International journal of radiation oncology, biology, physics · 2026
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.
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Høgsbjerg Kristine Wiborg, Petersen Stine Elleberg, Maae Else, Matthiessen Louise Wichmann, Møller Mette, Maraldo Maja Vestmø, Mogensen Marie Benzon, Nielsen Mette Holck, Kronborg Camilla Jensenius Skovhus, Offersen Birgitte Vrou
Аннотация
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.
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.