A Phase II Randomized Clinical Trial to Assess Toxicity and Quality of Life of Breast Cancer Patients with Hypofractionated vs. Conventional Fractionation Radiotherapy with Regional Nodal Irradiation

Abstract

To compare acute toxicity between conventional fractionated radiation therapy (CFRT) and hypofractionated radiation therapy (HFRT) for patients undergoing breast-conserving surgery or mastectomy with breast or chest wall and regional nodal irradiation (RNI). The secondary endpoints were acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Unblinded randomized trial with a total of 86 patients treated with CFRT (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus HFRT (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Women included for enrollment were 18 years or older and diagnosed with breast carcinoma, staging T1-4, with at least one positive lymph node (American Joint Committee on Cancer - AJCC 8th). The surgery performed was mastectomy or breast-conservative surgery with the investigation of sentinel lymph node or axillary dissection. Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE) and the Harvard/NSABP/RTOG scale. Patients-reported QoL was determined using the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23). The comparative analysis of categorical variables between the control and experimental groups used the Chi-square test and Fisher's exact test, while numerical variables basing on the Mann-Whitney U test. The intergroup comparison of the EORTC QLQ-C30 used the Generalized Equations Estimating method. All analyses used 2-sided α = 0.05 with R software version 4.1.2. Lymphedema determination compared volume differences between the affected and contralateral arms using the Casley-Smith volume formula. Grade 2 and grade 3 skin rash dermatitis were lower with HFRT than with CF-RT (28% vs. 52%, 0% vs. 6%; p = 0.022, respectively). HFRT vs. CFRT had lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005). Overall rates of any physician-assessed grade ≥ 2 and grade ≥ 3 acute toxicities were no different between HFRT vs. CFRT arms. There was no statistical difference between the CFRT and the HFRT regarding cosmesis, lymphedema rate (13% vs. 12% HFRT vs. CFRT; p = 1.000, respectively), and functional and symptom scales during irradiation and after six months of treatment. HF-RT showed lower rates of acute toxicity, with no changes in quality-of-life outcomes.