Joseph R Habib, Benedict Kinny-Köster, Ammar A Javed, Poitr Zelga, Lily V Saadat, Rachel C Kim, Myrte Gorris, Valentina Allegrini, Shuichi Watanabe, Jeremy Sharib, Massimo Arcerito, Jörg Kaiser, Kelly J Lafaro, Min Tu, Manish Bhandre, Chanjuan Shi, Michael P Kim, Camilo Correa, Lois A Daamen, Paul E Oberstein, C Max Schmidt, Nader N Hanna, Peter 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, Roberto Salvia, Markus W Büchler, Carlos Fernandez-Del Castillo, Marc G Besselink, Giovanni Marchegiani, Christopher L Wolfgang
{"title":"辅助化疗对切除的导管内乳头状黏液性肿瘤来源胰腺癌的影响:一项国际多中心研究的结果","authors":"Joseph R Habib, Benedict Kinny-Köster, Ammar A Javed, Poitr Zelga, Lily V Saadat, Rachel C Kim, Myrte Gorris, Valentina Allegrini, Shuichi Watanabe, Jeremy Sharib, Massimo Arcerito, Jörg Kaiser, Kelly J Lafaro, Min Tu, Manish Bhandre, Chanjuan Shi, Michael P Kim, Camilo Correa, Lois A Daamen, Paul E Oberstein, C Max Schmidt, Nader N Hanna, Peter 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, Roberto Salvia, Markus W Büchler, Carlos Fernandez-Del Castillo, Marc G Besselink, Giovanni Marchegiani, Christopher L Wolfgang","doi":"10.1200/JCO.23.02313","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>In 1,031 patients from 16 centers, nodal disease (HR, 2.88, <i>P</i> < .001) and elevated (≥37 to <200 µ/mL, HR, 1.44, <i>P</i> = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, <i>P</i> < .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 (<i>P</i> = .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit (<i>P</i> < .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all <i>P</i> > .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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":" ","pages":"4317-4326"},"PeriodicalIF":42.1000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study.\",\"authors\":\"Joseph R Habib, Benedict Kinny-Köster, Ammar A Javed, Poitr Zelga, Lily V Saadat, Rachel C Kim, Myrte Gorris, Valentina Allegrini, Shuichi Watanabe, Jeremy Sharib, Massimo Arcerito, Jörg Kaiser, Kelly J Lafaro, Min Tu, Manish Bhandre, Chanjuan Shi, Michael P Kim, Camilo Correa, Lois A Daamen, Paul E Oberstein, C Max Schmidt, Nader N Hanna, Peter 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, Roberto Salvia, Markus W Büchler, Carlos Fernandez-Del Castillo, Marc G Besselink, Giovanni Marchegiani, Christopher L Wolfgang\",\"doi\":\"10.1200/JCO.23.02313\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>In 1,031 patients from 16 centers, nodal disease (HR, 2.88, <i>P</i> < .001) and elevated (≥37 to <200 µ/mL, HR, 1.44, <i>P</i> = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, <i>P</i> < .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 (<i>P</i> = .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit (<i>P</i> < .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all <i>P</i> > .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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":\" \",\"pages\":\"4317-4326\"},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2024-12-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO.23.02313\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO.23.02313","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:由于证据非常有限,对导管内乳头状粘液瘤(IPMN)衍生的胰腺导管腺癌(PDAC)进行辅助治疗的益处仍不明确。虽然IPMN衍生的PDAC在生物学上是不同的实体,但其辅助治疗方法主要建立在胰腺上皮内瘤衍生的PDAC的基础上。我们旨在评估辅助化疗在 IPMN 衍生型 PDAC 中的作用:这项国际多中心回顾性队列研究(2005-2018 年)是在维罗纳循证医学会议上提出的。研究采用 Cox 回归确定了与总生存期(OS)相关的风险调整后危险比(HR)。生存分析采用卡普兰-梅耶曲线和对数秩检验。采用逻辑回归法确定辅助化疗的诱因。提出了一个决策树,并将患者分为过度治疗组、治疗不足组和最佳治疗组:在来自16个中心的1031名患者中,结节性疾病(HR,2.88,P < .001)和碳水化合物抗原19-9(CA19-9)升高(≥37 to P = .006)或明显升高(≥200 µ/mL,HR,2.53,P < .001)与较差的OS相关。CA19-9升高的结节阳性患者在辅助化疗后的中位OS可提高34.4个月(P = .047),而结节阳性且CA19-9明显升高的患者可获益12.6个月的生存期(P < .001)。结节阴性患者,无论 CA19-9 如何,都不会从辅助化疗中获益(所有 P > .05)。根据该模型,我们观察到18.1%的患者治疗不足,61.2%的患者治疗过度。与化疗相关的因素包括年龄较小、R1-边缘、分化较差和结节病:结论:近半数切除的IPMN衍生型PDAC患者可能治疗过度或治疗不足。对于结节阴性或CA19-9正常的患者,辅助化疗与生存获益无关,而对于结节阳性和CA19-9升高的患者,辅助化疗可使其获益。提出了一个决策树。需要进行随机对照试验进行验证。
Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study.
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.
期刊介绍:
The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.