Bio

Clinical Focus


  • Cancer > GI Oncology
  • Gastrointestinal Cancers
  • Neuroendocrine
  • Oncology (Cancer)
  • Medical Oncology
  • Esophageal Cancer
  • Cancer

Academic Appointments


Professional Education


  • Fellowship:Stanford University School of Medicine (2007) CA
  • Residency:Stanford University School of Medicine (2005) CA
  • Internship:Stanford University School of Medicine (2002) CA
  • Residency:Stanford University School of Medicine (2004) CA
  • Board Certification: Medical Oncology, American Board of Internal Medicine (2010)
  • Board Certification, Oncology, ABIM (2010)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2004)
  • Medical Education:Dartmouth Medical School (2001) NH

Research & Scholarship

Current Research and Scholarly Interests


I specialize in the treatment of gastrointestinal malignancies. My research involves clinical trials and epidemiologic studies, primarily in neuroendocrine and gastroesophageal cancers.

Clinical Trials


  • A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors Not Recruiting

    To determine objective response rates (RR) by RECIST guideline version 1.1 for all patients treated with this strategy consisting of initial therapy with pertuzumab as a single agent and then addition of erlotinib for those who have stable disease or progressive disease at three months (Simon design).

    Stanford is currently not accepting patients for this trial. For more information, please contact Heidi Kaiser, (650) 724 - 0079.

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  • A Study of MM-111 and Paclitaxel With Trastuzumab in Patients HER2 Positive Carcinomas of the Distal Esophagus, Gastroesophageal (GE) Junction and Stomach Recruiting

    To determine whether the combination of MM-111 plus paclitaxel and trastuzumab is more effective than paclitaxel and trastuzumab alone

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  • Ph II of Capecitabine, Carboplatin & Bevacizumab for Gastroesophageal Junction & Gastric Carcinoma Not Recruiting

    To investigate bevacizumab in combination with carboplatin and capecitabine for patients with unresectable or metastatic GEJ or gastric cancers. We hope that by adding bevacizumab to standard chemotherapy for this patient population we will improve Progression Free Survival by 80% over historical controls.

    Stanford is currently not accepting patients for this trial. For more information, please contact Prachi Nandoskar, (650) 725 - 0438.

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  • Phase II Gemcitabine + Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma Not Recruiting

    This multi-institutional trial aims to evaluate the potential benefit and side effects of adding fractionated stereotactic body radiotherapy/surgery (SBRT) before and after chemotherapy with gemcitabine for locally advanced pancreatic cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laurie Ann Columbo, 650-736-0792.

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  • A Study of Nilotinib Versus Imatinib in GIST Patients Not Recruiting

    This study will evaluate efficacy and safety of nilotinib versus imatinib in adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST).

    Stanford is currently not accepting patients for this trial. For more information, please contact Heidi Kaiser, (650) 724 - 0079.

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  • Phase II Capecitabine, Oxaliplatin & Bevacizumab for Metastatic / Unresectable Neuroendocrine Tumors Not Recruiting

    Given the lack of other viable treatment options for metastatic neuroendocrine tumors, contrasted with our positive anecdotal experience, and the relative tolerability of the treatment regimen for colorectal cancer patients, we propose a single-institution phase II trial investigating the efficacy of capecitabine, oxaliplatin and bevacizumab for patients with metastatic neuroendocrine tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Heidi Kaiser, (650) 724 - 0079.

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  • Phase IIa Desipramine in Small Cell Lung Cancer and Other High-Grade Neuroendocrine Tumors Recruiting

    Intrapatient dose escalation of desipramine. Start at 75 mg daily. Increase by 75 mg weekly to maximum of 450 mg daily. Taper desipramine upon disease progression, unacceptable toxicity or patient withdrawal from study.

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  • Pazopanib in Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors (GIST) Not Recruiting

    This study is being done to gather information about the safety (any harmful effects) and effectiveness (usefulness) of Pazopanib in the treatment of Gastrointestinal Stroma Tumors (GIST) that cannot be treated by surgery or has spread to other organs. The Food and Drug Administration (FDA) have approved Pazopanib for the treatment of advanced kidney cancer but it is not approved for the treatment of GIST. The investigators hope to learn about the safety and usefulness (effectiveness) of Pazopanib for patients with GIST. Primary Objective: Non-progression rate based on RECIST criteria (CR+PR+SD) Secondary Objectives: - Response per Choi criteria - 6 month progression-free survival - Safety and tolerability

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

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  • Everolimus and Octreotide With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery Not Recruiting

    This randomized phase II trial studies how well everolimus and octreotide with or without bevacizumab works in treating patients with locally advanced or metastatic pancreatic neuroendocrine tumors that cannot be removed by surgery. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide may interfere with and slow the growth of tumor cells. 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 and everolimus also may stop the growth of pancreatic neuroendocrine tumors by blocking blood flow to the tumor. It is not yet known whether giving everolimus and octreotide together is more effective with or without bevacizumab in treating pancreatic neuroendocrine tumors.

    Stanford is currently not accepting patients for this trial. For more information, please contact Deryn Warner, (650) 723 - 2876.

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  • Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer Not Recruiting

    This randomized phase II trial is studying giving paclitaxel and cixutumumab together to see how well they work compared to paclitaxel alone in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer. Drugs used in chemotherapy, such as paclitaxel, 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 paclitaxel together with cixutumumab may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Deryn Warner, (650) 723 - 2876.

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  • Avastin/[18-F]-5-fluorouracil PET/CT Imaging Feasibility Project Not Recruiting

    To determine whether using a radiolabelled analog of 5-FU, [18F]-5-fluorouracil, for PET/CT imaging can visually demonstrate differential chemotherapy delivery to known tumor sites before and after administration of bevacizumab and determine the optimal timing of bevacizumab administration to maximize the chemotherapy delivery into the tumor for improved cancer treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maurice Zissen, (650) 736 - 1365.

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  • Collection of Biospecimen & Clinical Information in Patients w/ Gastrointestinal Cancers Not Recruiting

    We have an active research program in gastrointestinal cancers including clinical trials, epidemiologic, and translational studies. We would like to establish a biospecimen bank linked to useful clinical information in order to learn more about diagnostic, predictive and prognostic markers for gastrointestinal cancers. PRIMARY OBJECTIVES: 1. To collect and store tumor and normal tissue (previously collected paraffin embedded or frozen specimen) and blood in patients with gastrointestinal (GI) cancers. SECONDARY OBJECTIVES: 1. Collect detailed clinical information via a patient questionnaire that includes demographic, socioeconomic, lifestyle, family, past medical, medication and cancer histories 2. Collect details about the tumor specimen extracted from patient charts.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Pitsiouni, (650) 498 - 6000.

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  • PII of SBRT & Chemo for Unresectable Cholangiocarcinoma Followed by Liver Transplantation Not Recruiting

    The purpose of this study is to determine progression-free survival at 12 months for stereotactic body radiotherapy (SBRT) and chemotherapy for unresectable hilar cholangiocarcinoma (CCA). Investigators hope to learn more about neoadjuvant SBRT and chemotherapy for unresectable CCA, and if SBRT followed by chemotherapy can lead to successful liver transplantation. This knowledge is important for this patient group as this disease is a highly lethal malignancy that often presents as unresectable, however surgery or transplantation are the only curative options.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laurie Ann Columbo, (650) 736 - 0792.

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  • A Study of EZN-2208 Administered With or Without Cetuximab in Patients With Metastatic Colorectal Carcinoma Not Recruiting

    This is a Phase 2, multicenter, multiple-arm, open-label study to evaluate the efficacy, safety, and tolerability of EZN-2208. EZN-2208 will be administered as a single agent in patients with K-RAS mutations in the tumors. Patients with wild type K-RAS in tumors will be randomized to EZN-2208 + cetuximab or to standard of care (Camptosar® + cetuximab), patients must have failed regimens containing irinotecan (Camptosar®, CPT-11), oxaliplatin (Eloxatin®), and fluoropyrimidine. After discontinuation of study treatment, patients will receive care as considered appropriate by the investigator. Patients will continue to be followed for disease progression, subsequent anticancer therapy, and survival.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Pitsiouni, (650) 721 - 3114.

