错配修复完整/微卫星稳定直肠癌新辅助放化疗序贯免疫治疗后MRI再评估时间窗探索性研究

张华清, 孙振, 李珂璇, 林国乐, 吴斌, 陆君阳, 徐徕, 张冠南, 牛备战, 肖毅

中国实用外科杂志 ›› 2026, Vol. 46 ›› Issue (9) : 1267-1274.

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中国实用外科杂志 ›› 2026, Vol. 46 ›› Issue (9) : 1267-1274. DOI: 10.19538/j.cjps.issn1005-2208.2026.09.18
论著

错配修复完整/微卫星稳定直肠癌新辅助放化疗序贯免疫治疗后MRI再评估时间窗探索性研究

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Exploratory study of the MRI reassessment interval after neoadjuvant chemoradiotherapy followed by immunotherapy in pMMR/MSS rectal cancer

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摘要

目的 探讨除传统放疗时间锚点外,免疫治疗是否同样可作为与错配修复完整(pMMR)/微卫星稳定(MSS)中低位局部进展期直肠癌病人新辅助放化疗序贯免疫治疗(inCRT)后MRI再评估准确性相关的重要时间锚点。方法 回顾性纳入2022年6月至2026年4月北京协和医院新辅助治疗后行根治性手术的406例病人。以inCRT组作为主分析队列(n=136),新辅助放化疗(nCRT)作为参照队列(n=270)。定义病理学器官保留适宜标准为ypT0~1N0,MRI标准为MRI肿瘤退缩分级(mrTRG)1~2级且治疗后无可疑残余淋巴结(ymrN0),两者判断一致为准确,以MRI器官保留判断准确性为主要终点。MRI再评估时间窗为末次相关抗肿瘤治疗结束至MRI再评估的间隔,以放疗结束至MRI再评估时间间隔作为敏感性分析。采用限制性立方样条和多因素Logistic回归分析诊断性能的时间-效应关系。结果 inCRT组病人年龄[M(Q1,Q3)]为60(52,67)岁,男性89例(65.4%),基线mrT4共29例(21.3%),mrN2共83例(61.0%),直肠系膜筋膜阳性63例(46.3%),壁外血管侵犯阳性76例(55.9%)。inCRT组中107例(78.7%)接受长程放疗。inCRT组有35例(25.7%)符合MRI器官保留适宜标准,术后病理则有66例(48.5%)符合病理学器官保留适宜标准。MRI判断准确率为65.4%,敏感度40.9%,特异度88.6%。inCRT组MRI判断准确者的末次免疫治疗后再评估时间窗长于判断不准确者[26(17,36)d vs. 18(9.5,33)d,P=0.017];时间每延长7 d,MRI判断准确性的调整后OR为1.273(95%CI:1.025~1.600,P=0.029)。限制性立方样条显示再评估时间窗与判断准确性存在总体关联(总体P=0.034),但非线性关联不显著(非线性P=0.158)。末次免疫治疗后第1~2周、第3~4周和第5~6周的平均调整后预测准确率分别为50.1%、69.7%和72.6%,其中第3~4周较第1~2周提高19.7个百分点(95%CI:3.0~36.9,P=0.046),第5~6周未较第3~4周进一步显著提高(P=1.000)。以放疗结束作为时间起点时,inCRT组准确率、敏感度及特异度均未见显著时间-效应关系。nCRT组判断准确者的时间间隔较短[15.5(5,25)d vs. 21(10,28.75)d,P=0.018],但Logistic分析及限制性立方样条总体检验均未显示诊断性能随时间延长而提高的趋势。结论 在接受新辅助放化疗序贯免疫治疗的pMMR/MSS局部进展期直肠癌病人中,适当延迟MRI再评估可能提高MRI对病理学器官保留适宜病人的识别能力。末次免疫治疗后第3~4周可能是兼顾评估可靠性与后续决策及时性的MRI再评估阶段,值得进一步前瞻性验证。

