Acute skin toxicity and cosmesis outcome in non-metastatic breast cancer patients treated with ultrahypofractionated radiotherapy: a randomized controlled phase II clinical trial comparing proton versus photon radiotherapy

BackgroundThe 1-week photon radiotherapy schedule of 26 Gy in 5 fractions is as safe and effective as the standard 3-week schedule of 40 Gy in 15 fractions for adjuvant local radiotherapy in early-stage breast cancer. Proton radiotherapy offers dosimetric advantages by sparing the heart and lung dose but may cause more acute skin toxicities than conventional fraction photon radiotherapy. The acute toxicity of ultra-hypofractionated proton therapy is currently unknown. Materials and MethodsIn this trial, non-metastatic breast cancer patients were randomly assigned to receive either proton or photon therapy with the same dose of 26 Gy in 5 fractions given on alternate days. The aim of this trial was to compare acute skin toxicity between proton radiotherapy and photon beam radiotherapy using ultra-hypofractionation. ResultsOut of 140 eligible patients, 72 were included in this initial analysis (36 proton, 36 photon). Only one patient in the proton arm experienced grade 2 radiation dermatitis, which was the highest recorded grade. The incidence of acute radiation dermatitis was significantly higher in the proton arm compared to the photon arm (97.2% vs. 75%, respectively, p=0.006). There was no significant difference in other acute toxicities between the two arms. Patients treated with photon had better cosmetic outcomes (41.7% vs. 13.9%, P= 0.007) and were more satisfied (80.6% vs. 58.3%, P=0.04) than those in the proton arm. At a median follow-up of 9 months (IQR: 6-11), no locoregional recurrence was observed between the two arms. ConclusionIn summary, this interim analysis found that ultra-hypofractionated proton therapy led to a higher rate of acute radiation dermatitis than the photon arm, although the dermatitis was mild. Patients in the photon arm had better cosmetic outcomes and higher satisfaction scores. However, further patient accrual and long-term follow-up are necessary to determine the long-term effects and effectiveness of proton therapy in breast cancer treatment.