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  • S0809: Capecitabine, Gemcitabine, and RT in Patients w/Cholangiocarcinoma of the Gallbladder or Bile Duct Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as capecitabine and gemcitabine, 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. 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 more than one drug (combination chemotherapy) together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving capecitabine together with gemcitabine followed by capecitabine and radiation therapy works in treating patients with cholangiocarcinoma of the gallbladder or bile duct.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

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  • Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor Not Recruiting

    This randomized phase III trial is studying giving octreotide acetate together with recombinant interferon alfa-2b to see how well it works compared with giving octreotide acetate together with bevacizumab in treating patients with metastatic or locally advanced, high-risk neuroendocrine tumor. Octreotide acetate and recombinant interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of cancer. 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 giving octreotide acetate together with recombinant interferon alfa-2b is more effective than giving octreotide acetate together with bevacizumab in treating patients with neuroendocrine tumor.

    Stanford is currently not accepting patients for this trial. For more information, please contact Deryn Warner, (650) 723 - 2876.

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  • A Phase 1 Dose Escalation Study of OMP-21M18 in Subjects With Solid Tumors Not Recruiting

    This is an open-label Phase 1 dose escalation study of OMP-21M18 in subjects with previously treated solid tumors for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit. Up to 30 subjects will be enrolled at up to 4 centers. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and efficacy. No formal interim analyses will be performed. Prior to enrollment, subjects will undergo screening to determine study eligibility. Upon enrollment, subjects will receive weekly intravenous (IV) infusions of OMP-21M18 for 9 weeks. After 9 weeks of treatment, subjects will be assessed for disease status. If there is no evidence of disease progression or if the tumor is smaller, then subjects may continue to receive IV infusions of OMP-21M18 every other week until disease progression. Dose escalation will be conducted to determine the maximum tolerated dose (MTD). The dose levels of OMP 21M18 will be 0.5, 1.0, 2.5, 5, and 10 mg/kg administered IV weekly for 9 doses. No dose escalation or reduction will be allowed within a dose cohort. The dose may be administered at any time during the day. Three subjects will be treated at each dose level if no dose-limiting toxicities (DLTs) are observed. If 1 of 3 subjects experience a DLT, that dose level will be expanded to 6 subjects. If 2 or more subjects experience a DLT, no further subjects will be dosed at that level and 3 additional subjects will be added to the preceding dose cohort unless 6 subjects have already been treated at that dose level. Subjects will be assessed for DLTs from the time of the first dose through 7 days after administration of the 4th dose, but prior to administration of the 5th dose (i.e., Days 0-28). Dose escalation, if appropriate, will occur after all subjects in a cohort have completed their Day 28 DLT assessment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) Recruiting

    The primary objective of the study is to confirm that at least 1 or more doses of telotristat etiprate compared to placebo is effective in reducing the number of daily bowel movements (BMs) from baseline averaged over the 12-week double-blind portion (Treatment Period) of the trial in patients not adequately controlled by current SSA therapy.

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  • A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours Recruiting

    The purpose of this study is to - compare Progression Free Survival (PFS) after treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in patients with inoperable, progressive (as determined by Response Evaluation Criteria in Solid Tumors [RECIST] Criteria), somatostatin receptor positive, well-differentiated neuroendocrine tumours of the small bowel (midgut carcinoid tumours). - compare the Objective Response Rate (ORR) between the two study arms - compare the Overall Survival (OS) between the two study arms - compare the Time to Tumour Progression (TTP) between the two study arms - evaluate the safety and tolerability of 177Lu-DOTA0-Tyr3-Octreotate - evaluate the health related quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-G.I.NET21 questionnaire - explore the correlation of toxicity outcomes and administered radiation doses corrected for body weight and body surface area - explore the correlation of clinical efficacy outcomes with the levels of the biomarkers Chromogranin-A (CgA) in the serum and 5-Hydroxyindoleacetic acid (5-HIAA) in the urine - evaluate dosimetry, pharmacokinetics (PK) and ECG in a subset of 20 patients - explore the correlation of clinical efficacy outcomes with OctreoScan® tumour uptake score - explore the correlation of clinical outcomes with serum levels of Alkaline Phosphatase (AP)

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  • A Study of HGS1036 in Combination With Chemotherapy in Subjects With Advanced Solid Malignancies Not Recruiting

    The primary purpose of this study is to determine the maximally tolerated dose (MTD) of HGS1036 when used in combination with the standard chemotherapeutic regimens paclitaxel plus carboplatin, cisplatin plus etoposide, or docetaxel.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Vargas, 650-723-0371 .

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  • AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors Not Recruiting

    This is a multi-center, 2-part phase 1b/2 study of AMG 655 in combination with AMG 479 to be conducted in the United States and Spain. Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerable. Part 2 will evaluate the safety and estimate the efficacy of AMG 655 at the dose selected in Part 1 in combination with AMG 479 for the treatment of patients with advanced NSCLC (non-squamous histology; squamous histology), CRC, pancreatic cancer, ovarian cancer, and sarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin Recruiting

    This study will assess the effectiveness and safety of pasireotide long-acting release in patients who have rare tumors of neuroendocrine origin.

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  • Phase 1 Trial of Oral Ixabepilone Not Recruiting

    This Phase 1 study of oral ixabepilone given every 6 hours for 3 doses on Day 1, every 21 days, was a dose-finding study designed to determine the maximum tolerated dose (MTD) and safety of this dosing schedule in participants with advanced cancer

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Stage I, Stage II, or Stage III Anal Cancer Not Recruiting

    RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Cetuximab may help cisplatin and fluorouracil work better by making tumor cells more sensitive to the drugs. It may also make tumor cells more sensitive to radiation therapy. Giving cetuximab together with chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin, fluorouracil, and radiation therapy works in treating immunocompetent patients with stage I (closed to accrual as of 11/3/2008), stage II, (some stage II closed to accrual as of 11/3/2008) or stage III anal cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Deryn Warner, (650) 723 - 2876.

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  • Study of Pasireotide Long Acting Release (LAR) in Patients With Metastatic Neuroendocrine Tumors (NETs) Not Recruiting

    The goal of this clinical research study is to learn if the study drug, Pasireotide LAR can shrink or slow the growth of Metastatic Neuroendocrine Carcinomas. The safety of this drug will also be studied. The patient's physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Pasireotide LAR is safe and effective.

    Stanford is currently not accepting patients for this trial. For more information, please contact Prachi Nandoskar, (650) 725 - 0438.

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  • A Study of CDX-1127 in Patients With Select Solid Tumor Types or Hematologic Cancers Recruiting

    This is a study of CDX-1127, a therapy that targets the immune system and may act to promote anti-cancer effects. The study enrolls patients with hematologic cancers (certain leukemias and lymphomas), as well as patients with select types of solid tumors.

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  • Capecitabine, Temozolomide and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors Recruiting

    This phase II trial studies the side effects and how well giving bevacizumab together with capecitabine and temozolomide works in treating patients with pancreatic neuroendocrine tumors that are metastatic or cannot be removed by surgery. 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. Drugs used in chemotherapy, such as capecitabine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells.

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  • Phase II NKTR-102 In Bevacizumab-Resistant High Grade Glioma Not Recruiting

    High Grade Gliomas, including anaplastic astrocytomas, anaplastic oligodendrogliomas and glioblastomas (GBM), are the most common and most aggressive primary brain tumors. Prognosis for patients with high-grade gliomas remains poor. The estimated median survival for patients with GBM is between 12 to 18 months. Recurrence after initial therapy with temozolomide and radiation is nearly universal. Since May 2009, the majority of patients in the US with an initial recurrence of high-grade glioma receive bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), which is thought to prevent angiogenesis in these highly vascular tumors. BEV has response rates from 32-62% and has improved overall median survival in patients with recurrent high-grade gliomas1. However, the response is short lived, and nearly 100% of patients eventually progress despite bevacizumab. No chemotherapeutic agent administered following progression through bevacizumab has made a significant impact on survival. Patients progress to death within 1-5 months after resistance develops. Therefore, patients with high-grade gliomas who have progressed through bevacizumab represent a population in dire need of a feasible and tolerable treatment. NKTR-102 is a topoisomerase I inhibitor polymer conjugate that was engineered by attaching irinotecan molecules to a polyethylene glycol (PEG) polymer using a biodegradable linker. Irinotecan released from NKTR-102 following administration is further metabolized to the active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN38), that causes DNA damage through inhibition of topoisomerase. The goal in designing NKTR-102 was to attenuate or eliminate some of the limiting side effects of irinotecan while improving efficacy by modifying the distribution of the agent within the body. The size and structure of NKTR-102 results in marked alteration in pharmacokinetic (PK) profile for the SN38 derived from NKTR-102 compared to that following irinotecan: the maximal plasma concentration (Cmax) is reduced 5- to 10-fold and the half-life (t1/2 ) of SN38 is increased from 2 days to approximately 50 days. This altered profile leads to constant exposure of the tumor to the active drug. In addition, the large NKTR-102 molecule does not freely pass out of intact vasculature, which may account for relatively higher concentrations of the compound and the active metabolites in tumor tissues in in vivo models, where the local vasculature may be relatively more permeable. A 145 mg/m2 dose of NKTR-102, the dose intended for use in this phase II clinical trial (and being used in the phase III clinical program), results in approximately the same plasma exposure to SN38 as a 350 mg/m2 dose of irinotecan, but exposure is protracted, resulting in continuous exposure between dosing cycles and lower Cmax. NKTR-102 was therefore developed as a new chemotherapeutic agent that may improve the clinical outcomes of patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cathy Recht, (650) 725 - 8630.

