Gastric adenocarcinoma (GA) is the second leading cause of cancer-related mortality worldwide.1 In the United States, an estimated 10,990 deaths were attributed to GA in 2014.2 Margin-negative surgical resection (R0) is the only potentially curative treatment for GA. Even after curative-intent gastrectomy, however, the 5-year survival rate remains approximately 28%.2,3
Despite these dismal statistics, surgery alone remained the mainstay of therapy in the United States until publication of results from the Intergroup 0116 (INT-0116) trial in May 2000. This phase III randomized controlled trial evaluated the impact of postoperative chemoradiotherapy (CRT) for patients with resected stomach/gastroesophageal junction adenocarcinoma. Patients receiving adjuvant CRT demonstrated significantly improved median disease-free survival (DFS; 30 vs 19 months; P<.001) and overall survival (OS; 36 vs 27 months; P=.005) compared with those undergoing surgery alone.4 This survival benefit persisted on longitudinal (ie, >10-year) follow-up.5 Despite criticism that CRT may have compensated for inadequate surgery6 (only 10% of patients underwent D2 lymphadenectomy, whereas 54% received D0 resections4), use of adjuvant multimodality therapy has since been incorporated into practice guidelines for GA management in the United States. Subsequently, several retrospective population-based studies have reaffirmed the benefit of adjuvant therapy in patients undergoing curative-intent gastrectomy.7–9
Based on these data, current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer10 recommend postoperative CRT for patients with localized GA4 or postoperative chemotherapy after D2 (to view the most recent version of these guidelines, visit NCCN.org).11 The latter recommendation reflects findings from the CLASSIC trial; specifically, improved DFS and OS in patients receiving adjuvant chemotherapy (capecitabine/oxaliplatin) compared with those undergoing surgery alone.11 Alternatively, patients may receive neoadjuvant chemotherapy, drawing on results from the MAGIC trial, which demonstrated a survival advantage with perioperative chemotherapy versus surgery alone comparable with that achieved from adjuvant CRT in INT-0116.12 Importantly, in patients selected to undergo a surgery-first approach, clinical adoption of these NCCN Guidelines has remained inadequate. A recent National Cancer Data Base (NCDB) study revealed that use of adjuvant therapy in eligible patients by INT-0116 criteria plateaued at approximately 40% per year between 2003 and 2007. Alarmingly, a substantial proportion of INT-0116–eligible patients (nearly 40% of cases per year) underwent surgery alone in 2007.13 Risk factors for the omission of adjuvant multimodality therapy in eligible patients have not been well characterized.
Using a contemporary cohort from the NCDB, we (1) assessed temporal trends in use of adjuvant multimodality therapy after surgical resection; (2) identified demographic and clinical factors predicting omission of guideline-appropriate adjuvant therapy; and (3) developed an internally validated preoperative risk stratification model discriminating patients at low, moderate, and high risk for adjuvant therapy omission (ATom) after gastrectomy. This tool identifies vulnerable populations in whom delivery of cancer care could be improved, allowing for a more rational selection of treatment strategy.
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. Hundahl SA Phillips JL Menck HR The National Cancer Data Base report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis. Cancer 2000; 88: 921– 932.
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. Enestvedt CK Diggs BS Shipley DK A population-based analysis of surgical and adjuvant therapy for resected gastric cancer: are patients receiving appropriate treatment following publication of the Intergroup 0116 results?Gastrointest Cancer Res 2009; 3: 233– 238.
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