A5085336500- Gastrointestinal Tumor Research and Treatment
- Sarcoma Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Gastrointestinal disorders and treatments
- Neurofibromatosis and Schwannoma Cases
- Vascular Tumors and Angiosarcomas
- Chronic Myeloid Leukemia Treatments
- Cardiac tumors and thrombi
- Lymphoma Diagnosis and Treatment
- Platelet Disorders and Treatments
- Microtubule and mitosis dynamics
- CAR-T cell therapy research
- Soft tissue tumor case studies
- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- Metastasis and carcinoma case studies
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- Colorectal Cancer Treatments and Studies
- Neuroendocrine Tumor Research Advances
- Monoclonal and Polyclonal Antibodies Research
- Renal cell carcinoma treatment
- Telomeres, Telomerase, and Senescence
Fox Chase Cancer Center
2016-2025
Temple University Health System
2015-2025
Novartis (Switzerland)
2004-2023
Dana-Farber Cancer Institute
2003-2023
Oregon Health & Science University
2003-2023
University of Turku
2003-2023
University of Helsinki
2003-2023
Smilow Cancer Hospital
2018
Yale Cancer Center
2018
Cleveland Clinic
2005-2018
Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis gastrointestinal stromal tumors. Imatinib mesylate, a selective inhibitor, has been shown preclinical models and preliminary clinical studies to have activity against such
Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to was examined a group patients with advanced GIST. Patients Methods: GISTs from 127 enrolled onto phase II study were PDGFRA. Mutation types correlated outcome. Results: Activating...
The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding molecular characteristics GISTs have improved diagnostic accuracy led to discovery novel immunomarkers new mechanisms resistance TKI therapy, which in turn resulted development treatment strategies. To address...
To assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors (GIST) at a standard dose (400 mg daily) versus high twice daily).Patients metastatic surgically unresectable GIST were eligible for this phase III open-label clinical trial. At registration, randomly assigned either high-dose imatinib, close interval follow-up. If objective progression occurred by Response Evaluation...
Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, other connective tissues. The evaluation treatment patients with requires multidisciplinary team demonstrated expertise in the management these tumors. complete NCCN Clinical Practice Guidelines Oncology (NCCN Guidelines) for Tissue Sarcoma provide recommendations diagnosis, evaluation,...
The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term imatinib mesylate is unknown. A previous report a randomized phase II trial in incurable GIST detailed high response rates at both the 400 600 mg/d dose levels. We conducted analysis on trial, including followed during an extension phase, to evaluate survival, patterns failure, potential prognostic factors, mutational status.Patients were enrolled onto open-label, multicenter randomly...
Purpose Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% patients with advanced GISTs experience benefit from However, imatinib resistance is an increasing problem. Patients and Methods One hundred forty-seven advanced, unresectable were enrolled onto a randomized, phase II study Specimens pretreatment and/or imatinib-resistant...
This multicenter study, to our knowledge, is the first phase III trial compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy an anthracycline and at least one additional systemic regimen.Patients were randomly assigned a 2:1 ratio receive intravenously every 3 weeks. The primary end point was overall survival (OS), secondary points disease control-progression-free (PFS), time progression, objective response rate, duration of...
The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). standard of practice rapidly changed after the introduction effective molecularly targeted therapy (such as imatinib and sunitinib) GIST. Because these changes, organized multidisciplinary panel composed experts in fields medical oncology, molecular diagnostics, pathology, radiation surgery to discuss optimal approach care patients with GIST at all stages...
Imatinib mesylate is standard treatment for patients who have advanced gastrointestinal stromal tumor (GIST), but not all benefit equally. In previous studies, GIST genotype correlated with outcome and optimal imatinib dosing.We examined the relationship between kinase 428 enrolled on North American phase III study SWOG S0033/CALGB 150105 treated either 400 mg or 800 daily doses of imatinib.The presence KIT exon 11-mutant (n = 283) improved when compared 9-mutant 32) wild-type (WT; n 67)...
