MC1635: Randomized Phase III Trial of Hypofractionated Radiotherapy to the Whole Breast After Breast Conserving Surgery

Purpose/Objective(s) Hypofractionated radiation therapy (RT) for localized breast cancer improves patient convenience and reduces treatment cost. Here, we report the early results of MC1635 randomized trial. Materials/Methods Between 04/04/2018 and 02/11/2020, patients with localized breast cancer (T1-T3, N0-N1, M0) managed with breast conserving surgery (BCS) were enrolled. Patients were randomized to receive whole breast RT with moderate hypofractionation to 40 Gy in 15 fractions (Arm A) or extreme hypofractionation to 25 Gy in 5 fractions (Arm B). An optional concurrent integrated boost to 48 Gy on Arm A or 30 Gy on Arm B was allowed. All patients were treated daily (Monday-Friday). Analysis of early toxicity ( 3 months), quality of life (QOL), cosmesis, and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) were done. QOL was assessed with patient-reported outcomes measurement information system (PROMIS), overall Linear Analogue Self-Assessment (LASA), and The Breast Cancer Treatment Outcome Scale (BCTOS). Deterioration of cosmesis was defined as going from excellent/good to fair/poor or from fair to poor according to the Harvard Cosmesis Scale. Results One hundred seven patients were randomized to either Arm A (n = 54) or Arm B (n = 53). Median follow-up was 20 months. Patient characteristics included: IDC 55%, ILC 20%, mixed 7%, DCIS 16%, other 3%; grade 1 or 2 72%, grade 3 28%; triple negative 9%, ER/PR+ 84%, and Her2+ 7%. Treatment characteristics included: sentinel lymph node biopsy 68%, axillary lymph node dissection 32%; spot scanned proton therapy 50%, 3D conformal x-rays 50%; and an integrated boost 21%. No significant differences in any characteristics were noted between the two arms. No grade 3 toxicities occurred on either arm. Grade 2 toxicities were seen in 7.4% of Arm A and 7.5% of Arm B. This primarily consisted of radiation dermatitis (6 patients) with 1 patient with fibrosis and 1 patient with lymphedema. Deterioration in cosmesis ≥ 3 months after RT was seen in 1.6% of Arm A and 1.7% of Arm B (P = 0.4). The average Harvard Cosmesis score was similar between arms at all timepoints. QOL was similar between arms, as well. Patient-reported radiation skin burns of ‘moderate to severe’ as assessed by PRO-CTCAE were more commonly reported in Arm A (58.7%) vs Arm B (27.9%) (odds ratio 3.7, CI 1.5-8.9; P = 0.004). Patient satisfaction with treatment was very high with more than 98% of patients in both arms saying that they would do RT again. No cancer recurrences or deaths have been seen in either arm. Conclusion Our early analysis of our randomized study suggests that extreme hypofractionation using 25 Gy in 5 fractions is well-tolerated and as safe as moderate hypofractionation. Patient-reported radiation skin burns were 3.7 times less likely with 25 Gy in 5 fractions. Further follow-up is warranted.