Kristen N Ganjoo

All Publications

• Detection of Circulating Tumor DNA in Patients With Uterine Leiomyomas JCO PRECISION ONCOLOGY Przybyl, J., Spans, L., Lum, D. A., Zhu, S., Vennam, S., Forgo, E., Varma, S., Ganjoo, K., Hastie, T., Bowen, R., Debiec-Rychter, M., van de Rijn, M. 2019; 3

  View details for DOI 10.1200/PO.18.00409

  View details for Web of Science ID 000491150900001

• Combination Approach for Detecting Different Types of Alterations in Circulating Tumor DNA in Leiomyosarcoma CLINICAL CANCER RESEARCH Przybyl, J., Chabon, J. J., Spans, L., Ganjoo, K. N., Vennam, S., Newman, A. M., Forgo, E., Varma, S., Zhu, S., Debiec-Rychter, M., Alizadeh, A. A., Diehn, M., van de Rijn, M. 2018; 24 (11): 2688?99

  View details for DOI 10.1158/1078-0432.CCR-17-3704

  View details for Web of Science ID 000433971400023

• Phase II Study of the Safety and Antitumor Activity of the Hypoxia-Activated Prodrug TH-302 in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma JOURNAL OF CLINICAL ONCOLOGY Chawla, S. P., Cranmer, L. D., Van Tine, B. A., Reed, D. R., Okuno, S. H., Butrynski, J. E., Adkins, D. R., Hendifar, A. E., Kroll, S., Ganjoo, K. N. 2014; 32 (29): 3299-?

  Abstract

  TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability.In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302.Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity.PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088).

  View details for DOI 10.1200/JCO.2013.54.3660

  View details for Web of Science ID 000342988000015

• 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

• Gastrointestinal stromal tumors, version 2.2014. Journal of the National Comprehensive Cancer Network von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Van Tine, B. A., Wayne, J. D., Bergman, M. A., Sundar, H. 2014; 12 (6): 853-862

  Abstract

  Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor ? (PDGFR?)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

  View details for PubMedID 24925196

• Soft Tissue Sarcoma, Version 2.2014 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Van Tine, B. A., Wayne, J. D., Bergman, M. A., Sundar, H. 2014; 12 (4): 473-483

  View details for Web of Science ID 000334014900006

• A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib. Annals of oncology Ganjoo, K. N., Villalobos, V. M., Kamaya, A., Fisher, G. A., Butrynski, J. E., Morgan, J. A., Wagner, A. J., D'adamo, D., McMillan, A., Demetri, G. D., George, S. 2014; 25 (1): 236-240

  Abstract

  Advanced GISTs are incurable, but often treatable for years with tyrosine kinase inhibitors (TKIs). The majority of GISTs harbor an oncogenic activating mutation in KIT or PDGFRA. Inhibition of this activating mutation with TKIs most often leads to durable disease control for many patients. However, almost all patients develop resistance to these TKIs, typically due to the development of secondary mutations, heralding the need for new therapeutic options. We conducted a phase II study evaluating the efficacy and toxicity of pazopanib, a broad spectrum TKI inhibiting KIT, VEGFRs (-1, -2, and -3), and PDGFR (-? and-?) in patients with advanced GIST following failure of at least imatinib and sunitinib.Patients received pazopanib 800 mg orally once daily. All patients were assessed for efficacy with CT scans every 8 weeks (two cycles). Patients continued pazopanib until progression or unacceptable toxicity. The primary end point was the 24-week nonprogression [complete response+partial response+stable disease (SD)] rate (NPR) per RECIST 1.1. Secondary end points included PFS, OS, and toxicity.Between August 2011 and September 2012, a total of 25 patients were treated at two institutions. Median number of prior therapy was 3 (range 2-7). A total of 90 cycles of pazopanib were administered, with a median of two cycles (range 1 to 17+) per patient. Best response of SD at any time was observed in 12 (48%) patients. The NPR was 17% [95% confidence interval (CI) 4.5-37]. All but one patient discontinued protocol either due to PD (n = 19) or intolerance (n = 4). One patient with succinate dehydrogenase (SDH)-deficient GIST exhibited continuing disease control after 17 cycles. The median PFS for the entire cohort was 1.9 months (95% CI 1.6-5.2), and the median OS was 10.7 months (95% CI 3.9-NR).Pazopanib was reasonably well tolerated with no unexpected toxicities. Pazopanib as a single agent has marginal activity in unselected heavily pretreated patients with advanced GIST.

  View details for DOI 10.1093/annonc/mdt484

  View details for PubMedID 24356634

• R1507, a Monoclonal Antibody to the Insulin-Like Growth Factor 1 Receptor, in Patients With Recurrent or Refractory Ewing Sarcoma Family of Tumors: Results of a Phase II Sarcoma Alliance for Research Through Collaboration Study JOURNAL OF CLINICAL ONCOLOGY Pappo, A. S., Patel, S. R., Crowley, J., Reinke, D. K., Kuenkele, K., Chawla, S. P., Toner, G. C., Maki, R. G., Meyers, P. A., Chugh, R., Ganjoo, K. N., Schuetze, S. M., Juergens, H., Leahy, M. G., Geoerger, B., Benjamin, R. S., Helman, L. J., Baker, L. H. 2011; 29 (34): 4541-4547

  Abstract

  The type 1 insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the pathogenesis of the Ewing sarcoma family of tumors (ESFT). We conducted a multicenter phase II study of the fully human IGF-1R monoclonal antibody R1507 in patients with recurrent or refractory ESFT.Patients ? 2 years of age with refractory or recurrent ESFT received R1507 at doses of 9 mg/kg intravenously one a week or 27 mg/kg intravenously every three weeks. Response was measured by using WHO criteria. Tumor imaging was performed every 6 weeks for 24 weeks and then every 12 weeks.From December 2007 through April 2010, 115 eligible patients from 31 different institutions were enrolled. The median age was 25 years (range, 8 to 78 years). The location of the primary tumor was bone in 57% of patients and extraskeletal in 43% of patients. A total of 109 patients were treated with R1507 9 mg/kg/wk, and six patients were treated with 27 mg/kg/3 wk. The overall complete response/partial response rate was 10% (95% CI, 4.9% to 16.5%). The median duration of response was 29 weeks (range, 12 to 94 weeks), and the median overall survival was 7.6 months (95% CI, 6 to 9.7 months). Ten of 11 responses were observed in patients who presented with primary bone tumors (P = .016). The most common adverse events of grades 3 to 4 were pain (15%), anemia (8%), thrombocytopenia (7%), and asthenia (5%).R1507 was a well-tolerated agent that had meaningful and durable benefit in a subgroup of patients with ESFT. The identification of markers that are predictive of a benefit is necessary to fully capitalize on this approach.

  View details for DOI 10.1200/JCO.2010.34.0000

  View details for Web of Science ID 000298136500021

  View details for PubMedID 22025149

• Current and Emerging Pharmacological Treatments for Gastrointestinal Stromal Tumour DRUGS Ganjoo, K. N., Patel, S. 2011; 71 (3): 321-330

  Abstract

  Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract, previously classified as leiomyosarcomas. Most GIST express KIT and the majority have mutations in the KIT gene. The most common KIT mutation occurs in the juxtamembrane domain of exon 11. These mutations lead to cellular proliferation and survival. GIST with exon 11 mutations respond better to tyrosine kinase inhibitors (TKIs) than those with exon 9 mutations. Most KIT-negative GIST express platelet-derived growth factor receptor (PDGFR)-?; however, a small percentage of GIST are negative for both KIT and PDGFR?. Imatinib and other TKIs have dramatically improved the outcome of patients with metastatic GIST. Newer and more advanced TKIs are under intense investigation as eventually all GIST patients develop resistant tumours. In addition, these drugs can be utilized in the preoperative setting for patients with unresectable localized tumours or those at high risk for surgical morbidity. TKIs have been given in the adjuvant setting for patients with resected tumours at high risk for recurrence. The duration of adjuvant therapy is currently under evaluation; however, it is possible that these patients would need to continue therapy indefinitely.

  View details for Web of Science ID 000288311600006

  View details for PubMedID 21319869

• A Phase I Study of the Safety and Pharmacokinetics of the Hypoxia-Activated Prodrug TH-302 in Combination with Doxorubicin in Patients with Advanced Soft Tissue Sarcoma ONCOLOGY Ganjoo, K. N., Cranmer, L. D., Butrynski, J. E., Rushing, D., Adkins, D., Okuno, S. H., Lorente, G., Kroll, S., Langmuir, V. K., Chawla, S. P. 2011; 80 (1-2): 50-56

  Abstract

  The purpose of this study was to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics and preliminary activity of TH-302, a hypoxia-activated prodrug, in combination with doxorubicin in patients with advanced soft tissue sarcoma. Patients andTH-302 was administered intravenously on days 1 and 8 and doxorubicin 75 mg/m² on day 1 (2 h after TH-302) of every 3-week cycle. TH-302 starting dose was 240 mg/m² with a classic 3 + 3 dose escalation. Pharmacokinetics were assessed on days 1 and 8 of cycle 1. Tumor assessments were performed after every second cycle.Sixteen patients enrolled. Prophylactic growth factor support was added due to grade 4 neutropenia. The MTD was 300 mg/m². DLTs at 340 mg/m² were neutropenia-associated infection and grade 4 thrombocytopenia. Common adverse events included fatigue, nausea and skin rash. There was no evidence of pharmacokinetic interaction between TH-302 and doxorubicin. Five of 15 (33%) evaluable patients had a partial response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria.The hematologic toxicity of doxorubicin is increased when combined with TH-302. This can be mitigated by prophylactic growth factor support. Toxicities were manageable and there was evidence of antitumor activity.

  View details for DOI 10.1159/000327739

  View details for Web of Science ID 000291753800007

  View details for PubMedID 21625179

• New Developments in Targeted Therapy for Soft Tissue Sarcoma CURRENT ONCOLOGY REPORTS Ganjoo, K. N. 2010; 12 (4): 261-265

  Abstract

  Soft tissue sarcomas (STS) are rare diseases, with an estimated 10,390 new cases in the United States in 2008. Unfortunately, only 50% are cured with surgical resection. The standard cytotoxic chemotherapeutic agents have not been successful in the treatment of metastatic disease. The standard single-agent chemotherapy for metastatic disease is doxorubicin, with only 20% to 25% response rates. The combination of doxorubicin with other agents, such as ifosfamide, has improved response rates, without any improvement in overall survival. New targeted therapies have shown some activity in STS; however, disease stabilization is seen more often than a true radiographic response. The combination of cytotoxic chemotherapy with more targeted and novel agents may be appropriate to improve outcome in these patients. The agents of interest in sarcomas at this time are multi-tyrosine kinase inhibitors, antiangiogenesis agents, inhibitors of mammalian target of rapamycin, hypoxia-activating prodrugs, insulin growth factor monoclonal antibodies, and tumor necrosis factor-related apoptosis-inducing ligand agonists.

  View details for DOI 10.1007/s11912-010-0107-2

  View details for Web of Science ID 000287500300007

  View details for PubMedID 20464642

• Soft Tissue Sarcoma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Demetri, G. D., Antonia, S., Benjamin, R. S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., Heslin, M. J., Hutchinson, R. J., Kane, J. M., Letson, G. D., McGarry, S. V., O'Donnell, R. J., Paz, I. B., Pfeifer, J. D., Pollock, R. E., Randall, R. L., Riedel, R. F., Schupak, K. D., Schwartz, H. S., Thornton, K., von Mehren, M., Wayne, J. 2010; 8 (6): 630-674

  View details for Web of Science ID 000279929100002

  View details for PubMedID 20581298

• NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Demetri, G. D., von Mehren, M., Antonescu, C. R., DeMatteo, R. P., Ganjoo, K. N., Maki, R. G., Pisters, P. W., Raut, C. P., Riedel, R. F., Schuetze, S., Sundar, H. M., Trent, J. C., Wayne, J. D. 2010; 8: S1-S43

  Abstract

  The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.

  View details for Web of Science ID 000279177400001

  View details for PubMedID 20457867

• Antiangiogenesis Agents in the Treatment of Soft Tissue Sarcomas CANCER Ganjoo, K., Jacobs, C. 2010; 116 (5): 1177-1183

  Abstract

  Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that includes >50 different subtypes, each with unique clinical and pathologic qualities. In general, there is a 50% cure rate, and most cures are achieved with complete surgical resection with or without radiation therapy. The results from chemotherapeutic agents for unresectable or metastatic disease have been disappointing with minimal long-term benefit. New targeted and novel agents are needed to improve response and survival. Tumor angiogenesis has been an intense focus in cancer therapy over the past decade. Several of numerous antiangiogenesis agents have been developed, and many already have been approved for the treatment of both solid and liquid tumors. Certain STSs are highly vascular tumors that often demonstrate angiogenesis markers. The objective of this review was to evaluate these angiogenesis markers in defining the role of angiogenesis in the treatment of patients with STS. In addition, the authors conducted an in-depth review of the results from using key antiangiogenesis agents in the treatment of STS.

  View details for DOI 10.1002/cncr.24859

  View details for Web of Science ID 000274772300006

  View details for PubMedID 20052715

• Trabectedin: an anticancer drug from the sea EXPERT OPINION ON PHARMACOTHERAPY Ganjoo, K. N., Patel, S. R. 2009; 10 (16): 2735-2743

  Abstract

  Trabectedin (ET-743) is an anticancer agent originally isolated from Ecteinascidia turbinata, a marine organism.The goal of this review is to describe the chemical characteristics, mechanism of action and the results of clinical trials with this compound. The toxicities are described, as well as the pharmacokinetics. The regulatory affairs and marketing strategies for this compound are also discussed.Medline and meeting proceedings were searched to accomplish our objectives.Trabectedin is a unique alkylating agent. It affects a variety of transcription factors, cell proliferation, and nucleotide excision repair mechanism. In addition, it inhibits the MDR-1 gene, which is responsible for the resistance of cancer cells to chemotherapeutic agents. The main toxicities of this agent are transaminitis and myelosuppression, both reversible and noncumulative. At present, trabectedin is approved in Europe for the treatment of sarcoma. The combination of this compound with other chemotherapeutics has been tested in Phase I studies in sarcomas and is feasible. This drug in combination with doxil has shown to improve outcome in relapsed ovarian cancer, compared with doxil alone. The results of this study may lead to an FDA approval of the combination in the USA, for the treatment of relapsed ovarian cancer.

