Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment
Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment
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DOI：
10.1001/jamaoncol.2020.3537
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发表时间：
2020-09-10
期刊：
影响因子：
28.4
通讯作者：
Besselink, Marc G.
中科院分区：
文献类型：
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作者：
van Roessel, Stijn;van Veldhuisen, Eran;Besselink, Marc G.
胰腺癌切除术后亚叶酸、氟尿嘧啶、伊立替康和奥沙利铂新辅助联合治疗后辅助化疗的获益目的评估胰腺癌切除术和新辅助FOLFIRINOX治疗后患者辅助化疗与总生存期（OS）的关系。回顾性队列研究于2012年1月1日至2018年12月31日进行。出于本研究的目的，更新并扩展了FOLFIRINOX后接受胰腺癌切除术的现有患者队列。从机构数据库中回顾性确定了在至少2个周期的新辅助FOLFIRINOX化疗治疗非转移性胰腺癌后接受胰腺手术的所有连续患者。可切除的胰腺癌、边缘性可切除的胰腺癌和局部晚期胰腺癌患者有资格参加本研究。排除了住院死亡或术后3个月内死亡的患者。在多变量考克斯模型中，在不同亚组中评估辅助化疗与OS的相关性，包括临床病理学参数与辅助治疗的相互作用项。总生存期被定义为从手术开始的时间加3个月（适合辅助治疗的时间），除非另有说明。结果我们纳入了来自19个国家31个中心的520例患者（中位数[四分位数范围]年龄，61 [53 - 66]岁; 279 [53.7%]男性）。FOLFIRINOX新辅助治疗周期的中位数为6个（四分位距，5 - 8）。总体而言，343例患者（66.0%）接受辅助化疗，其中68例（19.8%）接受FOLFIRINOX，201例（58.6%）接受基于吉西他滨的化疗，14例（4.1%）接受卡培他滨，45例（13.1%）接受联合或其他药物，15例（4.4%）接受未知类型的辅助化疗。中位OS为诊断后38个月（95% CI，36 - 46个月）和手术后31个月（95% CI，29 - 37个月）。未发现接受辅助化疗的患者与未接受辅助化疗的患者之间存在生存差异（中位OS，29 vs 29个月，单变量风险比[HR]，0.99; 95% CI，0.77 - 1.28; P = 0.93）。在多变量分析中，只有淋巴结分期与辅助治疗的相互作用项具有统计学意义：在病理证实的淋巴结阳性疾病患者中，辅助化疗与生存期改善相关（中位OS，26 vs 13个月;多变量HR，0.41 [95%CI，0.22 - 0.75]; P = 0.004）。在淋巴结阴性的患者中，辅助化疗与生存率的改善无关（中位OS，38 vs 54个月;多变量HR，0.85; 95% CI，0.35 - 2.10;结论和相关性这些结果表明，新辅助FOLFIRINOX和胰腺癌切除术后的辅助化疗仅在病理学上与生存率改善相关。确诊的淋巴结阳性疾病未来应进行随机研究以证实这一发现。
IMPORTANCE The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.OBJECTIVE To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.DESIGN, SETTING, AND PARTICIPANTS This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded. EXPOSURES The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise.RESULTS We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P =.93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P =.004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P =.73).CONCLUSIONS AND RELEVANCE These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.