二期临床试验（联盟A021501）中新辅助治疗及手术后边缘可切除胰腺癌患者的术后不良事件

Postoperative Adverse Events Following Neoadjuvant Therapy and Surgery for Borderline Resectable Pancreatic Cancer in a Phase 2 Clinical Trial (Alliance A021501)

ANNALS OF SURGICAL ONCOLOGY

影响因子:3.5

分区:医学2区 / 外科2区肿瘤学3区

发表日期:2024 Oct

作者: Rebecca A Snyder, Tyler J Zemla, Qian Shi, Diana Segovia, Syed A Ahmad, Eileen M O'Reilly, Joseph M Herman, Matthew H G Katz

DOI: 10.1245/s10434-024-15670-6

摘要

在国家合作组环境下，尚未有关于新辅助治疗联合胰腺切除术后边缘可切除胰腺导管腺癌（BR-PC）患者术后AEs（不良事件）发生情况的报道。本研究为预先设计的次级分析，旨在量化参与联盟A021501临床试验患者的围手术期不良事件发生率。A021501第2期试验将BR-PC患者随机分为接受8剂mFOLFIRINOX（A组）或7剂mFOLFIRINOX联合低分割放疗（A组）后行胰腺切除术（2016年12月31日至2019年5月31日）。在胰腺切除术后90天内对不良事件进行评估。共126名患者入组，其中51例（40%）接受了胰腺切除术（A组32例；B组19例），分布于28个机构。90天内需再次手术的患者有5例（10%）；至少出现一次Ⅲ级或以上不良事件的患者为27/48（56%），与对照组相比无显著差异（50% vs. 67%，p=0.37）。90天死亡率为2.0%。A组的再入院率较低（16% vs. 42%，p=0.05），但两组在再次手术（13% vs. 5%）、胰腺瘘或腹腔脓肿（9% vs. 16%）以及伤口感染（6% vs. 16%）的发生率上无显著差异。胰腺瘘或腹腔脓肿伴引流的发生与辅助治疗（p=0.012）有关。术后AEs的发生与总体生存无显著相关（风险比=1.1，95% CI：0.5-2.6）。本多中心研究显示，术后AEs发生率与既往报道一致。针对BR-PC的术前多模态治疗的临床试验可在合作组环境中安全进行，需严格的质量控制和安全监测。临床试验注册号：NCT02839343。

Abstract

Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates.The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy.Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6).In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring.Clinicaltrials.gov identifier: NCT02839343.