  View details for DOI 10.1517/14656560903277236

  View details for Web of Science ID 000271971500014

  View details for PubMedID 19743937

• Acute myeloid leukemia in patients with gastrointestinal stromal tumors treated with Gleevec LEUKEMIA & LYMPHOMA Ganjoo, K. N., Demetri, G. D., Jacobs, C., Patel, S. 2009; 50 (11): 1882-1884

  View details for DOI 10.3109/10428190903242610

  View details for Web of Science ID 000272145000031

  View details for PubMedID 19883316

• Endometriosis Malignant Transformation Review: Rhabdomyosarcoma Arising From an Endometrioma. JSLS : Journal of the Society of Laparoendoscopic Surgeons Nezhat, C., Vu, M., Vang, N., Ganjoo, K., Karam, A., Folkins, A., Nezhat, A., Nezhat, F. ; 23 (4)

  Abstract

  Endometriosis is a widely known benign disease, but 0.5%-1% of cases are associated with malignancy. It has been linked with ovarian neoplasms, particularly endometrioid and clear cell adenocarcinoma histology. Rhabdomyosarcomas are rarely associated with endometriosis.A 35-year-old patient underwent surgical management of endometriomas to optimize infertility treatment. She later developed abdominal pain with rapid recurrence of ovarian masses. This prompted additional surgery with biopsies diagnosing ovarian rhabdomyosarcoma. Retroactive review of pathologic specimens from her prior surgery demonstrated the neoplasm originated from her prior endometrioma. Focal areas suggested possible underlying ovarian adenosarcoma with stromal overgrowth.The incidence of rhabdomyosarcoma arising from endometriosis is exceedingly rare. The accuracy of diagnosing endometriosis and ruling out neoplasm requires coordinated efforts of a multidisciplinary team, involving radiologists, pathologists, oncologists, and gynecologic surgeons.

  View details for DOI 10.4293/JSLS.2019.00038

  View details for PubMedID 31624455

  View details for PubMedCentralID PMC6791399

• Updated results of phase 1 study of ripretinib (DCC-2618), a broad-spectrum KIT and PDGFRA inhibitor, in patients with gastrointestinal stromal tumor (GIST) by line of therapy (NCT02571036) Chi, P., Janku, F., Heinrich, M., Ganjoo, K., Gelderblom, H., Gordon, M., Jones, R., Razak, A., Trent, J., von Mehren, M., Hu, S., Su, Y., Ruiz-Soto, R., George, S. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1535-7163.TARG-19-C077

  View details for Web of Science ID 000510047200318

• Results of the TAPPAS trial: An adaptive enrichment phase III trial of TRC105 and pazopanib (P) versus pazopanib alone in patients with advanced angiosarcoma (AS) Jones, R. L., Ravi, V., Brohl, A. S., Chawla, S. P., Ganjoo, K., Italiano, A., Attia, S., Burgess, M., Thornton, K., Cranmer, L., Liu, L., Theuer, C., Maki, R. OXFORD UNIV PRESS. 2019: 683

  View details for Web of Science ID 000491295504327

• Ripretinib (DCC-2618) pharmacokinetics (PK) in a Phase I study in patients with gastrointestinal stromal tumors (GIST) and other advanced malignancies: A retrospective evaluation of the PK effects of proton pump inhibitors (PPIs) Janku, F., Heinrich, M., Chi, P., Razak, A., von Mehren, M., Gordon, M., Ganjoo, K., Trent, J., Jones, R. L., Gelderblom, H., Running, K., Wang, J., Ruiz-Soto, R., George, S. AMER ASSOC CANCER RESEARCH. 2019

  View details for DOI 10.1158/1538-7445.AM2019-CT058

  View details for Web of Science ID 000488129900053

• ANNOUNCE: A randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) plus olaratumab versus dox plus PBO in patients (pts) with advanced soft tissue sarcomas (STS). Tap, W. D., Wagner, A. J., Papai, Z., Ganjoo, K. N., Yen, C., Schoffski, P., Razak, A., Martin Broto, J., Spira, A. I., Kawai, A., Krarup-Hansen, A., Le Cesne, A., Van Tine, B., Naito, Y., Park, S., Soldatenkova, V., Mo, G., Shahir, A., Wright, J., Jones, R. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.18_suppl.LBA3

  View details for Web of Science ID 000489109800008

• Uterine sarcomas. Current problems in cancer Ganjoo, K. N. 2019

  Abstract

  Uterine sarcomas comprise a small percentage of uterine malignancies. The most common uterine sarcoma is leiomyosarcoma (LMS). Early stage uterine LMS is curable with complete hysterectomy with removal of an intact uterus. Patients with metastatic disease may achieve tumor responses with improvements in quality of life, but long-term remissions are rare. In this review article, I outline adjuvant therapies for early stage resected uterine LMS, as well as treatment of metastatic disease.

  View details for DOI 10.1016/j.currproblcancer.2019.06.001

  View details for PubMedID 31235185

• Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma JOURNAL OF CLINICAL ONCOLOGY Davis, L. E., Bolejack, V., Ryan, C. W., Ganjoo, K. N., Loggers, E. T., Chawla, S., Agulnik, M., Livingston, M. B., Reed, D., Keedy, V., Rushing, D., Okuno, S., Reinke, D. K., Riedel, R. F., Attia, S., Mascarenhas, L., Maki, R. G. 2019; 37 (16): 1424-+

  View details for DOI 10.1200/JCO.18.02374

  View details for Web of Science ID 000471946600008

• A phase II randomized study of CMB305 and atezolizumab versus atezolizumab in NY-ESO-1(+) soft tissue sarcoma: Analysis of immunogenicity, tumor control, and patient survival. Chawla, S. P., Van Tine, B., Pollack, S., Ganjoo, K. N., Elias, A. D., Riedel, R. F., Attia, S., Choy, E., Okuno, S. H., Agulnik, M., von Mehren, M., Livingston, M. B., Keedy, V., Verschraegen, C. F., Philip, T., Bohac, G. C., Yurasov, S., Lu, H., Chen, M., Maki, R. G. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804108

• A phase II study of ADI-PEG 20 in combination with gemcitabine and docetaxel for the treatment of soft tissue sarcoma. Van Tine, B., Bui, N., Prudner, B., Bomalaski, J. S., Wu, B., Chawla, S. P., Ganjoo, K. N., Oppelt, P., Hirbe, A. C. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345803233

• Multi-institutional analysis of outcomes in patients with dedifferentiated chondrosarcoma (DDCS). Bui, N., Dietz, H., Hirbe, A. C., Ganjoo, K. N., Van Tine, B., Keedy, V., Davis, E. J. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804124

• ABI-009 (nab-sirolimus) in advanced malignant perivascular epithelioid cell tumors (PEComa): Preliminary efficacy, safety, and mutational status from AMPECT, an open label phase II registration trial. Wagner, A. J., Ravi, V., Ganjoo, K. N., Van Tine, B., Riedel, R. F., Chugh, R., Cranmer, L. D., Gordon, E., Hornick, J. L., Kwiatkowski, D. J., Du, H., Grigorian, B., Schmid, A. N., Hou, S., Harris, K., Desai, N., Dickson, M. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345804102

• Responder analysis of patient-reported outcomes measurement information system (PROM'S) physical function (PF) and worst stiffness among patients with tenosynovial giant cell tumors (TGCT) in the ENLIVEN study. Tap, W. D., Speck, R. M., Ye, X., Palmerini, E., Stacchiotti, S., Desai, J., Wagner, A. J., Alcindor, T., Ganjoo, K. N., Broto, J., Wang, Q., Shuster, D., Gelhorn, H., Gelderblom, H. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.e18236

  View details for Web of Science ID 000487345802191

• Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Davis, L. E., Bolejack, V., Ryan, C. W., Ganjoo, K. N., Loggers, E. T., Chawla, S., Agulnik, M., Livingston, M. B., Reed, D., Keedy, V., Rushing, D., Okuno, S., Reinke, D. K., Riedel, R. F., Attia, S., Mascarenhas, L., Maki, R. G. 2019: JCO1802374

  Abstract

  PURPOSE: SARC024 is a phase II clinical trial of the multikinase inhibitor regorafenib in specific sarcoma subtypes, including advanced osteosarcoma. We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort.PATIENTS AND METHODS: This trial enrolled patients with progressive metastatic osteosarcoma with measurable disease by RECIST who had received at least one prior line of therapy. Patients were randomly assigned at a ratio of one to one to regorafenib or placebo. Crossover was allowed at time of disease progression. PFS was the primary end point of the study, which was powered to detect a difference of at least 3 months in median PFS.RESULTS: Forty-two patients from 12 centers were enrolled between September 2014 and May 2018. Median age was 37 years (range, 18 to 76 years). Patients had received an average of 2.3 prior therapy regimens. Ten patients receiving placebo crossed over to active drug at time of progression. Study enrollment was stopped early, after a data safety monitoring committee review. Median PFS was significantly improved with regorafenib versus placebo: 3.6 months (95% CI, 2.0 to 7.6 months) versus 1.7 months (95% CI, 1.2 to 1.8 months), respectively (hazard ratio, 0.42; 95% CI, 0.21 to 0.85; P = .017). In the context of the crossover design, there was no statistically significant difference in overall survival. Fourteen (64%) of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 events attributed to treatment, including one grade 4 colonic perforation.CONCLUSION: The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma. No new safety signals were observed. Regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma.

  View details for PubMedID 31013172

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2019; 42 (2): 166?71

  View details for DOI 10.1097/COC.0000000000000496

  View details for Web of Science ID 000465420000010

• Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet (London, England) Tap, W. D., Gelderblom, H., Palmerini, E., Desai, J., Bauer, S., Blay, J. Y., Alcindor, T., Ganjoo, K., Martín-Broto, J., Ryan, C. W., Thomas, D. M., Peterfy, C., Healey, J. H., van de Sande, M., Gelhorn, H. L., Shuster, D. E., Wang, Q., Yver, A., Hsu, H. H., Lin, P. S., Tong-Starksen, S., Stacchiotti, S., Wagner, A. J. 2019

  Abstract

  Tenosynovial giant cell tumour (TGCT), a rare, locally aggressive neoplasm, overexpresses colony-stimulating factor 1 (CSF1). Surgery is standard with no approved systemic therapy. We aimed to evaluate pexidartinib, a CSF1 receptor inhibitor, in patients with TGCT to provide them with a viable systemic treatment option, especially in cases that are not amenable to surgical resection.This phase 3 randomised trial had two parts. Part one was a double-blind study in which patients with symptomatic, advanced TGCT for whom surgery was not recommended were randomly assigned via an integrated web response system (1:1) to the pexidartinib or placebo group. Individuals in the pexidartinib group received a loading dose of 1000 mg pexidartinib per day orally (400 mg morning; 600 mg evening) for the first 2 weeks, followed by 800 mg per day (400 mg twice a day) for 22 weeks. Part two was an open-label study of pexidartinib for all patients. The primary endpoint, assessed in all intention-to-treat patients, was overall response at week 25, and was centrally reviewed by RECIST, version 1.1. Safety was analysed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02371369.Between May 11, 2015, and Sept 30, 2016, of 174 patients assessed for eligibility, 120 patients were randomly assigned to, and received, pexidartinib (n=61) or placebo (n=59). There were 11 dropouts in the placebo group and nine in the pexidartinib group. Emergence of mixed or cholestatic hepatotoxicity caused the data monitoring committee to stop enrolment six patients short of target. The proportion of patients who achieved overall response was higher for pexidartinib than placebo at week 25 by RECIST (24 [39%] of 61 vs none of 59; absolute difference 39% [95% CI 27-53]; p<0·0001). Serious adverse events occurred in eight (13%) of 61 patients in the pexidartinib group and one (2%) of 59 patients in the placebo group. Hair colour changes (67%), fatigue (54%), aspartate aminotransferase increase (39%), nausea (38%), alanine aminotransferase increase (28%), and dysgeusia (25%) were the most frequent pexidartinib-associated adverse events. Three patients given pexidartinib had aminotransferase elevations three or more times the upper limit of normal with total bilirubin and alkaline phosphatase two or more times the upper limit of normal indicative of mixed or cholestatic hepatotoxicity, one lasting 7 months and confirmed by biopsy.Pexidartinib is the first systemic therapy to show a robust tumour response in TGCT with improved patient symptoms and functional outcomes; mixed or cholestatic hepatotoxicity is an identified risk. Pexidartinib could be considered as a potential treatment for TGCT associated with severe morbidity or functional limitations in cases not amenable to improvement with surgery.Daiichi Sankyo.

  View details for DOI 10.1016/S0140-6736(19)30764-0

  View details for PubMedID 31229240

• A clinico-genomic analysis of soft tissue sarcoma patients reveals CDKN2A deletion as a biomarker for poor prognosis. Clinical sarcoma research Bui, N. Q., Przybyl, J., Trabucco, S. E., Frampton, G., Hastie, T., van de Rijn, M., Ganjoo, K. N. 2019; 9: 12

  Abstract

  Background: Sarcomas are a rare, heterogeneous group of tumors with variable tendencies for aggressive behavior. Molecular markers for prognosis are needed to risk stratify patients and identify those who might benefit from more intensive therapeutic strategies.Patients and methods: We analyzed somatic tumor genomic profiles and clinical outcomes of 152 soft tissue (STS) and bone sarcoma (BS) patients sequenced at Stanford Cancer Institute as well as 206 STS patients from The Cancer Genome Atlas. Genomic profiles of 7733 STS from the Foundation Medicine database were used to assess the frequency of CDKN2A alterations in histological subtypes of sarcoma.Results: Compared to all other tumor types, sarcomas were found to carry the highest relative percentage of gene amplifications/deletions/fusions and the lowest average mutation count. The most commonly altered genes in STS were TP53 (47%), CDKN2A (22%), RB1 (22%), NF1 (11%), and ATRX (11%). When all genomic alterations were tested for prognostic significance in the specific Stanford cohort of localized STS, only CDKN2A alterations correlated significantly with prognosis, with a hazard ratio (HR) of 2.83 for overall survival (p=0.017). These findings were validated in the TCGA dataset where CDKN2A altered patients had significantly worse overall survival with a HR of 2.7 (p=0.002). Analysis of 7733 STS patients from Foundation One showed high prevalence of CDKN2A alterations in malignant peripheral nerve sheath tumors, myxofibrosarcomas, and undifferentiated pleomorphic sarcomas.Conclusion: Our clinico-genomic profiling of STS shows that CDKN2A deletion was the most prevalent DNA copy number aberration and was associated with poor prognosis.