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  • A Study of Pharmacokinetic Drug Interaction Study of the Hedgehog Pathway Inhibitor GDC-0449 in Combination With Rosiglitazone or Combined Oral Contraceptive in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists Not Recruiting

    This is a single-arm, multicenter, Phase Ib study designed to describe the effect of GDC-0449 on the pharmacokinetics of rosiglitazone and oral contraceptives in patients with advanced solid tumors who are refractory to treatment or for whom no standard therapy exists.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ruth Lira, (650) 723 - 1367.

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  • Study of Cabozantinib (XL184) in Adults With Advanced Malignancies Not Recruiting

    The purpose of this study is to determine whether or not XL184 demonstrates anti-tumor activity in selected tumor types under a randomized discontinuation trial (RDT) design. Subjects who have responded to study drug after 12 weeks of open-label XL184 administration will continue to take XL184. Subjects who are clearly progressing will discontinue study treatment and subjects who demonstrate stable disease will be randomized to either XL184 or placebo. For individual patients, once disease progression is observed, the blind will be broken and subjects who were randomized to placebo will be offered the option to receive open-label XL184. Subjects who progressed while taking XL184 will discontinue study treatment. Emerging data may support enrollment in an open-label, non-randomized expansion cohort (NRE). There will be NRE cohorts for prostate and ovarian cancers.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Immunotherapy Study for Surgically Resected Pancreatic Cancer Recruiting

    The purpose of this study is to assess overall survival after treatment with a regimen of adjuvant therapy (Gemcitabine alone or with 5-FU chemoradiation) with or without HyperAcute®-Pancreas (algenpantucel-L) immunotherapy in subjects who have undergone surgical resection.

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  • Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors Recruiting

    This randomized phase II trial studies how well giving temozolomide with or without capecitabine works in treating patients with advanced pancreatic neuroendocrine tumors. Drugs used in chemotherapy, such as temozolomide and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether temozolomide is more effective with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors.

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  • A Study Using MABp1 To Increase Overall Survival In Patients With Colorectal Cancer And Weight Loss Recruiting

    The purpose of this study is to determine if the True Human Monoclonal antibody MABp1 can prolong the life of colorectal carcinoma patients who are losing weight.

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  • A Phase 1 Study of Safety and Bioactivity With FG-3019 in Combination With Gemcitabine and Erlotinib for Subjects With Locally Advanced or Metastatic Pancreatic Cancer Not Recruiting

    Objectives - Primary: To evaluate the safety and tolerability of FG-3019 in combination with gemcitabine and erlotinib - Secondary: To evaluate the efficacy and pharmacokinetics of FG-3019 in combination with gemcitabine and erlotinib

    Stanford is currently not accepting patients for this trial. For more information, please contact Donna Williams, (650) 498 - 6608.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Reassessment of the Current American Joint Committee on Cancer Staging System for Pancreatic Neuroendocrine Tumors JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Qadan, M., Ma, Y., Visser, B. C., Kunz, P. L., Fisher, G. A., Norton, J. A., Poultsides, G. A. 2014; 218 (2): 188-195

    Abstract

    Adopting a unified staging system for pancreatic neuroendocrine tumors (PNETs) has been challenging. Currently, the American Joint Committee on Cancer (AJCC) recommends use of the pancreatic adenocarcinoma staging system for PNETs. We sought to explore the prognostic usefulness of the pancreatic adenocarcinoma staging system for PNETs.The Surveillance, Epidemiology, and End Results program data were used to identify patients with PNETs who underwent curative-intent surgical resection from 1983 to 2008. The discriminatory ability of the AJCC system was examined and a new TNM system was devised using extent of disease variables.In 1,202 patients identified, lymph node metastasis was associated with worse 10-year overall survival after resection (51% vs 63%; p < 0.0001), as was the presence of distant metastatic disease (35% vs 62%; p < 0.0001). The current AJCC system (recorded by the Surveillance, Epidemiology, and End Results program in 412 patients since 2004) distinguished 5-year overall survival only between stages I and II (p = 0.01), but not between stages II and III (p = 0.97), or stages III and IV (p = 0.36). By modifying the T stage to be based on size alone (0.1 to 1.0 cm, 1.1 to 2.0 cm, 2.1 to 4.0 cm, and >4.0 cm) and revising the TNM subgroups, we propose a novel TNM system with improved discriminatory ability between disease stages (stages I vs II; p = 0.16; II vs III; p < 0.0001; and III vs IV; p = 0.008).In this study evaluating the current AJCC staging system for PNETs, there were no significant differences detected between stages II and III or stages III and IV. We propose a novel TNM system that might better discriminate between outcomes after surgical resection of PNETs.

    View details for DOI 10.1016/j.jamcollsurg.2013.11.001

    View details for Web of Science ID 000329763900008

    View details for PubMedID 24321190

  • Seventh Edition (2010) of the AJCC/UICC Staging System for Gastric Adenocarcinoma: Is there Room for Improvement? ANNALS OF SURGICAL ONCOLOGY Patel, M. I., Rhoads, K. F., Ma, Y., Ford, J. M., Visser, B. C., Kunz, P. L., Fisher, G. A., Chang, D. T., Koong, A., Norton, J. A., Poultsides, G. A. 2013; 20 (5): 1631-1638

    Abstract

    The gastric cancer AJCC/UICC staging system recently underwent significant revisions, but studies on Asian patients have reported a lack of adequate discrimination between various consecutive stages. We sought to validate the new system on a U.S. population database.California Cancer Registry data linked to the Office of Statewide Health Planning and Development discharge abstracts were used to identify patients with gastric adenocarcinoma (esophagogastric junction and gastric cardia tumors excluded) who underwent curative-intent surgical resection in California from 2002 to 2006. AJCC/UICC stage was recalculated based on the latest seventh edition. Overall survival probabilities were calculated using the Kaplan-Meier method.Of 1905 patients analyzed, 54 % were males with a median age of 70 years. Median number of pathologically examined lymph nodes was 12 (range, 1-90); 40 % of patients received adjuvant chemotherapy, and 31 % received adjuvant radiotherapy. The seventh edition AJCC/UICC system did not distinguish outcome adequately between stages IB and IIA (P = 0.40), or IIB and IIIA (P = 0.34). By merging stage II into 1 category and moving T2N1 to stage IB and T2N2, T1N3 to stage IIIA, we propose a new grouping system with improved discriminatory abilityIn this first study validating the new seventh edition AJCC/UICC staging system for gastric cancer on a U.S. population with a relatively limited number of lymph nodes examined, we found stages IB and IIA, as well as IIB and IIIA to perform similarly. We propose a revised stage grouping for the AJCC/UICC staging system that better discriminates between outcomes.

    View details for DOI 10.1245/s10434-012-2724-5

    View details for Web of Science ID 000317308200032

    View details for PubMedID 23149854

  • Consensus Guidelines for the Management and Treatment of Neuroendocrine Tumors PANCREAS Kunz, P. L., Reidy-Lagunes, D., Anthony, L. B., Bertino, E. M., Brendtro, K., Chan, J. A., Chen, H., Jensen, R. T., Kim, M. K., Klimstra, D. S., Kulke, M. H., Liu, E. H., Metz, D. C., Phan, A. T., Sippel, R. S., Strosberg, J. R., Yao, J. C. 2013; 42 (4): 557-577

    Abstract

    Neuroendocrine tumors are a heterogeneous group of tumors originating in various anatomic locations. The management of this disease poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The recent completion of several phase 3 trials, including those evaluating octreotide, sunitinib, and everolimus, demonstrate that rigorous evaluation of novel agents in this disease is possible and can lead to practice-changing outcomes. Nevertheless, there are many aspects to the treatment of neuroendocrine tumors that remain unclear and controversial. The North American Neuroendocrine Tumor Society published a set of consensus guidelines in 2010, which provided an overview for the treatment of patients with these malignancies. Here, we present a set of consensus tables intended to complement these guidelines and serve as a quick, accessible reference for the practicing physician.

