANCER RESEARCH Gorlick, R., Anderson, P., Andrulis, I., Arndt, C., Beardsley, G. P., Bernstein, M., Bridge, J., Cheung, N. K., Dome, J. S., Ebb, D., Gardner, T., Gebhardt, M., Grier, H., Hansen, M., Healey, J., Helman, L., Hock, J., Houghton, J., Houghton, P., Huvos, A., Khanna, C., Kieran, M., Kleinerman, E., Ladanyi, M., Lau, C., Malkin, D., Marina, N., MELTZER, P., Meyers, P., Schofield, D., Schwartz, C., Smith, M. A., Toretsky, J., Tsokos, M., Wexler, L., Wigginton, J., Withrow, S., Schoenfeldt, M., Anderson, B. 2003; 9 (15): 5442-5453

    Abstract

    Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.

    View details for Web of Science ID 000187014200004

    View details for PubMedID 14654523

  • Health status of adult long-term survivors of childhood cancer - A report from the childhood cancer survivor study JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hudson, A. M., Mertens, A. C., Yasui, Y., Hobbie, W., Chen, H. G., Gurney, J. G., Yeazel, M., Recklitis, C. J., Marina, N., Robison, L. R., Oeffinger, K. C. 2003; 290 (12): 1583-1592

    Abstract

    Adult survivors of childhood cancer are at risk for medical and psychosocial sequelae that may adversely affect their health status.To compare the health status of adult survivors of childhood cancer and siblings and to identify factors associated with adverse outcomes.Health status was assessed in 9535 adult participants of the Childhood Cancer Survivor Study, a cohort of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986. A randomly selected cohort of the survivors' siblings (n = 2916) served as a comparison group.Six health status domains were assessed: general health, mental health, functional status, activity limitations, cancer-related pain, and cancer-related anxiety/fears. The first 4 domains were assessed in the control group.Survivors were significantly more likely to report adverse general health (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.0; P<.001), mental health (OR, 1.8; 95% CI, 1.6-2.1; P<.001), activity limitations (OR, 2.7; 95% CI, 2.3-3.3; P<.001), and functional impairment (OR, 5.2; 95% CI, 4.1-6.6; P<.001), compared with siblings. Forty-four percent of survivors reported at least 1 adversely affected health status domain. Sociodemographic factors associated with reporting at least 1 adverse health status domain included being female (OR, 1.4; 95% CI, 1.3-1.6; P<.001), lower level of educational attainment (OR, 2.0; 95% CI, 1.8-2.2; P<.001), and annual income less than 20 000 dollars (OR, 1.8; 95% CI, 1.6-2.1; P<.001). Relative to those survivors with childhood leukemia, an increased risk was observed for at least 1 adverse health status domain among those with bone tumors (OR, 2.1; 95% CI, 1.8-2.5; P<.001), central nervous system tumors (OR, 1.7; 95% CI, 1.5-2.0; P<.001), and sarcomas (OR, 1.2; 95% CI, 1.1-1.5; P =.01).Clinicians caring for adult survivors of childhood cancer should be aware of the substantial risk for adverse health status, especially among females, those with low educational attainment, and those with low household incomes.

    View details for Web of Science ID 000185461300023

    View details for PubMedID 14506117

  • Dose escalation and pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in children with solid tumors: A pediatric oncology group study CLINICAL CANCER RESEARCH Marina, N. M., Cochrane, D., Harney, E., Zomorodi, K., Blaney, S., Winick, N., Bernstein, M., Link, M. P. 2002; 8 (2): 413-418

    Abstract

    To determine the maximum tolerated dose and pharmacokinetics of Doxil in children with recurrent or refractory solid tumors. Doxil is pegylated doxorubicin.Eligible patients were children with refractory tumors who had received cumulative anthracycline doses <300 mg/m(2). Cohorts of at least three patients each received escalating doses of Doxil starting at 40 mg/m(2) at 4-week intervals. If no dose-limiting toxicity occurred, dosages were escalated by increments of 10 mg/m(2) in subsequent cohorts. Originally, Doxil was administered over 60 min, but significant infusion reactions prompted longer infusion times of 4 h. Patients also received premedication with dexamethasone, ranitidine, and diphenhydramine 24 h before infusion, with ranitidine continued 24 h after infusion. Periodic blood samples were collected and plasma doxorubicin concentrations were quantified to characterize the pharmacokinetics of Doxil.Between January 1997 and June 2000, 22 children ages 4-21 years with refractory tumors were treated with Doxil. Most patients had received one to five prior chemotherapy regimens, and all but five had prior radiotherapy (two had no prior therapy). Doxil was escalated to a dosage of 70 mg/m(2). At that level, dose-limiting mucositis was seen during the first cycle in two of six patients, thus defining dose-limiting toxicity, and in one additional patient during a subsequent cycle. Grade 4 neutropenia lasting less than 7 days was documented in two of six patients. The dose-limiting toxicity among two of six patients at 70 mg/m(2) was grade 3 mucositis during the first cycle of therapy. Painful desquamating dermatitis of the hands and feet, palmar-plantar erythrodysesthesia, occurred in six patients. In two of those patients, palmar-plantar erythrodysesthesia started as grade 1 and progressed to grade 2 during subsequent courses. Mean estimates of central volume of distribution, clearance, and elimination half-life were 1.45 liters/m(2), 0.03 liter/h/m(2), and 36.4 h, respectively.The maximum tolerated dose of Doxil administered every 4 weeks to pediatric patients was 60 mg/m(2). The effect of Doxil on pediatric patients with malignancies remains to be determined and should be studied in pediatric Phase II trials.

    View details for Web of Science ID 000173908600013

    View details for PubMedID 11839657

  • Letter to the editor: Recurrent mercaptopurine-induced acute pancreatitis: A rare complication of chemotherapy for acute lymphoblastic leukemia in children MEDICAL AND PEDIATRIC ONCOLOGY Willert, J. R., Dahl, G. V., Marina, N. M. 2002; 38 (1): 73-74

    View details for Web of Science ID 000173123300017

  • New molecular targets and biological therapies in sarcomas CANCER TREATMENT REVIEWS Scappaticci, F. A., Marina, N. 2001; 27 (6): 317-326

    Abstract

    The treatment of patients with soft tissue and bone sarcomas has dramatically improved over the last decade. This improvement has been brought about through advances in diagnosis, surgical techniques, conformal radiotherapy, and combination chemotherapy. Further advances in the management of the diverse spectrum of sarcoma patients will reflect tailoring of therapy based on molecular abnormalities. The role of cytogenetics and molecular analysis of fusion or mutated genes in diagnosis, prognosis, and design of biological treatments is discussed. An example of this approach has been the recent success in treatment of patients with gastrointestinal stromal tumours expressing mutant c-kit with a specific tyrosine kinase inhibitor, STI571. Molecular rearrangements may also serve as targets for designing specific immunotherapies with the fusion gene product. The use of biological therapies with signal transduction inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors, immunotherapy, differentiation inducers, and gene therapy could complement existing treatments for long-term control of disease. As these newer biological agents take form, clinical trial design will undergo change to reflect the chronic nature of these therapies.

    View details for DOI 10.1053/ctrv.2001.0242

    View details for Web of Science ID 000175069200001

    View details for PubMedID 11908925

  • Carboplatin/ifosfamide window therapy for osteosarcoma: Results of the St Jude Children's Research Hospital OS-91 trial JOURNAL OF CLINICAL ONCOLOGY Meyer, W. H., Pratt, C. B., Poquette, C. A., Rao, B. N., Parham, D. M., Marina, N. M., Pappo, A. S., Mahmoud, H. H., Jenkins, J. J., Harper, J., Neel, M., Fletcher, B. D. 2001; 19 (1): 171-182

    Abstract

    To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin.Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation.The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P: = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% +/- 6.7% and 76.4% +/- 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity.This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

    View details for Web of Science ID 000166228500022

    View details for PubMedID 11134210

  • Acute lymphoblastic leukemia in a developing country: Preliminary results of a nonrandomized clinical trial in El Salvador JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Bonilla, M., Moreno, N., Marina, N., deReyes, G., Shurtleff, S. A., Downing, J. R., Behm, F. G., Harrison, P. L., Ribeiro, R. C., Pena, O., Crist, W. M., Antillon, F. G. 2000; 22 (6): 495-501

    Abstract

    To improve outcome and study biology of childhood acute lymphoblastic leukemia (ALL) in El Salvador.Between January 1994 and December 1996, 153 children of El Salvador had newly diagnosed ALL treated in a collaborative program between Hospital Benjamin Bloom and St. Jude Children's Research Hospital (SJCRH). Therapy was based on a modified SJCRH protocol, with uniform remission induction (prednisone, vincristine, L-asparaginase) followed-up by consolidation with teniposide/cytarabine and/or high-dose methotrexate. Continuation treatment was risk-stratified: 123 patients assigned to the high-risk group received weekly rotational drug pairs, and 16 assigned to the standard-risk group received daily 6-mercaptopurine, weekly methotrexate, and monthly pulses of vincristine plus dexamethasone. High risk was defined as: DNA index < 1.16, age 12 months or younger, white blood cell count > or = 50 x 10(9)/L, T-cell immunophenotype, anterior mediastinal mass, central nervous system leukemia at diagnosis, or t(4;11), t(1;19), or t(9;22). Duration of the continuation treatment was 2.5 years in both groups. The median age at diagnosis of all patients was 4.8 (range I d-17 yrs), median leukocyte count was 15 (range 1-766) x 10(9)/L, and sex distribution was equal.Immunophenotypes were early beta-progenitor in 79%, T-cell in 3.9%, and inconclusive in 17% of cases. DNA index was <1.16 in 80.5% and was > or = 1.16 in 19.5% of the 123 known cases. For the analyzes, patients who refused therapy (abandoned treatment) were considered to have treatment failure as of their last follow-up dates. Complete remission was achieved in 126 of 151 (82.4%) patients (11 abandoned therapy during induction). The overall 4-year event-free survival (EFS) rate +/- 1 standard error was 48 +/- 6%. The 4-year EFS rates in patients at high-risk and standard-risk were 46 +/- 7% (n = 121) and 69 +/- 15% (n = 16), respectively (P = 0.20). When patients who refused further treatment are censored, the corresponding 4-year estimates of EFS are 51 +/- 8% and 75 +/- 14%, respectively.These results suggest that the biology of childhood ALL in El Salvador appears to be similar to that seen in the United States. Risk-directed chemotherapy can successfully be used in developing countries, but risk factors must be carefully determined and applied.

    View details for Web of Science ID 000165933100004

    View details for PubMedID 11132215

  • Abnormalities of the thyroid in survivors of Hodgkin's disease: Data from the childhood cancer survivor study JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Sklar, C., Whitton, J., Mertens, A., Stovall, M., Green, D., Marina, N., Greffe, B., Wolden, S., Robison, L. 2000; 85 (9): 3227-3232

    Abstract

    Treatment for Hodgkin's disease (HD) is associated with a variety of thyroid abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neoplasms. Due to the small sample size and short follow-up time of most published studies, it has been difficult to appreciate the full extent of the problem and to characterize the interaction between various patient and treatment variables. To overcome these limitations we have assessed thyroid status in 1,791 (959 males) HD survivors from among 13,674 participants in the Childhood Cancer Survivor Study, a cohort of 5-yr survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. Survivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a median of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subjects were treated with radiation (median dose of radiation to the thyroid, 3,500 cGy; range, 0.37-5,500 cGy). Control data were available from 2,808 (1,346 males) sibling controls. Thirty-four percent of the entire cohort has been diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compared to sibling controls. Increasing dose of radiation, older age at diagnosis of HD, and female sex were all independently associated with an increased risk of hypothyroidism. Actuarial risk of hypothyroidism for subjects treated with 4,500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism was reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than the incidence reported by the controls. Thyroid dose of 3,500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid nodules was 27 times (P < 0.0001) that in sibling controls. Female sex and radiation dose to the thyroid of 2,500 cGy or more were independent risk factors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagnosed in 20 survivors, which is 18 times the expected rate for the general population. After taking into account the possibility that some of the relative risk estimates may be exaggerated due to ascertainment bias, abnormalities of the thyroid are still extremely common in young adult survivors of childhood HD, particularly among females treated with high doses of radiation to the neck.

    View details for Web of Science ID 000089166200039

    View details for PubMedID 10999813

  • Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Rodriguez-Galindo, C., Poquette, C. A., Marina, N. M., Head, D. R., Cain, A., Meyer, W. H., Santana, V. M., Pappo, A. S. 2000; 22 (4): 321-329

    Abstract

    Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies.The study group consisted of 73 patients with ESFT treated on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens incorporated the same agents but differed in cumulative drug dose, dose per course, and the use of G-CSF. Platelet counts and the mean corpuscular volume (MCV) of erythrocytes were determined at diagnosis and during follow-up visits after completion of treatment.Patients in the EW92 group had significantly greater MCVs after treatment than did the less intensively treated EW87 group. These changes persisted throughout the 40-month observation period. Patients in the EW92 group also had lesser mean platelet counts after treatment than those in the EW87 group. MCV differences (from baseline) were inversely related to platelet counts. The cumulative incidence of treatment-related acute myeloid leukemia was 7.8%+/-4.7% at 4 years in the EW92 group and zero in the EW87 group.Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.