  View details for DOI 10.1186/s13569-019-0122-5

  View details for PubMedID 31528332

• The Outcome of Patients With Localized Undifferentiated Pleomorphic Sarcoma of the Lower Extremity Treated at Stanford University. American journal of clinical oncology Kamat, N. V., Million, L., Yao, D., Donaldson, S. S., Mohler, D. G., van de Rijn, M., Avedian, R. S., Kapp, D. S., Ganjoo, K. N. 2018

  Abstract

  BACKGROUND: As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure.METHODS: We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins.RESULTS: 5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009).CONCLUSIONS: Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

  View details for PubMedID 30557163

• Initial results of phase I study of DCC-2618, a broad-spectrum KIT and PDGFRa inhibitor, in patients (pts) with gastrointestinal stromal tumor (GIST) by number of prior regimens George, S., Heinrich, M., Chi, P., Razak, A., von Mehren, M., Gordon, M., Ganjoo, K. N., Somaiah, N., Trent, J. C., Ahnert, J., Wolf, J., Ruiz-Soto, R., Rosen, O., Janku, F. OXFORD UNIV PRESS. 2018

  View details for Web of Science ID 000459277303372

• Aldoxorubicin therapy for the treatment of patients with advanced soft tissue sarcoma FUTURE ONCOLOGY Seetharam, M., Kolla, K. R., Ganjoo, K. N. 2018; 14 (23): 2323?33

  Abstract

  Soft tissue sarcomas are a group of rare tumors of mesenchymal origin, and account for less than 1% of all cancers. The most commonly used drug for the treatment of soft tissue sarcoma is anthracycline chemotherapeutic agent, doxorubicin. The major limitation for doxorubicin is cardiotoxicity. Hence, to overcome this limitation and to increase efficacy, aldoxorubicin was developed, which has demonstrated activity in soft tissue sarcomas without much cardiotoxicity. In this review article, we discuss mechanism of action, pharmacokinetics, preclinical studies, clinical trial data and safety profile of aldoxorubicin and its potential applicability in the future of sarcoma treatment.

  View details for DOI 10.2217/fon-2018-0047

  View details for Web of Science ID 000449031200002

  View details for PubMedID 29869517

• Pharmacokinetic (PK), safety, and tolerability profile of DCC-2618 in a phase I trial supports 150mg QD selected for a pivotal phase III trial in gastrointestinal stromal tumor (GIST) Janku, F., Heinrich, M., Razak, A., Gordon, M., Chi, P., Ganjoo, K., von Mehren, M., Somaiah, N., Lee, J., Kuida, K., Soto, R., Rosen, O., George, S. AMER ASSOC CANCER RESEARCH. 2018

  View details for DOI 10.1158/1538-7445.AM2018-CT029

  View details for Web of Science ID 000468818900028

• Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib JAMA ONCOLOGY Schuetze, S. M., Bolejack, V., Thomas, D. G., von Mehren, M., Patel, S., Samuels, B., Choy, E., D'Amato, G., Staddon, A. P., Ganjoo, K. N., Chow, W. A., Rushing, D. A., Forscher, C. A., Priebat, D. A., Loeb, D. M., Chugh, R., Okuno, S., Reinke, D. K., Baker, L. H. 2018; 4 (6): 814?20

  Abstract

  Gastrointestinal stromal tumors (GISTs) are life-threatening when metastatic or not amenable to surgical removal. In a few patients with advanced GISTs refractory to imatinib mesylate, treatment with sunitinib malate followed by regorafenib provides tumor control; however, additional active treatments are needed for most patients.To evaluate the 6-month progression-free survival (PFS), tumor objective response, and overall survival rates in patients with GISTs treated with dasatinib.This single-arm clinical trial used a Bayesian design to enroll patients 13 years or older with measurable imatinib-refractory metastatic GISTs treated at 14 sarcoma referral centers from June 1, 2008, through December 31, 2009. A control group was not included. Patients were followed up for survival for a minimum of 5 years from date of enrollment. Tumor imaging using computed tomography or magnetic resonance imaging was performed every 8 weeks for the first 24 weeks and every 12 weeks thereafter. Tumor response was assessed by local site using the Choi criteria. Treatment was continued until tumor progression, unacceptable toxic effects after reduction in drug dose, or patient or physician decision. Archival tumor tissue was evaluated for expression of the proto-oncogene tyrosine-protein kinase Src (SRC), phosphorylated SRC (pSRC), and succinate dehydrogenase complex iron sulfur subunit B (SDHB) proteins and for mutation in the V-Kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor ? (PDGFRA) genes. Data analysis was performed from May 19, 2017, through December 20, 2017.Dasatinib, 70 mg orally twice daily.The primary end point was the 6-month PFS estimate using greater than 30% as evidence of an active drug and less than 10% as evidence of inactive treatment.In this study, 50 patients were enrolled (median age, 60 years; age range, 19-78 years; 31 [62%] male and 19 [38%] female; 41 [82%] white), and 48 were evaluable for response. The estimated 6-month PFS rate was 29% in the overall population and 50% in a subset of 14 patients with pSRC in GISTs. Objective tumor response was observed in 25%, including 1 patient with an imatinib-resistant mutation in PDGFRA exon 18.Dasatinib may have activity in a subset of patients with imatinib-resistant GISTs. Further study is needed to determine whether pSRC is a prognostic biomarker.

  View details for PubMedID 29710216

• Mutation profile of drug resistant gastrointestinal stromal tumor (GIST) patients (pts) enrolled in the phase 1 study of DCC-2618. George, S., Heinrich, M. C., Razak, A., Chi, P., Gordon, M. S., Ganjoo, K. N., von Mehren, M., Somaiah, N., Trent, J. C., Su, Y., Ruiz-Soto, R., Rosen, O., Janku, F. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.11511

  View details for Web of Science ID 000442916003594

• CDKN2A deletion as a prognostic marker: A clinico-genomic analysis of sarcoma patients. Nam Bui, Przybyl, J., Million, L., Van De Rijn, M., Ganjoo, K. N. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.11543

  View details for Web of Science ID 000442916003625

• Soft Tissue Sarcoma, Version 2.2018 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Randall, R., Benjamin, R. S., Boles, S., Bui, M. M., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Keedy, V., Kim, E., Koon, H., Mayerson, J., McCarter, M., McGarry, S. V., Meyer, C., Morris, Z. S., O'Donnell, R. J., Pappo, A. S., Paz, I., Petersen, I. A., Pfeifer, J. D., Riedel, R. F., Ruo, B., Schuetze, S., Tap, W. D., Wayne, J. D., Bergman, M., Scavone, J. L. 2018; 16 (5): 536?63

  Abstract

  Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

  View details for DOI 10.6004/jnccn.2018.0025

  View details for Web of Science ID 000431928700012

  View details for PubMedID 29752328

• Circulating tumor DNA levels correlate with response to treatment in LMS patients Przybyl, J., Chabon, J. J., Spans, L., Ganjoo, K., Vennam, S., Newman, A. M., Forgo, E., Varma, S., Zhu, S., Debiec-Rychter, M., Alizadeh, A., Diehn, M., van de Rijn, M. AMER ASSOC CANCER RESEARCH. 2018: 38?39

  View details for Web of Science ID 000422882000043

• The Impact of Post-Operative Therapy on Primary Cardiac Sarcoma The Journal of Thoracic and Cardiovascular Surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018

  View details for DOI 10.1016/j.jtcvs.2018.04.127

• The impact of postoperative therapy on primary cardiac sarcoma. The Journal of thoracic and cardiovascular surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018; 156 (6): 2194?2203

  Abstract

  Primary cardiac sarcomas (PCS) are extremely rare, portend a very poor prognosis, and have limited outcomes data to direct management. This study evaluated the impact of postoperative chemotherapy and/or radiotherapy on survival for PCS.A retrospective chart review was conducted of 12 patients diagnosed with and who underwent resection for PCS at a single institution between 2000 and 2016. Data were collected on patient/tumor characteristics and analyzed with respect to treatment and outcome using Kaplan-Meier methods.Median age was 43 (range 21-73 years) with a 50:50 male-to-female ratio. The most common subtype was angiosarcoma (42%), and 25% presented with distant metastases (DMs). The initial treatment modality for all patients was surgery, with 58% having macroscopically positive (R2) margins. In total, 75% received postoperative chemotherapy and/or radiotherapy. Median progression-free survival (PFS) was 5.9 months, and median overall survival (OS) was 12.0 months. Achieving negative or microscopically positive margins (R0/R1) as compared with R2 resection significantly improved PFS (12.6 vs 2.7 months, P = .008) and OS (21.8 vs 7.2 months, P = .006). DM at presentation demonstrated a significantly shorter OS (7.0 vs 16.9 months, P = .04) and PFS (0.7 vs 7.9 months, P = .003) compared with localized disease. Patients given postoperative therapy had longer OS compared with surgery only, but this difference was not statistically significant (15.5 vs 2.6 months, P = .12).Gross total surgical resection can significantly improve PFS and OS in PCS, but DM at diagnosis is an extremely poor prognostic sign. Postoperative therapy should be considered, although this study was likely underpowered to demonstrate a statistically significant benefit.

  View details for PubMedID 30454911

• Combination approach for detecting different types of alterations in circulating tumor DNA in leiomyosarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research Przybyl, J., Chabon, J. J., Spans, L., Ganjoo, K., Vennam, S., Newman, A. M., Forgó, E., Varma, S., Zhu, S., Debiec-Rychter, M., Alizadeh, A. A., Diehn, M., van de Rijn, M. 2018

  Abstract

  The clinical utility of circulating tumor DNA (ctDNA) monitoring has been shown in tumors that harbor highly recurrent mutations. Leiomyosarcoma (LMS) represents a type of tumor with a wide spectrum of heterogeneous genomic abnormalities; thus, targeting hotspot mutations or a narrow genomic region for ctDNA detection may not be practical. Here we demonstrate a combinatorial approach that integrates different sequencing protocols for the orthogonal detection of single nucleotide variants (SNVs), small indels and copy number alterations (CNAs) in ctDNA.We employed Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for the analysis of SNVs and indels, together with a genome-wide interrogation of CNAs by Genome Representation Profiling (GRP). We profiled 28 longitudinal plasma samples and 25 tumor specimens from 7 patients with LMS.We detected ctDNA in 6 of 7 of these patients with >98% specificity for mutant allele fractions down to a level of 0.01%. We show that results from CAPP-Seq and GRP are highly concordant, and the combination of these methods allows for more comprehensive monitoring of ctDNA by profiling a wide spectrum of tumor-specific markers. By analyzing multiple tumor specimens in individual patients obtained from different sites and at different times during treatment, we observed clonal evolution of these tumors that was reflected by ctDNA profiles.Our strategy allows for a comprehensive monitoring of a broad spectrum of tumor-specific markers in plasma. Our approach may be clinically useful not only in LMS but also in other tumor types that lack recurrent genomic alterations.

  View details for PubMedID 29463554

• Anaplastic Thyroid Cancer With Extensive Skeletal Muscle Metastases on 18F-FDG PET/CT. Clinical nuclear medicine Yurkiewicz, I. R., Ganjoo, K. N., Iagaru, A. 2018

  Abstract

  A 61-year-old woman with newly diagnosed anaplastic thyroid cancer and known metastases to the brain, lungs, and adrenal glands complained of groin muscle pain. F-FDG PET/CT was performed to assess for extent of disease and showed extensive hypermetabolic lesions throughout the skeletal musculature concerning for metastatic disease. As this would be a very rare presentation for anaplastic thyroid carcinoma, a biopsy of the left gluteal muscle was conducted. Pathology demonstrated anaplastic thyroid carcinoma, metastatic to skeletal muscle.

  View details for PubMedID 29356736

• A multicenter phase II study of Q3 week or weekly paclitaxel in combination with bevacizumab for the treatment of metastatic or unresectable angiosarcoma. Rare tumors Bui, N., Kamat, N., Ravi, V., Chawla, S., Lohman, M., Ganjoo, K. N. 2018; 10: 2036361318771771

  Abstract

  Paclitaxel (P) and bevacizumab (B) are agents that provide clinical benefit in advanced angiosarcoma (AS). The objective of this study was to assess the efficacy and safety of P-B in two different scheduled regimens. Patients were to receive P 200mg/m2 IV with B 15mg/kg IV every 21 days (Regimen A) or P 90mg/m2 IV weekly D1, 8, 15 with B 15mg/kg IV D1 of a 28 day cycle (Regimen B) x6 cycles. Maintenance B followed at a dose of 15 mg/kg intravenously once every 21 days. The primary end point was 4 month non-progression rate (NPR). A total of 16 patients were enrolled. 4 month NPR was 62.5% with median overall survival 16 months and median progression free survival 5.06 months. 11 patients made it to cycle 3 and were evaluable for response with 1 CR (9%), 4 PR (36%), 2 SD (18%), and 6 PD (36%). There were ten grade 3 toxicities and four grade 4 toxicities. The breakdown between the two regimens revealed comparable efficacy and safety. Paclitaxel and Bevacizumab is an active regimen in angiosarcoma. Q3 week and weekly paclitaxel appear similar in efficacy and safety.

  View details for PubMedID 29760870

• Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial GYNECOLOGIC ONCOLOGY Hensley, M. L., Patel, S. R., von Mehren, M., Ganjoo, K., Jones, R. L., Staddon, A., Rushing, D., Milhem, M., Monk, B., Wang, G., McCarthy, S., Knoblauch, R. E., Parekh, T. V., Maki, R. G., Demetri, G. D. 2017; 146 (3): 531?37

  Abstract

  Trabectedin demonstrated significantly improved disease control in leiomyosarcoma and liposarcoma patients in a global phase 3 trial (NCT01343277). A post hoc analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in women with uterine leiomyosarcoma (uLMS), the largest subgroup of enrolled patients (40%).Of 577 patients randomized 2:1 to receive trabectedin 1.5mg/m2 by 24-hour IV infusion or dacarbazine 1g/m2 by 20-120-minute IV infusion once every three weeks, 232 had uLMS (trabectedin: 144; dacarbazine: 88). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR: complete responses+partial responses+stable disease [SD] for at least 18weeks), duration of response (DOR), and safety.PFS for trabectedin was 4.0months compared with 1.5months for dacarbazine (hazard ratio [HR]=0.57; 95% CI 0.41-0.81; P=0.0012). OS was similar (trabectedin 13.4months vs. dacarbazine 12.9months, HR=0.89; 95% CI 0.65-1.24; P=0.51) between groups. ORR was 11% with trabectedin vs. 9% with dacarbazine (P=0.82). CBR for trabectedin was 31% vs. 18% with dacarbazine (P=0.05); median DOR was 6.5months for trabectedin vs. 4.1months for dacarbazine (P=0.32). Grade 3/4 treatment-emergent adverse events observed in ?10% of patients in the trabectedin group included transient aminotransferase (aspartate/alanine) elevations, anemia, leukopenia, and thrombocytopenia.In this post hoc subset analysis of patients with uLMS who had received prior anthracycline therapy, trabectedin treatment resulted in significantly longer PFS versus dacarbazine, with an acceptable safety profile. There was no difference in OS.

