Clinical Outcomes, Cosmesis and Quality of Life in Hypofractionation Versus Conventional Fractionation Radiotherapy to Whole Breast and Regional Nodes: A Phase II Randomized Study

Abstract

Whole Breast Radiotherapy (WBRT) is indicated as adjuvant treatment in the multimodality management of Breast Cancer after Breast Cancer Surgery (BCS). Regional Nodal Irradiation (RNI) improves outcomes in patients with positive nodes after axillary dissection. Hypofractionation in WBRT is equivalent to standard fractionation in terms of long-term outcomes, but the role of hypofractionation in the settings of RNI has not been explored. We prospectively conducted a phase II randomized study comparing Hypofractionation and Standard fractionation in WBRT with RNI to evaluate clinical outcomes, cosmesis and quality of life (QOL) between the two modalities. Women aged ≥ 18 years with breast cancer undergoing BCS and axillary dissection were recruited in the study after Institutional Ethics Committee approval. 52 patients were randomized into two groups, with 26 patients in arm 1 (standard fractionation) WBRT 50Gy/25fraction/5weeks followed by boost 16Gy/8fraction and other 26 patients in arm II (hypofractionation) WBRT 40Gy/15fraction/3 weeks followed by boost 10Gy/4fraction. Contouring was done as per the standard RTOG guidelines. WBRT was planned using forward planning IMRT. Direct or oblique photon fields were used for RNI of SCF/ Axillary region as clinically indicated. Contouring and planning was done on MONACO treatment planning system. Clinical acute toxicity, late toxicity was noted with RTOG acute toxicity criteria. Quality of life (QOL) was assessed with EORTC BR 23 questionnaire. Statistical analysis was done with SPSS v 21 and p-value < 0.05 was considered as significant. All patients received planned allocated treatment and were eligible for analysis. At treatment completion, the Grade II skin toxicity was higher in arm I compared to arm II, with 84% vs 11% (p <0.01), Grade III skin toxicity was not noted in arm II, but present in 3(11%) patients of arm I (p <0.01). The skin toxicity at 6 months was similar at 6 months with only Grade I skin toxicity. At completion of radiation, good cosmesis was noted in 8(32%) patients of arm I and 20(77%) patients of arm II, whereas fair cosmesis was observed in 17 (65%) patients of arm I and 6(23%) patients of arm II. The cosmesis at 6 months post radiation was excellent in 21(80%) patients of arm I and 23(88%) patients of arm II, and good cosmesis was seen in 5(20%) patients of arm I and 3(12%) patients of arm II. The cosmesis improved in both the arms at 6 months, and the results were comparable between the groups. There was no significant difference in subcutaneous toxicity, arm toxicity or lymphedema between the two arms at 3 and 6 months. There was no difference in QOL between two arms at 3 and 6 months. WBRT with RNI is feasible with hypofractionation and it is not associated with decreased clinical outcomes as compared to standard fractionation. Lymphedema was similar with hypofractionation. The clinical acute toxicity, cosmesis and QOL was similar with hypofractionation and standard fractionation.