| BACKGROUND:Colorectal cancer(CRC)is a common malignant tumor threatening human health.Worldwide,The morbidity and mortality of CRC are at the forefront of all tumors.About 8%-10%of CRC have BRAF mutation,BRAF V600E mutation is the most common.At present,it is thought that the patients with BRAF V600E mutation have poor prognosis and low quality of life,and need to be treated with high-intensity chemotherapy or target drug combination therapy.However,the incidence and severity of adverse events in high-intensity chemotherapy are increased,and the novel target drugs are expensive and inaccessible,which will greatly affect the prognosis of patients.It has been found in clinical practice that the biological behavior and prognosis of BRAF V600E-mutant CRC are greatly different.It is suggested that patients with BRAF V600E-mutant CRC may need further stratification to be treated with different regimens,but how to develop stratification criteria guiding individualized treatment has become an urgent problem for clinicians.Some studies have shown that tumor burden(TB)may be a potential stratification criterion for BRAF V600E-mutant CRC.This study retrospectively analyzed the relationship between TB and prognosis and first-line treatment decisions of advanced BRAF V600E-mutant colorectal cancer.OBJECTIVE:To investigate the relationship between TB and overall survival(OS)as well as progression free survival(PFS)of patients with BRAF V600E-mutant advanced colorectal cancer.Moreover,to explore whether there is any difference in the influence on OS and PFS of different first-line regimens in patients with low TB,and to analyze the efficacy of different first-line treatment regimens for BRAF V600E-mutant advanced CRC.METHODS:The data of BRAF V600E-mutant advanced CRC treated in the Beijing Cancer Hospital from October 2009 to October 2020 were collected,including their basic information,pathological data and treatment.Formulating inclusion and exclusion criteria.Inclusion criteria:1.Colorectal cancer was confirmed by colonoscopic biopsy or surgical pathology;2.Tissue genetic test results suggest BRAF V600E mutation.3.There was distant metastasis or postoperative recurrence other than the primary lesion at the time of diagnosis;4.Having a clear baseline imaging examination to measure the lesions;5.Having received at least one cycle of standard systemic chemotherapy;6.ECOG score≤2 points.Exclusion criteria:1.Recurrence within 6 months after completion of adjuvant therapy;2.The presence of a second primary tumor;3.Patients with incomplete clinical data and pathological data;4.Follow-up information is incomplete,including survival status,information and time of loss to follow-up,etc.Finally,96 patients who met the above criteria were screened out.In terms of exploring the relationship between OS as well as PFS and TB in patients with BRAF V600E-mutant advanced CRC,and exploring differences in the influence of first-line treatment on OS and PFS in patients with low TB,patients were divided into low TB group and non-low TB group according to the number of affected organs,number of metastasis,ascites,peritoneum,bone and central nervous system involvement(low TB is defined as:Meet all of the following criteria:1.Number of metastases≤5;2.Maximum diameter of lesions≤5cm;3.Number of involved organs≤3;and 4.No ascites,no peritoneum,bone and central nervous system involvement).Both in the low TB and non-low TB group,patients were divided into two groups based on first-line treatment regimens:doublet(XELOX、XELIRI、FOLFOX or FOLFIRI)± Bevacizumab(Bev)and triplet(FOLFOXIRI or XELIRI)± Bev.The last follow-up was on February 18,2021.Chi-square test was used to compare whether there were differences in general conditions and clinicopathological characteristics among the groups.COX Ratio Risk model was used to univariate and multivariate analysis.Kaplan-Meier method was used for survival analysis.Log-rank test was used to compare the differences of PFS and OS in each group.In the aspect of exploring the efficacy of different first-line treatment regimens for BRAF V600E-mutant advanced CRC,96 patients who met the inclusion criteria were divided into two groups(doublet ± Bev and triplet ± Bev)according to different first-line treatment regimens.Chi-square test was used to compare whether there were differences in general conditions,clinicopathological characteristics,ORR and DCR among the groups.Binary Logistic Regression Model was used to univariate and multivariate analysis to find the factors related to curative effect.RESULT:A total of 96 patients were included in this study,with a male-female ratio of 1:1.04 and a median onset age of 57 years(range 24-81 years).Among them,32 patients with low TB(33.3%)and 64 patients with non-low TB(66.7%).The median follow-up time was 13.4 months(0.73 to 90.5 months)until February 18,2021 or at the time of death of the patient.Survival analysis showed that the median OS(mOS)of patients with low TB was 25.7 months and that of patients with non-low TB was 11.9 months(P=0.002),and multivariate analysis showed that TB(HR=0.482,95%CI:0.266-0.873,P=0.016)was an independent factor affecting OS.In the case of PFS,the median PFS(mPFS)of patients with low TB and non-low TB patients was 9.6 months and 5.8 months(P=0.006),respectively.Multivariate analysis showed that TB(HR=0.590,95%CI:0.354-0.983,P=0.043)was also an independent factor affecting PFS.In patients with low TB,the mOS was 27.1 months and 25.7 months in the doublet± Bev group and the triplet± Bev group,respectively,and the mPFS was 10.2 months and 10.4 months,respectively.First-line treatment regimens(HR=1.046,95%CI:0.361-3.025,P=0.934;HR=1.232,95%CI:0.520-2.922,P=0.636)were not independent factors affecting OS and PFS.In patients with non-low TB,the mOS was 13.3 months and 10.9 months in the doublet±Bev group and the triplet±Bev group,respectively,and the mPFS was 5.8 months and 5.0 months,respectively.First-line treatment regimens(HR=1.473,95%CI:0.733-2.961,P=0.276;HR=1.050,95%CI:0.545-2.022,P=0.884)were not independent factors affecting OS and PFS.In terms of treatment efficacy,There are 72 patients in the doublet ± Bev group(75%)and 24 patients in the triplet ± Bev group(25%).The ORR of doublet±Bev group and triplet±Bev group were 8.3%and 33.3%(P=0.006)respectively,and DCR was 72.2%and 79.2%(P=0.502)respectively.Patients in triplet±Bev group were more likely to achieve objective response(OR=4.466,95%CI:1.285-15.522,P=0.019).CONCLUSION:The results showed that:1.TB was an independent predictor of both OS and PFS in patients with advanced CRC with BRAF V600E mutation.2.In patients with low TB,there was no significant difference in the effects of first-line treatment regimens(doublet±Bev or triplet±Bev)on OS and PFS.3.Patients treated with triplet±Bev were more likely to achieve objective response. |
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