  View details for PubMedID 28651804

• Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial LANCET ONCOLOGY Tap, W. D., Papai, Z., Van Tine, B. A., Attia, S., Ganjoo, K. N., Jones, R. L., Schuetze, S., Reed, D., Chawla, S. P., Riedel, R. F., Krarup-Hansen, A., Toulmonde, M., Ray-Coquard, I., Hohenberger, P., Grignani, G., Cranmer, L. D., Okuno, S., Agulnik, M., Read, W., Ryan, C. W., Alcindor, T., Garcia del Muro, X. F., Budd, G., Tawbi, H., Pearce, T., Kroll, S., Reinke, D. K., Schoffski, P. 2017; 18 (8): 1089?1103

  Abstract

  Evofosfamide is a hypoxia-activated prodrug of bromo-isophosphoramide mustard. We aimed to assess the benefit of adding evofosfamide to doxorubicin as first-line therapy for advanced soft-tissue sarcomas.We did this international, open-label, randomised, phase 3, multicentre trial (TH CR-406/SARC021) at 81 academic or community investigational sites in 13 countries. Eligible patients were aged 15 years or older with a diagnosis of an advanced unresectable or metastatic soft-tissue sarcoma, of intermediate or high grade, for which no standard curative therapy was available, an Eastern Cooperative Oncology Group performance status of 0-1, and measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (1:1) to receive doxorubicin alone (75 mg/m2 via bolus injection administered over 5-20 min or continuous intravenous infusion for 6-96 h on day 1 of every 21-day cycle for up to six cycles) or doxorubicin (given via the same dose procedure) plus evofosfamide (300 mg/m2 intravenously for 30-60 min on days 1 and 8 of every 21-day cycle for up to six cycles). After six cycles of treatment, patients in the single-drug doxorubicin group were followed up expectantly whereas patients with stable or responsive disease in the combination group were allowed to continue with evofosfamide monotherapy until documented disease progression. A web-based central randomisation with block sizes of two and four was stratified by extent of disease, doxorubicin administration method, and previous systemic therapy. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival, analysed in the intention-to-treat population. Safety analyses were done in all patients who received any amount of study drug. This study was registered with ClinicalTrials.gov, number NCT01440088.Between Sept 26, 2011, and Jan 22, 2014, 640 patients were enrolled and randomly assigned to a treatment group (317 to doxorubicin plus evofosfamide and 323 to doxorubicin alone), all of whom were included in the intention-to-treat analysis. The overall survival endpoint was not reached (hazard ratio 1·06, 95% CI 0·88-1·29; p=0·527), with a median overall survival of 18·4 months (95% CI 15·6-22·1) with doxorubicin plus evofosfamide versus 19·0 months (16·2-22·4) with doxorubicin alone. The most common grade 3 or worse adverse events in both groups were haematological, including anaemia (150 [48%] of 313 patients in the doxorubicin plus evofosfamide group vs 65 [21%] of 308 in the doxorubicin group), neutropenia (47 [15%] vs 92 [30%]), febrile neutropenia (57 [18%] vs 34 [11%]), leucopenia (22 [7%] vs 17 [6%]), decreased neutrophil count (31 [10%] vs 41 [13%]), and decreased white blood cell count (39 [13%] vs 33 [11%]). Grade 3-4 thrombocytopenia was more common in the combination group (45 [14%]) than in the doxorubicin alone group (four [1%]), as was grade 3-4 stomatitis (26 [8%] vs seven [2%]). Serious adverse events were reported in 145 (46%) of 313 patients in the combination group and 99 (32%) of 308 in the doxorubicin alone group. Five (2%) patients died from treatment-related causes in the combination group (sepsis [n=2], septic shock [n=1], congestive cardiac failure [n=1], and unknown cause [n=1]) versus one (<1%) patient in the doxorubicin alone group (lactic acidosis [n=1]).The addition of evofosfamide to doxorubicin as first-line therapy did not improve overall survival compared with single-drug doxorubicin in patients with locally advanced, unresectable, or metastatic soft-tissue sarcomas and so this combination cannot be recommended in this setting.Threshold Pharmaceuticals.

  View details for PubMedID 28651927

• Long-term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non-Hodgkin lymphoma BRITISH JOURNAL OF HAEMATOLOGY Martin, P., Chen, Z., Cheson, B. D., Robinson, K. S., Williams, M., Rajguru, S. A., Friedberg, J. W., van der Jagt, R. H., LaCasce, A. S., Joyce, R., Ganjoo, K. N., Bartlett, N. L., Lemieux, B., VanderWalde, A., Herst, J., Szer, J., Bar, M. H., Cabanillas, F., Dodds, A. J., Montgomery, P. G., Pressnail, B., Ellis, T., Smith, M. R., Leonard, J. P. 2017; 178 (2): 250?56

  Abstract

  Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event-free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non-Hodgkin lymphoma.

  View details for PubMedID 28419413

  View details for PubMedCentralID PMC5737737

• A phase II trial of regorafenib (REGO) in patients (pts) with advanced Ewing sarcoma and related tumors (EWS) of soft tissue and bone: SARCO24 trial results Attia, S., Bolejack, V., Ganjoo, K. N., George, S., Agulnik, M., Rushing, D. A., Loggers, E., Livingston, M. B., Wright, J. A., Chawla, S. P., Okuno, S. H., Reinke, D. K., Riedel, R. F., Davis, L., Ryan, C. W., Maki, R. G. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.11005

  View details for Web of Science ID 000411932206156

• Phase III study of aldoxorubicin vs investigators' choice as treatment for relapsed/refractory soft tissue sarcomas Chawla, S. P., Ganjoo, K. N., Schuetze, S., Papai, Z., Van Tine, B., Choy, E., Liebner, D. A., Agulnik, M., Chawla, S., Wieland, S., Levitt, D. J. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.11000

  View details for Web of Science ID 000411932206152

• Improving care with portfolio of physician-led cancer quality measures at an academic center Porter, J., Smith, A., Winget, M., Rosenthal, E., Seshadri, S., Vetteth, Y., Kiamanesh, E. F., Badwe, A., Advani, R. H., Buyyounouski, M. K., Coutre, S., Dorigo, O., Ganjoo, K. N., Johnston, L. J., Recht, L., Shrager, J. B., Skinner, E. C., Swetter, S. M., Visser, B. C., Blayney, D. W. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for Web of Science ID 000443301600049

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study EUROPEAN RADIOLOGY Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2017; 27 (2): 732-740

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P?=?0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5?±?1.9 vs 2.7?±?2.6, P?=?0.027; average scores, 6?±?2.3 vs 1.3?±?2, P?=?0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.? Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours ? This non-invasive procedure can eradicate viable tumour in some cases ? Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments ? Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for DOI 10.1007/s00330-016-4376-5

  View details for Web of Science ID 000392142000034

• Phase 2 Study of Dasatinib in Patients With Alveolar Soft Part Sarcoma, Chondrosarcoma, Chordoma, Epithelioid Sarcoma, or Solitary Fibrous Tumor CANCER Schuetze, S. M., Bolejack, V., Choy, E., Ganjoo, K. N., Staddon, A. P., Chow, W. A., Tawbi, H. A., Samuels, B. L., Patel, S. R., von Mehren, M., D'Amato, G., Leu, K. M., Loeb, D. M., Forscher, C. A., Milhem, M. M., Rushing, D. A., Lucas, D. R., Chugh, R., Reinke, D. K., Baker, L. H. 2017; 123 (1): 90-97

  Abstract

  Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed.The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of ?50%. Cross-sectional imaging was performed before the start of treatment, every 2 months for 6 months, and then every 3 months during treatment. The 2- and 5-year survival rates were determined.One hundred sixteen patients were enrolled within 45 months, and 109 began treatment with dasatinib. The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively. The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%). More than 10% of the patients with ASPS, CS, or chordoma had stable disease for more than 1 year. Collectively, for all 5 subtypes, the 2- and 5-year overall survival rates were 44% and 13%, respectively. An objective response was observed in 18% of the patients with CS or chordoma.Dasatinib failed to achieve control of sarcoma growth for at least 6 months in more than 50% of the patients in this trial according to the Choi tumor response criteria. An objective tumor response and prolonged stable disease was observed in >10% of patients with CS or chordoma. Cancer 2017;90-97. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30379

  View details for Web of Science ID 000394719100012

• Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma Moding, E. J., Million, L., Avedian, R., Ghanouni, P., Kunder, C., Ganjoo, K. N. 2017; 2017: 2316839

  Abstract

  Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function.

  View details for PubMedID 28761389

• Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Porter, J. B. 2017; 13 (8): e673-e682

  Abstract

  Development and implementation of robust reporting processes to systematically provide quality data to care teams in a timely manner is challenging. National cancer quality measures are useful, but the manual data collection required is resource intensive, and reporting is delayed. We designed a largely automated measurement system with our multidisciplinary cancer care programs (CCPs) to identify, measure, and improve quality metrics that were meaningful to the care teams and their patients.Each CCP physician leader collaborated with the cancer quality team to identify metrics, abiding by established guiding principles. Financial incentive was provided to the CCPs if performance at the end of the study period met predetermined targets. Reports were developed and provided to the CCP physician leaders on a monthly or quarterly basis, for dissemination to their CCP teams.A total of 15 distinct quality measures were collected in depth for the first time at this cancer center. Metrics spanned the patient care continuum, from diagnosis through end of life or survivorship care. All metrics improved over the study period, met their targets, and earned a financial incentive for their CCP.Our quality program had three essential elements that led to its success: (1) engaging physicians in choosing the quality measures and prespecifying goals, (2) using automated extraction methods for rapid and timely feedback on improvement and progress toward achieving goals, and (3) offering a financial team-based incentive if prespecified goals were met.

  View details for DOI 10.1200/JOP.2017.021139

  View details for PubMedCentralID PMC5880618

• Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor. Cancer Schuetze, S. M., Bolejack, V., Choy, E., Ganjoo, K. N., Staddon, A. P., Chow, W. A., Tawbi, H. A., Samuels, B. L., Patel, S. R., von Mehren, M., D'Amato, G., Leu, K. M., Loeb, D. M., Forscher, C. A., Milhem, M. M., Rushing, D. A., Lucas, D. R., Chugh, R., Reinke, D. K., Baker, L. H. 2016

  Abstract

  Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed.The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of ?50%. Cross-sectional imaging was performed before the start of treatment, every 2 months for 6 months, and then every 3 months during treatment. The 2- and 5-year survival rates were determined.One hundred sixteen patients were enrolled within 45 months, and 109 began treatment with dasatinib. The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively. The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%). More than 10% of the patients with ASPS, CS, or chordoma had stable disease for more than 1 year. Collectively, for all 5 subtypes, the 2- and 5-year overall survival rates were 44% and 13%, respectively. An objective response was observed in 18% of the patients with CS or chordoma.Dasatinib failed to achieve control of sarcoma growth for at least 6 months in more than 50% of the patients in this trial according to the Choi tumor response criteria. An objective tumor response and prolonged stable disease was observed in >10% of patients with CS or chordoma. Cancer 2017;90-97. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30379

  View details for PubMedID 27696380

• Soft Tissue Sarcoma, Version 2.2016 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Conrad, E. U., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Koon, H., Mayerson, J., McCarter, M., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Petersen, I. A., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Tap, W. D., Wayne, J. D., Bergman, M. A., Scavone, J. 2016; 14 (6): 758-786

  Abstract

  Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

  View details for Web of Science ID 000377690100009

  View details for PubMedID 27283169

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study. European radiology Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2016: -?

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P?=?0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5?±?1.9 vs 2.7?±?2.6, P?=?0.027; average scores, 6?±?2.3 vs 1.3?±?2, P?=?0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.? Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours ? This non-invasive procedure can eradicate viable tumour in some cases ? Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments ? Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for PubMedID 27147222

• SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma. Cancer Schuetze, S. M., Wathen, J. K., Lucas, D. R., Choy, E., Samuels, B. L., Staddon, A. P., Ganjoo, K. N., von Mehren, M., Chow, W. A., Loeb, D. M., Tawbi, H. A., Rushing, D. A., Patel, S. R., Thomas, D. G., Chugh, R., Reinke, D. K., Baker, L. H. 2016; 122 (6): 868-874

  Abstract

  Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma.Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ?6 months) with a target of ?25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ?25%.A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ?25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients.Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity. Cancer 2016;122:868-74. © 2015 American Cancer Society.

  View details for DOI 10.1002/cncr.29858

  View details for PubMedID 26710211

• Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. Journal of clinical oncology Demetri, G. D., von Mehren, M., Jones, R. L., Hensley, M. L., Schuetze, S. M., Staddon, A., Milhem, M., Elias, A., Ganjoo, K., Tawbi, H., Van Tine, B. A., Spira, A., Dean, A., Khokhar, N. Z., Park, Y. C., Knoblauch, R. E., Parekh, T. V., Maki, R. G., Patel, S. R. 2016; 34 (8): 786-793

  Abstract

  This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen.Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control-progression-free survival (PFS), time to progression, objective response rate, and duration of response-as well as safety and patient-reported symptom scoring.A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm.Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies.

  View details for DOI 10.1200/JCO.2015.62.4734

  View details for PubMedID 26371143

• First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial. JAMA oncology Chawla, S. P., Papai, Z., Mukhametshina, G., Sankhala, K., Vasylyev, L., Fedenko, A., Khamly, K., Ganjoo, K., Nagarkar, R., Wieland, S., Levitt, D. J. 2015; 1 (9): 1272-1280

  Abstract

  Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies.To evaluate efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma.International, multicenter, phase 2b, open-label, randomized study at general community practices, private practices, or institutional practices. Between August 2012 and December 2013, 140 patients with previously untreated locally advanced, unresectable, or metastatic soft-tissue sarcoma were screened.Randomization (2:1) to aldoxorubicin 350 mg/m2 (dose equivalent to doxorubicin 260 mg/m2) or doxorubicin 75 mg/m2, administered once every 3 weeks for up to 6 cycles.Primary end point was progression-free survival. Secondary end points were 6-month progression-free survival, overall survival, tumor response rate, and safety. All efficacy end points were evaluated by independent and local review.A total of 126 patients were randomized, and 123 received aldoxorubicin (n = 83) or doxorubicin (n = 40). Median (range) patient age was 54.0 (21-77 years); 42 (34%) had leiomyosarcoma. By independent review, median progression-free survival was significantly improved (5.6 [95% CI, 3.0-8.1] vs 2.7 [95% CI, 1.6-4.3] months; P = .02) with aldoxorubicin compared with doxorubicin, as was the rate of 6-month progression-free survival (46% and 23%; P = .02). Median overall survival was 15.8 (95% CI, 13.0 to not available) months with aldoxorubicin and 14.3 (95% CI, 8.6-20.6) months with doxorubicin (P = .21). Overall tumor response rate (by Response Evaluation Criteria in Solid Tumors, version 1.1) by independent review was higher with aldoxorubicin than with doxorubicin (25% [20 patients, all partial response] vs 0%). Grade 3 or 4 neutropenia was more frequent with aldoxorubicin than with doxorubicin (24 [29%] vs 5 [12%]), but not grade 3 or 4 febrile neutropenia (12 [14%] vs 7 [18%]). No acute cardiotoxic effects were observed with either treatment, although left ventricular ejection fraction less than 50% occurred in 3 of 40 patients receiving doxorubicin.Single-agent aldoxorubicin therapy showed superior efficacy over doxorubicin by prolonging progression-free survival and improving rates of 6-month progression-free survival and tumor response. Aldoxorubicin therapy exhibited manageable adverse effects, without unexpected events, and without evidence of acute cardiotoxicity. Further investigation of aldoxorubicin therapy in advanced soft-tissue sarcoma is warranted.clinicaltrials.gov Identifier: NCT01514188.

