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Abstract：
Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC).
We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS).
One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively.
Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.
We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS).
One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively.
Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.
摘要：
背景：有关不匹配修复系统（MMR）缺陷的可用数据相互矛盾，并且来自小型研究。我们的研究旨在评估局部晚期直肠癌（LARC）患者MMR状态的治疗意义。
方法：我们回顾性收集了在意大利卡利亚里大学医院肿瘤科接受LARC治疗的318例患者的数据，IstitutoNazionaledeiTumoriMilan,还有AOUOspedaliRiunitiAncona.所有患者均接受新辅助放化疗。主要目标是主要TRG，次要目标是病理完全反应，无病生存期（DFS）和总生存期（OS）。
结果：160名患者（148pMMR和12dMMR）被纳入探索队列，158名患者（146pMMR和12dMMR）被纳入验证队列。在探索性和验证性队列中，有42.6%和43.1%的pMMR患者出现了一个主要的TRG，分别；而在两个队列的dMMR患者中均未显示主要TRG。与dMMR相比，探索性和验证性队列在pMMR患者中显示出统计学上显着的较高mDFS：NR与14个月和NRvs.17个月,分别。
结论：我们的结果表明dMMR与术前放化疗反应不良之间存在关联，它们代表了新新辅助治疗策略的假设产生数据。
方法：我们回顾性收集了在意大利卡利亚里大学医院肿瘤科接受LARC治疗的318例患者的数据，IstitutoNazionaledeiTumoriMilan,还有AOUOspedaliRiunitiAncona.所有患者均接受新辅助放化疗。主要目标是主要TRG，次要目标是病理完全反应，无病生存期（DFS）和总生存期（OS）。
结果：160名患者（148pMMR和12dMMR）被纳入探索队列，158名患者（146pMMR和12dMMR）被纳入验证队列。在探索性和验证性队列中，有42.6%和43.1%的pMMR患者出现了一个主要的TRG，分别；而在两个队列的dMMR患者中均未显示主要TRG。与dMMR相比，探索性和验证性队列在pMMR患者中显示出统计学上显着的较高mDFS：NR与14个月和NRvs.17个月,分别。
结论：我们的结果表明dMMR与术前放化疗反应不良之间存在关联，它们代表了新新辅助治疗策略的假设产生数据。