    View details for DOI 10.1097/MPA.0b013e31828e34a4

    View details for Web of Science ID 000317655200002

    View details for PubMedID 23591432

  • Phase II Study Evaluating 2 Dosing Schedules of Oral Foretinib (GSK1363089), cMET/VEGFR2 Inhibitor, in Patients with Metastatic Gastric Cancer PLOS ONE Shah, M. A., Wainberg, Z. A., Catenacci, D. V., Hochster, H. S., Ford, J., Kunz, P., Lee, F., Kallender, H., Cecchi, F., Rabe, D. C., Keer, H., Martin, A., Liu, Y., Gagnon, R., Bonate, P., Liu, L., Gilmer, T., Bottaro, D. P. 2013; 8 (3)

    Abstract

    The receptors for hepatocyte and vascular endothelial cell growth factors (MET and VEGFR2, respectively) are critical oncogenic mediators in gastric adenocarcinoma. The purpose is to examine the safety and efficacy of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR2 receptors, for the treatment of metastatic gastric adenocarcinoma.Foretinib safety and tolerability, and objective response rate (ORR) were evaluated in patients using intermittent (240 mg/day, for 5 days every 2 weeks) or daily (80 mg/day) dosing schedules. Thirty evaluable patients were required to achieve alpha = 0.10 and beta = 0.2 to test the alternative hypothesis that single-agent foretinib would result in an ORR of ? 25%. Up to 10 additional patients could be enrolled to ensure at least eight with MET amplification. Correlative studies included tumor MET amplification, MET signaling, pharmacokinetics and plasma biomarkers of foretinib activity.From March 2007 until October 2009, 74 patients were enrolled; 74% male; median age, 61 years (range, 25-88); 93% had received prior therapy. Best response was stable disease (SD) in 10 (23%) patients receiving intermittent dosing and five (20%) receiving daily dosing; SD duration was 1.9-7.2 months (median 3.2 months). Of 67 patients with tumor samples, 3 had MET amplification, one of whom had SD. Treatment-related adverse events occurred in 91% of patients. Rates of hypertension (35% vs. 15%) and elevated aspartate aminotransferase (23% vs. 8%) were higher with intermittent dosing. In both patients with high baseline tumor phospho-MET (pMET), the pMET:total MET protein ratio decreased with foretinib treatment.These results indicate that few gastric carcinomas are driven solely by MET and VEGFR2, and underscore the diverse molecular oncogenesis of this disease. Despite evidence of MET inhibition by foretinib, single-agent foretinib lacked efficacy in unselected patients with metastatic gastric cancer.

    View details for DOI 10.1371/journal.pone.0054014

    View details for Web of Science ID 000316407400003

    View details for PubMedID 23516391

  • Everolimus Causing Severe Hypertriglyceridemia and Acute Pancreatitis JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Subramaniam, S., Zell, J. A., Kunz, P. L. 2013; 11 (1): 5-9

    Abstract

    Everolimus is an mTOR inhibitor commonly used to treat metastatic pancreatic neuroendocrine tumors (pNETs) and renal cell carcinoma, and for posttransplant immunosuppression. This report presents a case of a 36-year-old man being treated with everolimus for a metastatic pNET who developed severe hypertriglyceridemia and acute pancreatitis. The incidence of hypertriglyceridemia reported in large prospective randomized trials is reviewed and the management of hypertriglyceridemic pancreatitis is discussed. Careful monitoring of triglyceride levels and dose adjustments of everolimus together with lipid-lowering therapy can allow patients to continue this medication. Because there are increasing indications for the use of everolimus, prescribing oncologists must be cognizant of the common and serious side effects.

    View details for Web of Science ID 000313575200003

    View details for PubMedID 23307976

  • Phase I trial of ixabepilone administered as three oral doses each separated by 6 hours every 3 weeks in patients with advanced solid tumors INVESTIGATIONAL NEW DRUGS Kunz, P. L., He, A. R., Colevas, A. D., Pishvaian, M. J., Hwang, J. J., Clemens, P. L., Messina, M., Kaleta, R., Abrahao, F., Sikic, B. I., Marshall, J. L. 2012; 30 (6): 2364-2370

    Abstract

    Ixabepilone, which stabilizes microtubules, has low susceptibility to drug resistance mediated by P-glycoprotein or ?III-tubulin.This study was designed to determine the maximum tolerated dose (MTD) of oral ixabepilone when administered every 6 h for three doses, every 3 weeks, to patients with refractory advanced cancers. Eighteen patients were treated with escalating doses of ixabepilone: three at cohort 1 (30 mg/dose; 90 mg on Day 1), nine at cohort 2 (40 mg/dose; 120 mg on Day 1), and six at cohort 3 (50 mg/dose; 150 mg on Day 1). Serial plasma samples were collected during cycle 1 for pharmacokinetic (PK) measurements.Of the 18 treated patients, eight were male and ten were female. The median age was 59 years, and most had an excellent performance status (KPS 90-100; 61%). There were two dose limiting toxicities (DLT): Grade 4 febrile neutropenia at the 120 mg dose and Grade 4 neutropenic sepsis at the 150 mg dose. Because of the severity and duration of neutropenic sepsis at level 3, level 2 (120 mg) was defined as the MTD and this cohort was expanded to nine patients. High inter-individual variability in plasma drug concentrations was observed during the study, with particularly high levels in two patients with DLT.On the basis of this safety profile, the MTD of oral ixabepilone was defined as 120 mg given as three 40 mg doses each separated by 6 h on Day 1 of a 3-week cycle. However, the PK variability observed makes further development of this oral formulation unlikely.

    View details for DOI 10.1007/s10637-012-9800-3

    View details for Web of Science ID 000310470100028

    View details for PubMedID 22331549

  • Neoadjuvant Imatinib for Borderline Resectable GIST JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Koontz, M. Z., Visser, B. M., Kunz, P. L. 2012; 10 (12): 1477-1482

    Abstract

    A 36-year-old woman presented to the emergency department with black stools and syncope. Her hemoglobin was 7.0 and her red blood cells were microcytic. Upper endoscopy did not identify a clear source of bleeding, but a bulge in the third portion of the duodenum was noted. A CT scan showed a large extraintestinal mass, and follow-up esophagogastroduodenoscopy/endoscopic ultrasound with biopsy revealed a spindle cell neoplasm, consistent with gastrointestinal stromal tumor (GIST). Because of the size of the lesion and association with the superior mesenteric vein and common bile duct, she was referred to medical oncology for consideration of neoadjuvant imatinib. Neoadjuvant tyrosine kinase inhibitor therapy for GISTs is emerging as a viable treatment strategy for borderline resectable tumors, although the dose, duration, and optimal imaging modalities have not been clearly established. Recent pathologic and radiographic data have provided insight into the mechanism and kinetics of this approach. This case report presents a patient for whom surgery was facilitated using neoadjuvant imatinib.

    View details for Web of Science ID 000312114200004

    View details for PubMedID 23221786

  • Capecitabine-Induced Chest Pain Relieved by Diltiazem AMERICAN JOURNAL OF CARDIOLOGY Ambrosy, A. P., Kunz, P. L., Fisher, G. A., Witteles, R. M. 2012; 110 (11): 1623-1626

    Abstract

    Five patients with primary colorectal adenocarcinoma or anal squamous cell carcinoma were started on a 2-weeks-on, 1-week-off capecitabine dosing regimen in addition to other chemotherapeutic agents and/or radiation. Within the first few doses, patients experienced chest pain and/or dyspnea at rest or with exertion. Acute electrocardiographic findings suggestive of ischemia were found in some cases at initial presentation, and 1 patient had troponin elevation consistent with an acute ST-segment elevation myocardial infarction. Subsequent ischemia evaluations were not suggestive of clinically significant coronary artery disease. All patients experienced immediate and sustained relief from chest pain after discontinuation of capecitabine and were able to successfully tolerate retreatment using a novel management strategy based on secondary prophylaxis with diltiazem. In conclusion, guidelines for the evaluation of and therapy for capecitabine-induced chest pain are proposed.

