背景:直观地认为,在切除的结肠癌(CC)患者中,早期复发与复发后(SAR)生存率低有关,但这从未被正式研究过。
方法:我们汇集了两项III期试验中使用奥沙利铂辅助治疗的III期患者的数据,分析复发时间(TTR)及其与SAR的关系。还根据分子状态(错配修复(MMR),RAS,和BRAFV600E)。早期复发患者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:4548例III期CC患者纳入本分析。缺陷型MMR(dMMR)CC患者的复发少于(p)MMRCC患者(18.8%对27.6%),但中位TTR明显较短(mTTR;0.74对1.40年,p<0.0001)。在pMMR患者中,与双野生型(WT)患者相比,BRAF和RAS突变也与早期mTTR相关(0.99年对1.38年对1.54年,分别,p<0.0001)。早期复发发生在397例患者中,并与中位SAR(2.2年对3.3年,p=0.0007)。然而,这种关联主要是由于pMMR/RAS和BRAFV600E突变的肿瘤,在dMMR和pMMR/双WT亚组中未得到证实.
结论:在接受基于奥沙利铂的标准辅助治疗的切除的III期CC中,TTR在dMMR、pMMR/RAS,或BRAFV600E突变和pMMR/双WT肿瘤。此外,早期复发与低生存率相关,主要是由于切除pMMR/RAS或BRAFV600E突变肿瘤的患者。
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.
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 BRAFV600E). Early relapsing patients were defined as patients having a TTR event within 12 months after starting adjuvant chemotherapy.
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 BRAFV600E mutated tumours and was not confirmed in dMMR and pMMR/double WT subgroups.
In resected stage III CC treated with standard oxaliplatin-based adjuvant therapy, TTR varies between dMMR, pMMR/RAS, or BRAFV600E 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 BRAFV600E mutated tumour.