  View details for DOI 10.1001/jamaoncol.2015.3101

  View details for PubMedID 26378637

• First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma A Phase 2b Randomized Clinical Trial JAMA ONCOLOGY Chawla, S. P., Papai, Z., Mukhametshina, G., Sankhala, K., Vasylyev, L., Fedenko, A., Khamly, K., Ganjoo, K., Nagarkar, R., Wieland, S., Levitt, D. J. 2015; 1 (9): 1272-1280

  View details for DOI 10.1001/jamaoncol.2015.3101

  View details for Web of Science ID 000383678300015

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study ANNALS OF SURGERY Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632-640

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P?=?0.002), grade 3 or higher complication (38% vs. 18%, P?=?0.024), and transfusion (66% vs. 33%, P?

  View details for DOI 10.1097/SLA.0000000000001455

  View details for Web of Science ID 000367999800009

• Combined F-18-NaF and F-18-FDG PET/CT in the Evaluation of Sarcoma Patients CLINICAL NUCLEAR MEDICINE Jackson, T., Mosci, C., von Eyben, R., Mittra, E., Ganjoo, K., Biswal, S., Gambhir, S. S., Iagaru, A. 2015; 40 (9): 720-724

  Abstract

  The combined administration of F-NaF and F-FDG in a single PET/CT scan has the potential to improve patient convenience and cancer detection. Here we report the use of this approach for patients with sarcomas.This is a retrospective review of 21 patients (12 men, 9 women; age, 19-66 years) with biopsy-proven sarcomas who had separate F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT scans for evaluation of malignancy. Two board-certified nuclear medicine physicians and 1 board-certified musculoskeletal radiologist were randomly assigned to review the scans. Results were analyzed for sensitivity and specificity, using linear regression and receiver operating characteristics.A total of 13 patients had metastatic disease on F-NaF PET/CT, F-FDG PET/CT, and combined F-NaF/F-FDG PET/CT. Skeletal disease was more extensive on the F-NaF PET/CT scan than on the F-FDG PET/CT in 3 patients, whereas in 1 patient, F-FDG PET/CT showed skeletal disease and the F-NaF PET/CT was negative. Extraskeletal lesions were detected on both F-FDG and combined F-NaF/F-FDG PET/CT in 20 patients, with 1 discordant finding in the lung.The combined F-NaF/F-FDG PET/CT scan allows for accurate evaluation of sarcoma patients. Further evaluation of this proposed imaging modality is warranted to identify the most suitable clinical scenarios, including initial treatment strategy and evaluation of response to therapy.

  View details for DOI 10.1097/RLU.0000000000000845

  View details for Web of Science ID 000359668600005

  View details for PubMedID 26053718

• Denosumab, a Potential Alternative to the Surgical Treatment of Distal Radius Giant Cell Tumor of Bone: Case Report. journal of hand surgery Park, M. J., Ganjoo, K. N., Ladd, A. L. 2015; 40 (8): 1620-1624

  Abstract

  Juxta-articular giant cell tumors can pose major surgical challenges. Aggressive distal radius giant cell tumors often require complex reconstructive procedures that are associated with numerous complications. We present a case of a 25-year old man with a Campanacci grade 3 giant cell tumor of the distal radius that was successfully treated with denosumab without complex reconstructive procedures. At 3.5-year follow-up and 1-year drug free period, the patient remained asymptomatic without histologic evidence of recurrent tumor. With denosumab therapy, patients can potentially avoid surgery and achieve a successful outcome.

  View details for DOI 10.1016/j.jhsa.2015.03.018

  View details for PubMedID 25935517

• Clinically Relevant Molecular Subtypes in Leiomyosarcoma. Clinical cancer research Guo, X., Jo, V. Y., Mills, A. M., Zhu, S. X., Lee, C., Espinosa, I., Nucci, M. R., Varma, S., Forgó, E., Hastie, T., Anderson, S., Ganjoo, K., Beck, A. H., West, R. B., Fletcher, C. D., van de Rijn, M. 2015; 21 (15): 3501-3511

  Abstract

  Leiomyosarcoma is a malignant neoplasm with smooth muscle differentiation. Little is known about its molecular heterogeneity and no targeted therapy currently exists for leiomyosarcoma. Recognition of different molecular subtypes is necessary to evaluate novel therapeutic options. In a previous study on 51 leiomyosarcomas, we identified three molecular subtypes in leiomyosarcoma. The current study was performed to determine whether the existence of these subtypes could be confirmed in independent cohorts.Ninety-nine cases of leiomyosarcoma were expression profiled with 3'end RNA-Sequencing (3SEQ). Consensus clustering was conducted to determine the optimal number of subtypes.We identified 3 leiomyosarcoma molecular subtypes and confirmed this finding by analyzing publically available data on 82 leiomyosarcoma from The Cancer Genome Atlas (TCGA). We identified two new formalin-fixed, paraffin-embedded tissue-compatible diagnostic immunohistochemical markers; LMOD1 for subtype I leiomyosarcoma and ARL4C for subtype II leiomyosarcoma. A leiomyosarcoma tissue microarray with known clinical outcome was used to show that subtype I leiomyosarcoma is associated with good outcome in extrauterine leiomyosarcoma while subtype II leiomyosarcoma is associated with poor prognosis in both uterine and extrauterine leiomyosarcoma. The leiomyosarcoma subtypes showed significant differences in expression levels for genes for which novel targeted therapies are being developed, suggesting that leiomyosarcoma subtypes may respond differentially to these targeted therapies.We confirm the existence of 3 molecular subtypes in leiomyosarcoma using two independent datasets and show that the different molecular subtypes are associated with distinct clinical outcomes. The findings offer an opportunity for treating leiomyosarcoma in a subtype-specific targeted approach. Clin Cancer Res; 21(15); 3501-11. ©2015 AACR.

  View details for DOI 10.1158/1078-0432.CCR-14-3141

  View details for PubMedID 25896974

• Leiomyosarcoma: One Disease or Distinct Biologic Entities Based on Site of Origin? JOURNAL OF SURGICAL ONCOLOGY Worhunsky, D. J., Gupta, M., Gholami, S., Tran, T. B., Ganjoo, K. N., van de Rijn, M., Visser, B. C., Norton, J. A., Poultsides, G. A. 2015; 111 (7): 808-812

  Abstract

  Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin.Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P?

  View details for DOI 10.1002/jso.23904

  View details for PubMedID 25920434

• Phase 1/2 Study of Ocaratuzumab, an Fc-Engineered Humanized Anti-CD20 Monoclonal Antibody, in Low-Affinity Fc?RIIIa Patients with Previously Treated Follicular Lymphoma. Leukemia & lymphoma Ganjoo, K. N., de Vos, S., Pohlman, B. L., Flinn, I. W., Forero-Torres, A., Enas, N. H., Cronier, D. M., Dang, N. H., Foon, K. A., Carpenter, S. P., Slapak, C. A., Link, B. K., Smith, M. R., Mapara, M. Y., Wooldridge, J. E. 2015; 56 (1): 42-48

  Abstract

  Abstract This phase 2 study assessed the safety and efficacy of ocaratuzumab, a humanized anti-CD20 monoclonal antibody. Fifty patients with previously treated follicular lymphoma (FL) and a low-affinity genotype of Fc?RIIIa received ocaratuzumab 375 mg/m(2) weekly for 4 weeks. Grade 3/4/5 adverse events (AEs) were reported in 11/1/1 patients, respectively. Serious AEs were reported by 11/50 patients, and three discontinued due to AEs. One patient died from aspiration pneumonia due to possibly drug-related nausea and vomiting. Investigator-assessed response rate was 30% (15/50), including four complete responses (CR), three CR unconfirmed (CRu) and eight partial responses (PR). Investigator-assessed median Progression-free survivial (PFS) was 38.3 weeks. Ocaratuzumab's pharmacokinetic profile was similar to that reported for rituximab. Lymphocyte subset analysis showed significant, selective reduction of B-cells during and after ocaratuzumab treatment. Ocaratuzumab at this dose and schedule is active and well tolerated in patients with previously treated FL with low affinity Fc?RIIIa genotypes. ClinTrials registry number: NCT00354926.

  View details for DOI 10.3109/10428194.2014.911859

  View details for PubMedID 24717109

• Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case-control Study. Annals of surgery Poultsides, G. A., Tran, T. B., Zambrano, E., Janson, L., Mohler, D. G., Mell, M. W., Avedian, R. S., Visser, B. C., Lee, J. T., Ganjoo, K., Harris, E. J., Norton, J. A. 2015; 262 (4): 632?40

  Abstract

  To examine the impact of major vascular resection on sarcoma resection outcomes.En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described.Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival.From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P?=?0.002), grade 3 or higher complication (38% vs. 18%, P?=?0.024), and transfusion (66% vs. 33%, P?

  View details for PubMedID 26366542

• Effects of denosumab on pain and analgesic use in giant cell tumor of bone: Interim results from a phase II study ACTA ONCOLOGICA Martin-Broto, J., Cleeland, C. S., Glare, P. A., Engellau, J., Skubitz, K. M., Blum, R. H., Ganjoo, K. N., Staddon, A., Dominkus, M., Feng, A., Qian, Y., Braun, A., Jacobs, I., Chung, K., Atchison, C. 2014; 53 (9): 1173-1179

  View details for DOI 10.3109/0284186X.2014.910313

  View details for Web of Science ID 000342282100006

• Active idiotypic vaccination versus control immunotherapy for follicular lymphoma. Journal of clinical oncology Levy, R., Ganjoo, K. N., Leonard, J. P., Vose, J. M., Flinn, I. W., Ambinder, R. F., Connors, J. M., Berinstein, N. L., Belch, A. R., Bartlett, N. L., Nichols, C., Emmanouilides, C. E., Timmerman, J. M., Gregory, S. A., Link, B. K., Inwards, D. J., Freedman, A. S., Matous, J. V., Robertson, M. J., Kunkel, L. A., Ingolia, D. E., Gentles, A. J., Liu, C. L., Tibshirani, R., Alizadeh, A. A., Denney, D. W. 2014; 32 (17): 1797-1803

  Abstract

  Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF.Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone. Those achieving sustained partial or complete remission (n=287 [44%]) were randomly assigned at a ratio of 2:1 to receive one injection per month for 7 months of MyVax or control immunotherapy. Anti-Id antibody responses (humoral immune responses [IRs]) were measured before each immunization. The primary end point was progression-free survival (PFS). Secondary end points included IR and time to subsequent antilymphoma therapy.At a median follow-up of 58 months, no significant difference was observed in either PFS or time to next therapy between the two arms. In the MyVax group (n=195), anti-Id IRs were observed in 41% of patients, with a median PFS of 40 months, significantly exceeding the median PFS observed in patients without such Id-induced IRs and in those receiving control immunotherapy.This trial failed to demonstrate clinical benefit of specific immunotherapy. The subset of vaccinated patients mounting specific anti-Id responses had superior outcomes. Whether this reflects a therapeutic benefit or is a marker for more favorable underlying prognosis requires further study.

  View details for DOI 10.1200/JCO.2012.43.9273

  View details for PubMedID 24799467

• Results of SARC 022, a phase II multicenter study of linsitinib in pediatric and adult wild-type (WT) gastrointestinal stromal tumors (GIST). von Mehren, M., George, S., Heinrich, M. C., Schuetze, S., Belinsky, M. G., Janeway, K. A., Rink, L., Ganjoo, K. N., Yu, J., Yap, J. T., Wright, J., Van den Abbeele, A. D. AMER SOC CLINICAL ONCOLOGY. 2014

  View details for Web of Science ID 000358613204640

• Bevacizumab and cyclosphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms: an Eastern Cooperative Oncology Group study (E2404). Leukemia & lymphoma Ganjoo, K., Hong, F., Horning, S. J., Gascoyne, R. D., Natkunam, Y., Swinnen, L. J., Habermann, T. M., Kahl, B. S., Advani, R. H. 2014; 55 (4): 768-772

  Abstract

  Peripheral T-cell lymphoma (PTCL) and natural killer (NK) cell lymphoma have poor survival with conventional cytotoxic chemotherapy. Because angiogenesis plays an important role in the biology of PTCL, a fully humanized anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (A), was studied in combination with standard cyclosphosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy (ACHOP) to evaluate its potential to improve outcome in these patients. Patients were treated with 6-8 cycles of ACHOP followed by eight doses of maintenance A (15 mg/kg every 21 days). Forty-six patients were enrolled on this phase 2 study from July 2006 through March 2009. Forty-four patients were evaluable for toxicity and 39 were evaluable for response, progression and survival. A total of 324 cycles (range: 2-16, median 7) were administered to 39 evaluable patients and only nine completed all planned treatment. The overall response rate was 90% with 19 (49%) complete response/complete response unconfirmed (CR/CRu) and 16 (41%) a partial response (PR). The 1-year progression-free survival (PFS) rate was 44% at a median follow-up of 3 years. The median PFS and overall survival (OS) rates were 7.7 and 22 months, respectively. Twenty-three patients died (21 from lymphoma, two while in remission). Grade 3 or 4 toxicities included febrile neutropenia (n = 8), anemia (n = 3), thrombocytopenia (n = 5), congestive heart failure (n = 4), venous thrombosis (n = 3), gastrointestinal hemorrhage/perforation (n = 2), infection (n = 8) and fatigue (n = 6). Despite a high overall response rate, the ACHOP regimen failed to result in durable remissions and was associated with significant toxicities. Studies of novel therapeutics are needed for this patient population, whose clinical outcome remains poor.

  View details for DOI 10.3109/10428194.2013.816700

  View details for PubMedID 23786456

• Soft tissue sarcoma, version 2.2014. Journal of the National Comprehensive Cancer Network von Mehren, M., Randall, R. L., Benjamin, R. S., Boles, S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R. J., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Pappo, A. S., Paz, I. B., Pfeifer, J. D., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Van Tine, B. A., Wayne, J. D., Bergman, M. A., Sundar, H. 2014; 12 (4): 473-483

  Abstract

  These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

  View details for PubMedID 24717567

• The Treatment Outcome for Adult Patients with Ewing's Sarcoma. Current oncology reports Ganjoo, K. N., Patel, S. 2013; 15 (4): 372-377

  Abstract

  Ewing's sarcoma is the second most common bone malignancy in children, but is extremely rare in adults. The outcome of patients with localized disease has improved over the past decades due to better combination chemotherapies, and better methods of local control. Unfortunately, patients with metastatic disease have a very poor outcome with current antineoplastic therapies. In this article, we will review the primary treatment for adult patients with Ewing's sarcoma, both for localized and metastatic disease. The prognostic factors in adult patients with EWS will also be reviewed.

