Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study

医学 内科学 危险系数 胰腺癌 导管内乳头状粘液性肿瘤 肿瘤科 胃肠病学 比例危险模型 化疗 队列 佐剂 辅助化疗 腺癌 辅助治疗 癌症 胰腺 置信区间 乳腺癌
作者
Joseph R. Habib,Benedict Kinny‐Köster,Ammar A. Javed,Piotr Zelga,Lily V. Saadat,Rachel C. Kim,Myrte Gorris,Valentina Allegrini,Shuichi Watanabe,Jeremy M. Sharib,Massimo Arcerito,Jörg Kaiser,Kelly J. Lafaro,Min Tu,Manish S. Bhandare,Chanjuan Shi,Michael P. Kim,Camilo Correa‐Gallego,Lois A. Daamen,Paul E. Oberstein,C. Max Schmidt,Nader Hanna,Peter J. Allen,Martin Loos,Shailesh V. Shrikhande,I. Quintus Molenaar,Isabella Frigerio,Matthew H. G. Katz,Kevin C. Soares,Yi Miao,Marco Del Chiaro,Jin He,Thilo Hackert,Giovanni Marchegiani,Markus W. Büchler,Carlos Fernández-del Castillo,Marc G. Besselink,Giovanni Marchegiani,Christopher L. Wolfgang,Laura R. Prakash,Mahip Grewal,Antonio Pea,Giovanni Butturini,Max Hecker,Floortje van Oosten
出处
期刊:Journal of Clinical Oncology [American Society of Clinical Oncology]
标识
DOI:10.1200/jco.23.02313
摘要

PURPOSE The benefit of adjuvant therapy for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) remains unclear because of severely limited evidence. Although biologically distinct entities, adjuvant therapy practices for IPMN-derived PDAC are largely founded on pancreatic intraepithelial neoplasia-derived PDAC. We aimed to evaluate the role of adjuvant chemotherapy in IPMN-derived PDAC. METHODS This international multicenter retrospective cohort study (2005-2018) was conceived at the Verona Evidence-Based Medicine meeting. Cox regressions were performed to identify risk-adjusted hazard ratios (HR) associated with overall survival (OS). Kaplan-Meier curves and log-rank tests were employed for survival analysis. Logistic regression was performed to identify factors motivating adjuvant chemotherapy administration. A decision tree was proposed and categorized patients into overtreated, undertreated, and optimally treated cohorts. RESULTS In 1,031 patients from 16 centers, nodal disease (HR, 2.88, P < .001) and elevated (≥37 to <200 µ/mL, HR, 1.44, P = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, P < .001) carbohydrate antigen 19-9 (CA19-9) were associated with worse OS. Node-positive patients with elevated CA19-9 had an associated 34.4-month improvement in median OS ( P = .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit ( P < .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all P > .05). Based on this model, we observed undertreatment in 18.1% and overtreatment in 61.2% of patients. Factors associated with chemotherapy administration included younger age, R1-margin, poorer differentiation, and nodal disease. CONCLUSION Almost half of patients with resected IPMN-derived PDAC may be overtreated or undertreated. In patients with node-negative disease or normal CA19-9, adjuvant chemotherapy is not associated with a survival benefit, whereas those with node-positive disease and elevated CA19-9 have an associated benefit from adjuvant chemotherapy. A decision tree was proposed. Randomized controlled trials are needed for validation.
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