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Is surgical resection of an asymptomatic primary colorectal tumor beneficial for patients with PowerPoint Presentation
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Is surgical resection of an asymptomatic primary colorectal tumor beneficial for patients with

Is surgical resection of an asymptomatic primary colorectal tumor beneficial for patients with

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Is surgical resection of an asymptomatic primary colorectal tumor beneficial for patients with

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  1. Major Morbidity Curative Resection Other Resection Death 100 135,000 Colorectal Cancer patients per year 80 Initial Presentation Stage IV Unresectable Colorectal Cancer Asymptomatic Primary Tumor Good Performance Status 27,000 (20%) Stage IV 60 Percent 7000 (5%) Curative Resection (primary + mets) 20,000 (15%) Not Resectable for cure 40 Chemotherapy Alone (mFOLFOX6 + Bevacizumab 5mg/kg) Q 14 days Until Excessive Toxicity or Disease Progression 20 0 0 6 12 18 24 30 Months 20,000 (15%) Not Resectable for cure 95% CI 75% have an asymptomatic primary tumor Major Morbidity=16.3% A Phase II Trial of 5-Fluorouracil, Leucovorin and Oxaliplatin (mFOLFOX6) Plus Bevacizumab for Patients with Unresectable Stage IV Colon Cancer and Synchronous Asymptomatic Primary Tumor: Results of NSABP C-10 L.E. McCahill, G.A. Yothers, S. Sharif, N.J. Petrelli, S. Lopa, M.J. O'Connell, N. Wolmark NSABP; Lacks Cancer Center, Grand Rapids, MI; NSABP Operations/Biostatistical Centers; University of Pittsburgh, Grad School of Public Health, Dept of Biostatistics, Pittsburgh, PA; NSABP; Allegheny General Hospital, Pittsburgh, PA; NSABP; Helen F. Graham Cancer Center, Newark, DE; NSABP Biostatistical Center; University of Pittsburgh Graduate School of Public Health Dept of Biostatistics, Pittsburgh, PA; NSABP, Pittsburgh, PA Surgical Goals in a Patient with an Asymptomatic Primary and Unresectable Distant Metastases NSABP C-10 Schema RESULTS NSABP C-10 Study Information Surgery Required Secondary Symptoms at Intact Primary Kaplan-Meier Estimates of Overall Survival with 95% CI Prevention of Symptoms of Primary Tumor Bleeding Perforation Obstruction • 10 resections of intact primary tumor required • Bleeding (0) • Perforation (1) • Obstruction (8) • Pain (1) • Bevacizumab had been discontinued (6) • Progressed on protocol (5) • Bev held for scheduled procedure (1) • On Bevacizumab at time of surgery (4) • 3 with primary anastomosis, no leak • 1 with loop transverse colostomy (extensive metastases) The Problem Medically ManagedUnresectedPrimary Tumors Bleeding (rare) Perforation (rare) Obstruction 9-29% Endpoints Patient Characteristics (Information derived from stage IV CRC treated with a two-drug chemotherapy regimen (fluorouracil and leucovorin), for which response rates are much lower than response rates for currently available chemotherapy) PRIMARY • Event rate related to intact primary tumor requiring surgery • Bleeding • Perforation / Fistula formation • Obstruction • Events related to intact primary tumor resulting in patient death SECONDARY • Morbidity related to intact primary requiring active treatment other than surgery • Stent placement • Transfusions for active GI bleed • NCI CTCAE v3.0 Grade 3, 4, 5 toxicities • Overall Survival Median OS = 19.9 95% CI (15.0-27.2) Secondary Endpoints Current U.S. Practice Patterns for Stage IV Disease • Four patients met secondary endpoint criteria • 3 obstructions • 2 required stent placement • 1 resolved with conservative management • 1 required percutaneous abscess drainage • Median survival was 19.9 mo (95% CI 15.0-27.2) • Other surgeries on primary tumor - 13 • Attempted cure - 10 • Other - 3 The Problem • SEER Database 2000 (1988-2000) • 26,764 patients presenting with Stage IV colorectal cancer • 66% had primary tumor resected • Resection more commonly performed: • for younger patients • colon >> rectal • right >> left Cook & McCahill, Ann Surg Oncology 2005: 12(8) CONCLUSIONS • The primary endpoint of the trial was met • Utilizing mFOLFOX6 + Bev does NOT result in unacceptable rates of obstruction, perforation, bleeding, or death related to the intact primary colon tumor in this prospective clinical trial • Survival does not appear to be compromised by leaving the primary colon tumor intact • Majority of the patients 72/86 (84%) were spared an initial non-curative resection of their primary colon tumor • Initial treatment of this patient population with chemotherapy + bevacizumab is a reasonable standard of care Cumulative Incidence of Major Morbidity and Competing Events Statistical Considerations Specific Hypothesis for NSABP C-10 Primary Endpoint • Event rate of 25% related to intact primary requiring surgery is considered acceptable • 85% power to r/o 40% primary endpoint event rate Primary Endpoint The elimination of initial surgery for patients receiving 3-drug systemic chemotherapy + bevacizumab will not lead to unacceptable morbidity related to the intact primary tumor Surgical resection required for symptoms or death from complications from intact primary tumor • 12 cases (14%) of major morbidity • Estimated Cumulative Incidence of Major Morbidity related to the intact primary tumor at 24 months is 16.3% (95% CI 7.6%-25.1%) • Tumor site • Right (six) • Transverse (one) • Left (five) Key Inclusion Criteria The Question • Asymptomatic primary colon cancer • >12 cm from anal verge on endoscopy • No clinical evidence of obstruction or perforation • No bleeding requiring active transfusions • Radiographic evidence of distant metastatic disease (Stage IV at presentation) • Metastases considered unresectable by treating physician/surgeon Is surgical resection of an asymptomatic primary colorectal tumor beneficial for patients with incurableStage IV disease? 10 (11.6%) required surgery Obstruction - 8 Perforation - 1 Pain – 1 • 2 (2.3%) resulted in death • Perforation - 1 • Obstruction – 1 Abstract #3527