  View details for DOI 10.1007/s11912-013-0317-5

  View details for PubMedID 23605781

• Soft Tissue Sarcoma, Version 2.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK von Mehren, M., Benjamin, R. S., Bui, M. M., Casper, E. S., Conrad, E. U., DeLaney, T. F., Ganjoo, K. N., George, S., Gonzalez, R., Heslin, M. J., Kane, J. M., Mayerson, J., McGarry, S. V., Meyer, C., O'Donnell, R. J., Paz, I. B., Pfeifer, J. D., Pollock, R. E., Randall, R. L., Riedel, R. F., Schuetze, S., Schupak, K. D., Schwartz, H. S., Shankar, S., Van Tine, B. A., Wayne, J., Sundar, H., McMillian, N. R. 2012; 10 (8): 951-960

  Abstract

  The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.

  View details for Web of Science ID 000307494000006

  View details for PubMedID 22878820

• Chest Wall Leiomyosarcoma After Breast-Conservative Therapy for Early-Stage Breast Cancer in a Young Woman With Li-Fraumeni Syndrome JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Henry, E., Villalobos, V., Million, L., Jensen, K. C., West, R., Ganjoo, K., Lebensohn, A., Ford, J. M., Telli, M. L. 2012; 10 (8): 939-942

  Abstract

  Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

  View details for PubMedID 22878818

• Cardiac toxicity associated with bevacizumab (Avastin) in combination with CHOP chemotherapy for peripheral T cell lymphoma in ECOG 2404 trial LEUKEMIA & LYMPHOMA Advani, R. H., Hong, F., Horning, S. J., Kahl, B. S., Manola, J., Swinnen, L. J., Habermann, T. M., Ganjoo, K. 2012; 53 (4): 718-720

  View details for DOI 10.3109/10428194.2011.623256

  View details for Web of Science ID 000302067100030

  View details for PubMedID 21916830

• Maintenance Bevacizumab is Associated With Increased Hemoglobin in Patients With Advanced, Nonsquamous, Non-Small Cell Lung Cancer CANCER INVESTIGATION Riess, J. W., Logan, A. C., Krupitskaya, Y., Padda, S., Clement-Duchene, C., Ganjoo, K., Colevas, A. D., San Pedro-Salcedo, M., Kuo, C. J., Wakelee, H. A. 2012; 30 (3): 231-235

  Abstract

  We retrospectively analyzed hematologic parameters in 22 patients with advanced, nonsquamous, NSCLC undergoing VEGF inhibition on a phase II clinical trial of bevacizumab, carboplatin, and gemcitabine. We also examined TTP in relation to hemoglobin changes. Median hemoglobin increased significantly from a 12.9 g/dL pretreatment to 13.8 g/dL (p =.01) after the second cycle of maintenance bevacizumab until the first off cycle measurement. There was no difference in TTP in patients who achieved a rise in hemoglobin compared with patients who did not (median 238 days vs. 268 days, p =.38.) Maintenance bevacizumab is associated with increased hemoglobin in advanced, nonsquamous, NSCLC patients.

  View details for DOI 10.3109/07357907.2012.656862

  View details for PubMedID 22360362

• Results of a Phase 1 Study of AME-133v (LY2469298), an Fc-Engineered Humanized Monoclonal Anti-CD20 Antibody, in Fc gamma RIIIa-Genotyped Patients with Previously Treated Follicular Lymphoma CLINICAL CANCER RESEARCH Forero-Torres, A., de Vos, S., Pohlman, B. L., Pashkevich, M., Cronier, D. M., Dang, N. H., Carpenter, S. P., Allan, B. W., Nelson, J. G., Slapak, C. A., Smith, M. R., Link, B. K., Wooldridge, J. E., Ganjoo, K. N. 2012; 18 (5): 1395-1403

  Abstract

  AME-133v is a humanized monoclonal antibody engineered to have increased affinity to CD20 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) better than rituximab. Safety, pharmacokinetics, and efficacy were assessed in a phase 1/2 trial in patients with previously treated follicular lymphoma (FL).AME-133v was characterized in vitro by ADCC and cell binding assays. A phase 1 study was conducted in which 23 previously treated patients with FL were assigned sequentially to one of five dose-escalation cohorts of AME-133v at 2, 7.5, 30, 100, or 375 mg/m(2) weekly × 4 doses.AME-133v showed a 13- to 20-fold greater binding affinity for CD20 and was 5- to 7-fold more potent than rituximab in ADCC assays. Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, and AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner. AME-133v was well tolerated by patients and common related adverse events included chills and fatigue. One patient experienced a dose-limiting toxicity of neutropenia. AME-133v showed nonlinear pharmocokinetics with properties similar to rituximab. Selective reduction of B cells during and after AME-133v treatment was shown by flow cytometry of peripheral blood. A partial or complete response was observed in 5 of 23 (22%) patients and the median progression-free survival was 25.4 weeks.AME-133v was safe and well tolerated at the doses tested. AME-133v showed encouraging results as an anti-CD20 therapy in heavily pretreated FL patients with the less favorable Fc?RIIIa F-carrier genotype.

  View details for DOI 10.1158/1078-0432.CCR-11-0850

  View details for Web of Science ID 000301040700023

  View details for PubMedID 22223529

• The Prognostic Value of Tumor-Associated Macrophages in Leiomyosarcoma A Single Institution Study AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Ganjoo, K. N., Witten, D., Patel, M., Espinosa, I., La, T., Tibshirani, R., van de Rijn, M., Jacobs, C., West, R. B. 2011; 34 (1): 82-86

  Abstract

  High numbers of tumor-associated macrophages (TAMs) have been associated with poor outcome in several solid tumors. In 2 previous studies, we showed that colony stimulating factor-1 (CSF1) is secreted by leiomyosarcoma (LMS) and that the increase in macrophages and CSF1 associated proteins are markers for poor prognosis in both gynecologic and nongynecologic LMS in a multicentered study. The purpose of this study is to evaluate the outcome of patients with LMS from a single institution according to the number of TAMs evaluated through 3 CSF1 associated proteins.Patients with LMS treated at Stanford University with adequate archived tissue and clinical data were eligible for this retrospective study. Data from chart reviews included tumor site, size, grade, stage, treatment, and disease status at the time of last follow-up. The 3 CSF1 associated proteins (CD163, CD16, and cathepsin L) were evaluated by immunohistochemistry on tissue microarrays. Kaplan-Meier survival curves and univariate Cox proportional hazards models were fit to assess the association of clinical predictors as well as CSF1 associated proteins with overall survival.A total of 52 patients diagnosed from 1983 to 2007 were evaluated. Univariate Cox proportional hazards models were fit to assess the significance of grade, size, stage, and the 3 CSF1 associated proteins in predicting OS. Grade, size, and stage were not significantly associated with survival in the full patient cohort, but grade and stage were significant predictors of survival in the gynecologic (GYN) LMS samples (P = 0.038 and P = 0.0164, respectively). Increased cathepsin L was associated with a worse outcome in GYN LMS (P = 0.049). Similar findings were seen with CD16 (P < 0.0001). In addition, CSF1 response enriched (all 3 stains positive) GYN LMS had a poor overall survival when compared with CSF1 response poor tumors (P = 0.001). These results were not seen in non-GYN LMS.Our data form an independent confirmation of the prognostic significance of TAMs and the CSF1 associated proteins in LMS. More aggressive or targeted therapies could be considered in the subset of LMS patients that highly express these markers.

  View details for DOI 10.1097/COC.0b013e3181d26d5e

  View details for PubMedID 23781555

• A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Nonsquamous Non-small Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Clement-Duchene, C., Krupitskaya, Y., Ganjoo, K., Lavori, P., McMillan, A., Kumar, A., Zhao, G., Padda, S., Zhou, L., San Pedro-Salcedo, M., Colevas, A. D., Wakelee, H. A. 2010; 5 (11): 1821-1825

  Abstract

  Bevacizumab improves responses and progression-free survival when added to first-line paclitaxel/carboplatin or cisplatin/gemcitabine for patients with advanced nonsquamous non-small cell lung cancer. This study was designed to evaluate toxicities and efficacy of gemcitabine/carboplatin/bevacizumab.Patients with untreated advanced nonsquamous non-small cell lung cancer, with no evidence of brain metastases and not on anticoagulation were eligible. Patients received gemcitabine 1000 mg/m on days 1 and 8; carboplatin area under the curve 5 day 1; and bevacizumab 15 mg/kg day 1 every 3 weeks for up to six cycles. Bevacizumab was then continued every 3 weeks until disease progression or unacceptable toxicity.From July 2006 to December 2008, 48 patients were enrolled: 23 (48%) men, 25 (52%) women, and 19 (40%) never smokers. One patient never received therapy and is not included in the analysis. Median cycle number was 8 (1-42) with 37 patients (78.7%) completing ?4 cycles of three drugs. Dose reductions occurred in 34 (72.3%) patients. Grade 3/4 toxicities included neutropenia (47%/15%), thrombocytopenia (11%/15%), anemia (6%/0%), dyspnea (6%/2%), bacterial pneumonia (4%/0%), and hypertension (4%/2%). No neutropenic fevers occurred. One patient died of hemoptysis. Grade 3 bleeding occurred in three other patients. There were seven (14.9%) partial responses. Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4 months (95% confidence interval: 4.8-7.9 months). The median overall survival (OS) was 12.8 months (95% confidence interval: 10.0-16.5). The OS is 57% at 1 year and 10% at 2 years.Although perhaps skewed by a high proportion of nonsmokers and women, treatment with gemcitabine/carboplatin/bevacizumab has an acceptable toxicity profile with promising median OS despite a low response rate.

  View details for DOI 10.1097/JTO.0b013e3181f1d23c

  View details for PubMedID 20881641

• TH-302, a tumor selective hypoxia activated prodrug, complements and enhances chemotherapy treatment with gemcitabine, docetaxel, pemetrexed, and doxorubicin 22nd European Organization for Research and Treatment of Cancer (EORTC)-National-Cancer-Institute(NCI)-American-Association-for-Cancer-Research(AACR) Symposium on Molecular Targets and Cancer Therapeutics Hart, C. P., Borad, M., Chawla, S. P., Infante, J. R., Ganjoo, K. N., Langmuir, V. K., KROLL, S., Curd, J. G. PERGAMON-ELSEVIER SCIENCE LTD. 2010: 124?24

  View details for Web of Science ID 000288460100384

• I-131-Tositumomab (BexxarA (R)) vs. Y-90-Ibritumomab (ZevalinA (R)) Therapy of Low-Grade Refractory/Relapsed Non-Hodgkin Lymphoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Mittra, E. S., Ganjoo, K., Knox, S. J., Goris, M. L. 2010; 12 (2): 198-203

  Abstract

  The American Cancer Society estimated 66,120 new cases of non-Hodgkin lymphoma (NHL) in the USA in 2008. Radioimmunotherapy has been shown in clinical trials to be an effective treatment for refractory/relapsed NHL. The available agents are Bexxar, a (131)I radiolabeled murine monoclonal antibody, and Zevalin, a (90)Y radiolabeled murine antibody. Both target CD20 receptors present on the surface of lymphocytes. We present our clinical experience with Bexxar and Zevalin in the management of low-grade refractory or relapsed NHL.This is a retrospective study (Jan 2000-Jul 2006) of 67 patients with NHL, who were treated with Bexxar (31 patients, group A) or Zevalin (36 patients, group B) for refractory/relapsed disease. Group A included 16 men and 15 women, 35-81 years old (average, 59.3 +/- 13.4). Group B included 27 men and nine women, 36-85 years old (average, 55.4 +/- 13.8). Therapeutic doses ranged 40-138 mCi (average, 78.1 +/- 28.2) for Bexxar and 17-34 mCi (average, 28.8 +/- 4.37) for Zevalin.Objective responses were induced in 22 of the 31 patients (70.9%) in group A and 28 of the 36 patients (77.8%) in group B. Complete response was noted in 11 patients (35.5%), partial response in seven patients (22.6%), and mixed response in four patients (12.9%) in group A. There were five patients (16.1%) with stable disease and four patients (12.9%) with disease progression in the same group. Complete response was noted in 15 patients (41.7%), partial response in nine patients (25%), and mixed response in four patients (11.1%) in group B. There were four patients (11.1%) with stable disease and another four patients (11.1%) with disease progression in the same group. The average decreases at posttherapy nadir were 36.9% +/- 0.33 (group A) and 52.6% +/- 0.32 (group B) for platelets, 27.8% +/- 0.27 (group A) and 34.2% +/- 0.38 (group B) for leukocytes, and 4.9% +/- 0.15 (group A) and 7.6% +/- 0.11 (group B) for hemoglobin. Grades 3 and 4 hematological toxicity occurred in 14 patients (45.2%) treated with Bexxar and 22 patients (61.1%) treated with Zevalin, but was reversible.Our study suggests that clinical practice of Bexxar and Zevalin radioimmunotherapy is an effective and safe adjunctive treatment for patients with NHL refractory/relapsed to conventional treatment. However, due to the small number of subjects, it was not possible to determine whether differences in the outcomes or toxicities from the two agents were statistically significant.

  View details for DOI 10.1007/s11307-009-0245-9

  View details for Web of Science ID 000275974900010

  View details for PubMedID 19543946

• Bendamustine Is Effective Therapy in Patients With Rituximab-Refractory, Indolent B-cell Non-Hodgkin Lymphoma Results From a Multicenter Study CANCER Kahl, B. S., Bartlett, N. L., Leonard, J. P., Chen, L., Ganjoo, K., Williams, M. E., Czuczman, M. S., Robinson, K. S., Joyce, R., Van der Jagt, R. H., Cheson, B. D. 2010; 116 (1): 106-114

  Abstract

  Bendamustine hydrochloride is a novel alkylating agent. In this multicenter study, the authors evaluated the efficacy and toxicity of single-agent bendamustine in patients with rituximab-refractory, indolent B-cell lymphoma.Eligible patients (N = 100, ages 31-84 years) received bendamustine at a dose of 120 mg/m(2) by intravenous infusion on Days 1 and 2 every 21 days for 6 to 8 cycles. Histologies included follicular (62%), small lymphocytic (21%), and marginal zone (16%) lymphomas. Patients had received a median of 2 previous regimens (range, 0-6 previous regimens), and 36%were refractory to their most recent chemotherapy regimen. Primary endpoints included overall response rate (ORR) and duration of response (DOR). Secondary endpoints were safety and progression-free survival (PFS).An ORR of 75% (a 14% complete response rate, a 3% unconfirmed complete response rate, and a 58% partial response rate) was observed. The median DOR was 9.2 months, and median PFS was 9.3 months. Six deaths were considered to be possibly treatment related. Grade 3 or 4 (determined using National Cancer Institute Common Toxicity Criteria [version 3.0.19]. reversible hematologic toxicities included neutropenia (61%), thrombocytopenia (25%), and anemia (10%). The most frequent nonhematologic adverse events (any grade) included nausea (77%), infection (69%), fatigue (64%), diarrhea (42%), vomiting (40%), pyrexia (36%), constipation (31%), and anorexia (24%).Single-agent bendamustine produced a high rate of objective responses with acceptable toxicity in patients with recurrent, rituximab-refractory indolent B-cell lymphoma.

