The Role Of Postmastectomy Radiation Therapy Based On Pathological Nodal Status In Breast Cancer Treated With Neoadjuvant Chemotherapy

Part I:The Role of postmastectomy radiation therapy based on pathological nodal status in clinical nodal positive stage ?-?breast cancer treated with neoadjuvant chemotherapyPurpose:The role of postmastectomy radiotherapy(PMRT)following neoadjuvant chemotherapy(NAC)remains controversial in patients with breast cancer.The aim of this study was to evaluate the effect of PMRT after NAC in breast cancer patients with clinically node-positive,stage II-III(cTl-4N1-2M0)disease.Patients and Methods:A total of 1963 patients from 12 institutions treated between 2000 and 2014 were retrospectively reviewed.Patients were classified into three cohorts based on the pathological lymph node status after NAC:pathological lymph node negative(ypNO),one to three pathological lymph nodes involved(ypN1),and more than three positive lymph nodes(ypN2-3).The role of PMRT was evaluated in each cohort separately.Loco-regional control(LRC),disease-free survival(DFS)and overall survival(OS)were estimated using the Kaplan-Meier method.The effect of PMRT was assessed by multivariable and propensity score-matched analyses.Results:With a median follow-up of 72.9 months,the 5-year LRC,DFS and OS were 86.3%,67.5%and 83.3%for all patients,respectively.There were 519(26.4%)patients in ypNO group,617(31.4%)patients in ypNl group and 827(42.2%)patients in ypN2-3 group.A total of 1406(71.6%)patients received PMRT,including 259(49.9%)in ypNO group,427(69.2%)in ypNl group and 720(87.1%)in ypN2-3 group.In ypNO group,compared with no-PMRT,PMRT significantly improved 5-year LRC(98.0%vs 94.3%,P=0.039),but not 5-year DFS(89.0%vs 84.8%,P=0.344)and OS(93.9%vs 95.5%,P=0.646).In ypNl group,PMRT significantly improved 5-year LRC(92.4%vs 81.6%,P<0.001)and DFS(76.8%vs 66.8%,P=0.037),but not 5-year OS(88.2%vs 87.8%,P=0.494).In ypN2-3 group,PMRT significantly improved the 5-year LRC(81.4%vs 52.4%,P<0.001),DFS(54.4%vs 31.9%,P<0.001)and OS(74.7%vs 57.6%,P<0.001).After PSM adjustment,the benefits of PMRT versus no-PMRT were consistent in each group.In subgroup analysis of patients with ypNl,PMRT significantly improved OS in those with clinical stage III disease.Conclusion:For patients with clinical axillary lymph node-positive breast cancer who received NAC and mastectomy,PMRT improve LRC in all ypNO,ypN1 and ypN2-3 patients.The OS benefit of PMRT is only observed in ypN2-3 patients but not in ypNO and ypN1 cohorts.Part ?:Delay of postmastectomy radiotherapy after neoadjuvant chemotherapy is associated with inferior survival outcomes for patients with locally advanced breast cancerPurpose:This study evaluated the effect of interval from surgery to radiotherapy(SRI)on survival outcomes in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy.Patients and Methods:A total of 1087 women treated with neoadjuvant chemotherapy and mastectomy from 11 hospitals in China were retrospectively analyzed.The patients were divided into early radiotherapy group(SRI<18 weeks)and delayed radiotherapy group(SRI>18 weeks)by using maxstat method.Cox regression model and Propensity score-matched analyses(PSM)were used to test the effect of timing of radiotherapy.Results:With median follow-up of 72.9 months,the 5-year disease free survival(DFS)and overall survival(OS)rates were 68.1%and 81.8%,respectively.In multivariate Cox regression analysis,hormone receptor status(P<0.001),pathological T stage(P<0.001),pathological N stage(P<0.001),and SRI(P=0.023)were independent prognostic factors of DFS.Hormone receptor status(P=0.013),pathological T stage(P=0.006),pathological N stage(P<0.001),endocrine therapy(P=0.013),and SRI(P=0.001)were associated with OS.After balancing the clinical and pathological factors with PSM,patients with SRI<18 weeks had superior DFS and OS to those with SRI>18 weeks.Conclusion:For locally advanced breast cancer patients treated with neoadjuvant chemotherapy followed by mastectomy and adjuvant chemotherapy,delay in initiating postmastectomy radiotherapy is associated with inferior survival outcomes.Radiotherapy should be performed within 18 weeks after mastectomy.Part ?:Predicting non-sentinel lymph node metastasis in breast cancer patients with 1-2 positive sentinel lymph nodesPurpose:To evaluate the risk factors for non-sentinel lymph node(NSLN)metastasis,and to develop a nomogram prediction model in breast cancer patients with 1-2 positive sentinel lymph node.Patients and Methods:Breast cancer patients who were diagnosed with 1-2 positive lymph nodes and underwent axillary lymph node dissection(ALND)from January 2008 to December 2014 were retrospectively analyzed.Based on the results of the multivariate logistic regression analysis,a nomogram prediction model for NSLN metastasis was developed.The predictive accuracy of nomogram model was evaluated using the area under the receiver operating characteristic curve(AUC)and calibration curves.Results:A total of 270 patients had 1-2 sentinel positive lymph metastases.Of them,87(32.2%)patients had NSLN metastases.The median age,number of SLNs and number of axillary lymph nodes of the 270 patients were 46 years old(21-80 years),4(1-10),and 20(10-41),respectively.Univariate analysis showed that the histological grade,the size of SLN metastasis,the number of positive SLN and the number of negative SLN were the risk factors of NSLN metastasis.Multivariate analysis showed that histological grade,number of positive SLN,number of negative SLN were independent risk factors of NSLN metastasis.The AUC value of nomogram predictive model for NSLN metastasis was 0.70.The false negative rate of nomogram was 10.5%when predictive probability cut-off points was 15%.Conclusion:The nomogram is a useful predictive model for evaluating NSLN metastasis.The ALND or axillary radiotherapy can be avoided for patients with low probability of NSLN metastasis.