Comparison Of Survival Outcomes Between External Irradiation And Intraoperative Radiotherapy After Breast Conserving Surgery Based On SEER Database

Background and purpose:The surgical methods of early breast cancer usually include improved radical resection of breast cancer and breast conserving surgery.At present,breast conserving surgery has become one of the first surgical methods for patients with early breast cancer.The breast conserving surgery not only retains the normal body,but also avoids the psychological problems and social influence caused by breast loss of patients.External irradiation radiotherapy(External beam radiotherapy EBRT)is the standard adjuvant therapy for early breast cancer after breast-conserving surgery,which can significantly reduce local recurrence in breast cancer patients.Studies have shown that most of local recurrence after breast conserving surgery occurs within 3 cm of tumor bed,indicating that control of tumor bed is crucial in reducing local recurrence.Intraoperative radiotherapy(Intraoperative Radiotherapy IORT)has achieved local control effect comparable to external irradiation in some low-risk patients,and some studies have shown that IORT has achieved better local control as intensive tumor treatment.IORT also has some specific advantages.IORT avoids the migration of tumor bed positioning caused by suture of residual cavity tissue after breast preservation surgery,and improves the accuracy of radiotherapy.Secondly,IORT is one-time irradiation,which reduces the time and economic cost related to treatment.IORT is significantly better than EBRT in radiation-related adverse reactions,especially skin or radiation pneumonia.Studies have shown that the efficacy of IORT in some highly selected patients is not worse than that of EBRT,however,some literature have reported that IORT patients have higher risk of local recurrence than IORT as the only adjuvant radiotherapy after breast conservation surgery,believing that IORT alone may only be suitable for highly selected low-risk breast cancer patients,as an alternative radiotherapy for ERT.Therefore,it is crucial to grasp the appropriate population for IORT.In the real world,IORT is increasingly used due to its convenience,economic and time advantages.Does IORT achieve the same clinical benefits in the real world?We included 4400 patients with early breast cancer in the Surveillance,Epidemiology,End Results Program,SEER)database(2200,EBRT:2200).We compared survival outcomes between the IORT and EBRT groups and also examined factors significantly associated with clinical outcomes in intraoperative radiotherapy and external irradiation radiotherapy groups for analyzing whether IORT achieves comparable survival benefits to EBRT in the real world and other factors affecting prognosis in these patients.Methods:In total,we collected clinical data from 293691 female breast cancer patients undergoing BCS from 2010 to 2018,and a total of 153253 patients were excluded after exclusion screening,for a total of 140438 eligible patients.According to age,T grade,N grade,2200),ER/PR status,HER 2 expression status,tumor histological grade,2200 patients received IORT with 2200 EBRT groups and achieved good matching.Survival analysis between the IORT and EBRT groups was performed using the Kaplan-Meier method,hypothesis test using univariate COX regression to determine independent prognostic factors associated with improved OS and BCSS,and multivariate COX regression to analyze the treatment effect of IORT or EBRT on OS and BCSS,reporting the corresponding hazard ratio(HR)and 95% confidence interval(CI).In addition,IORT and EBRT were stratified for analysis,and IORT and EBRT were divided into different levels according to suspected risk confounders,and then the strength of association between exposure and treatment was analyzed within each layer,respectively。Results:Clinical data of 4400 early breast cancer patients undergoing breast conserving surgery(after bias score matching:2200 in the IORT group and 2200 in the EBRT group).With a median follow-up of 5.54 years,255 deaths,54(21%)were cancer-related,IORT deaths were 36(1.64%),9 cancer-related deaths(0.41%),A total of 219 deaths(9.95%)occurred in the EBRT group,45 cancer-related deaths(2.05%)。3-year overall survival was 99.1% in the IORT group,97.8% in the EBRT group,5-year overall survival was 97.0% in the IORT group and 95.5% in the EBRT group,a statistically significant difference(HR=1.58,95% CI 1.09-2.29,P=0.015).Three-year cancer-specific survival was 99.0% in the IORT,99.5% in the EBRT。The 5-year cancer-specific survival in the IORT group was 99.4%,The 5-year cancer-specific survival in the EBRT group was 98.9%,with no significant differences(HR=1.40,95% CI 0.66-2.96,P=0.381).Our data showed that the IORT group was better than the EBRT group in overall survival,but this benefit was mainly derived from non-breast-related deaths but than breast cancer-related deaths,and both groups received consistent clinical benefit in terms of death due to breast cancer.In univariate analysis,ER positive,PR positive,T2,N1,adjuvant therapy,triple negative breast cancer and grade Grade Ⅱ tumors were significantly associated with OS and BCSS,age older than 5 5 years,invasive lobular cancer,whole breast beam irradiation,single(never married)were associated with OS,and chemotherapy factors were associated with BCSS(all P <0.05).In the multifactor analysis Patients with PR negative tumors had significant OS and BCSS benefit compared with positive PR(OS:HR=0.66,95% CI 0.450.95,P=0.027 BCSS:HR=0.41,95% CI 0.200.82,P=0.012);Compared with patients in stage T1,the associated risk factors for OS and B CSS in stage T2 were statistically significant(OS:HR=2.38,95% CI 1.753.22,P <0.001 BCSS:HR=3.66,95% CI 2.08 6.46 P <0.001).For age greater than 55 years,separation/divorce/widowed/unknown,mixed cancer was only significantly associated with OS,N1,histology grade 2/3 were risk prognostic factors for BCSS(all P <0.05).Further research on the deep forest map found that:Using OS as the study endpoint,For age over 55 years(HR=1.69,95% CI 1.14-2.52),nonHispanic(HR=1.69,95% CI 1.13-2.54),T1(HR=1.88,95% CI 1.19-2.97),NO(HR=1.71,95% CI 1.15-2.55),unknown condition without chemotherapy/chemotherapy(HR=1.54,95% CI 1.04-2.29),no systemic treatment(HR=1.81,95% CI 1.03-3.15)Non-triple-negative breast cancer(HR=1.50,95% CI 1.02-2.22),ER positive(HR=1.57,95% CI 1.05-2.36),PR positive(HR=1.65,95% CI 1.06-2.56),middle and low level income region(HR=1.50,95% CI 1.02-2.19),histology grade Ⅱ(HR=1.99,95% of CI 1.11-3.56)of breast cancer patients,More inclined to benefit from IORT treatment,Statistically different(all p <0.05);Using the BCSS as the study endpoint:None of the BCSS were statistically different。Conclusion:1.In terms of overall survival,IORT group was superior to EBRT group,but this benefit was mainly derived from non-breast cancer-related deaths rather than breast cancer-related deaths,and both groups received consistent clinical benefit in terms of death due to breast cancer.2.Intraoperative radiotherapy may be a reasonable option for some highly selected early-stage low-risk breast cancer populations,for example,age> 55 years,T1,NO,ER positive,PR positive,HER 2 negative,and histological grade Ⅱ.