    View details for DOI 10.1016/j.amjcard.2012.07.026

    View details for Web of Science ID 000311868000011

    View details for PubMedID 22939579

  • Long-Term Survivors of Gastric Cancer: A California Population-Based Study JOURNAL OF CLINICAL ONCOLOGY Kunz, P. L., Gubens, M., Fisher, G. A., Ford, J. M., Lichtensztajn, D. Y., Clarke, C. A. 2012; 30 (28): 3507-3515

    Abstract

    In the United States, gastric cancer is rapidly fatal with a 25% 5-year survival. Of the few patients who survive, little is known about their demographic, clinical, and tumor characteristics.Data regarding all cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed in California between 1988 and 2005 were obtained from the California Cancer Registry, a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. A Cox proportional hazards model was constructed to understand the independent relationships of patient demographic, disease, and treatment factors with survival.We identified 47,647 patients diagnosed with gastric or GEJ cancer. Of those, only 9,325 (20%) survived at least 3 years. Variables associated with longer survival were localized stage (hazard ratio [HR], 0.20), surgery with diagnosis in 2002 or later (HR, 0.34), surgery with diagnosis in 2001 or before (0.37), regional stage (HR, 0.53), chemotherapy (HR, 0.56), intestinal histology (HR, 0.74), well- or moderately differentiated tumors (HR, 0.76), radiation (HR, 0.80), Asian/Pacific Islander race (HR, 0.81), treatment at an academic hospital (HR, 0.85), fundus/body/antrum location (HR, 0.90), highest socioeconomic status quintile (HR, 0.91), female sex (HR, 0.92), Hispanic race (HR, 0.92), and hospital size more than 150 beds (HR, 0.94). Kaplan-Meier curves showed longer median disease-specific survival (DSS) in patients with tumors originating in the fundus/body/antrum compared with esophagus/cardia (13.4 v 10.8 months). Intestinal histology had significantly longer median DSS (28.9 months) compared with other (11.0 months) or diffuse (10.1 months) histology.Patients who survive gastric and GEJ cancer more than 3 years after diagnosis have demographic and pathologic characteristics distinct from those who do not survive.

    View details for DOI 10.1200/JCO.2011.35.8028

    View details for Web of Science ID 000309517700016

    View details for PubMedID 22949151

  • Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features MODERN PATHOLOGY Chang, D. T., Pai, R. K., Rybicki, L. A., DiMaio, M. A., Limaye, M., Jayachandran, P., Koong, A. C., Kunz, P. A., Fisher, G. A., Ford, J. M., Welton, M., Shelton, A., Ma, L., Arber, D. A., Pai, R. K. 2012; 25 (8): 1128-1139

    Abstract

    Recent literature suggests an increasing incidence of colorectal carcinoma in young patients. We performed a histologic, molecular, and immunophenotypic analysis of patients with sporadic early-onset (?40 years of age) colorectal carcinoma seen at our institution from the years 2000-2010 and compared these tumors to a cohort of consecutively resected colorectal carcinomas seen in patients >40 years of age. A total of 1160 primary colorectal adenocarcinomas were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were diagnoses in patients ?40 years of age of which 13 (17%) demonstrated abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline genetic disorders (two patients with familial adenomatous polyposis, one patient with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160, 5%) and were compared with a control group comprising 73 consecutively resected colorectal carcinomas with proficient DNA mismatch repair in patients >40 years of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%) were diagnosed between the age of 35 and 40 years of age. Compared with the control group, the early-onset colorectal carcinoma group was significantly different with respect to tumor location (P<0.007) with 80% (44/55 cases) identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%). Morphologically, early-onset colorectal carcinomas more frequently displayed adverse histologic features compared with the control colorectal carcinoma group such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P=0.021), perineural invasion (16/55, 29% vs 8/73, 11%, P=0.009) and venous invasion (12/55, 22% vs 4/73, 6%, P=0.006). A precursor adenomatous lesion was less frequently identified in the early-onset colorectal carcinoma group compared with the control group (19/55, 35% vs 39/73, 53%, P=0.034). Of the early-onset colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS mutations, although this difference did not reach statistical significance (P=0.13). BRAF V600E mutations were not identified in the early-onset colorectal carcinoma group. No difference was identified between the two groups with regard to tumor stage, tumor size, number of lymph node metastases, lymphatic invasion, tumor budding, mucinous histology, or tumor-infiltrating lymphocytes. Both groups had similar recurrence-free (P=0.28) and overall survival (P=0.73). However, patients in the early-onset colorectal carcinoma group more frequently either presented with or developed metastatic disease during their disease course compared with the control colorectal carcinoma group (25/55, 45% vs 18/73, 25%, P=0.014). In addition, 8/55 patients (15%) in the early-onset colorectal carcinoma group developed local recurrence of their tumor while no patients in the control colorectal carcinoma group developed local recurrence (P<0.001), likely due to the increased incidence of rectal carcinoma in the patients with early-onset colorectal carcinoma. Our study demonstrates that colorectal carcinoma is not infrequently diagnosed in patients ?40 years of age and is not frequently the result of underlying Lynch syndrome or associated with other cancer-predisposing genetic conditions or chronic inflammatory conditions. These tumors have a striking predilection for the distal colon, particularly the sigmoid colon and rectum and are much more likely to demonstrate adverse histologic factors, including signet ring cell differentiation, venous invasion, and perineural invasion.

    View details for DOI 10.1038/modpathol.2012.61

    View details for Web of Science ID 000307222200008

    View details for PubMedID 22481281

  • Pancreatic Neuroendocrine Tumors: Radiographic Calcifications Correlate with Grade and Metastasis ANNALS OF SURGICAL ONCOLOGY Poultsides, G. A., Huang, L. C., Chen, Y., Visser, B. C., Pai, R. K., Jeffrey, R. B., Park, W. G., Chen, A. M., Kunz, P. L., Fisher, G. A., Norton, J. A. 2012; 19 (7): 2295-2303

    Abstract

    Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear.From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival.Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications.Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.

    View details for DOI 10.1245/s10434-012-2305-7

    View details for Web of Science ID 000305558000030

    View details for PubMedID 22396008

  • Neuroendocrine Tumors Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Kulke, M. H., Benson, A. B., Bergsland, E., Berlin, J. D., Blaszkowsky, L. S., Choti, M. A., Clark, O. H., Doherty, G. M., Eason, J., Emerson, L., Engstrom, P. F., Goldner, W. S., Heslin, M. J., Kandeel, F., Kunz, P. L., Kuvshinoff, B. W., Moley, J. F., Pillarisetty, V. G., Saltz, L., Schteingart, D. E., Shah, M. H., Shibata, S., Strosberg, J. R., Vauthey, J., White, R., Yao, J. C., Freedman-Cass, D. A., Dwyer, M. A. 2012; 10 (6): 724-764
  • HER2 Expression in Gastric and Gastroesophageal Junction Adenocarcinoma in a US Population: Clinicopathologic Analysis With Proposed Approach to HER2 Assessment APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Kunz, P. L., Mojtahed, A., Fisher, G. A., Ford, J. M., Chang, D. T., Balise, R. R., Bangs, C. D., Cherry, A. M., Pai, R. K. 2012; 20 (1): 13-24

    Abstract

    Recent evidence suggests that trastuzumab, a monoclonal antibody which targets HER2, in combination with chemotherapy is a therapeutic option in patients with HER2-positive gastric or gastroesophageal junction cancer. Widely accepted guidelines for HER2 testing in gastric and gastroesophageal junction cancer have not been established. The purpose of this study was to analyze the incidence and patterns of HER2 expression in gastric and gastroesophageal junction cancer using a tissue microarray approach, which closely simulates small biopsies routinely tested for HER2. One hundred sixty-nine patients, including 99 primary gastric adenocarcinomas and 70 primary gastroesophageal junction carcinomas were analyzed for HER2 overexpression by immunohistochemistry and HER2 gene amplification by fluorescence in situ hybridization using scoring schemes proposed by both American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) and the results of the recently published Trastuzumab for Gastric Cancer (ToGA) trial. In our analysis, 19 adenocarcinomas were HER2 positive, defined as either a HER2/CEP17 ratio >2.2 and/or a 3+ HER2 immunohistochemistry score with either the ASCO/CAP or ToGA scoring schemes. Of the 19 HER2-positive adenocarcinomas, 8 (42%) exhibited a characteristic strongly intense basolateral membranous staining pattern which would be interpreted as negative (1+) using the accepted ASCO/CAP scoring scheme for HER2 assessment in breast carcinoma, but were correctly labeled as 3+ positive using the proposed ToGA scoring scheme. Of the 19 HER2-positive adenocarcinomas, 8 (42%) demonstrated heterogeneous HER2 protein expression by immunohistochemistry. Twelve of 99 (12%) gastric carcinomas were positive for HER2. Of these, HER2 was more often identified in intestinal-type adenocarcinomas (10 of 52, 19%) compared with diffuse (2 of 34, 6%) adenocarcinoma. Seven of 70 (10%) gastroesophageal junction carcinomas were positive for HER2 of which all were intestinal type (7 of 58, 12%). HER2 status or primary tumor site did not correlate with patient survival. Gastric and gastroesophageal junction adenocarcinomas typically display a characteristic basolateral membranous pattern of HER2 expression which is often heterogeneous rendering routine evaluation of HER2 status on small tissue samples challenging.