    View details for Web of Science ID 000088737300008

    View details for PubMedID 10959902

  • Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Marina, N. M., Poquette, C. A., Cain, A. M., Jones, D., Pratt, C. B., Meyer, W. H. 2000; 22 (2): 112-118

    Abstract

    The aim of this study was to assess renal tubular toxicity (RTT) of ifosfamide-containing regimens (ICR) in patients with newly diagnosed sarcomas at St. Jude Children's Research Hospital.The authors reviewed the records of 199 patients receiving ICR at St. Jude between June 1986 and December 31, 1994 for evidence of RTT. Their median age was 13.3 years (range 1.2-24.8); 150 patients were white and 112 were male patients. Diagnoses included osteosarcoma (n = 82), Ewing sarcoma (n = 82), rhabdomyosarcoma (n = 28), and a group of other tumors (n = 7).The authors estimated the proportion of patients with severe RTT during the first five cycles of ICR and within 1 year after therapy for three groups of patients receiving ifosfamide (IFOS, n = 110), ifosfamide/cisplatin (IFOS/CDDP, n = 51), and ifosfamide/carboplatin (IFOS/CARBO, n = 38). The IFOS/CDDP patients received three cycles of IFOS before receiving CDDP and received only 200 mg/m2 by cycle 5, whereas the IFOS/CARBO patients received both agents simultaneously. The authors compared the probability of severe RTT among treatment groups using a generalized linear model for the first five cycles of ICR, as well as the probability of severe RTT within 1 year after therapy among treatment groups for patients receiving all prescribed IFOS using an exact chi-square test with pairwise comparisons when the three-way P value was less than 0.10. The proportion of patients with severe RTT during the first three cycles of ICR was significantly greater in the IFOS/CARBO group than in the other two. Although the proportion of patients with severe RTT in the IFOS/CDDP group increased during cycles 4/5, the proportion of patients with severe RTT remained significantly greater in the IFOS/ CARBO group. Within 1 year after therapy, the proportion of patients with severe RTT differed among the three groups, and pairwise comparisons revealed a significant difference between the IFOS and the IFOS/CDDP group. Severe RTT developed in four IFOS/CDDP patients more than 1 year after therapy, suggesting a long-term effect of CDDP on tubular function.Chemotherapy regimens including IFOS/ CARBO produce severe acute RTT more frequently than regimens including IFOS or IFOS/CDDP. Patients receiving IFOS/ CDDP appear at risk for delayed RTT. Long-term follow-up of these patients is essential to assess whether the number of patients receiving IFOS/CDDP with severe RTT continues to increase over time and to evaluate the long-term significance of these abnormalities.

    View details for Web of Science ID 000086470500005

    View details for PubMedID 10779023

  • Surgical resection alone is effective treatment for ovarian immature teratoma in children and adolescents: A report of the Pediatric Oncology Group and the Children's Cancer Group AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Cushing, B., Giller, R., Ablin, A., Cohen, L., Cullen, J., Hawkins, E., Heifetz, S. A., Krailo, M., Lauer, S. J., Marina, N., Rao, P. V., Rescorla, F., Vinocur, C. D., Weetman, R. M., Castleberry, R. P. 1999; 181 (2): 353-358

    Abstract

    In both adult women and children the potential for malignant recurrence from ovarian immature teratoma has prompted the standard use of chemotherapy after complete resection of the primary tumor. The efficacy of postoperative chemotherapy in children and adolescents with ovarian immature teratoma, however, has not been established. A pediatric intergroup trial (INT 0106) was designed to determine the need for postoperative chemotherapy in patients with ovarian immature teratoma after management with surgical resection only. Study Design: Between 1990 and 1995, 44 patients with completely resected ovarian immature tumor and without postoperative chemotherapy, who were able to undergo assessment, were accrued. Tumor tissue was evaluated by central pathology review to confirm diagnosis and determine tumor grading of immature neural elements. Patients were followed carefully for recurrence of disease with appropriate diagnostic imaging and serum marker studies.Thirty-one patients had pure ovarian immature teratoma with a tumor grade of 1 (n = 17), 2 (n = 12), or 3 (n = 2). Age at diagnosis ranged between 1.5 and 15 years (median, 10). Of the 29 patients studied, the serum alpha-fetoprotein level was elevated in 10 (34%); the median level was 25 ng/ml. Thirteen patients had ovarian immature teratoma plus microscopic foci of yolk sac tumor. Tumor grade was 1, 2, or 3 in 1, 6, and 6 patients, respectively. Age ranged between 6 and 20 years (median, 12). In the 12 patients evaluated for serum alpha-fetoprotein, 10 (83%) had elevated levels; the median level was 262 ng/ml. The 4-year event-free and overall survival for the ovarian immature teratoma group and for the ovarian immature teratoma plus yolk sac tumor group was 97.7% (95% confidence interval, 84.9%-99.7%) and 100%, respectively. The only yolk sac tumor relapse occurred in a child with ovarian immature teratoma and yolk sac tumor who was then treated with chemotherapy and is alive and free of disease 57 months after recurrence.The results of this study suggest that surgery alone is curative for most children and adolescents with resected ovarian immature teratoma of any grade, even when elevated levels of serum alpha-fetoprotein or microscopic foci of yolk sac tumor are present. This experience strongly supports avoiding the long-term effects of chemotherapy in most children with ovarian immature teratoma by reserving postoperative therapy for cases with relapse.

    View details for Web of Science ID 000082161300035

    View details for PubMedID 10454682

  • Complete surgical excision is effective treatment for children with immature teratomas with or without malignant elements: A pediatric oncology group/children's cancer group intergroup study JOURNAL OF CLINICAL ONCOLOGY Marina, N. M., Cushing, B., Giller, R., Cohen, L., Lauer, S. J., Ablin, A., Weetman, R., Cullen, J., Rogers, P., Vinocur, C., Stolar, C., Rescorla, F., Hawkins, E., Heifetz, S., Rao, P. V., Krailo, M., Castleberry, R. P. 1999; 17 (7): 2137-2143

    Abstract

    To determine whether the 3-year event-free survival (EFS) of children with completely resected immature teratomas is greater than 85%.Patients with immature teratomas treated at Pediatric Oncology Group or Children's Cancer Group institutions were eligible. Pathology was centrally reviewed to confirm diagnosis and tumor grading. Follow-up included physical examination, measurement of tumor markers (alpha fetoprotein and human chorionic gonadotropin), and imaging. All patients were monitored for events, defined as tumor recurrence, second malignancy, or death.Seventy-three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study. Primary tumor sites included ovarian (n = 44), testicular (n = 7), and extragonadal (n = 22). However, on review, 23 patients had foci of yolk sac tumor (n = 21) or primitive neuroectodermal tumor (n = 2), whereas 50 had pure immature teratomas. Twenty-five patients had increased alpha fetoprotein (n = 18), human chorionic gonadotropin (n = 5), or both (n = 2); nine had foci of yolk sac tumor on review. Pathology review identified 23 patients with grade 1, 29 with grade 2, and 21 with grade 3 immature teratomas. With a median follow-up of 35 months, the overall 3-year EFS was 93% (95% confidence interval, 86% to 98%), with 3-year EFS of 97.8%, 100%, and 80% for patients with ovarian, testicular, and extragonadal tumors, respectively. Only four of 23 patients with immature teratoma and malignant foci developed recurrence, suggesting that surgical resection followed by close observation are effective treatment. Overall, five patients had disease recurrence 4 to 7 months from diagnosis, and four (80%) are disease free after platinum-based therapy. The fifth patient has residual tumor after cisplatin, etoposide, and bleomycin treatment requiring further therapy.Surgical excision is safe and effective treatment for 80% to 100% of children with immature teratoma.

    View details for Web of Science ID 000081264300026

    View details for PubMedID 10561269

  • Gender and age do not alter actuarial incidence of cardiac dysfunction following anthracycline chemotherapy of childhood malignancy Rosenthal, D. N., Chin, C., Bernstein, D., Marina, N. M. NATURE PUBLISHING GROUP. 1999: 30A?30A

    View details for Web of Science ID 000079476700166

  • Late effects of treatment for germ cell tumors during childhood and adolescence JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Hale, G. A., Marina, N. M., Jones-Wallace, D., Greenwald, C. A., Jenkins, J. J., Rao, B. N., Luo, X. L., Hudson, M. M. 1999; 21 (2): 115-122

    Abstract

    To evaluate the long-term sequelae of treatment for malignant germ cell tumors (GCT) during childhood and adolescence.Of 128 patients treated for GCT at St. Jude Children's Research Hospital between 1962 and 1988, 73 are long-term survivors (continuously disease-free for > or =5 years after diagnosis), with a median follow-up of 11.3 years). Survivors' ages at diagnosis ranged from birth to 18.3 years (median, 9.2 years); 64% (47 patients) were female. Initial surgical resection was followed by observation for stage I germinomas (n = 2), testicular tumors (n = 13), and selected cases of ovarian or sacrococcygeal tumors (n = 2), and by radiation therapy (RT) for patients with stage II to III germinoma (n = 8). The remaining 48 patients received postoperative chemotherapy (vincristine, dactinomycin, and cyclophosphamide [VAC] +/- doxorubicin, 1962 to 1978; VAC and/or cisplatin, vinblastine, and bleomycin [PVB], 1979 to 1988). RT was added to the chemotherapy for 21 patients. Late complications involving various organ systems and their relationship to treatment were evaluated.More than two-thirds of long-term survivors (n = 50) had at least 1 complication, and half (n = 38) had > 1 organ system affected. The systems most often involved included the musculoskeletal (41% of survivors), endocrine (42%), cardiovascular (16% excluding those who had only abnormal chest radiograph), gastrointestinal (25%), genitourinary tract (23%), pulmonary (19%), and neurologic (16%) systems. High-frequency hearing loss occurred in 58% (11 of 19) of patients treated with cisplatin. Musculoskeletal, gastrointestinal, and urinary tract abnormalities were most frequent in patients whose treatment included RT.A high frequency of late effects after treatment for pediatric GCT, particularly in patients who received RT, was demonstrated. Treatment sequelae could be anticipated from the intensity and type of therapeutic modalities. Treatment-directed screening evaluations may improve quality of life in long-term survivors of pediatric GCT through timely identification of sequelae that can be prevented or ameliorated.

    View details for Web of Science ID 000079510200007

    View details for PubMedID 10206457

  • Biology and therapy of pediatric malignant solid tumors. Cancer chemotherapy and biological response modifiers Marina, N. 1999; 18: 550-589

    View details for PubMedID 10800501

  • Chemotherapy dose-intensification for pediatric patients with Ewing's family of tumors and desmoplastic small round-cell tumors: A feasibility study at St. Jude Children's Research Hospital JOURNAL OF CLINICAL ONCOLOGY Marina, N. M., Pappo, A. S., Parham, D. M., Cain, A. M., Rao, B. N., Poquette, C. A., Pratt, C. B., Greenwald, C., Meyer, W. H. 1999; 17 (1): 180-190

    Abstract

    To evaluate the feasibility of dose-intensification for patients with Ewing's family of tumors (EFT) and desmoplastic small round-cell tumors.From February 1992 to June 1996, we treated 53 consecutive patients on our Ewing's protocol. Induction comprised three cycles of ifosfamide/etoposide on days 1 to 3 and cyclophosphamide (CTX)/doxorubicin on day 5, followed by granulocyte colony-stimulating factor. Local control using surgery and/or radiotherapy started at week 9 along with vincristine/dactinomycin. Maintenance included four alternating cycles of ifosfamide/etoposide and doxorubicin/CTX, with randomization to one of two CTX dose levels to determine the feasibility of dose-intensification during maintenance.Patients had a median age of 13.4 years (range, 4.5 to 24.9 years); 34 patients were male and 43 patients were white. Nineteen patients presented with metastatic disease, 29 had tumors greater than 8 cm in diameter, and 26 had primary bone tumors. These patients received 155 induction cycles, 91% of which resulted in grade 4 neutropenia, 68% in febrile neutropenia, and 68% in grade 3 to 4 thrombocytopenia. During maintenance, grade 4 neutropenia and grade 3 to 4 thrombocytopenia occurred in 81% and 85% of cycles, respectively. Thirty-five patients (66%) completed all therapy, only 13 without significant delays; three developed secondary myeloid malignancies. The toxicity and time to therapy completion were similar in both CTX arms. Estimated 3-year survival and event-free survival were 72%+/-8% and 60%+/-9%, respectively.Although intensifying therapy seems feasible for 25% of patients on this study, toxicity was considerable. Therefore, the noninvestigational use of dose-intensification in patients with EFT should await assessment of its impact on disease-free survival.