  View details for DOI 10.1002/cncr.24714

  View details for Web of Science ID 000273864600015

  View details for PubMedID 19890959

• Breast Angiosarcoma: Case Series and Expression of Vascular Endothelial Growth Factor. Case reports in oncology Brar, R., West, R., Witten, D., Raman, B., Jacobs, C., Ganjoo, K. 2009; 2 (3): 242-250

  Abstract

  PURPOSE: Angiosarcoma of the breast is a rare, malignant tumor for which little is known regarding prognostic indicators and optimal therapeutic regimens. To address this issue, we performed a retrospective analysis of breast angiosarcoma cases seen at Stanford University along with immunohistochemical analysis for markers of angiogenesis. METHODS: Breast angiosarcoma cases seen between 1980 and 2008 were examined. Viable tissue blocks were analyzed for expression of vascular endothelial growth factor and its receptors. RESULTS: A total of 16 cases were identified. Data was collected regarding epidemiology, treatment, response rates, disease-free survival, and the use of various imaging modalities. Five tissue blocks remained viable for immunohistochemical analysis. Vascular endothelial growth factor-A was positively expressed in 3 of these samples. CONCLUSION: Angiosarcoma of the breast is an aggressive malignancy with a propensity for both local recurrence and distant metastases. Angiogenesis inhibition may represent a novel therapeutic modality in this rare, vascular malignancy.

  View details for PubMedID 20737044

• Cardiac Toxicity Associated with the Anti-VEGF Monoclonal Antibody Bevacizumab (Avastin) in Combination with CROP (A-CHOP) Chemotherapy for Peripheral T Cell Lymphoma (PTCL): The ECOG 2404 Trial. Advani, R. H., Hong, F., Ganjoo, K. N., Manola, J. B., Swinnen, L. J., Habermann, T. M., Horning, S. J. AMER SOC HEMATOLOGY. 2009: 667

  View details for Web of Science ID 000272725802039

• A phase II first line study of gemcitabine, carboplatin and bevacizumab in advanced stage non-squamous non-small cell lung cancer Clement-Duchene, C., Krupitskaya, Y., Ganjoo, K., Lavori, P., Kumar, A., Zhao, G., Padda, S., San Pedro-Salcedo, M., Wakelee, H. LIPPINCOTT WILLIAMS & WILKINS. 2009: S674?S674

  View details for Web of Science ID 000269496002133

• Mid-treatment PET predicts progression in hypofractionated accelerated radiation therapy for lung tumors Chang, C. N., Fillion, E., Chapman, C., Rao, A., Wakelee, H., Ganjoo, K., Le, Q., Maxim, P., Quon, A., Graves, E. E., Loo, B. W. LIPPINCOTT WILLIAMS & WILKINS. 2009: S939?S939

  View details for Web of Science ID 000269496002721

• Coordinate Expression of Colony-Stimulating Factor-1 and Colony-Stimulating Factor-1-Related Proteins Is Associated with Poor Prognosis in Gynecological and Nongynecological Leiomyosarcoma AMERICAN JOURNAL OF PATHOLOGY Espinosa, I., Beck, A. H., Lee, C., Zhu, S., Montgomery, K. D., Marinelli, R. J., Ganjoo, K. N., Nielsen, T. O., Gilks, C. B., West, R. B., van de Rijn, M. 2009; 174 (6): 2347-2356

  Abstract

  Previously, we showed that the presence of high numbers of macrophages correlates with poor prognosis in nongynecological leiomyosarcoma (LMS). In gynecological LMS, a similar trend was noted but did not reach statistical significance. Colony-stimulating factor-1 (CSF1) is a major chemoattractant for macrophages. Here we show that in a subset of LMS cases, CSF1 is expressed by the malignant cells. Previously, we found that CSF1 is translocated and highly expressed in tenosynovial giant cell tumors (TGCTs), and this observation allowed us to identify genes that showed a coordinate expression with CSF1. Here, we evaluated the expression of CSF1 and TGCT-associated proteins in 149 cases of LMS. The coordinate expression of CSF1 and three TGCT-associated proteins (CD163, FCGR3a, and CTSL1) identified cases with poor prognosis in both gynecological LMS (P = 0.00006) and nongynecological LMS (P = 0.03). In gynecological LMS, the coordinate expression of these four markers was the only independent prognosticator in multivariate analysis (hazard ratio, 4.2; 95% CI, 1.12 to 16; P = 0.03). Our findings indicate that CSF1 may play an important role in the clinical behavior of LMS that may open a window for new therapeutic reagents.

  View details for DOI 10.2353/ajpath.2009.081037

  View details for PubMedID 19443701

• Opportunistic enteroviral meningoencephalitis: an unusual treatable complication of rituximab therapy LEUKEMIA & LYMPHOMA Ganjoo, K. N., Raman, R., Sobel, R. A., Pinto, H. A. 2009; 50 (4): 673-675

  View details for DOI 10.1080/10428190902782210

  View details for Web of Science ID 000265361500031

  View details for PubMedID 19373672

• Breast Angiosarcoma: Case Series and Expression of Vascular Endothelial Growth Factor CASE REPORTS IN ONCOLOGY Brar, R., West, R., Witten, D., Raman, B., Jacobs, C., Ganjoo, K. 2009; 2 (3): 242?50

  View details for DOI 10.1159/000264637

  View details for Web of Science ID 000216899300014

• Breast angiosarcomas: Case series and expression of vascular endothelial growth factor Case Reports in Oncology Rondeep Brar, Robert West, Daniela Witten, Bhargav Raman, Charlotte Jacobs, Kristen Ganjoo 2009; 2: 242-50
• Preliminary results of a Phase I study of AME-133v, an Fc-engineered humanized monoclonal antibody, in low-affinity Fc gamma RIIIa patients with previously-treated follicular lymphoma Forero, A., de Vos, S., Pohlman, B., Enas, N., Ganjoo, K. N., Cronier, D., Dang, N. H., Carpenter, S. P., Smith, M. R., Link, B. K., Wooldridge, J. E. AMER ASSOC CANCER RESEARCH. 2008

  View details for DOI 10.1158/1538-7445.AM2008-LB-70

  View details for Web of Science ID 000454834700006

• Results of a Phase 3 trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to non-specific immunotherapy, KLH with GM-CSF, in patients with follicular non-Hodgkin's lymph Levy, R., Robertson, M. J., Ganjoo, K., Leonard, J., Vose, J., Denney, D. AMER ASSOC CANCER RESEARCH. 2008

  View details for DOI 10.1158/1538-7445.AM2008-LB-204

  View details for Web of Science ID 000454834700022

• The importance of angiogenesis markers in the outcome of patients with diffuse large B cell lymphoma: a retrospective study of 97 patients JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY Ganjoo, K. N., Moore, A. M., Orazi, A., Sen, J. A., Johnson, C. S., An, C. S. 2008; 134 (3): 381-387

  Abstract

  The role of angiogenesis has been extensively evaluated in solid tumors and more recently in hematologic malignancies. Several surrogate markers of angiogenesis including tumor VEGF, VEGF receptors, and microvessel density have correlated with outcome in some lymphoma studies. This is a single institution retrospective study evaluating the role of angiogenesis markers in the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL).A total of 97 patients with DLBCL diagnosed and managed at Indiana University between 1993 and 2001 were included. Archived tumor samples were stained for VEGF-A, VEGF-C, VEGF-R1, and CD31 and graded as negative or positive (1+, 2+, 3+). The relationship between the expression of these markers and the international prognostic variables as well as the progression free survival (PFS) and the overall survival (OS) was evaluated.VEGF-A, VEGF-C, VEGF-R1 were expressed in 77, 98, and 18% of tumors, respectively. VEGF-A negative patients had an improved OS compared to VEGF-A (1+) (P = 0.0502). VEGF-C correlated with both LDH (r = 0.28, P = 0.0502) and IPI score (r = 0.25, P = 0.013). VEGF-R1 negative patients had a superior survival compared to those with VEGF-R1 (2+) (P = 0.0154).The presence of tumor associated angiogenesis may alter the outcome of patients with DLBCL and could be a prognostic factor. Further clinical studies are needed to correlate the degree of angiogenesis with response to anti-angiogenesis agents.

  View details for DOI 10.1007/s00432-007-0294-x

  View details for Web of Science ID 000252627000012

  View details for PubMedID 17694324

• Review of erlotinib in the treatement of advanced non-small cell lung cancer Biologics; Targets & Therapy Kristen N Ganjoo, Heather Wakelee 2008
• Review of erlotinib in the treatment of advanced non-small cell lung cancer. Biologics : targets & therapy Ganjoo, K. N., Wakelee, H. 2007; 1 (4): 335-346

  Abstract

  Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Once stimulated by ligand, the downstream pathway is activated leading to cell growth, survival, and carcinogenesis. There are several methods of EGFR inhibition including monoclonal antibodies directed against the external region and small molecule inhibitors of TK domain. Erlotinib and gefitinib are orally available small molecule EGFR TK inhibitors, with proven efficacy in NSCLC. The most common side effects are skin toxicity and diarrhea. Erlotinib has been shown to improve survival compared to placebo in second or third-line therapy for NSCLC. However, erlotinib in combination with chemotherapy failed to show a survival advantage in two first-line studies which could be due to the timing of chemotherapy administration. In general, patients with adenocarcinoma histology, female gender, Asian ethnicity, and never smokers have a better response when treated with erlotinib. This could be related to the presence of EGFR mutations, lack of KRAS mutations, or overexpression of EGFR as measured by fluorescent in-situ hybridization (FISH) analysis. Future studies should concentrate on further development of predictors of clinical benefit with erlotinib, overcoming resistance to erlotinib that develops in initial responders, as well as more effective sequencing of erlotinib with chemotherapy and combinations of the drug with other "targeted" therapeutic agents.

  View details for PubMedID 19707304

  View details for PubMedCentralID PMC2721286

• Comparison of I-131-Tositumomab (Bexxar (R)) and Y-90-Ibritumomab (Zevalin (R)) therapy of refractory/relapsed non-Hodgkin lymphoma Iagaru, A., Zhu, H., Mari, C., Knox, S. J., Ganjoo, K., Goris, M. L. SPRINGER. 2007: S168

  View details for Web of Science ID 000253283900232

• Non-Hodgkin lymphoma of the breast CANCER Ganjoo, K., Advani, R., Mariappan, M. R., McMillan, A., Horning, S. 2007; 110 (1): 25-30

  Abstract

  Primary lymphoma of the breast has been reported to have a high local and central nervous system recurrence (CNS) rate, suggesting the need for consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to evaluate the institutional experience in this patient population.In all, 37 patients with lymphoma involving the breast at initial diagnosis and managed at Stanford University from 1981-2005 were included. Diagnostic tissue biopsies were obtained either from the breast mass or an involved lymph node. Treatment and response data, patterns of recurrence, and outcomes were reviewed.Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes were seen in 38%. Most patients presented with an incidental breast mass in stage I(E) or II(E). Four (11%) patients presented with bilateral breast involvement, with only 1 patient presenting with CNS disease. DLBCL patients received doxorubicin-based chemotherapy, with 70% receiving involved field radiotherapy and a single patient receiving intrathecal therapy. No recurrences occurred in the involved breast and a single parenchymal CNS recurrence was recorded. Among the DLBCL patients, the 5-year progression-free survival (PFS) was 61%, with a median follow-up of 3.8 years (range, 5 months to 19 years) and the 5-year overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had an estimated 5-year PFS of 76% and an OS of 92%.DLBCL of the breast was successfully treated with doxorubicin-based chemotherapy alone or with involved field radiotherapy in an estimated 61% of patients at 5 years. A single CNS recurrence was observed in our series of patients, most of whom presented with limited disease.

  View details for DOI 10.1002/cncr.22753

  View details for PubMedID 17541937

• Antiangiogenesis: A new approach to the treatment of lymphoma LEUKEMIA & LYMPHOMA Ganjoo, K. 2007; 48 (3): 454-455

  View details for DOI 10.1080/10428190701200059

  View details for Web of Science ID 000245108100006

  View details for PubMedID 17454583

• Rituximab, Bevacizumab and CHOP (RA-CHOP) in untreated diffuse large B-cell lymphoma: Safety, biomarker and pharmacokinetic analysis LEUKEMIA & LYMPHOMA Ganjoo, K. N., An, C. S., Robertson, M. J., Gordon, L. I., Sen, J. A., Weisenbach, J., Li, S., Weller, E. A., Orazi, A., Horning, S. J. 2006; 47 (6): 998-1005

  Abstract

  Bevacizumab is a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF-A). Non-Hodgkin's lymphoma patients with high serum VEGF levels have an inferior survival compared to patients with low VEGF levels. Bevacizumab was administered through a central line at 15 mg kg(-1) IV on day 1 followed by rituximab (R) and CHOP on day 2 for cycle 1 and day 1 for cycles 2 - 8. Serum levels of bevacizumab and R were measured at specified time points to assess pharmacokinetics (PK). Plasma and urine samples were also analysed for VEGF. Tumor samples were stained for VEGF, CD31 and factor VIII by immunohistochemistry. Thirteen patients with newly-diagnosed DLBCL received a total of 88 cycles (range 2 - 8, median 7). Best response included five CR, six PR, one SD and one PD with an overall response rate of 85% and complete response rate of 38%. The 12-month PFS is 77% and a median follow-up of 16.9 months for the surviving patients. All tumor samples stained strongly positive for VEGF and there was a marginal association between baseline plasma VEGF and response (p = 0.04). Patients with higher plasma VEGF levels were generally younger and had bulky disease. Micro-vessel density did not correlate with presenting disease characteristics, VEGF expression or response. The PK of bevacizumab and rituximab were not influenced by combined treatment. In this patient population, treatment with RA-CHOP did not result in any episodes of grade 3 or 4 proteinuria, heart failure or hemorrhage. The RA-CHOP combination was generally well tolerated and safe.

