Acute Radiation Side Effects of Proton Versus Photon Therapy Following Surgery for Early Breast Cancer, a Substudy of the Randomized Controlled Danish Breast Cancer Group Proton Trial.

PURPOSE: Proton therapy (PT) is associated with favorable dosimetric characteristics compared with photon radiation therapy (γRT) in invasive breast cancer; however, clinical evidence on acute toxicity remains limited. This study aimed to compare acute treatment-related side effects between moderately hypofractionated PT and γRT in breast cancer.

METHODS AND MATERIALS: The Danish Breast Cancer Group Proton trial-acute side effects was a preplanned substudy of the national, phase 3 randomized trial, the Danish Breast Cancer Group Proton trial. Patients with invasive breast cancer or ductal carcinoma in situ scheduled for adjuvant radiation therapy (RT), who were expected to receive a high cardiac and/or pulmonary dose based on γRT planning computed tomography scan, were randomized 1:1 to PT or γRT. Acute side effects were prospectively assessed during RT and up to 6 months posttreatment. Outcomes included skin-related side effects, respiratory symptoms, dysphagia, fatigue, and arm/shoulder side effects.

RESULTS

A total of 167 patients (186 treated breasts) were included (PT 84 and γRT 83). Skin-related side effects peaked at week 5, with higher grade 2 to 3 dermatitis (71% PT vs 20% γRT), pruritus (20% vs 5%), and local pain (17% vs 4%) after PT compared with γRT. All skin-related grade 2 to 3 side effects were transient, resolving to grade 0 to 1 within 2 to 4 weeks after peaking. Respiratory symptoms, dysphagia, and fatigue were mild and similar between groups. Clinically relevant arm/shoulder morbidity was rare. No treatment discontinuations because of side effects were observed.

CONCLUSIONS

Acute side effects after breast cancer RT were primarily skin-related, higher but transient after PT compared with γRT. Non-skin-related side effects, including respiratory symptoms, 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 ductal carcinoma in situ, while acknowledging the higher incidence of transient acute skin-related side effects.