    View details for Web of Science ID 000077927400023

    View details for PubMedID 10458232

  • Wilms' tumour - Optimal treatment strategies DRUGS Suryanarayan, K., Marina, N. 1998; 56 (4): 597-605

    Abstract

    Wilms' tumour (WT) is the most common renal tumour in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. The improved outcome has mainly resulted from the availability of cooperative national and international trials involving the National Wilms' Tumour Study Group (NWTS) and the International Society of Paediatric Oncology (SIOP). These groups have focused on optimising postoperative (NWTS) and preoperative (SIOP) therapy, respectively. The early studies by the NWTS (1 and 2) identified the following separate subgroups of patients (based on age and stage) that benefited either from the addition of irradiation to postoperative chemotherapy or from combination chemotherapy as opposed to single agents, and those patients who did not benefit from prolonged chemotherapy administration. Additionally, these studies identified histologic features associated with a poor outcome. The more recent studies by NWTS (3 and 4) concentrated on reducing treatment for low risk patients to avoid long term sequelae while intensifying therapy for patients with high risk features, such as those with unfavourable histology and/or metastatic disease. The early SIOP trials (1, 2 and 5) concluded that patients treated with preoperative therapy (chemotherapy alone or combined with irradiation) experienced fewer intraoperative tumour ruptures compared with patients who had immediate surgery. However, preoperative chemotherapy preserved tumour histology at surgical exploration better than preoperative irradiation. The more recent SIOP trials (6, 9 and 93-01) have compared the use of different preoperative treatment regimens as well as the intensity and duration of postoperative therapy based on prognostic features (stage and histology). These studies have also identified groups benefiting from the addition of irradiation and/or the use of a third chemotherapeutic agent. Bilateral WT occurs in a small percentage of patients and treatment strategies, although efficacious, are limited by the need to maximise residual renal parenchyma. Recurrent WT occurs in 10 to 15% of cases and although a proportion of patients are curable, the overall outcome is poor with 3-year survival being in the range of 30%. There are several ongoing studies utilising new drug combinations (carboplatin, cyclophosphamide and etoposide) attempting to improve the outcome for these patients. Overall, the majority of patients with WT will be cured and become long term survivors. Cooperative group studies continue to address the issue of minimising long term morbidity for low risk patients while maximising outcome for high risk patients.

    View details for Web of Science ID 000076711400007

  • Wilms' tumour. Optimal treatment strategies. Drugs Suryanarayan, K., Marina, N. 1998; 56 (4): 598-605

    Abstract

    Wilms' tumour (WT) is the most common renal tumour in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. The improved outcome has mainly resulted from the availability of cooperative national and international trials involving the National Wilms' Tumour Study Group (NWTS) and the International Society of Paediatric Oncology (SIOP). These groups have focused on optimising postoperative (NWTS) and preoperative (SIOP) therapy, respectively. The early studies by the NWTS (1 and 2) identified the following separate subgroups of patients (based on age and stage) that benefited either from the addition of irradiation to postoperative chemotherapy or from combination chemotherapy as opposed to single agents, and those patients who did not benefit from prolonged chemotherapy administration. Additionally, these studies identified histologic features associated with a poor outcome. The more recent studies by NWTS (3 and 4) concentrated on reducing treatment for low risk patients to avoid long term sequelae while intensifying therapy for patients with high risk features, such as those with unfavourable histology and/or metastatic disease. The early SIOP trials (1, 2 and 5) concluded that patients treated with preoperative therapy (chemotherapy alone or combined with irradiation) experienced fewer intraoperative tumour ruptures compared with patients who had immediate surgery. However, preoperative chemotherapy preserved tumour histology at surgical exploration better than preoperative irradiation. The more recent SIOP trials (6, 9 and 93-01) have compared the use of different preoperative treatment regimens as well as the intensity and duration of postoperative therapy based on prognostic features (stage and histology). These studies have also identified groups benefiting from the addition of irradiation and/or the use of a third chemotherapeutic agent. Bilateral WT occurs in a small percentage of patients and treatment strategies, although efficacious, are limited by the need to maximise residual renal parenchyma. Recurrent WT occurs in 10 to 15% of cases and although a proportion of patients are curable, the overall outcome is poor with 3-year survival being in the range of 30%. There are several ongoing studies utilising new drug combinations (carboplatin, cyclophosphamide and etoposide) attempting to improve the outcome for these patients. Overall, the majority of patients with WT will be cured and become long term survivors. Cooperative group studies continue to address the issue of minimising long term morbidity for low risk patients while maximising outcome for high risk patients.

    View details for PubMedID 9806106

  • Peritoneal metastases in children with cancer CANCER Kaste, S. C., Marina, N., Fryrear, R., Hedlund, G. L., Jones, L., Poe, D., Jenkins, J. J. 1998; 83 (2): 385-390

    Abstract

    This study attempted to evaluate the childhood malignancies associated with computed tomography (CT) detected peritoneal metastases as well as the diagnostic imaging characteristics of these metastases as shown on CT.The authors reviewed all available pathology specimens and abdominopelvic CT scans of patients identified as having peritoneal metastases at three childhood cancer centers. Patient demographics, primary diagnosis, and CT characteristics of such metastases were evaluated.Peritoneal metastases were identified by CT in 32 children with cancer either at diagnosis (n = 20) or up to 6.2 years from diagnosis (n = 12). On CT, peritoneal disease appeared as a mass in 26 cases, as studding in 11 cases, as peritoneal enhancement in 15 cases, and as diffuse caking in 4 cases (15 patients had > 1 category of peritoneal metastasis). Thirteen patients had concurrent metastases in other sites. Fourteen patients died of progressive disease at a median of 10 months from the time peritoneal metastases were identified on CT. At last follow-up, the remaining 18 patients were alive, with follow-up ranging from 1 month to 9.7 years. As expected, peritoneal metastases were identified in patients with germ cell tumors and colon carcinoma. However, they also were observed in patients with epithelioid carcinoma, leiomyosarcoma, pineoblastoma, neuroblastoma, melanoma, and peripheral neuroectodermal tumor.Peritoneal metastases have variable appearance on CT, but most commonly appear mass-like. They are associated with a wider range of primary diagnoses than reported previously. The outcome varies with the type of the primary tumor and its responsiveness to existing therapies.

    View details for Web of Science ID 000074651200025

    View details for PubMedID 9669824

  • Nongestational choriocarcinoma in the postpartum period: A case report JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Suryanarayan, K., O'Hanlan, K. A., Surti, U., Ishwad, C. S., Nowels, K., Letourneau, D., Marina, N. 1998; 20 (2): 169-173

    Abstract

    To determine the tissue of origin (gestational versus nongestational) of an extensive metastatic choriocarcinoma in an 18-year-old woman to determine prognosis and treatment.DNA microsatellite polymorphisms after polymerase chain reaction (PCR) amplification of the tumor tissue and blood from the patient, husband, and daughter were used to determine the tissue of origin.Molecular analyses revealed that the tumor shared the genetic features of only the patient. She responded well to multiagent chemotherapy.Molecular analysis is a useful tool to determine whether a choriocarcinoma occurring in a female patient of child-bearing age is gestational or nongestational when clinical findings are not clearly indicative of the primary.

    View details for Web of Science ID 000075231100016

    View details for PubMedID 9544172

  • Clinical effects and pharmacokinetics of the fusion protein PIXY321 in children receiving myelosuppressive chemotherapy CANCER CHEMOTHERAPY AND PHARMACOLOGY Furman, W. L., Rodman, J. H., Tonda, M. E., Luo, X. L., Arnold, B., Marina, N., Garrison, L., Hanna, R., Pratt, C. B., Meyer, W. H. 1998; 41 (3): 229-236

    Abstract

    A hemopoietin with the ability to accelerate both platelet and granulocyte recovery after intensive chemotherapy would have great clinical utility. The recombinant fusion protein composed of human granulocyte-macrophage colony-stimulating factor and interleukin-3 (PIXY321), showed some promise in early adult trials. However, studies for pediatric patients are limited, and there are no systematic data on the pharmacokinetics of PIXY321 given over prolonged periods at current dosage levels.To determine the safety, clinical effects and plasma concentrations of increasing doses of PIXY321 in children treated with myelosuppressive chemotherapy.A total of 39 children with relapsed or high-risk solid tumors were enrolled in this phase I/II study. PIXY321 was administered once or twice daily by subcutaneous injection in total doses of 500 to 1000 microg/m2 per day for 14 days after each course of chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). Pharmacokinetic studies were performed on day 1 of the first course in 33 patients and repeated on day 14 in 13 patients (once-daily schedule only).Although mild local skin reactions and fever were frequent, no dose-limiting toxicity was identified at the maximum dose studied (1000 microg/m2 per day). There were no statistically significant differences in chemotherapy-induced hematologic toxicity with increasing doses of PIXY321 or with twice-daily vs once-daily dosing. On day 1, the median PIXY321 clearance was 657 ml/min per m2 (range 77 1804 ml/min per m2) and the median half-life was 3.7 h (range 2.1-20.8 h). On day 14, clearance increased in all patients studied (median increase 63%), with a corresponding decrease in the median 12-h concentration (from 1.2 to 0.25 ng/ml). Maximum concentrations were < 1 ng/ml in 81% of patients, and only two patients had maximum plasma concentrations equivalent to those required for consistent activity in vitro.The recombinant fusion protein PIXY321 proved safe in children treated with myelosuppressive ICE chemotherapy but had no demonstrable clinical benefits. The pharmacokinetic studies suggest that the observed lack of hematologic benefit may be explained by low plasma concentrations resulting from increased clearance with prolonged administration. Moreover, the significant increase in PIXY321 systemic clearance in the absence of increased circulating myeloid cells suggests that the upregulation of either extravascular compartment hematopoietic progenitor cells or nonhematopoietic cells may play an important role in controlling circulating concentrations of this unique cytokine. These findings highlight the importance of a thorough assessment of the systemic disposition of cytokines when determining the dose and schedule necessary to achieve clinical activity in patients.

    View details for Web of Science ID 000071082400008

    View details for PubMedID 9443640

  • Comparison of cytokines in children with recurrent solid tumors treated with intensive chemotherapy JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Furman, W. L., Luo, X. L., Marina, N., Garrison, L., Pratt, C. B., Meyer, W. H. 1998; 20 (1): 62-68

    Abstract

    To compare the relative hematopoietic protective effects of recombinant human interleukin-1alpha (rhuIL-1alpha), recombinant human granulocyte macrophage colony-stimulating factor (rhuGM-CSF), and PIXY321, a genetically engineered fusion protein combining interleukin-3 and rhuGM-CSF, in children with refractory solid tumors after treatment with ifosfamide, carboplatin, and etoposide (ICE).A total of 53 children who had not responded to at least one earlier chemotherapy regimen were enrolled on consecutive trials of ICE chemotherapy alone (n = 14) or with rhuGM-CSF (n = 8), rhuIL-1alpha (n = 10), or PIXY321 (n = 21). The relative hematopoietic effects of these three cytokines were compared retrospectively to each other and to values for patients who received ICE alone. Because one cannot assume that hematopoietic toxicity and response to a given cytokine are independent of the course of chemotherapy, the analysis was restricted to the first treatment course.In this retrospective comparison, 1000 microg/m2/day of rhuGM-CSF reduced the median duration of grade 4 neutropenia (<500/microL) from a median of 17 days (range 3 to 34) in children who received ICE alone to 9 days (range 5 to 11, p = 0.003); it appeared to have a beneficial effect on severe thrombocytopenia (<20,000/microL), reducing the median duration from 4.5 days with ICE alone to 3 days (p = 0.08) and the number of platelet transfusions from a median of 5.75 transfusions (range 0 to 13) to 0 in these two cohorts. No significant improvement in these measures was seen with rhuIL-1alpha or PIXY321.This analysis suggests that 1000 microg/m2/day of rhuGM-CSF has clinically significant effects on platelet recovery and more effectively ameliorates thrombocytopenia and neutropenia than either rhuIL-1alpha or PIXY321 in the context of ICE chemotherapy. Further dose-intensification will require a combination of cytokines; the optimal dose and combination of these agents awaits further study.

