Here is a preplanned subanalysis of the phase 3 Danish Breast Cancer Group Proton Trial that randomized 167 women receiving moderately hypofractionated adjuvant breast/chest wall radiation to proton versus photon therapy. The trial’s ambitious primary endpoint of 10-year radiation-associated cardiac events has not yet been reported. As seen before, proton therapy produced substantially more grade 2–3 dermatitis (71% vs 20%), pruritus (20% vs 5%), and local pain (17% vs 4%), with these skin toxicities peaking around week 5 and resolving within 2–4 weeks thereafter. Non-skin acute events were mild and comparable between groups with no treatment discontinuations. Some may argue optimization was not, in fact, optimal though the protocol did specify no more than 2% of the target could receive more than 108% of prescription (40 Gy in 15 fractions). Regardless, it appears that proton therapy to the breast and chest wall is clearly associated with more, albeit transient, acute skin events without (and possibly even with?) extremely rigorous skin optimization as a trade-off for as-of-yet unclear cardiac health benefits. | Høgsbjerg, Int J Radiat Oncol Biol Phys 2026
