Risk Factor Of Locoregional Recurrence And Role Of Radiotherapy After Postmastectomy For Early Stage Intermediate Risk (T1-2N1M0) Breast Cancer

Part Ⅰ:Risk factor of locoregional recurrence and role of postmastectomy radiotherapy for early stage intermediate risk (T1-2N1M0) breast cancerObjective:The aim of this study was to evaluate risk factor of locoregional recurrence and role of postmastectomy radiotherapy (PMRT) for early stage intermediate risk (T1-2N1M0) breast cancer, and to analyze failure pattern to define the clinical target volume (CTV).Material and methods:1348 patients with T1-2 breast cancer and 1 to 3 positive lymph nodes treated with mastectomy with or without PMRT during 1999-2010 were retrospectively analyzed.630 (46.7%) patients were T1 and 709 (52.6%) were T2.667 (49.5%),417 (30.9%) and 264 (19.6%) patients have 1,2 and 3 axillary positive lymph node. The molecular subtypes included luminal A (67.5%), luminal B (10.9%), overexpressed HER2 (5.5%) and triple negative (13.6%). After mastectomy,235 (17.4%) received radiotherapy,1249 (92.7%) received adjuvant chemotherapy,958 (73.5%) received adjuvant hormonal therapy, and 39 (2.9%) received adjuvant trastuzumab. Overall survival (OS) and locoregional recurrence rate (LRR) rates were calculated by Kaplan-Meier analysis and compared by log-rank test. Cox logistic regression analysis was performed. P values of less than 0.05 were considered statistically significant. Results:The median survival time was 79 months. Overall, the 5-year and 10-year LRFS were 97.0% and 94.8%, and cumulative LRFS were 95.7% and 91.6%, respectively. The 5-year LRFS were not statistically different between patients with or without PMRT (95.9% VS 94.5%, p= 0.338). However, multivariate analysis showed that patient who did not receive PMRT was a significant predictor of LRR (p= 0.037, HR= 2.519,95% CI 1.058-6.000). On Multivariate analysis, significant factors associated with an increased risk of LRR were T2 stage (p= 0.014, HR= 2.146,95% CI 1.170-3.936), PR negative (p= 0.017, HR= 2.651,95% CI 1.189-5.911) and percentage of positive lymph node (PLN)>10%(p=0.026, HR=0.532,95% CI 0.305-0.928) in patients who did not receive PMRT. Molecular subtype were not prognostic factors for LRR, and only Luminal A showed a trend (p= 0.080) for better prognosis.In patients with 3 risk factors without PMRT, the 5-year and 10-year LRR was both 15.7%.Supraclavicular region and chest wall were the primary failure pattern of recurrence, with similar risk of 48.1% and 50.0%.Conclusion:In patients with intermediate risk breast cancer, LRR rates after mastectomy are low. Risk factors of LRR included T2 stage,PR negative and PLN>10%.PMRT should be considered for patients with all 3 risk factors, and suppose to cover the CTV of supraclavicular region and chest wall.The value of molecular subtype for LRR is not clear, further research on this subject is justified.Part Ⅱ:A prospective study of intensity-modulated radiotherapy with integrated boost after breast conservative surgery in breast cancer patientsObjective:To prospectively evaluate the efficacy and toxicity of intensity modulated radiotherapy (IMRT) with integrated boost after breast conservative surgery.Material and methods:From January 2006 to June 2010,128 patients with stages I-III breast cancer treated with breast conservative surgery were recruited. All patients received whole breast IMRT with integrated tumor bed boost. A total dose of 50 Gy in 25 fractions with 2 Gy per fraction was delivered to the whole breast, while 60 Gy with 2.4 Gy per fraction was delivered to the tumor bed concomitantly. Supraclavicular fossa was irradiated to 50 Gy in 9 patients (7.1%) who had more than 3 involved axillary lymph nodes.104 patients (81.3%) received chemotherapy.93 (94.9%) of patients received endocrine therapy. Cosmetic evaluation is based on the Harvard system. Acute and late toxicities were scored according to CTCAE version 3. Survival rates were calculated by Kaplan-Meier method.Results:The 5-year locoregional recurrence-free survival, disease-free survival and overall survival was 98.4%,97.7%, and 95.3%, respectively. The acute skin toxicity was grade 1 in 65.6%, grade 2 in 15.6%, and grade 3 in 2.3% of all patients. Grade 2 radiation pneumonitis (RP) was developed in 4.7%of this cohort, grade 1 in 22.5%. Grade 1-2 arm edema developed in 28.9%. One patient (0.8%) developed whole breast depigmentation. Four patients (3.1%) had chromatosis.77.3% of patients had "excellent or good" cosmetic outcome at 5 years, compared to 85.9% of patients before radiotherapy. However,28 patients (21.9%) had "fair" cosmetic outcome and 1 patient had "poor" appearance at 5 years. Eighteen patients (14.1%) experienced improved cosmetic outcome at 5 years compare to that before radiotherapy while 34 patients (26.6%) had an inferior appearance.Conclusion:IMRT with integrated boost after breast-conserving surgery for breast cancer patients is well tolerated, with relatively good cosmetic outcome and moderate toxicity. Meanwhile,5-year local control and survival are excellent.Part Ⅲ:Dosimetric comparation of standard whole breast tangential fields and whole axilla radiation breast cancer patients treated with breast conservative surgeryObjective:This study aimed to evaluate the coverage of the Level Ⅰ and Ⅱ axilla with standard whole breast tangential fields (WBTF) irradiation, and the dose to normal tissues with axillary IMRT.Methods:Fifteen left breast cancer patients treated with breast conservative surgery and whole breast radiation were studied. All patients had inverse IMRT plan using WBTF with prescription dose of 50 Gy to 95% of the planning target volume (PTV), defined as the whole breast. Level Ⅰ and Ⅱ axilla were contoured according to the RTOG atlas. The dose distribution and coverage of Level Ⅰ and Ⅱ axilla with WBTF was calculated. New IMRT plans delivering 50 Gy to 95% of the whole breast as well as Level Ⅰ and Ⅱ axilla (WB+AX) were designed. The homogeneity index (HI= D5/D95) of the whole breast and conformal index (CI= VRI/TV, TV= target volume, VRI= Volume of the Reference Isodose) of the two plan, the dose to the heart, lung, left anterior descending coronary artery (LAD) and contralateral breast were compared between WBTF and WB+AX.Results:The volume of levels Ⅰ and Ⅱ axilla was 71.7 and 26.5 cm3, respectively. With WBTF, the average dose to Levels Ⅰ and Ⅱ axilla was 34.39 Gy and 21.90 Gy, respectively. The V50 and V40 were 22.57% and 49.86% for Level Ⅰ axilla,5.99% and 21.99% for Level Ⅱ axilla. WB+AX significantly increased the HI of the whole breast, and CI of the two plans and also significantly increased the dose to the ipsilateral lung and heart as compared with WBTF. There was no significant difference in mean dose to LAD between WBTF and WB+AX.Conclusion:Standard whole breast tangential field doesn’t offer optimal coverage of Level Ⅰ and Ⅱ axilla. IMRT improved the dose coverage of axilla with increased dose to the nomral tissues.