To evaluate the safety and efficacy of trabectedin in a phase II, open-label, multicenter, randomized study adult patients with unresectable/metastatic liposarcoma or leiomyosarcoma after failure prior conventional chemotherapy including anthracyclines ifosfamide.Patients were randomly assigned to one two regimens (via central venous access): 1.5 mg/m(2) 24-hour intravenous infusion once every 3 weeks (q3 24-hour) versus 0.58 3-hour IV week for 4-week cycle (qwk 3-hour). Time progression...
Abstract Background Therapy for gastrointestinal stromal tumors (GIST) has changed significantly with the use of imatinib mesylate (IM). Despite success this drug in metastatic GIST, disease progression remains a perplexing clinical issue suggesting need multimodality management. There have been no prospective studies either evaluating neoadjuvant IM primary GIST or as preoperative cytoreduction agent GIST. Methods RTOG 0132/ACRIN 6665 was phase II study safety and efficacy (600 mg/day)...
PURPOSE To study the pharmacokinetics (PK) of imatinib (IM) in patients with advanced GI stromal tumors (GISTs) treated a randomized phase II and to explore potential relationship between IM plasma levels long-term clinical outcomes. PATIENTS AND METHODS Patients were randomly assigned receive at 400 mg versus 600 daily. analyzed subset (n = 73) for whom PK data on day 1 steady-state (SS, 29) available. was evaluated using population approach. The exposure outcome explored by grouping into...
To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment metastatic or locally advanced angiosarcoma epithelioid hemangioendotheliomas.In this single-arm phase II trial, 32 patients were enrolled they received bevacizumab 15 mg/kg IV infusion 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status ≤1, adequate organ...
Wild-type (WT) gastrointestinal stromal tumors (GISTs), which lack KIT and PDGFRA gene mutations, are the primary form of GIST in children occasionally occur adults. They respond poorly to standard targeted therapy. Better molecular clinical characterization could improve management.To evaluate tumor genomic features WT GIST.Patients enrolled an observational study at National Institutes Health starting 2008 were evaluated a clinic held once or twice yearly. Patients provided access existing...
Purpose To assess the safety, pharmacokinetics, and preliminary evidence of antitumor activity mapatumumab (HGS-ETR1, TRM-1), a fully human agonist monoclonal antibody directed to tumor necrosis factor–related apoptosis-inducing ligand receptor-1 (TRAIL-R1). Patients Methods with advanced solid malignancies were treated escalating doses intravenously (IV) administered over 30 120 minutes, initially as single dose then repetitively. Plasma concentrations measured serum was assayed detect...
Purpose The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year adjuvant imatinib prolonged recurrence-free survival (RFS) after resection primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome. Patients Methods There were 328 patients assigned placebo arm 317 arm. Median follow-up was 74 months. 645 specimens available for mitotic...
Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, other connective tissues. The evaluation treatment patients with requires multidisciplinary team demonstrated expertise in the management these tumors. complete NCCN Guidelines for Tissue Sarcoma (available at NCCN.org) provide recommendations diagnosis, evaluation, extremity/superficial...
This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment management considerations AYA patients with cancer. Compared older adults cancer, have unique needs regarding treatment, fertility counseling, psychosocial behavioral issues, supportive care services. The complete version of addresses additional aspects caring patients, including risk factors, screening, diagnosis, survivorship.
The NCCN Guidelines for Soft Tissue Sarcoma provide recommendations the diagnosis, evaluation, treatment, and follow-up patients with soft tissue sarcomas. These Insights summarize panel discussion behind recent important updates to guidelines, including development of a separate distinct guideline gastrointestinal stromal tumors (GISTs); reconception management desmoid tumors; inclusion further diagnosis extremity/body wall, head/neck sarcomas, retroperitoneal sarcomas; modification...