Bando Hideaki, Tsukada Yuichiro, Ito Masaaki, Yoshino Takayuki
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
Clin Colorectal Cancer. 2022 Mar;21(1):3-9. doi: 10.1016/j.clcc.2021.10.001. Epub 2021 Oct 16.
Chemoradiotherapy (CRT) followed by radical surgery is one of the standard therapies for patients with locally advanced rectal cancer (LARC). Various combination therapies have been developed to improve the efficacy of preoperative therapies. One promising approach is the combination of ionizing radiation and immune checkpoint inhibitors (ICIs) because it enhances both local and distal immunogenic efficacy according to several xenograft models. To date, promising short-term efficacy results of 23% to 37.5% of the pathological complete response (pCR) rate have been reported in clinical trials investigating the combination of CRT and ICIs in patients with microsatellite stable (MSS) LARC. In patients with high-level microsatellite instability (MSI-H) LARC, CRT followed by ICI also achieved a 60% (3/5) pCR rate according to the data of the VOLTAGE study, suggesting increased efficacy of ICIs in this subgroup, albeit with a small sample size. In patients with MSS LARC, programmed cell death-ligand 1 tumor proportion score positivity, elevated CD8/effector regulatory T cell ratio, higher immune-score, consensus molecular subtype 1, and higher tumor mutational burden appear to be positive predictors of ICIs efficacy. In addition, various prospective studies combining CRT with ICI, chemotherapy, and target agents are currently being conducted. To confirm the survival benefits of these approaches, confirmatory phase III trials are needed.
同步放化疗（CRT）后行根治性手术是局部晚期直肠癌（LARC）患者的标准治疗方法之一。为提高术前治疗的疗效，已开发出多种联合治疗方法。一种有前景的方法是将电离辐射与免疫检查点抑制剂（ICI）联合使用，因为根据几种异种移植模型，这种联合使用可增强局部和远处的免疫原性疗效。迄今为止，在对微卫星稳定（MSS）LARC患者进行的同步放化疗与ICI联合治疗的临床试验中，已报告了有前景的短期疗效结果，病理完全缓解（pCR）率为23%至37.5%。根据VOLTAGE研究的数据，在微卫星高度不稳定（MSI-H）LARC患者中，同步放化疗后使用ICI也达到了60%（3/5）的pCR率，这表明尽管样本量较小，但ICI在该亚组中的疗效有所提高。在MSS LARC患者中，程序性细胞死亡配体1肿瘤比例评分阳性、CD8/效应调节性T细胞比值升高、免疫评分较高、共识分子亚型1以及肿瘤突变负荷较高似乎是ICI疗效的阳性预测指标。此外，目前正在进行多项将同步放化疗与ICI、化疗和靶向药物联合使用的前瞻性研究。为证实这些方法的生存获益，需要进行确证性III期试验。
