Acute radiation side effects of proton versus photon therapy following surgery for early breast cancer, a sub-study of the randomised controlled DBCG Proton Trial.

Abstract

Proton therapy (PT) is associated with favorable dosimetric characteristics compared with photon radiotherapy (γRT) in invasive breast cancer; however, clinical evidence on acute toxicity remains limited. This study aims to compare acute treatment-related side effects between moderately hypofractionated PT and γRT in breast cancer. The DBCG PROTON Trial - Acute Side Effects was a preplanned sub-study of the national, phase III randomised trial, the DBCG Proton Trial. Patients with invasive breast cancer or DCIS scheduled for adjuvant radiotherapy, who were expected to receive a high cardiac and/or pulmonary dose based on γRT planning CT, were randomised 1:1 to PT or γRT. Acute side effects were prospectively assessed during radiotherapy and up to 6 months post-treatment. Outcomes included skin -related side effects, respiratory symptoms, dysphagia, fatigue, and arm/shoulder side effects. A total of 167 patients (186 treated breasts) were included (PT 84, γRT 83). Skin-related side effects peaked at week five, with higher grade 2-3 dermatitis (71% PT vs 20% γRT), pruritus (20% vs 5%), and local pain (17% vs 4%) after PT compared to γRT. All skin-related grade 2-3 side effects were transient, resolving to grade 0-1 within 2-4 weeks. Respiratory symptoms, dysphagia, and fatigue were mild and similar between groups. Clinically relevant arm/shoulder morbidity was rare. No treatment discontinuations due to side effects were observed. Acute side effects after breast cancer radiotherapy were primarily skin-related, higher but transient after PT compared to γRT. Non-skin-related side effects, including respiratory, fatigue, and arm/shoulder morbidity, were comparable between PT and γRT. These prospective data, using modern techniques and moderate hypofractionation, suggest that PT is a feasible and clinically acceptable treatment approach for adjuvant treatment of invasive breast cancer or DCIS, while acknowledging the higher incidence of transient acute skin toxicity.