肿瘤负荷与BRAF^(V600E)突变晚期结直肠癌患者预后及一线治疗决策的关系

Relationship of tumor burden with prognosis and decision-making of first-line chemotherapy in BRAF^(V600E)-mutant advanced colorectal cancer

目的探讨肿瘤负荷(tumor burden,TB)与BRAF^(V600E)突变晚期结直肠癌(colorectal cancer,CRC)患者预后及一线治疗决策的关系。方法选取2009年10月至2020年10月就诊于北京大学肿瘤医院的BRAF^(V600E)突变晚期CRC患者96例为研究对象,依据TB将患者分为低TB组(32例)和高TB组(64例),依据一线治疗方案将患者分为两药±贝伐珠单抗(bevacizumab,Bev)组和三药±Bev组,比较各组患者临床资料、总生存(overall survival,OS)时间和无进展生存(progress free survive,PFS)时间、客观有效率(objective response rate,ORR)和疾病控制率(disease control rate,DCR)。采用K-M法进行生存分析,Cox比例风险模型进行单因素和多因素分析。结果低TB组患者中位OS时间和中位PFS时间均显著长于高TB组(均P<0.05)。Cox多因素分析结果显示,TB是影响BRAF^(V600E)突变晚期CRC患者OS时间(HR=0.474,95%CI:0.269~0.836,P=0.010)和PFS时间(HR=0.563,95%CI:0.338~0.938,P=0.027)的独立因素。在低TB组和高TB组患者中,一线治疗方案均非影响OS时间和PFS时间的独立因素(均P>0.05)。BRAF^(V600E)突变晚期CRC患者中一线接受两药±Bev治疗者ORR显著低于接受三药±Bev治疗者(8.3%∶33.3%,P=0.008),但二者DCR比较差异无统计学意义(72.2%∶79.2%,P=0.502)。结论TB是BRAF^(V600E)突变晚期CRC患者,OS时间和PFS时间的独立预测因素。在不同TB患者中,一线治疗方案(两药±Bev或三药±Bev)对OS时间和PFS时间的影响并无差异。一线应用三药±Bev的患者有更高的ORR。

Objective To investigate the relationship between tumor burden(TB)with prognosis and decision-making of first-line chemotherapy in BRAF^(V600E)-mutant advanced colorectal cancer(CRC).Method A total of 96 patients with BRAF^(V600E)-mutant advanced CRC treated in the Peking University Cancer Hospital from October 2009 to October 2020 were enrolled for the research.Patients were divided into low TB group and high TB group according to the TB,and patients were divided into two groups based on first-line treatment regimens:doublet±bevacizumab(Bev)group and triplet±Bev group.The clinical data,overall survival(OS),progress free survive(PFS)time,objective response rate(ORR)and disease control rate(DCR)were compared between each group.K-M method was used for survival analysis.Cox ratio risk model was used to univariate and multivariate analysis.Result Both the median OS(mOS)and the median PFS(mPFS)of patients with low TB group were significantly longer than high TB group(all P<0.05).Cox multivariate analysis showed that TB was an independent factor affecting OS(HR=0.474,95%CI:0.269~0.836,P=0.010)and PFS(HR=0.563,95%CI:0.338~0.938,P=0.027)in advanced CRC patients with BRAF^(V600E)-mutant.In patients with both low TB group and high TB group,first-line treatment regimens were not independent factors affecting OS and PFS(all P>0.05).In patients with BRAF^(V600E)-mutant advanced CRC,the ORR of patients treated with doublet±Bev was significantly lower than triplet±Bev(8.3%∶33.3%,P=0.008),but there was no significant difference in DCR between the two regimens(72.2%∶79.2%,P=0.502).Conclusion TB is an independent predictor of both OS time and PFS time in patients with BRAF^(V600E)-mutant advanced CRC.In patients with different TB,there is no significant difference in the effects of first-line treatment regimens(doublet±Bev or triplet±Bev)on OS time and PFS time.Patients taking triplet±Bev as first-line treatment regimen have higher ORR.