Wang Hesong, Zhang Xueyuan, Zhao Xiaohan, Song Chunyang, Deng Wenzhao, Shen Wenbin
Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Front Immunol. 2024 Jan 11;14:1330928. doi: 10.3389/fimmu.2023.1330928. eCollection 2023.
For locally advanced, inoperable esophageal cancer, concurrent chemoradiotherapy (CCRT) becomes the norm. Combining immunotherapy with radiotherapy has been shown to improve efficacy. Circulating tumor DNA (ctDNA) is a strong predictor of effectiveness and tumor recurrence and is indicative of minimal residual disease (MRD). Patients with inoperable stage II-III esophageal squamous cell carcinoma (ESCC) are enrolled in the ECMRD-001 trial to evaluate changes in MRD status before and after CCRT combined with immunotherapy and adjuvant immunotherapy following neoadjuvant immunochemotherapy.
The ECMRD-001 trial is a prospective cohort study. Eligible patients will receive radical concurrent chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy, followed by adjuvant immunotherapy for at least one year. Follow-up will be up to three years. MRD-related blood and tissue samples and T-cell immunohistobank related blood and tissue samples collected before, during and after treatment and follow-up will be grouped into sample collection time points. The relationship between MRD status at different time points and treatment efficacy is the primary outcome. Correlation between MRD status and immune microenvironment, radiotherapy dose, and tumor recurrence are the secondary outcomes. Examination of ctDNA mutations is the exploratory outcome.
ctDNA-based MRD may be a potential predictive marker for the efficacy and tumor recurrence of inoperable ESCC patients. Elevated ctDNA-MRD may predict tumor recurrence earlier than imaging. ctDNA-based MRD analysis and ctDNA-based MRD guided diagnosis and treatment should be implemented into clinical practice to improve efficacy and reduce tumor recurrence of inoperable stage II-III ESCC.
The ECMRD-001 study has been registered at ClinicalTrials.gov as NCT05952661 (July 19, 2023), https://classic.clinicaltrials.gov/ct2/show/NCT05952661.
对于局部晚期、无法手术切除的食管癌，同步放化疗（CCRT）已成为标准治疗方法。免疫治疗与放疗联合已显示可提高疗效。循环肿瘤DNA（ctDNA）是疗效和肿瘤复发的有力预测指标，且可指示微小残留病（MRD）。无法手术切除的II-III期食管鳞状细胞癌（ESCC）患者被纳入ECMRD-001试验，以评估新辅助免疫化疗后同步放化疗联合免疫治疗及辅助免疫治疗前后MRD状态的变化。
ECMRD-001试验是一项前瞻性队列研究。符合条件的患者在新辅助免疫化疗后将接受根治性同步放化疗联合免疫治疗，随后进行至少一年的辅助免疫治疗。随访时间长达三年。治疗前、治疗期间、治疗后及随访期间收集的与MRD相关的血液和组织样本以及与T细胞免疫组织库相关的血液和组织样本将按样本采集时间点分组。不同时间点的MRD状态与治疗疗效之间的关系是主要结局。MRD状态与免疫微环境、放疗剂量及肿瘤复发之间的相关性是次要结局。ctDNA突变检测是探索性结局。
基于ctDNA的MRD可能是无法手术切除的ESCC患者疗效和肿瘤复发的潜在预测标志物。ctDNA-MRD升高可能比影像学更早预测肿瘤复发。应将基于ctDNA的MRD分析及基于ctDNA的MRD指导的诊断和治疗应用于临床实践，以提高无法手术切除的II-III期ESCC的疗效并减少肿瘤复发。
ECMRD-001研究已在ClinicalTrials.gov注册，注册号为NCT05952661（2023年7月19日），https://classic.clinicaltrials.gov/ct2/show/NCT05952661 。
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