Prognostic Analysis,Initiating Of Radiotherapy,and Cardiac Toxicity In Patients Receiving Radiotherapy After Breast Conserving Surgery For Early-stage Breast Cancer

Part ?:Prognosis and risk factors of breast conserving therapy for patients with early-stage breast cancerPurpose:To investigate the prognosis of early-stage breast cancer after breast conserving surgery,and analyze the risk factors affecting locoregional recurrence(LRR),distant metastasis(DM)and survival.Patients and methods:We retrospectively analysed 1791 patients who underwent breast conserving surgery without neoadjuvant therapy.All patients were diagnosed with histologically-proven infiltrating breast carcinoma without ipsilateral supraclavicular or internal mammary lymph node involvement,and distant metastases at initial diagnosis.Survival curves were estimated by the Kaplan-Meier method and compared with a log-rank test.Cox proportional hazards regression was performed for multivariate analysis.Results:The median follow-up time was 4.2 years.For all patients,the 5-year LRR,DM,disease free survival(DFS)and overall survival(OS)were 3.6%,4.6%,93.0%and 97.4%,respectively.The 5-year LRR and OS were not significantly different between axillary dissection and sentinel lymph node biopsy in patients with node-negative disease(3.3%vs.3.2%,P=0.859;98.0%vs.98.5%,P=0.586).Postoperative radiotherapy significantly reduced the 5-year LRR compared with surgery alone(2.5%vs.12.9%,P<0.001).The 5-year LRR rate of the conventional fractionated radiotherapy and the hypofractionated radiotherapy were 3.1%and 2.5%(P=0.87),respectively.In multivariate analysis,age,lymphovascular invasion,pathologic tumor stage,radiotherapy,ER/PR status and endocrine therapy were independent prognostic factors of LRR(all P<0.05).Grade,pathologic node stage were independent prognostic factors of DM(all P<0.05).Age,lymphovascular invasion,pathologic tumor stage,pathologic node stage,radiotherapy,ER/PR status and endocrine therapy were independent prognostic factors of DFS.Grade,pathologic node stage,ER/PR status and endocrine therapy were independent prognostic factors of OS.Conclusions:Patients with early-stage breast cancer after breast conserving therapy had favorable outcomes.Local regional recurrence and distant metastasis had different unfavorable factors.Part ?:Prognostic analysis of initiating of chemotherapy and radiotherapy after breast conserving surgery for early-stage breast cancerPurpose:To investigate the optimal sequence of chemotherapy and radiotherapy after breast conserving surgery(BCS)for women with breast cancer.Patients and methods:We retrospectively analysed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy.Of these,488 women received chemotherapy first(CT-first group)while the other 412 received radiotherapy first(RT-first group).Locoregional recurrence(LRR),distant metastasis(DM),disease-free survival(DFS),and overall survival(OS)rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching(PSM)and the Cox proportional hazards model.The optimal cut-off value of interval time from surgery to the start of chemotherapy was calculated by Maxstat.Results:With a median follow-up of 7.1 years,the 8-year OS,DFS,LRR,and DM rates were 92.1%,86.5%,5.2%,and 11.0%,respectively for the entire cohort.In pre-match analysis,the CT-first group had a significantly higher 8-year DFS rate than the RT-first group(90.4%vs.83.1%,P=0.005).PSM analysis of 528 patients indicated that the 8-year DFS(91.0%vs.83.3%,P=0.005)and DM(8.6%vs.14.6%,P=0.017)were significantly better in the CT-first group,but that the LRR(P=0.434)and OS((P=0.096)were similar.We found the optimal cut-off value of interval from surgery to chemotherapy was 12 weeks.Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes(LRR:HR 2.08,95%CI 1.11-3.91,P=0.023;DM:HR 1.89,95%CI 1.23-2.87,P=0.003;DFS:HR 2.36,95%CI 1.57-3.55;P<0.001;OS:HR 1.88,95%CI 1.13-3.11;P=0.015).Conclusions:For women with breast cancer who require both chemotherapy and radiotherapy after BCS,adjuvant chemotherapy should be started within 12 weeks.Delaying the initiation of radiotherapy,for administration of long-course chemotherapy,does not compromise outcomes.Part ?:Subclinical heart injury in patients receiving hypofractionated radiotherapy after breast conserving surgery:an analysis of a prospective studyObjectives:To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery,and to investigate the correlation between cardiac injury and heart dose.Materials and methods:We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation using either deep inspiration breath-hold(DIBH)or free breathing(FB)radiotherapy technique.Cardiac examinations that included N-terminal pro-B-type natriuretic peptide(NT-proBNP),electrocardiogram,and myocardial perfusion imaging were performed routinely before and after radiotherapy.The effects of heart dose,systemic therapy and individual factors(Framingham score)on the incidence of cardiac events were analyzed.Results:The median age was 48 years.The mean dose(Dmean)of the heart,left anterior descending coronary artery(LAD),left ventricular(LV),and right ventricular(RV)were 402.7 cGy,1684.9 cGy,627.2 cGy,and 443.5 cGy,respectively.With a median follow-up of 13.4 months,no patient had clinical cardiac abnormalities.The incidence rates of subclinical cardiac events at 1-6-and 12-month were 23.5%,31.6%,and 41.3%,respectively.Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean>4 Gy,LAD V40>20%,LV Dmean>6 Gy,RV Dmean>7 Gy,or cumulative doses of anthracycline or taxane>300mg/m2(all P<0.05).Anti-HER2 targeted therapy,endocrine therapy,or Framingham score were not associated with the incidence of subclinical cardiac events(all P>0.05).Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events.Conclusions:Early subclinical heart injury were found in patients with left-sided breast cancer after hypofractionated radiotherapy.The increased incidence of subclinical cardiac events after radiotherapy was positively associated with the cardiac radiation doses.