    View details for Web of Science ID 000072048600010

    View details for PubMedID 9482415

  • Treatment of children with peripheral primitive neuroectodermal tumor or extraosseous Ewing's tumor with Ewing's-directed therapy 30th Annual Meeting of the American-Society-of-Clinical-Oncology Gururangan, S., Marina, N. M., Luo, X. L., Parham, D. M., Tzen, C. Y., Greenwald, C. A., Rao, B. N., Kun, L. E., Meyer, W. H. LIPPINCOTT WILLIAMS & WILKINS. 1998: 55?61

    Abstract

    We report the treatment and outcome of patients with peripheral primitive neuroectodermal tumor (PNET) and extraosseous Ewing's tumor (EOE) using Ewing's-directed therapy, including an ifosfamide and etoposide window.Seventeen pediatric patients with peripheral PNET (n = 14) or EOE (n = 3) were enrolled between 1988 and 1992 on our institutional Ewing's protocol. Induction therapy comprised a 9-week "window" of ifosfamide and etoposide, followed by 9 weeks of therapy with cyclophosphamide and Adriamycin (Adria Laboratories, Columbus, OH). Response assessment after 17 weeks was followed by surgery and/or radiotherapy (doses based on tumor size and response to induction), repeat evaluation, and maintenance chemotherapy with alternating courses of vincristine/dactinomycin, ifosfamide/etoposide, and cyclophosphamide/Adriamycin for a total of 45 weeks.At diagnosis, 8 patients had large lesions (>8 cm) and 3 had pulmonary metastases (1 with large tumor). Surgical resection was performed at diagnosis for 9 patients and after induction therapy for 5. During window therapy, all of the 9 evaluable patients responded (8 partial, I objective), and no patient without measurable disease developed disease progression. Responses were maintained or improved during subsequent induction in six of the patients with residual disease. Fourteen patients received local radiotherapy. At 49 to 94 months after diagnosis, 12 patients are disease-free (1 in second remission), 4 have died, and 1 is alive with disease. The five-year overall and progression-free survival rates are 77 +/- 13% and 62 +/- 16%, respectively.The use of consistent Ewing's-directed combined-modality therapy for patients with soft tissue peripheral PNET/EOE results in survival similar to that of patients with osseous Ewing's tumor. The combination of ifosfamide and etoposide appears active and should be incorporated in future treatment protocols.

    View details for Web of Science ID 000072048600009

    View details for PubMedID 9482414

  • Congenital myelomonocytic and pre-B leukemias with t(11;19)(q23;p13): Relation of phenotype to HRX fusion partner. DiMartino, J., MILATOVICH, A., Bangs, D., CORNBLEET, J., Marina, N., Cleary, M. L., Dahl, G. V. AMER SOC HEMATOLOGY. 1997: 3763?63

    View details for Web of Science ID A1997YG42501073

  • Long-term survivors of childhood cancer - The medical consequences of cure PEDIATRIC CLINICS OF NORTH AMERICA Marina, N. 1997; 44 (4): 1021-?

    Abstract

    The late effects of cancer therapy are a significant problem and the risk can be predicted based on each individual's prior therapy. Although the use of effective therapy has led to the development of sequelae involving various organ systems, recognition of these complications has led to the design of new therapy targeted at minimizing these effects, especially in patients with good risk. Unfortunately, the risks of the late effects must be accepted in patients with cancers that are aggressive or in advanced stages to maximize the chance for cure. Continued education of cancer survivors regarding their risks of late effects is essential and gives them the ability to maintain healthy lifestyles, avoiding cancer-promoting behaviors such as smoking. It also gives survivors the opportunity to participate in screening programs to help in early recognition of the late consequences of therapy and to learn self-examination to detect second malignancies early. It is hoped that the use of early intervention will lead to an improved long-term outcome. Finally, continued surveillance of this population is essential to monitor the impact of the therapeutic modifications on late complications and potentially to detect the sequelae produced by newer treatment strategies. Because the number of childhood cancer survivors will continue to increase, it is imperative that the pediatricians and internists in the community who care for these survivors are aware of their risks for late effects so that they have access to and can benefit from early intervention.

    View details for Web of Science ID A1997XT84000015

    View details for PubMedID 9286298

  • Is primitive neuroectodermal tumor of the kidney a distinct entity? CANCER RodriguezGalindo, C., Marina, N. M., Fletcher, B. D., Parham, D. M., BODNER, S. M., Meyer, W. H. 1997; 79 (11): 2243-2250

    Abstract

    Primitive neuroectodermal tumors (PNETs) constitute a family of neoplasms of presumed neuroectodermal origin, most often presenting as bone or soft tissue masses in the trunk or axial skeleton in adolescents and young adults. As a soft tissue neoplasm, PNET arising in the kidney has not been well described, with only three cases previously reported.Four patients with PNET of the kidney were diagnosed and treated at St. Jude Children's Research Hospital. The authors reviewed the clinical, radiologic, and pathologic features and outcomes of these cases and of those previously described.The authors' patients were age 4-20 years. They presented with unilateral renal masses and metastatic disease in the lymph nodes (three patients), lungs (three patients), bone (two patients), liver (one patient), and bone marrow (one patient). Treatment included surgery, radiotherapy, and multiagent chemotherapy. Three of the patients died of progressive disease within 14 months of diagnosis. Features and outcomes were similar to those of the three previously reported cases.PNET of the kidney appears to be a distinct entity. Although rare, it must be included in the differential diagnosis of renal tumors in children and young adults. Patients usually present with advanced disease and show poor response to combined-modality therapy.

    View details for Web of Science ID A1997XA43300024

    View details for PubMedID 9179073

  • Phase I trial of subcutaneous interleukin-1 alpha in children with malignant solid tumors MEDICAL AND PEDIATRIC ONCOLOGY Furman, W. L., Luo, X. L., Fairclough, D., Garrison, L., Marina, N., Pratt, C. B., Bleyer, A., Meyer, W. H. 1997; 28 (6): 444-450

    Abstract

    Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models of cancer chemotherapy and is similarly beneficial in adults treated with carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation. There are no trials of this agent in children. Our purpose was to determine the toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3, carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL-1 alpha before either the first or second course of therapy. After the MTD of rhuIL-1 alpha was determined an additional group of patients received rhuIL-1 alpha at the dose immediately following ICE chemotherapy. The dose-limiting toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day. There were no differences in chemotherapy-induced hematologic toxicity with increasing doses of rhuIL-1 alpha or in comparisons before or after ICE chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving myelosuppressive chemotherapy, clinical usefulness would mandate a significant hematopoietic benefit in view of the trouble some side effects identified. We saw no evidence of a hematoprotective effect.

    View details for Web of Science ID A1997WX01300010

    View details for PubMedID 9143391

  • Biology and treatment of pediatric malignant solid tumors. Cancer chemotherapy and biological response modifiers Marina, N. M. 1997; 17: 642-671

    View details for PubMedID 9551234

  • Local control in synchronous bilateral Wilms tumor 37th ASTRO Annual Meeting Paulino, A. C., Wilimas, J., Marina, N., Jones, D., Kumar, M., Greenwald, C., Chen, G., Kun, L. E. ELSEVIER SCIENCE INC. 1996: 541?48

    Abstract

    To evaluate the role of radiation therapy (RT), chemotherapy (CT), and surgery in the local control of synchronous bilateral Wilms Tumor (WT).Between 1962 to 1993, 45 children were treated for bilateral WT; 38 patients with synchronous tumors were reviewed. Initial surgery depended on the era of treatment and included unilateral nephrectomy (N)/partial nephrectomy (PN) and contralateral PN in 6, unilateral N/PN alone in 7, and biopsy only in 25. Chemotherapy (CT) consisted of vincristine, actinomycin-D, and adriamycin in 32 and vincristine/ actinomycin-D in 6. Radiation therapy (RT) was given to 32 patients. Treatment included both kidneys in 20, unilateral kidney plus contralateral renal bed in 9, unilateral kidney in 2, and unilateral renal bed in 1. Follow-up was 16 months to 25 years (median: 6.3 years).Local control (LC) has been maintained in 66 out of 76 sites (87%). For Stage I-II disease with initial N/PN, LC was 10 out of 12 with RT and 11 out of 11 without RT; for Stage III with initial N/PN, LC was 8 out of 9 with RT and 1 out of 1 without RT. Initial CT and RT was followed by delayed N/PN for 20 sites; LC was 15 out of 17 in post induction Stage I-II and 1 out of 3 in postinduction Stage III. In 23 sites undergoing biopsy and chemotherapy, LC was 19 out of 20 with RT and 1 out of 3 without RT. Seven of 23 sites had a complete response (CR) after induction CT, and LC was maintained in four out of four with RT and one out of three without RT. Univariate Cox Regression analysis demonstrated that sites receiving two drugs had a statistically significant increase in loco-regional relapse when compared to sites receiving three drugs (p = 0.004). Major morbidities related to multimodality therapy have included renal failure in one patient and small bowel obstruction requiring lysis of adhesions in two patients.Local control does not seem to be compromised by renal conservation therapy. Local control is excellent in sites treated with radiation therapy in combination with three drug chemotherapy.

    View details for Web of Science ID A1996VW12600002

    View details for PubMedID 8948337

  • Response of pediatric malignant solid tumors following ifosfamide or ifosfamide/carboplatin/etoposide: A single hospital experience MEDICAL AND PEDIATRIC ONCOLOGY Pratt, C. B., Luo, X. L., Fang, L., Marina, N., Avery, L., Furman, W. L. 1996; 27 (3): 145-148

    Abstract

    One hundred thirty-eight pediatric patients have received treatment for malignant solid tumors with ifosfamide with mesna, and 71 have received a combination with ifosfamide/carboplatin/etoposide (ICE). Responses were obtained in many types of pediatric tumors, yet comparison of responses was not possible because of inadequate numbers of tumors of differing histiotypes. Comparison of results between patients with all tumors treated with ifosfamide or ICE indicated that there was a higher response rate for patients treated with ICE, with an estimated odds ratio of 2.74 (95% C.I. 1.45-5.179). Excluding patients without prior chemotherapy and radiotherapy, the odds ratio for 2.801 (95% C.I. 1.45-5.4) suggests a similar result. There remain no guarantees that the more costly treatment with ICE, which requires cytokine support, will offer therapeutic benefits against resistant solid tumors.

    View details for Web of Science ID A1996VA64700003

    View details for PubMedID 8699990

  • Sacrococcygeal yolk sac carcinoma: Imaging findings during treatment PEDIATRIC RADIOLOGY Kaste, S. C., Bridges, J. O., Marina, N. M. 1996; 26 (3): 212-219

    Abstract

    Sacrococcygeal teratomas and their malignant counterparts (germ cell tumors) are the most common solid tumors in neonates. Prompt diagnosis is essential because the frequency of malignant transformation increases from 10-20 % in neonates to 67 % in patients over 2 months of age. Cross-sectional imaging has largely replaced surgical exploration for staging these tumors and assessing their response to chemotherapy. Radiologists must be familiar with changes in the imaging findings of these tumors during and after treatment so that they can advise clinicians regarding the efficacy of therapy and the presence or absence of recurrent disease. From our study, magnetic resonance imaging appears to be a better modality for assessing sacral invasion and metastases and distinguishing fibrotic masses from recurrent tumor.

    View details for Web of Science ID A1996UB04600012

    View details for PubMedID 8599013

  • St Jude Children's Research Hospital's international outreach program LEUKEMIA Ribeiro, R. C., Marina, N., Crist, W. M. 1996; 10 (3): 570-574

    Abstract

    Over 80% of children with cancer live in developing countries, where access to medical services is limited to varying degrees. In many of these countries, economic conditions and general health care have improved sufficiently to permit the development of more sophisticated medical services. The introduction of pediatric oncology programs becomes appropriate as deaths from malnutrition and infections decrease and cancer emerges as an important cause of childhood mortality. In the absence of such services, the worldwide war against pediatric cancer will ultimately be lost because of the rapidly growing pediatric populations in developing countries that now lack the facilities and expertise to treat childhood malignancies. We believe that the development of pediatric cancer centers in many of these countries is both appropriate and feasible. Partnerships in which established pediatric oncology centers work with the governments and private sectors of developing nations to implement key facilities are an efficient and cost-effective way to introduce such services. The challenges of these outreach efforts are significant -- as are the expected benefits.

    View details for Web of Science ID A1996UF39600027

    View details for PubMedID 8642877

  • Cytomegalovirus causing pericarditis with tamponade in an adolescent with cancer MEDICAL AND PEDIATRIC ONCOLOGY Razzouk, B. I., Patrick, C. C., Marina, N. 1996; 26 (1): 70-70

    View details for Web of Science ID A1996TH13900011

    View details for PubMedID 7494516

  • SERIAL PULMONARY-FUNCTION STUDIES IN CHILDREN TREATED FOR NEWLY-DIAGNOSED HODGKINS-DISEASE WITH MANTLE RADIOTHERAPY PLUS CYCLES OF CYCLOPHOSPHAMIDE, VINCRISTINE, AND PROCARBAZINE ALTERNATING WITH CYCLES OF DOXORUBICIN, BLEOMYCIN, VINBLASTINE, AND DACARBAZINE CANCER Marina, N. M., Greenwald, C. A., Fairclough, D. L., Thompson, E. I., Wilimas, J. A., Mackert, P. W., Hudson, M. M., Stokes, D. C., BOZEMAN, P. M. 1995; 75 (7): 1706-1711

    Abstract

    The pulmonary toxicity of bleomycin-containing chemotherapy combined with mantle radiotherapy in children treated for Hodgkin's disease was longitudinally assessed.The results of serial pulmonary function studies in 37 children, newly diagnosed and treated at St. Jude Children's Research Hospital between September 23, 1983, and June 30, 1988, with cyclophosphamide, vincristine, and procarbazine (COP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus low dose mantle radiotherapy are analyzed. All patients had pulmonary function studies at least before the first bleomycin dose, after completion of radiotherapy, and serially upon discontinuation of therapy. Bleomycin therapy was withheld whenever measured carbon monoxide diffusing capacity was less than 50% of the predicted value.Vital capacity, diffusing capacity, and diffusing capacity per unit of alveolar volume declined during the first 6 months of therapy but improved there after. At 2 years postdiagnosis, diffusing capacity per unit of alveolar volume remained significantly reduced. Only one patient was symptomatic at the 2-year point. The survival rate of these patients was 95% at a median follow up of 93 months.If bleomycin is with held when diffusing capacity is diminished to 50% predicted, clinical compromise of pulmonary function appears to be minimal in pediatric patients receiving alternating cycles of COP/ ABVD in combination with low-dose mantle radiotherapy. Survival was excellent, even with reduction of the total bleomycin dose.