    View details for DOI 10.1097/PAI.0b013e31821c821c

    View details for Web of Science ID 000298846500003

    View details for PubMedID 21617522

  • SINGLE-FRACTION STEREOTACTIC BODY RADIATION THERAPY AND SEQUENTIAL GEMCITABINE FOR THE TREATMENT OF LOCALLY ADVANCED PANCREATIC CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Schellenberg, D., Kim, J., Ciristman-Skieller, C., Chun, C. L., Columbo, L. A., Ford, J. M., Fisher, G. A., Kunz, P. L., Van Dam, J., Quon, A., Desser, T. S., Norton, J., Hsu, A., Maxim, P. G., Xing, L., Goodman, K. A., Chang, D. T., Koong, A. C. 2011; 81 (1): 181-188

    Abstract

    This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT).Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT.All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year.Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

    View details for DOI 10.1016/j.ijrobp.2010.05.006

    View details for Web of Science ID 000294093300025

    View details for PubMedID 21549517

  • Intensity-Modulated Radiation Therapy Versus Conventional Radiation Therapy for Squamous Cell Carcinoma of the Anal Canal CANCER Bazan, J. G., Hara, W., Hsu, A., Kunz, P. A., Ford, J., Fisher, G. A., Welton, M. L., Shelton, A., Kapp, D. S., Koong, A. C., Goodman, K. A., Chang, D. T. 2011; 117 (15): 3342-3351

    Abstract

    The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).Forty-six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty-five patients received 5-fluorouracil with mitomycin C (n = 39) or cisplatin (n = 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow-up was 26 months (CRT) and 32 months (IMRT). T3-T4 stage (P = .18) and lymph node-positive disease (P = .6) were similar between groups.The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P = .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P = .003). The 3-year overall survival (OS), locoregional control (LRC), and progression-free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC.The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal.

    View details for DOI 10.1002/cncr.25901

    View details for Web of Science ID 000293103800008

    View details for PubMedID 21287530

  • Pancreatic Endocrine Tumors With Major Vascular Abutment, Involvement, or Encasement and Indication for Resection ARCHIVES OF SURGERY Norton, J. A., Harris, E. J., Chen, Y., Visser, B. C., Poultsides, G. A., Kunz, P. C., Fisher, G. A., Jensen, R. T. 2011; 146 (6): 724-732

    Abstract

    Surgery for pancreatic endocrine tumors (PETs) with blood vessel involvement is controversial.Resection of PETs with major blood vessel involvement can be beneficial.The combined databases of the National Institutes of Health and Stanford University hospitals were queried.Operation, pathologic condition, complications, and disease-free and overall survival.Of 273 patients with PETs, 46 (17%) had preoperative computed tomography evidence of major vascular involvement. The mean size for the primary PET was 5.0 cm. The involved major vessel was as follows: portal vein (n = 20), superior mesenteric vein or superior mesenteric artery (n = 16), inferior vena cava (n = 4), splenic vein (n = 4), and heart (n = 2). Forty-two of 46 patients had a PET removed: 12 (27%) primary only, 30 (68%) with lymph nodes, and 18 (41%) with liver metastases. PETs were removed by either enucleation (n = 7) or resection (n = 35). Resections included distal or subtotal pancreatectomy in 23, Whipple in 10, and total in 2. Eighteen patients had concomitant liver resection: 10 wedge resection and 8 anatomic resections. Nine patients had vascular reconstruction: each had reconstruction of the superior mesenteric vein and portal vein, and 1 had concomitant reconstruction of the superior mesenteric artery. There were no deaths, but 12 patients had complications. Eighteen patients (41%) were immediately disease free, and 5 recurred with follow-up, leaving 13 (30%) disease-free long term. The 10-year overall survival was 60%. Functional tumors were associated with a better overall survival (P < .001), and liver metastases decreased overall survival (P < .001).These findings suggest that surgical resection of PETs with vascular abutment/invasion and nodal or distant metastases is indicated.

    View details for Web of Science ID 000291851500018

    View details for PubMedID 21690450

  • F-18-5-fluorouracil dynamic positron emission tomography/computed tomography shows decreased tracer activity after bevacizumab in colorectal metastases NUCLEAR MEDICINE COMMUNICATIONS Zissen, M. H., Kunz, P., Subbarayan, M., Chin, F. T., Conti, P. S., Fisher, G. A., Quon, A. 2011; 32 (5): 343-347

    Abstract

    The aim of this study was to evaluate the potential of fluorine-18 (F)-5-fluorouracil (F-5-FU) positron emission tomography/computed tomography (PET/CT) to show differences in 5-FU activity in metastatic colorectal cancer before and after treatment with bevacizumab.This was a pilot study of five patients with newly diagnosed and untreated metastatic colorectal adenocarcinoma. The presence of cancer was confirmed by histopathological analysis before enrollment. Patients underwent F-5-FU PET/CT scanning before treatment and at approximately 24 h postbevacizumab. PET/CT scanning consisted of a dynamic acquisition of images taken 0-20 min after injection of radiotracer. The degree of F-5-FU activity at the metastatic sites was assessed using visual interpretation and semiquantitative standardized uptake value analyses.The sizes of the metastatic lesions ranged from the smallest lesion measuring 3.04 × 1.50 cm to the largest measuring 4.19 × 2.76 cm. By drawing regions of interest, time-activity curves were generated at each tumor site and area under the curve (AUC) analyses were carried out. At baseline, during the first 5 min after F-5-FU injection the mean AUCtumor/AUCaorta ratio was 1.24 ± 0.30 (range, 0.424-2.14). Less than 24 h after the administration of bevacizumab, the AUCtumor/AUCaorta ratio decreased to 1.06 ± 0.32 (range, 0.23-2.13, P=0.04), which represented an average decline of 20.2% (range, 0.4-45%). Radiotracer uptake on the 5, 10, 15, and 20-min images did not show any significant change between baseline and posttreatment. Follow-up CT imaging showed stable tumor size in one patient and a decrease in metastasis size in the remaining four patients.In this pilot study of five patients with metastatic colorectal carcinoma, F-5-FU PET/CT scanning showed a significant perfusion-related decrease in tracer activity 24 h postbevacizumab.

    View details for DOI 10.1097/MNM.0b013e328344894b

    View details for Web of Science ID 000289761500003

    View details for PubMedID 21412178

  • (18)FLUORODEOXYGLUCOSE PET IS PROGNOSTIC OF PROGRESSION-FREE AND OVERALL SURVIVAL IN LOCALLY ADVANCED PANCREAS CANCER TREATED WITH STEREOTACTIC RADIOTHERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Schellenberg, D., Quon, A., Minn, A. Y., Graves, E. E., Kunz, P., Ford, J. M., Fisher, G. A., Goodman, K. A., Koong, A. C., Chang, D. T. 2010; 77 (5): 1420-1425

    Abstract

    This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT).Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed.For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03).PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.

