| BackgroundOvarian cancer is the most lethal gynecological malignancy and has no typical clinical symptoms in its early stage.There is no effective diagnosis method;therefore,the vast majority of patients have reached the advanced stage at diagnosis.Even after standard treatment,70%of patients have disease recurrence within 3 years,and the five-year survival rate is less than 40%.For ovarian cancer patients with FIGO stageⅢ/Ⅳ,the maximum cytoreductive surgery(R1,residual lesions less than 1 cm;R0,no residual lesions)is the most critical factor affecting the prognosis;however,if it is difficult to remove metastatic lesions in the intestine,spleen,liver due to extensive tumor metastasis,not all patients can achieve satisfactory resection from primary debulking surgery(PDS).Therefore,neoadjuvant chemotherapy(NACT)followed by interval debulking surgery(IDS)can be used as an alternative treatment to achieve maximum resection of lesions.To date,several clinical trials have confirmed that there was no significant difference between NACT-IDS and PDS in the prognoses of ovarian cancer patients.Ovarian cancer patients with BRCA1/2 mutations(BRCAmut),compared with BRCA1/2 wild-type(BRCAwt)patients,have a higher efficacy of platinum-based chemotherapy,a longer recurrence interval due to the presence of homologous recombination defects,and maintain a higher response rate to platinum-based chemotherapy after recurrence.Thus,the treatment of ovarian cancer patients can be divided into two groups based on the mutational status of BRCA1/2.Whether NACT followed by IDS has a differential effect on prognosis due to BRCA1/2 mutations has not been confirmed by current studies;therefore,we conducted this retrospective study to explore the effect of BRCA1/2 mutations on neoadjuvant chemotherapy.MethodsAll patients included in this retrospective study were admitted to Qilu Hospital of Shandong University between January 2009 and June 2020,and germline BRCA1/2 mutation were tested.Patients in stage ⅢB,ⅢC,and Ⅳ,re-staged by FIGO 2014,were selected for analysis.All patients with NACT received 1-3 cycles of platinumcontaining(carboplatin,cisplatin,or nedaplatin)chemotherapy.Patients who received maintenance therapy after chemotherapy were not eligible for this study.Relevant medical data and follow-up information of the patients were also collected.Student’s t-test was used to compare the differences in continuous variables.The chi-square test was performed to analyze differences in clinical characteristics.PFS and OS analyses were performed by Kaplan-Meier method.Multivariate proportional odds models were used to identify variables associated with PFS outcome of BRCAmut group,and hazard ratios(HR)with 95%confidence intervals(CI)were calculated.All statistical analyses were performed by Prism 8 version 8.4.0.ResultsA total of 322 patients were enrolled in the study,including 112 patients with BRCA1/2 mutations(BRCAmut),and 210 patients with BRCA1/2 wild-type(BRCAwt).In the two groups,40 BRCAmut patients(35.7%)and 69 BRCAwt patients(32.9%)received neoadjuvant chemotherapy.Regardless of the BRCA1/2 mutational status,there were no statistical differences in prognoses between patients in the NACT-IDS and PDS groups for PFS,(median:15.4 vs.15.6 months,HR=0.85;p=0.211)or OS(median:57.1 vs.64.7 months,HR=1.12;p=0.486).Further analysis found that the PFS of BRCAmut patients was significantly reduced after NACT(median,14.9 vs.18.5months,HR=0.59;p=0.03);however,there was no statistical difference in OS(median,75.1 vs.72.8months,HR=0.93;p=0.798).Whether BRCAwt patients received NACT had no significant effect on PFS(median,13.5 vs.16.0 months,HR=1.05;p=0.781)or OS(median,54.0 vs.56.4 months,HR=1.23;p=0.323).Cox regression multivariate analyses were performed.The strongest predictors of prolonged PFS for all patients included in the study were BRCA mutation(p=0.007),absence of residual lesions(p=0.003)and low CA-125 level(p=0.004);for BRCAmut patients,the predictors were FIGO Ⅲ stage(p=0.020),PDS(p=0.001),and absence of residual lesions(p=0.012);for BRCAwt patients,low CA-125 level(p=0.011),absence of residual lesions(p=0.028)were predictors of prolonged PFS.Further analysis of OS showed that,regardless of the patient’s other clinical characteristics,PARP inhibitor was the independent predictor(all patients,p=0.000;BRCAmut,p=0.000;BRCAwt p=0.000).ConclusionIn conclusion,for advanced-stage ovarian cancer patients treated with NACT followed by IDS,PFS and OS were not significantly affected in BRCAwt patients.In BRCAmut patients,NACT-IDS resulted in a shortened PFS,but had no further effect on OS.Further analysis of OS showed that,regardless of the patient’s other clinical characteristics,PARP inhibitor was the independent predictor.This study is the first to investigate the effect of BRCA1/2 germline mutation on neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer,included patients who have a long follow-up time,and complete collection of clinical baseline characteristics.data.The disadvantage is that our study is a single-center retrospective study and cannot fully explain the reasons for the shortening of PFS in patients with BRCAmut caused by neoadjuvant chemotherapy,and further multi-center prospective clinical studies are needed to explore. |
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