    View details for Web of Science ID A1995QN81300022

    View details for PubMedID 8826931

  • A PHASE-I STUDY OF SULOFENUR IN REFRACTORY PEDIATRIC MALIGNANT SOLID TUMORS INVESTIGATIONAL NEW DRUGS Pratt, C. B., Bowman, L. C., Marina, N., Pappo, A., Avery, L., Luo, X. L., Meyer, W. H. 1995; 13 (1): 63-66

    Abstract

    The diarylsulfonylureas have shown promise in xenograft models of childhood cancer. Sulofenur has been evaluated in phase I and II trials in adults with a variety of solid tumors, but the toxicity and maximum tolerated dose of sulofenur in children and adolescents have not been determined. In a phase I study, sulofenur was administered to 13 patients with refractory pediatric malignant solid tumors. Daily dosages of 640, 800, and 960 mg/M2 in two divided oral doses were given for 5 consecutive days each week for 3 weeks. The primary and dose-limiting toxicity was methemoglobinemia, which occurred at all dose levels and required transfusions of packed red blood cells, administration of methylene blue, or both. Anemia and, less frequently, leukopenia and thrombocytopenia were also observed. A maximum tolerated daily dosage was not defined, as methemoglobinemia was noted with each dosage level. There were no measurable tumor responses. The toxicity of this agent makes it unattractive for further investigation in pediatric patients.

    View details for Web of Science ID A1995RX43300009

    View details for PubMedID 7499110

  • REFINING THERAPEUTIC STRATEGIES FOR PATIENTS WITH RESISTANT WILMS-TUMOR AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Marina, N. M., Wilimas, J. A., Meyer, W. H., Jones, D. P., Douglass, E. C., Pratt, C. B. 1994; 16 (4): 296-300

    Abstract

    Despite the excellent prognosis for 90% of patients with Wilms' tumor, survival remains poor among those with recurrent or advanced disease or tumors of unfavorable histology. We sought to identify a chemotherapy regimen for this subset of patients that offers potential efficacy with minimal nephrotoxicity.Through a review of patients' medical records, we compared the efficacy and nephrotoxicity of ifosfamide, cisplatin, cisplatin/etoposide, and ifosfamide/carboplatin/etoposide (ICE) regimens in 32 patients with recurrent (n = 23), refractory (n = 1), or metastatic (n = 8) Wilms' tumor, including six with tumors having unfavorable histologic features.Single-agent ifosfamide was minimally nephrotoxic and induced responses in three of 11 patients, but none have survived. Cisplatin with or without etoposide induced responses in six of 18 patients with recurrent Wilms' tumor (there is one long-term survivor). Seven of eight patients with newly diagnosed extensive metastatic disease responded to cisplatin/etoposide plus vincristine, dactinomycin, adriamycin, and radiotherapy. This regimen produced three long-term survivors, but was associated with significant nephrotoxicity. The ifosfamide, carboplatin, and etoposide regimen induced responses in four of five patients treated, and had minimal nephrotoxicity. Two remain free of disease progression 22 months after recurrence.Although long-term survival remains to be determined, the ICE combination appears to be effective against recurrent Wilms' tumor without endangering the patients' single remaining kidney. Myelotoxicity can be ameliorated by administering growth factors. We suggest that ICE chemotherapy be considered for the primary treatment of high-risk patients with Wilms' tumor.

    View details for Web of Science ID A1994PV10300002

    View details for PubMedID 7978044

  • RESPONSE OF IMMUNOCOMPROMISED CHILDREN WITH SOLID TUMORS TO A CONJUGATE VACCINE FOR HAEMOPHILUS-INFLUENZAE TYPE-B JOURNAL OF PEDIATRICS Shenep, J. L., Feldman, S., Gigliotti, F., Roberson, P. K., Marina, N., FORESCHLE, J. E., FULLEN, G. H., Lott, L., BRODKEY, T. O. 1994; 125 (4): 581-584

    Abstract

    Serum antibody response to a conjugated Haemophilus influenzae type b polyribosylribitol phosphate-diphtheria toxoid vaccine was assessed in nonvaccinated children aged 1 1/2 to 5 years receiving chemotherapy for solid tumors. Responses occurred in 21 (42%) of 50 children after first vaccination, and in 10 (45%) of 22 revaccinated children.

    View details for Web of Science ID A1994PK52900012

    View details for PubMedID 7931877

  • LACK OF HERITABILITY IN OVARIAN GERM-CELL MALIGNANCIES 61st Annual Meeting of the Central-Association-of-Obstetricians-and-Gynecologists Shulman, L. P., Muram, D., Marina, N., Jones, C., Portera, J. C., Wachtel, S. S., Simpson, J. L., Elias, S. MOSBY-ELSEVIER. 1994: 1803?8

    Abstract

    Our purpose was to determine whether relatives of patients with ovarian germ cell malignancies not associated with sex chromosome abnormalities are at increased risk for similar tumors.We reviewed pedigrees of 78 presumptive 46,XX patients (ages ranging from newborn to 20 years) with malignant ovarian germ cell tumors, excluding cases of dysgerminoma and gonadoblastoma. A three-generation family history of each proband was reviewed specifically to identify cancer in any family member.Seventy-eight mothers, 87 sisters, 135 aunts, and 156 grandmothers were surveyed. None had a malignant ovarian germ cell neoplasm or other malignant ovarian neoplasm.First- and second-degree relatives of probands with ovarian germ cell malignancies do not have an increased risk for similar tumors. These findings were not predicted because of the well-recognized association of hereditary tumors and early age of onset.

    View details for Web of Science ID A1994NR67700030

    View details for PubMedID 8203441

  • PHASE-I STUDY OF ESCALATING TARGETED DOSES OF CARBOPLATIN COMBINED WITH IFOSFAMIDE AND ETOPOSIDE IN TREATMENT OF NEWLY-DIAGNOSED PEDIATRIC SOLID TUMORS JOURNAL OF THE NATIONAL CANCER INSTITUTE Marina, N. M., Rodman, J. H., Murry, D. J., Shema, S. J., Bowman, L. C., Jones, D. P., Furman, W., Meyer, W. H., Pratt, C. B. 1994; 86 (7): 544-548

    Abstract

    The combination of carboplatin, ifosfamide, and etoposide has shown promising activity in a variety of relapsed childhood solid tumors but has not been studied in newly diagnosed patients.The tolerance for and activity of escalating targeted doses of carboplatin combined with ifosfamide and etoposide (ICE) were assessed in children with advanced germ cell tumors or other rare solid tumors for which no standard therapy exists.Fifteen children with newly diagnosed solid tumors received ICE chemotherapy. Individualized carboplatin doses were calculated to achieve a target area under the concentration x time curve (AUC) and adjusted for the glomerular filtration rate (estimated by 99mTc-labeled diethylene-triamine pentaacetic acid clearance). Cohorts of at least three patients received carboplatin at an initial target AUC of 6 mg.min/mL, with escalations of 2 mg.min/mL in subsequent cohorts. Carboplatin was given on day 1, followed by ifosfamide at 2 g/m2 per day and etoposide at 100 mg/m2 per day on days 2 through 4. All patients received at least two courses of therapy in the absence of progressive disease, and as many as eight courses could be given.The 15 patients received a total of 46 assessable courses of ICE. Myelosuppression was the dominant toxicity; 30 courses (67%) resulted in hospitalization for febrile neutropenia. Neutropenia was dose limiting at the carboplatin target AUC of 12 mg.min/mL. One complete and eight partial responses were seen in the 14 assessable patients; two additional patients had at least partial responses documented at surgery or autopsy. Six patients are without evidence of disease at a median of 548 days after diagnosis.ICE chemotherapy, with the carboplatin dose based on a target AUC of 10 mg.min/mL, is tolerable and has significant activity in a variety of rare malignancies, including extragonadal germ cell tumors. Implications: The combination of carboplatin, etoposide, and ifosfamide holds promise in the treatment of rare pediatric malignancies.

    View details for Web of Science ID A1994ND81100017

    View details for PubMedID 8133538

  • PHASE-I STUDY OF TOPOTECAN FOR PEDIATRIC-PATIENTS WITH MALIGNANT SOLID TUMORS JOURNAL OF CLINICAL ONCOLOGY Pratt, C. B., Stewart, C., Santana, V. M., Bowman, L., Furman, W., Ochs, J., Marina, N., Kuttesch, J. F., Heideman, R., Sandlund, J. T., Avery, L., Meyer, W. H. 1994; 12 (3): 539-543

    Abstract

    To determine the dose-limiting toxicity and potential efficacy of topotecan in pediatric patients with refractory malignant solid tumors.In this phase I clinical trial, 27 patients received topotecan 0.75-1.9 mg/m2 by continuous intravenous infusion daily for 3 days. Fifty-three treatment courses were given to these patients.Myelosuppression was the dose-limiting toxicity at levels of 1.3 to 1.9 mg/m2 for 3 days, requiring significant support with transfused packed RBCs and platelets. Myelosuppression was variable in severity at the 1.0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF). Other toxicities were not significant. One patient with neuroblastoma had a complete response that lasted for 8 months. Stable disease activity was recorded for other patients with neuroblastoma, rhabdomyosarcoma, and islet cell carcinoma. Pharmacokinetic studies showed that topotecan plasma concentrations ranged from 1.6 to 7.5 ng/mL during infusions of 1.0 mg/m2/d, and that there was a biphasic plasma distribution with a mean terminal half-life of 2.9 +2- 1.0 hours.Topotecan is a promising anticancer agent that deserves phase II testing in pediatric solid tumors. We recommend that pediatric phase II topotecan trials use 1.0 mg/m2/d for 3 days as a constant intravenous infusion, followed by G-CSF for 14 days, and that these treatment courses be repeated every 21 days.

    View details for Web of Science ID A1994MZ76300015

    View details for PubMedID 8120551

  • PRIMARY MALIGNANCY OF THE SALIVARY-GLAND IN CHILDREN JOURNAL OF PEDIATRIC SURGERY Rogers, D. A., Rao, B. N., Bowman, L., Marina, N., Fleming, I. D., Schropp, K. P., Lobe, T. E. 1994; 29 (1): 44-47

    Abstract

    Seventeen pediatric patients with a major salivary gland malignancy (16 parotid, 1 submaxillary) were reviewed. Eight patients presented with carcinoma. The usual presentation was a mass over the affected gland. Six patients had localized disease, which was treated by excision. This was accomplished by either a total or subtotal parotidectomy or resection of the submaxillary gland. Two patients received adjuvant radiation therapy. All six patients with localized carcinoma are alive, without evidence of disease. Two patients presented with metastatic disease and died of the disease despite treatment with multiagent chemotherapy, and in one case, radiation therapy. Nine patients had rhabdomyosarcoma (RMS). The usual presentation was a mass at the angle of the mandible. Five patients had involvement of one or more cranial nerves, and two had concomitant cervical adenopathy. Eight patients had a biopsy and then were treated according to an existing prospective institutional protocol. The ninth patient initially underwent a superficial parotidectomy. Seven patients received radiation therapy. In one patient, rapid progression of the disease precluded this treatment. Seven patients died of progressive local and distant disease 2 months to 2 years (median, 6 months) from the time of diagnosis. Two patients are alive, without evidence of disease, 3 and 7 years after presentation. We conclude that carcinoma should be managed with complete excision. For RMS of the salivary gland, a biopsy should be performed, and treatment should consist of chemotherapy and radiation therapy.

    View details for Web of Science ID A1994MR27200010

    View details for PubMedID 8120760

  • SUCCESSFUL TREATMENT OF ACUTE LYMPHOBLASTIC-LEUKEMIA IN A CHILD WITH CYSTIC-FIBROSIS MEDICAL AND PEDIATRIC ONCOLOGY Gururangan, S., Horner, M., Rodman, J. H., Marina, N. M. 1994; 22 (6): 414-416

    Abstract

    A 3 1/2 year old girl with cystic fibrosis who underwent successful treatment for acute lymphoblastic leukemia remains in complete remission 36 months after diagnosis. We also report high clearance rates of three antineoplastic agents in this patient. Drug doses were adjusted to achieve optimal systemic exposure.