    View details for DOI 10.1016/j.ijrobp.2009.06.049

    View details for Web of Science ID 000280459700020

    View details for PubMedID 20056345

  • Pathological response after chemoradiation for T3 rectal cancer COLORECTAL DISEASE Chennupati, S. K., Kamaya, A., Fisher, G. A., Ford, J. M., Kunz, P., Itakura, H., Welton, M. L., Shelton, A., Van Dam, J., Koong, A. C., Chang, D. T. 2010; 12 (7): E24-E30
  • Pathological response after chemoradiation for T3 rectal cancer. Colorectal disease Chennupati, S. K., Kamaya, A., Fisher, G. A., Ford, J. M., Kunz, P., Itakura, H., Welton, M. L., Shelton, A., Van Dam, J., Koong, A. C., Chang, D. T. 2010; 12 (7 Online): e24-30

    Abstract

    The aim of this study was to investigate the effect of preoperative chemoradiotherapy (CRT) on nodal disease in locally advanced rectal adenocarcinoma.Thirty-two patients staged uT3N0 and 27 patients staged uT3N1 rectal adenocarcinoma who underwent pre-CRT staging using endoscopic ultrasound or rectal protocol CT were included. The median radiation dose was 50.4 Gy (range: 45-50.4 Gy) at 1.8 Gy per fraction and all patients received concurrent 5-FU or capecitabine-based chemotherapy. Low anterior resection or abdomino-perineal resection occurred at a median of 46 days (range: 27-112 days) after CRT.Eleven of 32 uT3N0 patients (34.4%) and 13 of 26 uT3N1 patients (50.0%) had ypN+ (P = 0.29). For patients with uT3N0, 10 of 20 (50.0%) with ypT2-3 and 1 of 12 (8.3%) with ypT0-1 were ypN+ (P = 0.02). For patients with uT3N1, 12 of 20 (60.0%) with ypT2-3 and 1 of 6 (16.7%) with ypT0-1 were ypN+ (P = 0.16). Overall, the ypN+ rate was 11.1% in the ypT0-yT1 group compared with 55.0% in the ypT2-yT3 group (P = 003). Among patients with uT3N0 disease, the ypN+ rate in patients who had surgery > 46 days vs 46 days vs 46 days vs

    View details for DOI 10.1111/j.1463-1318.2009.02013.x

    View details for PubMedID 19614668

  • Advances in the treatment of gastroenteropancreatic neuroendocrine tumors. Clinical and experimental gastroenterology Kunz, P. L., Fisher, G. A. 2010; 3: 79-86

    Abstract

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare and heterogeneous class of neoplasms. While surgical resection is the mainstay of treatment, non-surgical therapies play a role in the setting of unresectable and metastatic disease. The goals of medical therapy are directed both at alleviating symptoms of peptide release and shrinking tumor mass. Biotherapies such as somatostatin analogs and interferon can decrease the secretion of peptides and inhibit their end-organ effects. A second objective for treatment of unresectable GEP-NETs is limiting tumor growth. Options for limiting tumor growth include somatostatin analogs, systemic chemotherapy, locoregional therapies, ionizing radiation, external beam radiation, and newer targeted agents. In particular, angiogenesis inhibitors, tyrosine kinase inhibitors, and mTOR inhibitors have shown early promising results. The rarity of these tumors, their resistance to standard chemotherapy, and the excellent performance status of most of these patients, make a strong argument for consideration of novel therapeutic trials.

    View details for PubMedID 21694850

  • Multimodality treatment with intensity modulated radiation therapy for esophageal cancer DISEASES OF THE ESOPHAGUS La, T. H., Minn, A. Y., Su, Z., Fisher, G. A., Ford, J. M., Kunz, P., Goodman, K. A., Koong, A. C., Chang, D. T. 2010; 23 (4): 300-308

    Abstract

    The objective of this study is to determine the feasibility and report the outcome of patients with locally advanced esophageal cancer treated with preoperative or definitive chemoradiotherapy (CRT) using intensity-modulated radiation therapy (IMRT). Between 2003 and 2007, 30 patients with non-cervical esophageal cancer received concurrent chemotherapy and IMRT at Stanford University. Eighteen patients were planned for definitive CRT and 12 were planned for preoperative CRT. All patients had computed tomography-based treatment planning and received IMRT. The median dose delivered was 50.4 Gy. Patients planned for preoperative CRT underwent surgery 4-13 weeks (median 8.3 weeks) following completion of CRT. Median follow-up of surviving patients from start of RT was 24.2 months (range 8.2-38.3 months). The majority of tumors were adenocarcinomas (67%) and poorly differentiated (57%). Tumor location was 7% upper, 20% mid, 47% lower, and 27% gastroesophageal junction. Actuarial 2-year local-regional control (LRC) was 64%. High tumor grade was an adverse prognostic factor for LRC and overall survival (OS) (P= 0.015 and 0.012, respectively). The 2-year LRC was 83% vs. 51% for patients treated preoperatively vs. definitively (P= 0.32). The 2-year disease-free and OS were 38% and 56%, respectively. Twelve patients (40%) required feeding tube placement, and the average weight loss from baseline was 4.8%. Twelve (40%) patients experienced grade 3+ acute complications and one patient died of complications following feeding tube placement. Three patients (10%) required a treatment break. Eight patients (27%) experienced grade 3 late complications. No grade 4 complications were seen. IMRT was effective and well tolerated. Disease recurrence remains a challenge and further investigation with dose escalation to improve LRC and OS is warranted.

    View details for DOI 10.1111/j.1442-2050.2009.01004.x

    View details for Web of Science ID 000278109300005

    View details for PubMedID 19732129

  • Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis JOURNAL OF TRANSLATIONAL MEDICINE Chang, S. T., Zahn, J. M., Horecka, J., Kunz, P. L., Ford, J. M., Fisher, G. A., Le, Q. T., Chang, D. T., Ji, H., Koong, A. C. 2009; 7

    Abstract

    Pancreatic cancer continues to prove difficult to clinically diagnose. Multiple simultaneous measurements of plasma biomarkers can increase sensitivity and selectivity of diagnosis. Proximity ligation assay (PLA) is a highly sensitive technique for multiplex detection of biomarkers in plasma with little or no interfering background signal.We examined the plasma levels of 21 biomarkers in a clinically defined cohort of 52 locally advanced (Stage II/III) pancreatic ductal adenocarcinoma cases and 43 age-matched controls using a multiplex proximity ligation assay. The optimal biomarker panel for diagnosis was computed using a combination of the PAM algorithm and logistic regression modeling. Biomarkers that were significantly prognostic for survival in combination were determined using univariate and multivariate Cox survival models.Three markers, CA19-9, OPN and CHI3L1, measured in multiplex were found to have superior sensitivity for pancreatic cancer vs. CA19-9 alone (93% vs. 80%). In addition, we identified two markers, CEA and CA125, that when measured simultaneously have prognostic significance for survival for this clinical stage of pancreatic cancer (p < 0.003).A multiplex panel assaying CA19-9, OPN and CHI3L1 in plasma improves accuracy of pancreatic cancer diagnosis. A panel assaying CEA and CA125 in plasma can predict survival for this clinical cohort of pancreatic cancer patients.

    View details for DOI 10.1186/1479-5876-7-105

    View details for Web of Science ID 000272889900001

    View details for PubMedID 20003342

  • Escherichia coli O157 : H7 infection in nursing homes: Review of literature and report of recent outbreak JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Reiss, G., Kunz, P., Koin, D., Keeffe, E. B. 2006; 54 (4): 680-684

    Abstract

    Escherichia coli O157:H7 is a well-described cause of hemorrhagic colitis in isolated cases and outbreaks. The postdiarrhea complications of this infection (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) have historically been linked to illness in children aged 5 to 10, but in an elderly, institutionalized population, E. coli O157:H7 is associated with high morbidity and mortality. This geriatric population is at high risk for developing gastrointestinal infections for a number of reasons, including age- and medication-related achlorhydria, antibiotic usage, and comorbid medical conditions. The combination of age-related risk factors with those associated with group living makes nursing facilities a high-risk environment for outbreaks of infectious diseases. E. coli O157:H7 may be more likely to cause disease outbreaks in this population because of the low inoculum required for clinical infection. Moreover, the prevalence of potential competing diagnoses, such as lower gastrointestinal bleeding from neoplastic or diverticular disease, complicates the diagnosis. Clinical presentation and laboratory studies are unpredictable and pose diagnostic challenges. This report reviews the literature on nursing home outbreaks of E. coli O157:H7 and presents an outbreak that occurred in an assisted living community in San Mateo County, California, in October 2003. The purpose of this literature review and report of an outbreak is to heighten awareness of the unique susceptibility of elderly, institutionalized patients for E. coli O157:H7 infection and its sequelae.

