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.

The 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 reducing heart and lung dose but may be associated with increased acute skin toxicity, and the acute toxicity of ultra-hypofractionated proton therapy remains unknown. In this randomized trial, non-metastatic breast cancer patients were assigned to receive either proton or photon radiotherapy at a dose of 26 Gy in 5 fractions delivered on alternate days, with the aim of comparing acute skin toxicity between the two modalities. Of 140 eligible patients, 72 were included in this interim analysis, with 36 patients in each treatment arm. The highest observed toxicity was grade 2 radiation dermatitis, which occurred in one patient in the proton arm. The incidence of acute radiation dermatitis was significantly higher in the proton arm than in the photon arm (97.2% vs. 75%, P = 0.006), while no significant differences were observed in other acute toxicities. Patients treated with photon radiotherapy demonstrated better cosmetic outcomes (41.7% vs. 13.9%, P = 0.007) and higher satisfaction scores (80.6% vs. 58.3%, P = 0.04) compared with those treated with proton radiotherapy. At a median follow-up of 9 months (IQR: 6-11), no locoregional recurrence was observed in either treatment arm. This interim analysis indicates that ultra-hypofractionated proton therapy is associated with a higher incidence of mild acute radiation dermatitis, whereas photon radiotherapy results in superior cosmetic outcomes and patient satisfaction, with longer follow-up required to determine long-term outcomes.