Machado Antonio Pizuorno, Shatila Malek, De Toni Enrico N, Török Helga-Paula, Philpott Jessica, Zhao Dan, Zhou Yan, Varatharajalu Krishnavathana, Shafi Mehnaz A, Zhang Hao Chi, Thomas Anusha S, Wang Yinghong
Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USA.
Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Cancer. 2023 Aug 28;14(14):2686-2693. doi: 10.7150/jca.86635. eCollection 2023.
While the occurrence of colitis during immune checkpoint inhibitor (ICI) treatment is recognized as a sign of robust immune activation and correlates with better oncological outcomes, the long-term impact of ICI-mediated colitis on the colonic mucosa has not been studied. We thus aim to describe the colonoscopy and histology findings in patients at a follow-up time of ≥ 6 months post initial colitis event. This retrospective analysis included adult cancer patients diagnosed with ICI colitis at a tertiary cancer center between October 2013 and June 2020. The study group included patients diagnosed with immune mediated colitis who had also undergone a follow up colonoscopy or flex sigmoidoscopy. The control group was patients exposed to ICI without immune mediated colitis. We reported patients' colitis clinical course, treatment, outcomes, and endoscopic and histologic features at diagnosis and at follow-up time of ≥ 6 months. Total 39 patients met the study criteria, with 82% being male, and 35.8% having melanoma. Most patients received a combination of CTLA-4 and PD-1/L1 inhibitors (82%). On initial endoscopic evaluation, inflammation without ulceration was reported in 76.9% of patients and active inflammation on histologic examination in 79.3% of patients. Most patients (79.4%) received corticosteroids, and 56.4% received add-on selective immunosuppressive therapy. Four patients received fecal microbiota transplantation. On follow-up, new incidence of colonic polyps was reported in 51.2% of patients, including adenomas in 33.3% among the colitis patients with median follow up duration of 12 months. The incidence of adenoma polyps 12 months after the colitis event was significantly higher compared to the control group without colitis based on the time-to-event analysis (p=0.041). At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer.
虽然免疫检查点抑制剂(ICI)治疗期间发生结肠炎被认为是强大免疫激活的标志,且与更好的肿瘤学结果相关,但ICI介导的结肠炎对结肠黏膜的长期影响尚未得到研究。因此,我们旨在描述在初次结肠炎事件发生后≥6个月的随访时间点患者的结肠镜检查和组织学结果。这项回顾性分析纳入了2013年10月至2020年6月期间在一家三级癌症中心被诊断为ICI结肠炎的成年癌症患者。研究组包括被诊断为免疫介导性结肠炎且还接受了随访结肠镜检查或乙状结肠镜检查的患者。对照组是暴露于ICI但无免疫介导性结肠炎的患者。我们报告了患者的结肠炎临床病程、治疗、结局以及诊断时和≥6个月随访时的内镜和组织学特征。共有39名患者符合研究标准,其中82%为男性,35.8%患有黑色素瘤。大多数患者接受了CTLA-4和PD-1/L1抑制剂联合治疗(82%)。在初次内镜评估中,76.9%的患者报告有炎症但无溃疡,79.3%的患者在组织学检查中有活动性炎症。大多数患者(79.4%)接受了皮质类固醇治疗,56.4%的患者接受了附加的选择性免疫抑制治疗。4名患者接受了粪便微生物群移植。在随访中,51.2%的患者报告有结肠息肉新发病例,其中结肠炎患者中有33.3%为腺瘤,中位随访时间为12个月。基于事件发生时间分析,结肠炎事件发生12个月后腺瘤性息肉的发生率显著高于无结肠炎的对照组(p = 0.041)。在初次结肠炎诊断后的中位随访12个月时,51.2%的患者有结肠息肉新发病例,其中三分之一为腺瘤,其发生率显著高于无结肠炎的对照组。需要更大样本量的研究来进一步明确结肠炎及其治疗对结肠健康的长期影响,并完善结肠腺瘤和结直肠癌监测的建议。