    View details for Web of Science ID A1994NG22700011

    View details for PubMedID 8152404

  • FAILURE OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR TO REDUCE FEBRILE NEUTROPENIA IN CHILDREN WITH RECURRENT SOLID TUMORS TREATED WITH IFOSFAMIDE, CARBOPLATIN, AND ETOPOSIDE CHEMOTHERAPY MEDICAL AND PEDIATRIC ONCOLOGY Marina, N. M., Shema, S. J., Bowman, L. C., Rodman, J., Douglass, E. C., Furman, W. L., Pappo, A., Santana, V. M., Hudson, M., Meyer, W. H., Pratt, C. B. 1994; 23 (4): 328-334

    Abstract

    Ifosfamide, carboplatin, and etoposide (ICE) chemotherapy has promising activity against various solid tumors but produces significant myelotoxicity that might be ameliorated by hematopoietic growth factors. Twelve patients with relapsed solid tumors were treated with ICE chemotherapy. Carboplatin was given on day 1 at a targeted area under the concentration-time curve (AUC) of 8 mg/mL x min (adjusted for each patient's glomerular filtration rate), followed by ifosfamide 2 g/m2 and etoposide 100 mg/m2 on days 2 through 4. Granulocyte-macrophage colony-stimulating factor (GM-CSF), 1,000 micrograms/m2/day, was started 24 hours after each course and given for 17 days or until the absolute neutrophil count (ANC) reached 10 x 10(9)/L. Myelotoxicity and responses in these patients were compared to those of eight patients who received the same therapy without GM-CSF. Patients received a median of three courses (range, 1-8). All 20 patients developed grade 4 neutropenia and grade 3 or 4 thrombocytopenia. The median duration of neutropenia was significantly shorter in patients who received GM-CSF (16.75 vs. 10 days, P = 0.005). However, the two groups did not differ in the proportion of courses associated with hospitalization for febrile neutropenia, the duration of hospitalization, or the median duration of thrombocytopenia. There were two complete, four partial, and three objective responses in the 12 patients treated with ICE plus GM-CSF, and two partial and three objective responses in the 8 patients treated with ICE only. GM-CSF did not reduce the occurrence of febrile neutropenia or the duration of thrombocytopenia associated with ICE chemotherapy. Studies of other hematopoietic growth factors in conjunction with this promising combination are merited.

    View details for Web of Science ID A1994PD28400002

    View details for PubMedID 8058003

  • USE OF HBA-71 AND ANTI-BETA(2)-MICROGLOBULIN TO DISTINGUISH PERIPHERAL NEUROEPITHELIOMA FROM NEUROBLASTOMA HUMAN PATHOLOGY Pappo, A. S., Douglass, E. C., Meyer, W. H., Marina, N., Parham, D. M. 1993; 24 (8): 880-885

    Abstract

    Peripheral neuroepithelioma (PN) can be difficult to distinguish from undifferentiated neuroblastoma (NBL) in the absence of molecular and cytogenetic studies. These primitive neural tumors of childhood are similar in morphology and immunocytochemistry, despite their distinct biochemical and behavioral characteristics. The recently developed monoclonal antibody HBA 71 is specific for the product MIC2, a marker of peripheral primitive neuroectodermal tumors. Because beta 2-microglobulin also is selectively expressed by most tumors in this subset, we examined whether a combination of the antibodies HBA 71 and anti-beta 2-microglobulin could facilitate the differentiation of the two malignancies. We histologically confirmed the diagnoses of 45 paraffin-embedded tumors of presumed neuroectodermal origin (19 PNs and 26 NBLs) from the pathology files of St Jude Children's Research Hospital. Samples were immunohistochemically stained using HBA 71 and anti-beta 2-microglobulin. Molecular and cytogenetic data were correlated with the results in a subset of eight patients. Sixteen (84%) of the 19 PNs reacted with HBA 71 and 13 (76%) of 17 PNs reacted with anti-beta 2-microglobulin. None of the NBLs reacted with either antibody. Three PNs were identified by HBA 71 alone and one was identified by anti-beta 2-microglobulin alone. Cellular genetic findings were consistent with the results. HBA 71 and anti-beta 2-microglobulin, when used in combination, can facilitate the differential diagnosis of PN and NBL.

    View details for Web of Science ID A1993LT27400009

    View details for PubMedID 8375858

  • CANDIDA-TROPICALIS INFECTIONS IN CHILDREN WITH LEUKEMIA LEUKEMIA & LYMPHOMA Flynn, P. M., Marina, N. M., Rivera, G. K., Hughes, W. T. 1993; 10 (4-5): 369-376

    Abstract

    The Candida species account for approximately three-fourths of fungal infections in patients with cancer. Although Candida albicans is the most frequent cause, C. tropicalis is increasingly implicated as an important pathogen. Over a 12 year period 19 children treated for leukemia at our institution developed C. tropicalis infections. We describe their clinical presentation, extent of fungal infection, treatment, and outcome. Fungemia without meningitis in 11 children was treated successfully, whereas C. tropicalis meningitis in 7 children was uniformly fatal. An additional patient had unsuspected, widespread infection detected at autopsy. Multiple sites, including the cerebrospinal fluid yielded C. tropicalis. Previously reported risk factors including neutropenia, broad-spectrum antibiotic usage, corticosteroid therapy, and total parenteral nutrition were observed in our cases. A high index of suspicion and the early use of aggressive antifungal therapy are critical to the successful management of C. tropicalis infections in children with leukemia.

    View details for Web of Science ID A1993LT61100016

    View details for PubMedID 8220136

  • A PHASE-I STUDY OF IFOSFAMIDE WITH MESNA GIVEN DAILY FOR 3 CONSECUTIVE DAYS TO CHILDREN WITH MALIGNANT SOLID TUMORS CANCER Pratt, C. B., Meyer, W. H., Douglass, E. C., Bowman, L., Wilimas, J., Ochs, J., Marina, N., Avery, L., Thompson, E. I. 1993; 71 (11): 3661-3665

    Abstract

    The authors conducted a Phase I dose escalation trial of ifosfamide given daily for 3 consecutive days to 29 children with malignant solid tumors. Twenty-eight of these children had received prior chemotherapy.Patients were assigned to dosage cohorts separately on the basis of prior exposure to the platinum alkylating agents cisplatin or carboplatin (n = 20) or the absence of such exposure (n = 9). At least three patients in each category were treated at a starting dosage of 2133 mg/m2/d for 3 days. This dosage represented 80% of the total dose delivered in the prior study of ifosfamide given daily over 5 days with dosage escalation of 20% in subsequent cohorts.Myelosuppression was dose-limiting at the second dosage level (2560 mg/m2/d) for patients previously treated with platinum and at the third dosage level (3072 mg/m2/d) for those not previously treated with platinum. Dose-limiting neurotoxicity was seen at 2560 mg/m2/d for the former group, but was not encountered in the latter group.Delivery of ifosfamide daily for 3 days is feasible and safe at recommended dosages of 2133 mg/m2/d for children with prior exposure to platinum and 3000 mg/m2/d for those without prior exposure.

    View details for Web of Science ID A1993LE41900030

    View details for PubMedID 8490914

  • ACUTE HYPERSENSITIVITY REACTIONS TO ETOPOSIDE IN A VEPA REGIMEN FOR HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Hudson, M. M., Weinstein, H. J., Donaldson, S. S., Greenwald, C., Kun, L., Tarbell, N. J., HUMPHREY, W. A., Rupp, C., Marina, N. M., Wilimas, J., Link, M. P. 1993; 11 (6): 1080-1084

    Abstract

    We report an unexpectedly high incidence of hypersensitivity to etoposide among 45 patients with newly diagnosed Hodgkin's disease treated with vinblastine, etoposide, prednisone, and doxorubicin (VEPA) plus radiation.Twenty-three of 45 patients (51%) had one or more acute hypersensitivity reactions to etoposide administration. The 23 patients were 8 to 18 years of age (median, 15 years); 12 were males. Four patients had experienced prior allergic reactions to antibiotics or intravenous contrast media.Hypersensitivity reactions followed the first or second dose of VEPA in most cases. The reactions occurred at a median time of 5 minutes (range, 3 to 120) from the start of the etoposide infusion. Fifteen patients reacted early (within 10 minutes), four midway through the infusion, and four after completion of the infusion. Signs and symptoms included flushing, respiratory problems, changes in blood pressure, and abdominal pain with or without nausea and vomiting. Respiratory problems included dyspnea, chest pain/tightness, bronchospasm, and cyanosis. Symptoms were alleviated by discontinuing the etoposide infusions and administering diphenhydramine and/or hydrocortisone; epinephrine was required to reverse bronchospasm in three cases. All 23 patients recovered without adverse sequelae and were rechallenged with etoposide. Fifteen patients tolerated subsequent etoposide infused at a slower rate, with antihistamine and/or corticosteroid premedication; five had recurrent hypersensitivity despite these measures. Three of these five developed similar symptoms when teniposide was substituted for etoposide. Three patients who had isolated episodes of hypotension on completion of the etoposide infusion successfully received subsequent infusions without premedication or change in infusion rate or concentration.Despite this unexpectedly high incidence of hypersensitivity among Hodgkin's disease patients treated with etoposide, rechallenge with the drug was successful in 78% of cases.

    View details for Web of Science ID A1993LF31000011

    View details for PubMedID 8501494

  • BRAIN METASTASES IN OSTEOSARCOMA - REPORT OF A LONG-TERM SURVIVOR AND REVIEW OF THE ST-JUDE-CHILDRENS-RESEARCH-HOSPITAL EXPERIENCE CANCER Marina, N. M., Pratt, C. B., Shema, S. J., Brooks, T., Rao, B., Meyer, W. H. 1993; 71 (11): 3656-3660

    Abstract

    Brain metastasis has been considered a rare event in osteosarcoma, although with prolonged survival an increasing incidence has been suggested. There have been no prior reports of long-term survivors among patients with this complication.The authors describe a child treated for osteosarcoma who is alive and free of disease 8 years after the detection of brain metastases. Of 254 patients with primary osteosarcoma referred to St. Jude Children's Hospital between 1962 and 1989, 13 developed brain metastases, all after relapse or recurrence in another site. Concomitant active lung metastases were present in all of the patients except the one long-term survivor, whose pulmonary disease had responded to treatment with cisplatin and doxorubicin. Log-rank analyses were used to compare survival duration and the frequency of brain metastases among patients treated before and after 1982, when effective multiagent therapy was initiated.Log-rank analyses comparing patients treated before and after 1982 showed that the introduction of effective modern therapy improved survival among patients at risk for brain metastases (i.e., those with recurrent and progressive disease, P = 0.007) but was not associated with a statistically significant increase in the frequency of brain metastases (15.5% versus 4.5%, P = 0.125).Although the outlook for patients with this complication remains bleak, the resolution of brain metastases after eight courses of ifosfamide in the patient described in this article suggests that enrollment of selected patients in Phase II trials is merited.

    View details for Web of Science ID A1993LE41900029

    View details for PubMedID 8490913

  • PROGRESS IN THE TREATMENT OF ADOLESCENTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA WORKSHOP ON CHILDREN WITH CANCER Rivera, G. K., Pui, C. H., Santana, V. M., Hancock, M. L., Mahmoud, H., Sandlund, J. T., Ribeiro, R. C., Furman, W., Marina, N., Crist, W. M. WILEY-BLACKWELL. 1993: 3400?3405

    Abstract

    BACKGROUND AND METHODS. The authors studied the clinical and biologic features and treatment response of 358 children with acute lymphoblastic leukemia (ALL), including 90 adolescents, treated on a single multiagent protocol (St. Jude Total Study XI, 1984-1988). This was done to clarify whether the disease differed in adolescents and to determine the degree of improvement in treatment outcome produced by this modern intense chemotherapy.Compared with the younger children (1-9 years of age; infants 1 year old or younger excluded; n = 257), adolescents (10-18 years of age; n = 90) were significantly more likely to have adverse prognostic features, including T-cell phenotype, L2 blast cell morphologic characteristics, blasts with negative findings for common ALL antigen, and ploidy other than hyperdiploidy greater than 50. Eighty-six of the 90 (96%) adolescents achieved a complete remission, a rate similar to that of the children (97%). Although the event-free survival (EFS) of adolescents was shorter than that of younger children (5-year EFS of 66 +/- 8% versus 75 +/- 5%, respectively; P = 0.04), in this analysis of consecutively treated patients with ALL it showed a significant statistical and clinical improvement as compared with that in our previous study (St. Jude Total Study X, 1979-1983; 5-year EFS rate of 66 +/- 8% versus 37 +/- 5%, respectively; P < 0.001). Within the adolescent group treated on Total Study XI, the EFS was worse for those older than 15 years of age than for those 10-14 years old (46 +/- 15% versus 75 +/- 8%, respectively; P = 0.007). Toxic effects primarily included myelosuppression without severe sequelae. Approximately 96% of the therapy was administered in the outpatient setting.The increased frequency of unfavorable clinical and biologic features undoubtedly accounts for the poorer prognosis of adolescents with ALL, a conclusion supported by the lack of independent prognostic importance of age in this study. The authors conclude that approximately two-thirds of adolescents can be cured when treated with this intensive but tolerable therapy, showing that this form of treatment significantly has changed the prognosis of adolescents with ALL.