Abstract

Objective To determine whether, beyond the conventional radiotherapy-based time anchor, the interval from the last immunotherapy administration to MRI reassessment also constitutes a key time anchor influencing assessment accuracy in patients with proficient mismatch repair/microsatellite-stable (pMMR/MSS) mid-to-low locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by immunotherapy (inCRT). Methods This retrospective study included 406 patients who underwent radical surgery after neoadjuvant therapy at Peking Union Medical College Hospital between June 2022 and April 2026. The inCRT cohort (n=136) was the primary analysis cohort, and the neoadjuvant chemoradiotherapy (nCRT) cohort (n=270) served as the reference. Pathologic suitability for organ preservation was defined as ypT0-1N0, and MRI suitability as MRI tumor regression grade (mrTRG) 1-2 with no suspicious residual lymph nodes (ymrN0). Concordance between MRI and pathology was considered an accurate assessment and served as the primary endpoint. The MRI reassessment interval was defined as the time from completion of the last relevant antitumor treatment to MRI reassessment; the interval from completion of radiotherapy to MRI was examined in sensitivity analyses. Multivariable Logistic regression and restricted cubic spline (RCS) models were used to evaluate time-effect associations of diagnostic performance. Results In the inCRT cohort, the median age was 60 years (Q1, 52; Q3, 67), 89 patients (65.4%) were male, 29 (21.3%) had baseline mrT4 disease, 83 (61.0%) had mrN2 disease, 63 (46.3%) had mesorectal fascia involvement, and 76 (55.9%) had extramural vascular invasion; 107 patients (78.7%) received long-course radiotherapy. 35 patients (25.7%) met the MRI criteria for suitability for organ preservation, whereas 66 patients (48.5%) met the pathologic criterion. The accuracy, sensitivity, and specificity of MRI assessment were 65.4%, 40.9%, and 88.6%, respectively. The interval from the last immunotherapy administration to MRI was longer in patients with accurate than inaccurate assessments [26 (17, 36) vs. 18 (9.5, 33) days, P=0.017]. Each 7-day increase in the interval was associated with greater odds of an accurate MRI assessment (adjusted OR, 1.273; 95%CI 1.025-1.600; P=0.029). RCS analysis showed a significant overall association between the interval and assessment accuracy (overall P=0.034), without evidence of nonlinearity (P for nonlinearity=0.158). Mean adjusted predicted accuracies during weeks 1-2, 3-4, and 5-6 after the last immunotherapy administration were 50.1%, 69.7%, and 72.6%, respectively. Accuracy during weeks 3-4 was 19.7 percentage points higher than during weeks 1-2 (95%CI 3.0-36.9 percentage points; P=0.046), whereas no further significant improvement was observed during weeks 5-6 (P=1.000). When the interval was anchored to completion of radiotherapy, no significant time-dependent associations were observed for accuracy, sensitivity, or specificity in the inCRT cohort. In the nCRT cohort, the interval was shorter in patients with accurate assessments [15.5 (5, 25) vs. 21 (10, 28.75) days, P=0.018], but neither Logistic regression nor the overall RCS test showed improved diagnostic performance with increasing interval. Conclusion In patients with pMMR/MSS locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by immunotherapy, an appropriate delay in MRI reassessment after the last immunotherapy administration may improve identification of patients pathologically suitable for organ preservation. Reassessment at 3-4 weeks may provide a reasonable balance between assessment reliability and timely subsequent decision-making and warrants further prospective validation.

关键词

直肠肿瘤 / 新辅助治疗 / 免疫治疗 / 磁共振成像 / 器官保留

Key words

rectal neoplasms / neoadjuvant therapy / immunotherapy / magnetic resonance imaging / organ preservation

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导出引用
张华清, 孙振, 李珂璇, 等. 错配修复完整/微卫星稳定直肠癌新辅助放化疗序贯免疫治疗后MRI再评估时间窗探索性研究[J]. 中国实用外科杂志. 2026, 46(9): 1267-1274 https://doi.org/10.19538/j.cjps.issn1005-2208.2026.09.18
ZHANG Hua-qing, SUN Zhen, LI Ke-xuan, et al. Exploratory study of the MRI reassessment interval after neoadjuvant chemoradiotherapy followed by immunotherapy in pMMR/MSS rectal cancer[J]. Chinese Journal of Practical Surgery. 2026, 46(9): 1267-1274 https://doi.org/10.19538/j.cjps.issn1005-2208.2026.09.18
中图分类号: R6   

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基金

中央高水平医院临床科研业务费项目(2025-PUMCH-A-076)
中央高水平医院临床科研业务费项目(2026-PUMCH-A-034)
北京市研究型病房卓越临床研究计划项目(BRWEP2024W034010108)

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