III 期结肠癌患者切除术后复发时间及其与复发后生存的关系。
Time to recurrence and its relation to survival after recurrence in patients resected for stage III colon cancer.
机构信息
Department of Gastroenterology and GI Oncology, Georges Pompidou European Hospital, SIRIC CARPEM, Université Paris-Cité, Paris, France; Department of Oncology, Veneto Institute of Oncology IRCCS, Padua, Italy; Medical Oncology 3, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, team Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, AP-HP,Centre Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges Pompidou, Paris, France.
出版信息
Eur J Cancer. 2023 Nov;194:113321. doi: 10.1016/j.ejca.2023.113321. Epub 2023 Sep 9.
BACKGROUND
It is intuitively thought that early relapse is associated with poor survival after recurrence (SAR) in resected colon cancer (CC) patients, but this has never been formally studied.
METHODS
We pooled data from stage III patients treated with oxaliplatin-based adjuvant therapy in two phase III trials, to analyse time to recurrence (TTR) and its relationship with SAR. TTR and SAR were also studied according to molecular status (mismatch repair (MMR), RAS, and BRAF). Early relapsing patients were defined as patients having a TTR event within 12 months after starting adjuvant chemotherapy.
RESULTS
4548 stage III CC patients were included in the present analysis. Deficient MMR (dMMR) CC patients experienced fewer recurrences than proficient (p)MMR CC patients (18.8% versus 27.6%) but had a significantly shorter median TTR (mTTR; 0.74 versus 1.40 years, p < 0.0001). In pMMR patients, BRAF and RAS mutations were also associated with earlier mTTR as compared to double wild-type (WT) patients (0.99 versus 1.38 versus 1.54 years, respectively, p < 0.0001). Early recurrence occurred in 397 patients and was associated with a median SAR (2.2 versus 3.3 years, p = 0.0007). However, this association was mainly due to pMMR/RAS and BRAF mutated tumours and was not confirmed in dMMR and pMMR/double WT subgroups.
CONCLUSION
In resected stage III CC treated with standard oxaliplatin-based adjuvant therapy, TTR varies between dMMR, pMMR/RAS, or BRAF mutated and pMMR/double WT tumours. In addition, early relapse is associated with poor survival, mainly due to patients resected for a pMMR/RAS or BRAF mutated tumour.
背景
人们直观地认为，在接受奥沙利铂为基础的辅助治疗的结肠癌（CC）患者中，早期复发与复发后（SAR）的生存不良相关，但这从未得到过正式研究。
方法
我们汇总了两项 III 期临床试验中接受奥沙利铂为基础的辅助治疗的 III 期患者的数据，以分析无复发生存时间（TTR）及其与 SAR 的关系。还根据分子状态（错配修复（MMR）、RAS 和 BRAF）研究了 TTR 和 SAR。早期复发的患者被定义为在开始辅助化疗后 12 个月内发生 TTR 事件的患者。
结果
本分析纳入了 4548 例 III 期 CC 患者。dMMR CC 患者的复发率低于 pMMR CC 患者（18.8%比 27.6%），但中位 TTR（mTTR）明显缩短（0.74 年比 1.40 年，p<0.0001）。与双 WT 患者相比，pMMR 患者的 BRAF 和 RAS 突变也与更早的 mTTR 相关（分别为 0.99 年比 1.38 年比 1.54 年，p<0.0001）。397 例患者发生早期复发，与中位 SAR（2.2 年比 3.3 年，p=0.0007）相关。然而，这种关联主要是由于 pMMR/RAS 和 BRAF 突变型肿瘤引起的，在 dMMR 和 pMMR/double WT 亚组中未得到证实。
结论
在接受标准奥沙利铂为基础的辅助治疗的 III 期 CC 患者中，TTR 在 dMMR、pMMR/RAS 或 BRAF 突变和 pMMR/double WT 肿瘤之间存在差异。此外，早期复发与生存不良相关，主要是由于切除了 pMMR/RAS 或 BRAF 突变型肿瘤的患者。
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