Kamarajah Sivesh K, White Steven A, Naffouje Samer A, Salti George I, Dahdaleh Fadi
Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK.
Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, Newcastle, UK.
Ann Surg Oncol. 2021 Oct;28(11):6790-6802. doi: 10.1245/s10434-021-09823-0. Epub 2021 Mar 30.
Data supporting the routine use of adjuvant chemotherapy (AC) compared with no AC (noAC) following neoadjuvant chemotherapy (NAC) and resection for pancreatic ductal adenocarcinoma (PDAC) are lacking. This study aimed to determine whether AC improves long-term survival in patients receiving NAC and resection.
Patients receiving resection for PDAC following NAC from 2004 to 2016 were identified from the National Cancer Data Base (NCDB). Patients with a survival rate of < 6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression analysis were performed to account for selection bias and analyze the impact of AC on overall survival.
Of 4449 (68%) noAC patients and 2111 (32%) AC patients, 2016 noAC patients and 2016 AC patients remained after PSM. After matching, AC was associated with improved survival (median 29.4 vs. 24.9 months; p < 0.001), which remained after multivariable adjustment (HR 0.81, 95% confidence interval [CI] 0.75-0.88; p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (hazard ratio [HR] 0.80, 95% CI 0.72-0.90; p < 0.001), N1 (HR 0.76, 95% CI 0.67-0.86; p < 0.001), R0 margin status (HR 0.82, 95% CI 0.75-0.89; p < 0.001), R1 margin status (HR 0.77, 95% CI 0.64-0.93; p = 0.007), no neoadjuvant radiotherapy (NART; HR 0.84, 95% CI 0.74-0.96; p = 0.009), and use of NART (HR 0.80, 95% CI 0.73-0.88; p < 0.001). Stratified analysis by nodal, margin, and NART status demonstrated consistent results.
AC following NAC and resection is associated with improved survival, even in margin-negative and node-negative disease. These findings suggest completing planned systemic treatment should be considered in all resected PDACs previously treated with NAC.
缺乏支持在新辅助化疗(NAC)及切除术后常规使用辅助化疗(AC)与不使用辅助化疗(noAC)治疗胰腺导管腺癌(PDAC)的数据。本研究旨在确定AC是否能提高接受NAC及切除术患者的长期生存率。
从国家癌症数据库(NCDB)中识别出2004年至2016年接受NAC后行PDAC切除术的患者。排除生存率<6个月的患者以消除不朽时间偏倚。进行倾向评分匹配(PSM)和Cox回归分析以消除选择偏倚并分析AC对总生存的影响。
在4449例(68%)noAC患者和2111例(32%)AC患者中,PSM后分别有2016例noAC患者和2016例AC患者。匹配后,AC与生存率提高相关(中位生存期29.4个月对24.9个月;p<0.001),多变量调整后仍然如此(风险比[HR]0.81,95%置信区间[CI]0.75 - 0.88;p<0.001)。在多变量交互分析中,无论淋巴结状态如何,这种益处均持续存在:N0(风险比[HR]0.80,95%CI 0.72 - 0.90;p<0.001)、N1(HR 0.76,95%CI 0.67 - 0.86;p<0.001)、R0切缘状态(HR 0.82,95%CI 0.75 - 0.89;p<0.001)、R1切缘状态(HR 0.77,95%CI 0.64 - 0.93;p = 0.007)、未行新辅助放疗(NART;HR 0.84,95%CI 0.74 - 0.96;p = 0.009)以及使用NART(HR 0.80,95%CI 0.73 - 0.88;p<0.001)。按淋巴结、切缘和NART状态进行分层分析显示结果一致。
NAC及切除术后使用AC与生存率提高相关,即使是切缘阴性和淋巴结阴性的疾病。这些发现表明,对于所有先前接受NAC治疗的切除性PDAC患者,应考虑完成计划的全身治疗。