  View details for DOI 10.1080/10428190600563821

  View details for Web of Science ID 000239037000007

  View details for PubMedID 16840188

• Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia CANCER Frankel, A. E., Surendranathan, A., Black, J. H., White, A., Ganjoo, K., Cripe, L. D. 2006; 106 (10): 2158-2164

  Abstract

  The safety and efficacy of the interleukin-2 diphtheria toxin fusion protein (DAB(389)IL2; denileukin diftitox) directed against the IL-2 receptor (IL-2R) was tested in patients with recurrent or refractory chronic lymphocytic leukemia (CLL).Denileukin diftitox was administered as 60-minute intravenous infusions for 5 days every 21 days at a dose of 18 mug/kg per day for up to 8 cycles. In total, 28 patients were treated in 2 multiinstitutional studies with similar eligibility criteria and treatment protocols. Twenty-two patients receive > or = 2 cycles of denileukin diftitox and were evaluable for response.Twelve of 22 patients achieved reductions of peripheral CLL cells, with 5 of 12 patients achieving >80% reductions. Six of 22 patients achieved reductions in the size of lymph node on examination and computed tomography scans, and all 6 of those patients met the criteria for a partial or complete response that lasted > or = 2 months. Bone marrow biopsies before and after treatment confirmed a complete remission that lasted for 1 year in 1 patient. Overall, denileukin diftitox produced complete remission in 1 of 22 patients (4%) and partial remission in 5 of 22 patients (23%) for a total remission rate of 27%. Progression-free intervals in the responders were 2 months in 2 patients and 4 months, 6 months, 7 months, and 12 months in 1 patient each. Toxicities were moderate. No infections associated with immunosuppression were seen. There was no significant correlation of response or toxicities with the numbers of denileukin diftitox cycles received or with CD25 levels.Follow-up studies will be required to identify predictors of response that may improve the response rate to denileukin diftitox in patients with CLL.

  View details for DOI 10.1002/cncr.21851

  View details for Web of Science ID 000237278300010

  View details for PubMedID 16586495

• A phase II study of single agent gemcitabine in relapsed or refractory follicular or small lymphocytic non-Hodgkin lymphomas - A hoosier oncology group study AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Ganjoo, K. N., Robertson, M. J., Fisher, W., Jung, S. H., McClean, J., Huh, S. Y., Bufill, J., Williams, S., Cripe, L. D. 2005; 28 (2): 169-172

  Abstract

  Gemcitabine is a pyrimidine analog that is active in patients with aggressive lymphomas and Hodgkin disease. This study assessed tumor response in patients with previously treated follicular or small lymphocytic non-Hodgkin lymphoma. This was a 2-stage phase II trial with the first stage requiring 2 of 13 responses to proceed to the second stage. Gemcitabine was given as a single agent to patients with previously treated follicular or small lymphocytic lymphomas. Gemcitabine was administered at 1250 mg/m2 over 30 minutes on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Thirteen patients were treated with 1 to 6 cycles of chemotherapy. Two patients experienced grade 4 toxicity with neutropenia. No grade 4 nonhematologic toxicity was seen. There was 1 partial response and 8 patients (61%) had either minimal response or stable disease. Single-agent gemcitabine administered at this dose and schedule produced 1 partial remission and half the patients had stable disease. However, the study had to be stopped early because of lack of meaningful response.

  View details for DOI 10.1097/01.coc.0000144812.74663.d0

  View details for Web of Science ID 000228240600013

  View details for PubMedID 15803012

• Unusual locations of involvement by malignancies - Case 1. Testicular plasmacytoma JOURNAL OF CLINICAL ONCOLOGY Shafqat, A., Yum, M. N., Abanour, R., Ganjoo, K. N. 2003; 21 (17): 3368-3369

  View details for DOI 10.1200/JCO.2003.09.049

  View details for Web of Science ID 000185091300029

  View details for PubMedID 12947074

• Phase II study of gemcitabine plus docetaxel in advanced pancreatic cancer: A Hoosier Oncology Group study ONCOLOGY Schneider, B. P., Ganjoo, K. N., Seitz, D. E., Picus, J., Fata, F., Stoner, C., Calley, C., Loehrer, P. J. 2003; 65 (3): 218-223

  Abstract

  To determine the response rate, duration of response and survival with weekly gemcitabine plus docetaxel in metastatic or unresectable pancreatic cancer.Forty patients were enrolled, and 38 patients were evaluable for survival and toxicity. Thirty-seven patients were evaluable for response. Nine patients (24%) had locally advanced disease and 29 (76%) had metastatic disease at the time of enrollment. Median Eastern Cooperative Oncology Group performance status was 1. Patients received gemcitabine 750 mg/m(2) i.v. and docetaxel 35 mg/m(2) i.v. weekly for 3 out of 4 weeks for a maximum of 6 cycles.Patients received a median of 4 cycles (range 1-6) of chemotherapy. An objective response was obtained in 10 patients (27%) with a median duration of 17 weeks. Median survival was 7 months, and 1-year survival was 19.3%. Eight patients experienced at least one form of grade 4 toxicity and 27 patients experienced at least one type of grade 3 toxicity.The combination of gemcitabine and docetaxel is a well-tolerated regimen with clinical efficacy. The ultimate role of this combination versus single-agent gemcitabine can only be determined by a randomized phase III trial.

  View details for DOI 10.1159/000074474

  View details for Web of Science ID 000186975500005

  View details for PubMedID 14657595

• A phase I study of weekly gemcitabine and docetaxel in patients with advanced cancer: A Hoosier Oncology Group study ONCOLOGY Ganjoo, K. N., GORDON, M. S., Sandler, A. B., Warner, R. E., Fife, K., Poirier, S., Seshadri, R., Loehrer, P. J. 2002; 62 (4): 299-304

  Abstract

  To determine the maximum tolerated dose (MTD) of weekly gemcitabine plus docetaxel, a dose escalation trial of both drugs was developed with each administered weekly for 3 weeks out of 4.Dose levels for gemcitabine (mg/m(2)) and docetaxel (mg/m(2)) were as follows: level 1: 600/25; level 2: 600/35; level 3: 750/35; and level 4: 900/35. Sixteen patients with adequate renal, hepatic, and hematologic function and an Eastern Cooperative Oncology Group performance status of 0-2 were treated. Primary sites included pancreas (12) and others (4).Three patients were treated at each dose level from level 1 through level 4. The dose-limiting toxicity (DLT) was neutropenia, the maximum tolerated dose being 750 mg/m(2) of gemcitabine and 35 mg/m(2) of docetaxel. No grade 4 nonhematologic toxicity was seen. Three patients had grade 4 neutropenia. Of the 12 patients with pancreatic cancer, 1 had a partial remission and 7 had stable disease with a median duration of 8 weeks.Gemcitabine and docetaxel can be safely administered weekly at a dose of 750 and 35 mg/m(2), respectively. The DLT was neutropenia. Disease stabilization suggests that this may be an active regimen in patients with metastatic pancreatic cancer.

  View details for Web of Science ID 000176987000003

  View details for PubMedID 12138236

• Germ cell tumor associated primitive neuroectodermal tumors JOURNAL OF UROLOGY Ganjoo, K. N., Foster, R. S., Michael, H., Donohue, J. P., Einhorn, L. H. 2001; 165 (5): 1514-1516

  Abstract

  This retrospective review was done to assess the prognosis and response in patients presenting with primitive neuroectodermal tumor admixed with germ cell tumor.Of the 40 patients treated at our institution from 1984 to 1999, 15 had initial stage I and 25 had initial metastatic disease. Median followup after the diagnosis was 25 months (range 4 to 142).Of the 40 patients 15 presented with clinical stage I disease, including 9 treated with retroperitoneal lymph node dissection and 6 who elected surveillance. Seven of the 9 patients had normal lymph nodes and all continuously had no evidence of disease. Two of the 9 patients had lymph nodes involved with teratoma with or without primitive neuroectodermal tumor. Retroperitoneal relapse in 5 of the 6 patients on surveillance was treated with cisplatin based chemotherapy followed by post-chemotherapy retroperitoneal lymph node dissection. Residual primitive neuroectodermal tumor was noted in 4 of the 5 patients and only 3 of 6 are currently without disease at a median followup of 17 months (range 15 to 69). A total of 25 patients presented with metastatic disease, of whom 23 underwent cisplatin based chemotherapy. Only 3 patients achieved complete remission with chemotherapy alone and 2 of the 3 subsequently relapsed. Of the remaining 20 patients 16 underwent post-chemotherapy retroperitoneal lymph node dissection, including 11 with primitive neuroectodermal tumor in the resected specimen. Two of these 11 patients have continuously had no evidence of disease, while an additional 3 currently have no evidence of disease after further therapy. Teratoma was present in the resected specimen in 5 of 16 patients, of whom 2 have continuously had no evidence of disease, while an additional 2 currently have no evidence of disease after further surgical resection. Therefore, 11 of 25 patients who presented with metastatic disease currently have no evidence of disease at a median followup of 19 months (range 2 to 111).Primitive neuroectodermal tumor in the orchiectomy specimen has adverse prognostic significance. This condition in the retroperitoneum is potentially curable by retroperitoneal lymph node dissection but rarely eradicated by chemotherapy. Therefore, we recommend retroperitoneal lymph node dissection for all clinical stage I cases with primitive neuroectodermal tumor in the orchiectomy specimen. Patients who present with metastatic primitive neuroectodermal tumor should be treated aggressively with surgical resection as an integral part of the therapeutic strategy.

  View details for Web of Science ID 000168321500030

  View details for PubMedID 11342908

• Results of modern therapy for patients with mediastinal nonseminomatous germ cell tumors 35th Annual Meeting of the American-Society-of-Clinical-Oncology Ganjoo, K. N., Rieger, K. M., Kesler, K. A., Sharma, M., Heilman, D. K., Einhorn, L. H. JOHN WILEY & SONS INC. 2000: 1051?56

  Abstract

  The aim of this study was to determine the effects of independent prognostic variables, such as prechemotherapy tumor markers, the extent of disease at diagnosis, the tumor markers postchemotherapy (PC), and the pathology of the PC residual mass on the overall survival of patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCT).The authors undertook a retrospective review of 39 patients with PMNSGCT between 1983 and 1997 who received their initial chemotherapy at Indiana University and 36 additional patients referred for PC resection. All patients received chemotherapy based on the combination of cisplatin and etoposide. The median follow-up was 22 months (range, 12-144 months).The prechemotherapy tumor markers did not affect overall survival. Extent of disease (mediastinal only vs. visceral metastases) was an important prognostic factor for survival in univariate analysis (P = 0.042). Sixty-two of 75 patients underwent PC resection of residual disease. Fifteen of the 62 patients achieved a CR with chemotherapy alone, as the PC resection revealed only necrosis. Fourteen of these 15 patients continuously had no evidence of disease (NED). Forty-seven of the 62 patients had NED with chemotherapy and PC resection, including 31 with teratoma and 16 with carcinoma. However, 11 of 31 with teratoma and 11 of 16 with carcinoma subsequently relapsed. Although 18 patients had elevated tumor markers at the time of PC resection, 6 of 18 had only necrosis and 4 had teratoma. The PC tumor markers did not affect survival. The pathology of the resected specimen was the most significant predictor of survival in multivariate analysis (P < 0.001).Twenty-eight of 39 patients (71.8%) with PMNSGCT treated at Indiana University achieved NED status, but only 16 (41%) continuously had NED. Twenty of 36 (55.5%) referred for resection continuously had NED. Disease confined to the mediastinum and necrosis in the PC specimen were important prognostic factors for survival.

  View details for Web of Science ID 000085745800015

  View details for PubMedID 10699894

• Positron emission tomography scans in the evaluation of postchemotherapy residual masses in patients with seminoma 35th Annual Meeting of the American-Society-of-Clinical-Oncology Ganjoo, K. N., Chan, R. J., Sharma, M., Einhorn, L. H. AMER SOC CLINICAL ONCOLOGY. 1999: 3457?60

  Abstract

  To assess the ability of positron emission tomography (PET) scans in differentiating between necrosis and viable seminoma in postchemotherapy (PC) residual disease.We conducted a prospective study of 29 patients with seminoma at Indiana University. All patients had PC residual disease. Computed tomography and PET scans were performed for 19 patients after primary chemotherapy (group A) and for 10 patients after salvage chemotherapy (group B).In group A, the PC masses were >/= 3 cm in 14 patients, less than 3 cm in three patients, and not quantified in two patients. All of the patients in group A had negative PET scan results and have had stable or decreasing residual mass size (median follow-up duration, 11.5 months; range, 6 to 26 months). In group B, the PC masses were >/= 3 cm in four patients, less than 3 cm in five patients, and not quantified in one patient. One patient had a positive PET scan result for a posterior mediastinal mass. Pathologic diagnosis of the PET-positive mass showed only necrotic tissue. The same patient had a negative PET scan of the retroperitoneal mass but relapsed in that area. Overall, of patients in group B, five have stable or decreasing mass (median follow-up duration, 8 months; range, 7 to 22 months), and five had relapsed disease.PET scans have no apparent benefit in PC evaluation of residual masses in bulky seminoma.

  View details for Web of Science ID 000083473700014

  View details for PubMedID 10550142

• Primary mediastinal nonseminomatous germ cell tumors: The influence of postchemotherapy pathology on long-term survival after surgery 79th Annual Meeting of the American-Association-for-Thoracic-Surgery Kesler, K. A., Rieger, K. M., Ganjoo, K. N., Sharma, M., Fineberg, N. S., Einhorn, L. H., Brown, J. W. MOSBY-ELSEVIER. 1999: 692?700

  Abstract

  The treatment of nonseminomatous germ cell tumors with cisplatin-based chemotherapy followed by aggressive surgical resection of residual disease is one of the most successful models for multimodality cancer therapy. We reviewed the case histories of 91 patients treated at our institution from 1981 to 1998 with primary mediastinal nonseminomatous germ cell tumors to evaluate variables that may influence survival after surgery.Twelve of the 91 patients did not undergo postchemotherapy resection because of progressive disease. Seventy-nine of them underwent 82 thoracic surgical procedures and are the basis of this review. The majority (71/75) had elevated serum tumor markers, 75% (n = 50) of which returned to normal levels after first- or second-line chemotherapy.There were 3 operative deaths and 1 late death, attributed to pulmonary complications. Twenty-four patients died of recurrent disease and 3 of leukemia, for an overall survival of 61% after an average follow-up of 48 months. The pathologic findings of complete tumor necrosis (n = 19) and benign teratoma (n = 28) in the surgical specimen predicted excellent and good long-term survival, respectively, which was statistically better than that of patients having persistent nonseminomatous germ cell tumors (n = 24) or carcinomatous/sarcomatous degeneration (n = 8).Primary nonseminomatous germ cell tumors of the mediastinum can be cured with a multimodality therapy, particularly in the subset of patients with postchemotherapy pathologic findings of tumor necrosis and teratoma. Survival is poor but possible in patients with unfavorable pathologic findings after chemotherapy, currently justifying an aggressive surgical approach in patients with otherwise operable disease.

  View details for Web of Science ID 000083129400021

  View details for PubMedID 10504636

• Lung cancer presenting with solitary bone metastases - Case 1: Metastatic adenocarcinoma to the patella JOURNAL OF CLINICAL ONCOLOGY Ganjoo, K. N., Loyal, J. A., Cramer, H. M., Loehrer, P. J. 1999; 17 (9): 2995-2997

  View details for Web of Science ID 000082381000044

  View details for PubMedID 10561377