    View details for Web of Science ID A1993LD57000041

    View details for PubMedID 8490889

  • PHASE-I STUDY OF ESCALATING TARGETED DOSES OF CARBOPLATIN COMBINED WITH IFOSFAMIDE AND ETOPOSIDE IN CHILDREN WITH RELAPSED SOLID TUMORS JOURNAL OF CLINICAL ONCOLOGY Marina, N. M., Rodman, J., Shema, S. J., Bowman, L. C., Douglass, E., Furman, W., Santana, V. M., Hudson, M., Wilimas, J., Meyer, W., Madden, T., Pratt, C. 1993; 11 (3): 554-560

    Abstract

    The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors.To reduce interpatient variability in carboplatin systemic exposure, 45 children were treated with doses individualized to a target area under the serum concentration versus time curve (AUC) based on renal function, using technetium 99-diethyl-enetriamine pentaacetic acid (99mTc-DTPA) clearance to estimate glomerular filtration rate (GFR). Cohorts of at least three patients received carboplatin at an initial target AUC of 2 mg/mL x min, with escalations of 1 mg/mL x min in subsequent cohorts. Courses consisted of carboplatin on day 1 followed by IFOS 2 g/m2 plus VP-16 100 mg/m2 on days 2 and 3. Patients received at least two courses, with a maximum of eight courses possible in the absence of progressive disease. When only moderate toxicity occurred after escalation to 5 mg/mL x min, a third dose of IFOS plus VP-16 was added. After three patients were treated at this level, carboplatin escalation proceeded.Neutropenia and thrombocytopenia were the dominant toxicities in the 43 assessable patients. At the target AUC of 8 mg/mL x min, 13 of 20 cycles were associated with febrile neutropenia. For phase II trials, we recommend a carboplatin target AUC of 6 mg/mL x min with three doses of IFOS and VP-16 for patients with prior craniospinal irradiation or high-dose cisplatin (CDDP)/VP-16, or 7 mg/mL x min for patients without such histories. There were two complete responses (CRs), 13 partial responses (PRs), and 17 objective responses (ORs).The ICE regimen shows promising activity in pediatric solid tumors. The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy.

    View details for Web of Science ID A1993KP40400025

    View details for PubMedID 8445431

  • NUCLEOSIDE TRANSPORT IN NORMAL AND NEOPLASTIC-CELLS ADVANCES IN ENZYME REGULATION Belt, J. A., Marina, N. M., Phelps, D. A., Crawford, C. R. 1993; 33: 235-252

    Abstract

    The permeation of nucleosides across the plasma membrane of mammalian cells is complex and mediated by at least five distinct transporters that differ in their sensitivity to inhibitors and in their specificity for nucleosides. The basic properties and permeant specificity of these transporters are summarized in Table 3. It appears that there may be differences in the distribution of these transporters in tumors and normal tissues that might be exploited for chemotherapeutic purposes. The human tumor cell lines examined express predominantly the NBMPR-sensitive equilibrative transporter es which can be blocked by low concentrations of NBMPR and dipyridamole. It is reasonable to expect that tumors with transport properties similar to the CCRF-CEM and Rh28 cell lines (Table 1) that have no detectable NBMPR-insensitive transport activity will be highly susceptible to the therapeutic approach of combining a transport inhibitor such as dipyridamole or NBMPR with an inhibitor of de novo pyrimidine biosynthesis. On the other hand, this approach to therapy is unlikely to succeed against tumors with transport phenotypes similar to the WI-L2 cell line that may permit the salvage nucleosides in the presence of these inhibitors. The majority of tumor cells examined, however, fall between these extremes, and it is not yet known what level of NBMPR-insensitive transport activity can be tolerated without seriously compromising this therapeutic approach. With respect to normal tissues, the mature absorptive cells of the intestine have predominantly Na(+)-dependent nucleoside transporters that are insensitive to NBMPR and dipyridamole. The proliferating crypt cells also appear to have Na(+)-dependent nucleoside transport, although they may also have an NBMPR-sensitive component of transport (Belt, unpublished data). Bone marrow granulocyte-macrophage progenitor cells also appear to have one or more concentrative nucleoside transporters. Thus these tissues, which are most vulnerable to the toxicity of antimetabolites, may be able to salvage nucleosides in the presence of inhibitors of equilibrative transport and be protected from the toxicity of de novo synthesis inhibitors. It is likely, however, that a successful application of this therapeutic approach will require the analysis of the nucleoside transport phenotype of individual tumors in order to identify those patients that may benefit from such therapy. Since the development of antibodies and cDNA probes for the various nucleoside transporters is currently underway in several laboratories, it is likely that analysis of the nucleoside transport phenotype of tumors from biopsy material will be feasible in the future.

    View details for Web of Science ID A1993LJ63200018

    View details for PubMedID 8356910

  • NUCLEOSIDE TRANSPORT IN NORMAL AND NEOPLASTIC-CELLS 33RD SYMP ON REGULATION OF ENZYME ACTIVITY AND SYNTHESIS IN NORMAL AND NEOPLASTIC TISSUES Belt, J. A., Marina, N. M., Phelps, D. A., Crawford, C. R. PERGAMON PRESS LTD. 1993: 235?252

    View details for Web of Science ID A1993BY41V00018

  • EFFICACY AND TOXICITY OF MULTIAGENT CHEMOTHERAPY AND LOW-DOSE INVOLVED-FIELD RADIOTHERAPY IN CHILDREN AND ADOLESCENTS WITH HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Hudson, M. M., Greenwald, C., Thompson, E., Wilimas, J., Marina, N., Fairclough, D., Kauffman, W., BOZEMAN, P., Mackert, P. W., Abromowitch, M., Jenkins, J., BOULDEN, T., Kun, L. 1993; 11 (1): 100-108

    Abstract

    Between May 1980 and September 1990, 85 patients with Hodgkin's disease were treated with a regimen designed to increase cure rates while reducing late toxicity.Therapy consisted of five cycles of cyclophosphamide, Oncovin (vincristine; Eli Lilly and Co, Indianapolis, IN), and procarbazine (COP), alternated with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and low-dose (20 Gy) regional radiotherapy. Vincristine and cyclophosphamide were administered as tolerated during irradiation and during the 2- to 4-week rest period between radiation volumes. The need for staging laparotomy was defined by clinical presentation.The median age at diagnosis was 14 years (range, 4 to 20), and 56% of patients were male. The majority (67%) had stage III or IV disease and 68% (19 of 28) of stage II patients had bulky mediastinal disease. Nodular sclerosing histology predominated (67%). Ninety-three percent of patients were alive without disease with a median follow-up of 4.1 years. Abnormalities were detected on chest roentgenograms and/or pulmonary function tests in 58% and 25% of clinically asymptomatic patients who were tested at least 1 year after completion of therapy. The only symptomatic patient had pulmonary fibrosis after treatment with bleomycin (20 U/m2) and mantle (20 Gy)/lung (13 Gy) irradiation, and developed multiple spontaneous pneumothoraces that required cortical stripping. One patient had congestive heart failure 19 months post-treatment, and two had abnormalities on echocardiograms. Thyroid abnormalities occurred in 21 (27%) patients who were assessable for late toxicity. The majority of female patients have had regular menstrual cycles. Six developed ovarian failure, and 10 have had a total of 17 pregnancies. Other than one documented case of oligospermia, information was not available on male fertility.The results demonstrate excellent disease control for the COP/ABVD regimen, with acceptable toxicity.

    View details for Web of Science ID A1993KF53100017

    View details for PubMedID 8418221

  • DIAGNOSIS AND TREATMENT OF THE MOST COMMON SOLID TUMORS IN CHILDHOOD PRIMARY CARE Marina, N. M., Krance, R., Ribeiro, R. C., Crist, W. M. 1992; 19 (4): 871-889

    Abstract

    Childhood cancer is the leading cause of death from disease in children between 1 and 15 years of age. Since the introduction of modern multimodality therapy, the prognosis for solid tumors has improved dramatically, with 50% to 60% cure rates. Advances in cytogenetic and molecular genetic techniques are now being used for risk-based treatment in various tumors, including neuroblastoma and rhabdomyosarcoma. Further use of these research tools may lead to a better understanding of oncogenic molecular events, permitting treatment targeted to specific genetic lesions. This article focuses on the clinical features, treatment, and potential future research directions for this diverse group of diseases.

    View details for Web of Science ID A1992LA26600015

    View details for PubMedID 1334564

  • IMPROVED PROGNOSIS OF CHILDREN WITH OSTEOSARCOMA METASTATIC TO THE LUNG(S) AT THE TIME OF DIAGNOSIS CANCER Marina, N. M., Pratt, C. B., Rao, B. N., Shema, S. J., Meyer, W. H. 1992; 70 (11): 2722-2727

    Abstract

    A poor outcome is traditionally ascribed to osteosarcoma metastatic to the lungs, but data have been unavailable regarding the outcome of such patients after systematic treatment on clinical trials.The clinical course and outcome of 31 patients who had osteosarcoma metastatic to the lungs diagnosed between 1962 and 1990 at St. Jude Children's Research Hospital were reviewed to determine whether the use of increasingly aggressive multimodality therapy has improved their outcome. The patients were grouped by treatment eras, based on major changes in therapy (i.e., single-agent or two-agent era, 1962-1972; standard multiagent era, 1972-1982; and intensive multiagent era, 1982-1990).With increasingly intensive chemotherapy, more aggressive efforts to resect metastatic disease, and earlier detection of pulmonary metastases by computed tomography, the survival of these patients has improved significantly over the 28-year study period. Those treated since 1982 have a 50% estimated probability of survival at 3 years, whereas there were no survivors at 3 years in the two earlier eras. Survival for the former group reached a plateau of 30% at 4 years.The use of aggressive multimodality therapy, coupled with modern pediatric imaging techniques to detect pulmonary disease, has improved the traditionally dismal outlook in pediatric patients with osteosarcoma and synchronous pulmonary metastases.

    View details for Web of Science ID A1992JY88000024

    View details for PubMedID 1423203

  • LEUKEMIAS AND LYMPHOMAS IN CHILDREN PRIMARY CARE Ribeiro, R. C., Krance, R., Marina, N. M., Crist, W. M. 1992; 19 (4): 853-869

    Abstract

    Leukemias and lymphomas, the most common type of neoplasms in children, represent a heterogenous group of diseases that display a wide spectrum of clinical, morphologic, immunologic, cytogenetic, and molecular features. Modern treatment is curative for most children with lymphoid neoplasms; however, new approaches to therapy of acute nonlymphoblastic leukemias are necessary if current results are to be improved. This article focuses on the clinical and biologic characteristics, and the modalities of treatment of this group of diverse diseases.

    View details for Web of Science ID A1992LA26600014

    View details for PubMedID 1465492

  • TREATMENT OF CHILDHOOD GERM-CELL TUMORS - REVIEW OF THE ST JUDE EXPERIENCE FROM 1979 TO 1988 CANCER Marina, N., Fontanesi, J., Kun, L., Rao, B., Jenkins, J. J., Thompson, E. I., Etcubanas, E. 1992; 70 (10): 2568-2575

    Abstract

    The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. The authors assessed the outcome of treatment with multiagent chemotherapy (with or without radiation therapy) in children treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH).Sixty children with germ cell tumors were treated between January 1979 and June 1988. Postsurgical treatment was based on tumor site, stage, and histology. Most patients received chemotherapy with vincristine, actinomycin-D, and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin, and vinblastine [PVB]); in the absence of response to initial therapy, patients received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were patients with Stage I testicular tumors (observation only) and ovarian germinomas (Stage I tumors measuring less than 10 cm, observation only; tumors larger than 10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus radiation).The estimated 5-year survival is 100% for patients with Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of any stage or with Stage I-II ovarian tumors had 100% 5-year survival. Extragonadal tumors responded poorly to VAC alone with recurrent or progressive disease in eight of nine patients. Treatment for those tumors was changed to alternating courses of VAC and PVB, which failed in only one of seven patients. Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC; these patients then received PVB, which was effective in four cases.For patients with advanced germ cell cancers, intensification of therapy or the development of new approaches is necessary. In contrast, future trials in children with limited stage should focus on reducing acute and long-term toxicities.

