背景:胰腺腺癌,胰腺细胞中出现的恶性肿瘤,是一种病因不明,预后通常较差的毁灭性疾病。局部晚期胰腺癌,肿瘤已经显著生长但尚未扩散到远处器官的阶段,在治疗中提出了独特的挑战。本文旨在讨论当前的策略,挑战,以及局部晚期胰腺腺癌(LAPC)治疗的未来方向。
目的:探讨程序性细胞死亡因子1(PD-1)抑制剂辛替利麦联合同步放化疗治疗LAPC的可行性和疗效。
方法:符合条件的患者患有LAPC,东部合作肿瘤学组表现状态为0或1,器官和骨髓功能充足,之前没有抗癌治疗.在观察组中,参与者每3周接受一次静脉注射Sintilimab200毫克,并接受同步放化疗(同时进行常规分割放疗,计划目标体积50.4Gy和总肿瘤体积60Gy的剂量分为28个部分,在21天周期的第1-14天每天两次口服S-140mg/m2,在21天周期的第1天和第8天静脉注射吉西他滨1000mg/m2,持续8个周期,直至疾病进展,死亡,或不可接受的毒性)。在对照组中,参与者仅接受同步放化疗.从2020年4月到2021年11月,64名参与者最终被纳入,其中34名为观察组,30名为对照组。
结果:34名患者完成了计划的放化疗疗程,观察组32例(94.1%)接受辛替利玛联合同步放化疗,2例停用辛替利玛。对照组30例患者完成了计划的放化疗疗程。根据实体瘤指南中的反应评估标准,对观察组的分析显示,11例患者(32.4%)出现部分缓解,19例患者病情稳定(55.9%),4例(11.8%)患者出现疾病进展;6例(20.0%)患者出现部分缓解,18例疾病稳定(60%),对照组中6例(20%)疾病进展。主要毒性作用是白细胞减少和恶心。观察组严重不良事件(AEs)(3级或4级)发生率为26.5%(9/34),对照组为23.3%(7/30)。没有治疗相关的死亡。与对照组相比,观察组的中位总生存期(22.1个月比15.8个月)(P<0.05)和无进展生存期(12.2个月比10.1个月)(P<0.05)明显更长。观察组与对照组严重不良事件发生率比较差异无统计学意义(P>0.05)。
结论:Sindilimab联合同步放化疗对LAPC患者有效且安全,并需要进一步调查。
BACKGROUND: Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC).
OBJECTIVE: To investigate the feasibility and efficacy of programmed cell death 1 (PD-1) inhibitor
sintilimab plus concurrent chemoradiotherapy for LAPC.
METHODS: Eligible patients had LAPC, an Eastern cooperative oncology group performance status of 0 or 1, adequate organ and marrow functions, and no prior anticancer therapy. In the observation group, participants received intravenous
sintilimab 200 mg once every 3 wk, and received concurrent chemoradiotherapy (concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-1 40 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression, death, or unacceptable toxicity). In the control group, participants only received concurrent chemoradiotherapy. From April 2020 to November 2021, 64 participants were finally enrolled with 34 in the observation group and 30 in the control group.
RESULTS: Thirty-four patients completed the scheduled course of chemoradiotherapy, while 32 (94.1%) received
sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing
sintilimab in the observation group. Thirty patients completed the scheduled course of chemoradiotherapy in the control group. Based on the Response Evaluation Criteria in Solid Tumors guidelines, the analysis of the observation group revealed that a partial response was observed in 11 patients (32.4%), stable disease was evident in 19 patients (55.9%), and 4 patients (11.8%) experienced progressive disease; a partial response was observed in 6 (20.0%) patients, stable disease in 18 (60%), and progressive disease in 6 (20%) in the control group. The major toxic effects were leukopenia and nausea. The incidence of severe adverse events (AEs) (grade 3 or 4) was 26.5% (9/34) in the observation group and 23.3% (7/30) in the control group. There were no treatment-related deaths. The observation group demonstrated a significantly longer median overall survival (22.1 mo compared to 15.8 mo) (P < 0.05) and progression-free survival (12.2 mo vs 10.1 mo) (P < 0.05) in comparison to the control group. The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group (P > 0.05).
CONCLUSIONS: Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients, and warrants further investigation.