Neoadjuvant Immunotherapy for Patients With Microsatellite Instability-High or POLE-Mutated Locally Advanced Colorectal Cancer With Bulky Tumors: New Optimization Strategy

IF 3.2 3区医学 Q2 ONCOLOGY

Clinical colorectal cancer Pub Date : 2024-07-09 DOI:10.1016/j.clcc.2024.07.001

Yingjie Li , Fei Liang , Zhongwu Li , Xiaoyan Zhang , Aiwen Wu

{"title":"Neoadjuvant Immunotherapy for Patients With Microsatellite Instability-High or POLE-Mutated Locally Advanced Colorectal Cancer With Bulky Tumors: New Optimization Strategy","authors":"Yingjie Li , Fei Liang , Zhongwu Li , Xiaoyan Zhang , Aiwen Wu","doi":"10.1016/j.clcc.2024.07.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with microsatellite instability-high (MSI-H) or DNA polymerase ε (POLE)-mutated locally advanced colorectal cancer (LACRC) with bulky tumors. </div></div><div><h3>Patients</h3><div>We retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors (>8 cm in diameter) who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy. </div></div><div><h3>Main Outcome Measures</h3><div>Pathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan-Meier method. Multiplex immunofluorescence analysis were performed before and after treatment. </div></div><div><h3>Results</h3><div>The incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1-8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%. </div></div><div><h3>Conclusions</h3><div>Preoperative immunotherapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR rate.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 18-31.e2"},"PeriodicalIF":3.2000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical colorectal cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S153300282400063X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective

To evaluate the efficacy and safety of neoadjuvant immunotherapy for patients with microsatellite instability-high (MSI-H) or DNA polymerase ε (POLE)-mutated locally advanced colorectal cancer (LACRC) with bulky tumors. 

Patients

We retrospectively reviewed 22 consecutive patients with MSI-H or POLE-mutated LACRC with bulky tumors (>8 cm in diameter) who received preoperative programmed death-1 blockade, with or without CapOx chemotherapy. 

Main Outcome Measures

Pathological complete response (pCR), clinical complete response (cCR), toxicity, R0 resection rate, and complications were evaluated. Survival outcomes were analyzed using the Kaplan-Meier method. Multiplex immunofluorescence analysis were performed before and after treatment. 

Results

The incidence of immune-related adverse events (irAEs) was 36.4% (8/22). Five of 22 patients presented with surgical emergencies, most commonly perforation or obstruction. The 22 patients underwent a median 4 (1-8) cycles. Two patients were evaluated as cCR and underwent a watch and wait strategy. The R0 resection rate was 100.0% (20/20) and pCR rate was 70.0% (14/20). Twelve of 14 cT4b patients (85.7%) avoided multivisceral resection, and 10 of them achieved pCR or cCR. In the two patients with POLE mutations, one each achieved pCR and cCR. No Grade III/IV postoperative complications occurred. The median follow-up was 16.0 months. Two-year event-free and overall survival for the whole cohort was both 100%. 

Conclusions

Preoperative immunotherapy is the optimal option for MSI-H or POLE-mutated LACRC with bulky tumors, especially cT4b. Preoperative immunotherapy in patients with T4b CRC can reduce multivisceral resection and achieve high CR rate.

查看原文本刊更多论文

针对微卫星不稳定性高或 POLE 突变的大块肿瘤局部晚期结直肠癌患者的新辅助免疫疗法：新的优化策略

目的评价微卫星不稳定性高（MSI-H）或DNA聚合酶ε (POLE)突变局部晚期结直肠癌（LACRC）伴大体积肿瘤患者新辅助免疫治疗的疗效和安全性。 患者我们回顾性分析了22例连续的MSI-H或pole突变LACRC患者，这些患者伴有大体积肿瘤（直径8cm），术前接受程序性死亡-1阻断，伴或不伴CapOx化疗。 主要观察指标评估病理完全缓解（pCR）、临床完全缓解（cCR）、毒性、R0切除率、并发症。生存结果采用Kaplan-Meier法进行分析。治疗前后进行多重免疫荧光分析。 结果免疫相关不良事件（irAEs）发生率为36.4%（8/22）。22例患者中有5例出现手术紧急情况，最常见的是穿孔或梗阻。22例患者的平均周期为4（1-8）个周期。2例患者被评估为cCR，并接受观察和等待策略。R0切除率为100.0% (20/20)，pCR率为70.0%（14/20）。14例cT4b患者中有12例（85.7%）避免了多脏器切除，其中10例实现了pCR或cCR。在2例POLE突变患者中，各有1例实现了pCR和cCR。无III/IV级术后并发症发生。中位随访时间为16.0个月。整个队列的2年无事件生存率和总生存率均为100%。 结论对于体积较大的肿瘤，尤其是cT4b， MSI-H或pole突变的LACRC，术前免疫治疗是最佳选择。T4b结直肠癌患者术前免疫治疗可减少多脏器切除，达到较高的CR率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical colorectal cancer 医学-肿瘤学

CiteScore

5.50

自引率

2.90%

发文量

审稿时长

27 days

期刊介绍： Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.