    View details for Web of Science ID A1992JX89400027

    View details for PubMedID 1384951

  • IFOSFAMIDE PLUS ETOPOSIDE IN NEWLY DIAGNOSED EWINGS-SARCOMA OF BONE JOURNAL OF CLINICAL ONCOLOGY Meyer, W. H., Kun, L., Marina, N., Roberson, P., Parham, D., Rao, B., FLETCHER, B., Pratt, C. B. 1992; 10 (11): 1737-1742

    Abstract

    We assessed the activity of ifosfamide plus etoposide against newly diagnosed Ewing's sarcoma of bone by administering this drug pair before standard induction therapy (the upfront window approach).Twenty-six children and adolescents with newly diagnosed, previously untreated Ewing's sarcoma of bone were enrolled onto this pilot study (EW-87). Eighteen were at a higher risk of treatment failure, with a primary tumor size of more than 8 cm or metastases at diagnosis. Window therapy with ifosfamide (1.6 g/m2/d with mesna uroprotection) and etoposide (100 mg/m2/d) was given in three 5-day cycles at 21-day intervals. Responses were evaluated clinically and radiologically. Subsequent induction therapy comprised three cycles of cyclophosphamide and doxorubicin. Radiation therapy was the primary local control modality; surgery was limited to biopsy or resection of expendable bones. After the local control phase, alternating courses of vincristine plus dactinomycin, ifosfamide plus etoposide, and cyclophosphamide plus doxorubicin were given as maintenance therapy.There were four complete responses and 21 partial responses to ifosfamide/etoposide window therapy (overall response rate 96%; 95% confidence interval [CI], 80% to 99%). Disease progression was observed in four patients during the cyclophosphamide/doxorubicin phase. Chemotherapy was well tolerated; only 16% (20 of 125) of all ifosfamide/etoposide window and maintenance cycles resulted in hospitalization for fever and neutropenia. Two patients developed chemotherapy-induced cystitis.The combination of ifosfamide and etoposide is highly active against previously untreated Ewing's sarcoma and generally is well tolerated. The ultimate impact of these two agents on outcome will be determined in randomized multicenter studies.

    View details for Web of Science ID A1992JV90000011

    View details for PubMedID 1403056

  • OVARIAN-CANCER IN CHILDREN AND ADOLESCENTS ADOLESCENT AND PEDIATRIC GYNECOLOGY Muram, D., GALE, C. L., Thompson, E., Marina, N. 1992; 5 (1): 21-26

    View details for Web of Science ID A1992HH12400005

  • CANDIDA-TROPICALIS AND CANDIDA-ALBICANS FUNGEMIA IN CHILDREN WITH LEUKEMIA CANCER Marina, N. M., Flynn, P. M., Rivera, G. K., Hughes, W. T. 1991; 68 (3): 594-599

    Abstract

    The records were reviewed for all patients hospitalized at a pediatric oncology center for complications of leukemia (n = 822) or lymphoma (n = 290) during an 8-year period. The results of surveillance cultures (throat, rectal, and urine) and blood cultures were analyzed to identify cases of Candida tropicalis and C. albicans colonization and/or fungemia. None of the patients with lymphoma who had positive surveillance cultures for C. albicans (n = 89) or C. tropicalis (n = 23) had fungemia. Among patients with leukemia, significant fungal infection was documented in 12 of 107 colonized with C. tropicalis (11.2%) versus 14 of 700 (2%) colonized with C. albicans (P less than 0.001). The two groups of children with fungemia were similar in primary diagnoses (predominantly acute lymphoblastic leukemia) and in the frequency of several known risk factors for infection, including the duration of neutropenia (absolute neutrophil counts, less than 500/microliters). Patients with C. tropicalis fungemia all had disseminated disease compared with nine of 14 patients with C. albicans fungemia. Also, subcutaneous abscesses were unique to patients with C. tropicalis in this series. Two patients in each group died of their infection; central nervous system involvement was present in both fatal cases of C. tropicalis fungemia. A high index of suspicion and the early institution of appropriate antifungal therapy are critical to the successful management of these infections in patients with leukemia.

    View details for Web of Science ID A1991FY16100024

    View details for PubMedID 2065280

  • THE ROLE OF 2ND-LOOK SURGERY IN THE MANAGEMENT OF ADVANCED GERM-CELL MALIGNANCIES CANCER Marina, N. M., Rao, B., Etcubanas, E., Jenkins, J. J., Kun, L., Thompson, E. I. 1991; 68 (2): 309-315

    Abstract

    The need for second-look surgery after chemotherapy in children with advanced germ cell tumors is controversial, particularly when levels of the tumor markers alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta HCG) are elevated at diagnosis. The authors evaluated the outcome of second-look surgery in relationship to tumor marker status in 27 patients with Stage III to IV disease who had completed four courses of chemotherapy. Markers were elevated at diagnosis in 19 patients. After chemotherapy, markers normalized in 12 of these patients. Second-look surgery confirmed complete response (CR) in these 12 patients, two of whom had residual masses on computed tomography (CT) scan (mature teratoma and necrotic tumor). The AFP decreased but did not normalize in seven patients; five had residual disease at second look and the other two later developed measurable disease. Of the eight patients with normal AFP at diagnosis, second look confirmed clinical CR in four. The other four patients had CT evidence of residual masses: surgery showed necrotic tissue in two cases, mature glial elements in one, and mature teratoma with glial elements in one. Thus second-look surgery added no information for treatment planning in children with elevated tumor markers at diagnosis and might best be reserved for patients without tumor markers at diagnosis and residual masses on CT scan, and those with persistent elevation of tumor markers and potentially resectable residual disease. Because of the possibility of small amount of residual tumor, second-look surgery may also be useful in patients whose markers normalize but who have residual masses on CT scans.

    View details for Web of Science ID A1991FX14500016

    View details for PubMedID 1712663

  • INFRARED, THERMISTOR, AND GLASS-MERCURY THERMOMETRY FOR MEASUREMENT OF BODY-TEMPERATURE IN CHILDREN WITH CANCER CONF ON FEVER AND TYMPANIC THERMOMETRY Shenep, J. L., ADAIR, J. R., Hughes, W. T., Roberson, P. K., Flynn, P. M., BRODKEY, T. O., FULLEN, G. H., KENNEDY, W. T., Oakes, L. L., Marina, N. M. SAGE PUBLICATIONS INC. 1991: 36?41

    Abstract

    Body temperature is often the sole determinant of whether or not the neutropenic cancer patient is admitted to the hospital for empiric antibiotic therapy. Recently developed infrared tympanic thermometers offer rapid readings, but their accuracy has not been established. We studied two infrared thermometers (FirstTemp and Thermoscan) and a thermistor (IVAC) in children with cancer. Mean infrared measurements did not differ significantly between right and left ear canals, and the mean IVAC temperature did not differ significantly from the left to the right axilla (P greater than 0.05, paired t test). IVAC predictive mode mean temperature was 0.2 degrees C lower than monitor mode mean temperature in the axilla (P less than 0.0001), but 0.1 degree C higher than monitor mode orally (P less than 0.0001). Aiming the infrared instrument at the tympanic membrane using an ear tug resulted in a 0.2 degree C higher mean temperature than casual placement in the ear canal (P less than 0.0001). After compensation for the mean difference in reference oral glass-mercury versus test instrument temperatures, the FirstTemp, Thermoscan, and oral and axillary predictive mode IVAC measurements yielded sensitivities for the detection of fever of 84%, 84%, 82%, and 86%; specificities of 100%, 99%, 100%, and 100%; positive predictive values of 100%, 93%, 100%, and 100%; and negative predictive values of 95%, 98%, 98%, and 98%, respectively. We conclude that each of these instruments detects fever with comparable reliability. Infrared instruments are especially attractive alternatives due to their time efficiency.

    View details for Web of Science ID A1991FM61200011

    View details for PubMedID 2029817

  • EFFECT OF NUCLEOSIDE TRANSPORT INHIBITORS ON THYMIDINE SALVAGE AND THE TOXICITY OF NUCLEOSIDE ANALOGS IN MOUSE BONE-MARROW GRANULOCYTE-MACROPHAGE PROGENITOR CELLS CANCER COMMUNICATIONS Marina, N. M., Belt, J. A. 1991; 3 (12): 367-372

    Abstract

    In an attempt to elucidate the types of nucleoside transporters present in bone marrow stem cells, this study examined the effect of nucleoside transport inhibitors on the toxicity of nucleoside analogs and on the salvage of thymidine by mouse bone marrow granulocyte and macrophage progenitor cells using the CFU-GM assay. Concentrations of NBMPR (nitrobenzylmercaptopurine riboside) as low as 10 nM protected these cells from the toxicity of the adenosine analog tubercidin and provided a partial block of thymidine-rescue of the granulocyte-macrophage progenitor cells from methotrexate toxicity. Dipyridamole had similar effects but generally required higher concentrations. These results suggested that the major nucleoside transporter in these cells is the NBMPR-sensitive equilibrative carrier, es. In contrast to the results with tubercidin, the toxicity of 2-chlorodeoxyadenosine was increased 8- to 10-fold by 1 microM NBMPR. These results suggested that the bone marrow granulocyte-macrophage progenitor cells also have a concentrative nucleoside transporter that is capable of pumping 2-chlorodeoxyadenosine into the cells while efflux of the nucleoside via es is blocked by NBMPR.

    View details for Web of Science ID A1991HJ66900002

    View details for PubMedID 16296002

  • USE OF MR IMAGING TO ASSESS RESULTS OF CHEMOTHERAPY FOR EWING SARCOMA AMERICAN JOURNAL OF ROENTGENOLOGY LEMMI, M. A., Fletcher, B. D., Marina, N. M., SLADE, W., Parham, D. M., Jenkins, J. J., Meyer, W. H. 1990; 155 (2): 343-346

    Abstract

    MR imaging was used to monitor the results of initial chemotherapy of primary Ewing sarcoma of bone. The signal intensities of the soft-tissue and marrow components of the tumor were evaluated on T2-weighted images obtained in 10 patients (nine with responsive tumors) at presentation and during and immediately after completion of two cycles of chemotherapy. MR evidence of marrow and soft-tissue involvement was seen in all tumors at presentation. After treatment, the bone-marrow component of the nine drug-sensitive tumors showed an increase in signal intensity that in eight cases became comparable to that of water. Changes in signal intensity of the soft-tissue component were variable, consisting of increases in two of the responsive lesions, no change in three, a decrease in two, and complete resolution of the soft-tissue mass in two. There was no increase in signal intensity of either the bone-marrow or the soft-tissue component of the single nonresponsive tumor. All of the responsive tumors showed advanced healing, and abundant bony sclerosis was apparent on CT. Bone-marrow examinations, performed in seven of the nine patients with responsive lesions, disclosed no evidence of tumor in four. Two patients had residual extramedullary tumor; the nonresponsive lesion contained sheets of tumor cells. The increase in marrow signal intensity on T2-weighted images was associated with replacement of marrow elements by a loose, hypocellular myxoid matrix containing modest amounts of collagen, consistent with response to chemotherapy and eradication of disease. Therefore, an increase in the T2-weighted signal intensity of the bone-marrow component of Ewing sarcoma of bone reflected a favorable response to chemotherapy. MR signal changes, however, were not predictive of resolution of malignant disease within adjacent soft tissue.

    View details for Web of Science ID A1990DP36600024

    View details for PubMedID 2115265

  • PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMOR (PERIPHERAL NEUROEPITHELIOMA) IN CHILDREN - A REVIEW OF THE ST JUDE EXPERIENCE AND CONTROVERSIES IN DIAGNOSIS AND MANAGEMENT CANCER Marina, N. M., Etcubanas, E., Parham, D. M., Bowman, L. C., Green, A. 1989; 64 (9): 1952-1960

    Abstract

    All patients diagnosed with primitive neuroectodermal tumor (PNET) and extraosseous Ewing's sarcoma in one institution between 1962 and 1987 were reviewed. Of the 26 cases studied, 16 had been diagnosed originally as PNETs, seven tumors were rediagnosed as PNET or EOE by histologic review, and three tumors had an original diagnosis of extraosseous Ewing's sarcoma. To determine whether these diagnoses determine a group of tumors with unique biologic behavior and identifiable pathologic characteristics, clinical and treatment response data were compiled, and electron microscopic and immunohistochemical studies were done for those patients with adequate samples. With combined modality therapy, this group achieved a substantially shorter disease control interval than patients with disseminated osseous Ewing's sarcoma or disseminated neuroblastoma--10.8 months versus 17 months and 16 months, respectively. The pattern of relapse and distant spread also differed among these tumor types. Immunohistochemical studies (for example, neuron-specific enolase and beta 2 microglobulin) were helpful in confirming the diagnosis but were not definitive in themselves. Tentative diagnostic criteria are proposed for use in studies designed to provide further information on the nature and treatment of PNET. Some of the controversies regarding diagnosis are discussed. The authors propose a uniform approach to treatment of extraosseous Ewing's sarcoma and PNET in order to try to clarify their relation.

    View details for Web of Science ID A1989AV83300030

    View details for PubMedID 2551479

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