    View details for DOI 10.1111/j.1532-5415.2006.00682.x

    View details for Web of Science ID 000236585100018

    View details for PubMedID 16686882

  • Cost-effectiveness of photodynamic therapy for high-grade dysplasia in Barrett's esophagus GASTROINTESTINAL ENDOSCOPY Vij, R., Triadafilopoulos, G., Owens, D. K., Kunz, P., Sanders, G. D. 2004; 60 (5): 739-756

    Abstract

    Photodynamic therapy appears to be effective in ablating high-grade dysplasia in Barrett's esophagus. Our aim was to identify the most effective and cost-effective strategy for managing high-grade dysplasia in Barrett's esophagus without associated endoscopically visible abnormalities.By using decision analysis, the lifetime costs and benefits of 4 strategies for which long-term data exist were estimated by us: esophagectomy, endoscopic surveillance, photodynamic therapy, followed by esophagectomy for residual high-grade dysplasia; and photodynamic therapy followed by endoscopic surveillance for residual high-grade dysplasia. It was assumed by us that there was a 30% prevalence of cancer in high-grade dysplasia patients and a 77% efficacy of photodynamic therapy for high-grade dysplasia and early cancer.Esophagectomy cost 24,045 dollars, with life expectancy of 11.82 quality-adjusted life years. In comparison, photodynamic therapy followed by surveillance for residual high-grade dysplasia was the most effective strategy, with a quality-adjusted life expectancy of 12.31 quality-adjusted life years, but it also incurred the greatest lifetime cost (47,310 dollars) for an incremental cost-effectiveness of 47,410 dollars/quality-adjusted life years. The results were sensitive to post-surgical quality of life and survival, and to cancer prevalence if photodynamic therapy efficacy for cancer was less than 50%.Photodynamic therapy followed by endoscopic surveillance for residual high-grade dysplasia appears to be cost effective compared with esophagectomy for patients diagnosed with high-grade dysplasia in Barrett's esophagus. Clinical trials directly comparing these strategies are warranted.

    View details for Web of Science ID 000225449000010

    View details for PubMedID 15557950

  • Tandem mass spectrometry and newborn screening: Pilot data and review PEDIATRIC NEUROLOGY Filiano, J. J., Bellimer, S. G., Kunz, P. L. 2002; 26 (3): 201-204

    Abstract

    United States legislatures are debating whether to use tandem mass spectrometry to expand the roster of inherited disorders tested in newborn screening programs. The debate is hampered because published financial data comparing charges associated with late vs early diagnosis are not readily available. We provide pilot financial data comparing late diagnosis vs presumptive diagnosis and early management taken from consecutive patients with propionic acidemia diagnosed from 1995-1998 in New Hampshire. We extrapolated from these data and the incidence of treatable inborn errors of metabolism to estimate the projected yearly savings of critical care charges if expanded newborn screening were instituted. We conclude that institution of expanded screening will bring diminished morbidity and large savings in yearly chronic care and critical care charges.

    View details for Web of Science ID 000175077500005

    View details for PubMedID 11955927

  • Molecular analysis and prenatal diagnosis of human fumarase deficiency MOLECULAR GENETICS AND METABOLISM Coughlin, E. M., Christensen, E., Kunz, P. L., Krishnamoorthy, K. S., Walker, V., Dennis, N. R., Chalmers, R. A., Elpeleg, O. N., Whelan, D., Pollitt, R. J., Ramesh, V., Mandell, R., Shih, V. E. 1998; 63 (4): 254-262

    Abstract

    Fumarase deficiency is a rare autosomal recessive disorder of the citric acid cycle causing severe neurological impairment. The cDNA for both the rat and human enzymes has been cloned previously and shown to encode a coding region of 1.46 kb. To scan for mutations in fumarase-deficient patients we amplified the coding region of fumarase from fibroblast/lymphoblast cDNA employing the oligonucleotide primers designed from the published human and rat cDNA sequence. We then directly sequenced the polymerase chain reaction product. In seven unrelated patients, we detected four missense mutations (A265T, D383V, F269C, K187R), a nonsense mutation (W458X), a 3-bp AAA insertion that introduces an additional lysine residue at codon 435, and a spontaneous new mutation resulting in a 74-bp deletion (66del74). Seven at-risk pregnancies were monitored with one prenatal diagnosis of fumarase deficiency by molecular analysis and favorable outcome of the other pregnancies as predicted by enzyme assay of cultured fetal cells or molecular analysis.

    View details for Web of Science ID 000074266300002

    View details for PubMedID 9635293

Conference Proceedings


  • Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma Abelson, J. A., Murphy, J. D., Minn, A. Y., Chung, M., Fisher, G. A., Ford, J. M., Kunz, P., Norton, J. A., Visser, B. C., Poultsides, G. A., Koong, A. C., Chang, D. T. ELSEVIER SCIENCE INC. 2012: E595-E601

    Abstract

    To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma.Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively.The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%).Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

    View details for DOI 10.1016/j.ijrobp.2011.09.035

    View details for Web of Science ID 000300980300003

    View details for PubMedID 22197234

  • Expression of p16(INK4A) But Not Hypoxia Markers or Poly Adenosine Diphosphate-Ribose Polymerase Is Associated With Improved Survival in Patients With Pancreatic Adenocarcinoma Chang, D. T., Chapman, C. H., Norton, J. A., Visser, B., Fisher, G. A., Kunz, P., Ford, J. M., Koong, A. C., Pai, R. K. WILEY-BLACKWELL. 2010: 5179-5187

    Abstract

    Pancreatic cancer is associated with mutations in the tumor suppressor gene cyclin-dependent kinase inhibitor 2A (p16(INK4A) ), a regulator of the cell cycle and apoptosis. This study investigates whether immunohistochemical expression of p16(INK4A) as well as hypoxia markers and poly adenosine diphosphate-ribose polymerase (PARP) correlates with survival in patients with resected pancreatic adenocarcinoma.Seventy-three patients with pancreatic adenocarcinoma who underwent curative resection at Stanford University were included. From the surgical specimens, a tissue microarray was constructed using triplicate tissue cores from the primary tumor and used for immunohistochemical staining for the following markers: carbonic anhydrase IX, dihydrofolate reductase, p16(INK4A) , and PARP1/2. Staining was scored as either positive or negative and percentage positive staining. Staining score was correlated with overall survival (OS) and progression-free survival (PFS).Of the markers tested, only immunohistochemical expression of p16(INK4A) correlated with clinical outcome. On univariate analysis, p16(INK4A) expression in the tumor was associated with improved OS (P = .038) but not PFS (P = .28). The median survival for patients with positive versus negative p16(INK4A) staining was 28.8 months versus 18 months. On multivariate analysis, p16(INK4A) expression was associated with improved OS (P = .026) but not PFS (P = .25). Age (P = .0019) and number of nodes involved (P = .025) were also significant for OS. Adjuvant chemotherapy and margin status did not correlate with OS or PFS.Expression of p16(INK4A) is associated with improved OS in patients with resected pancreatic adenocarcinoma. Further investigation is needed for validation, given conflicting data in the published literature. .

    View details for DOI 10.1002/cncr.25481

    View details for Web of Science ID 000284047400009

    View details for PubMedID 20665497

  • Comparison of Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy as Adjuvant Therapy for Gastric Cancer Minn, A. Y., Hsu, A., La, T., Kunz, P., Fisher, G. A., Ford, J. M., Norton, J. A., Visser, B., Goodman, K. A., Koong, A. C., Chang, D. T. JOHN WILEY & SONS INC. 2010: 3943-3952

    Abstract

    The current study was performed to compare the clinical outcomes and toxicity in patients treated with postoperative chemoradiotherapy for gastric cancer using intensity-modulated radiotherapy (IMRT) versus 3-dimensional conformal radiotherapy (3D CRT).Fifty-seven patients with gastric or gastroesophageal junction cancer were treated postoperatively: 26 with 3D CRT and 31 with IMRT. Concurrent chemotherapy was capecitabine (n=31), 5-fluorouracil (5-FU) (n=25), or none (n=1). The median radiation dose was 45 Gy. Dose volume histogram parameters for kidney and liver were compared between treatment groups.The 2-year overall survival rates for 3D CRT versus IMRT were 51% and 65%, respectively (P=.5). Four locoregional failures occurred each in the 3D CRT (15%) and the IMRT (13%) patients. Grade>or=2 acute gastrointestinal toxicity was found to be similar between the 3D CRT and IMRT patients (61.5% vs 61.2%, respectively) but more treatment breaks were needed (3 vs 0, respectively). The median serum creatinine from before radiotherapy to most recent creatinine was unchanged in the IMRT group (0.80 mg/dL) but increased in the 3D CRT group from 0.80 mg/dL to 1.0 mg/dL (P=.02). The median kidney mean dose was higher in the IMRT versus the 3D CRT group (13.9 Gy vs 11.1 Gy; P=.05). The median kidney V20 was lower for the IMRT versus the 3D CRT group (17.5% vs 22%; P=.17). The median liver mean dose for IMRT and 3D CRT was 13.6 Gy and 18.6 Gy, respectively (P=.19). The median liver V30 was 16.1% and 28%, respectively (P<.001).Adjuvant chemoradiotherapy was well tolerated. IMRT was found to provide sparing to the liver and possibly renal function.

    View details for DOI 10.1002/cncr.25246

    View details for Web of Science ID 000280677100025

    View details for PubMedID 20564136

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