KEY POINTS
- This was a preplanned acute-toxicity substudy of the national phase III randomized DBCG Proton Trial (NCT04291378). It included 167 patients and 186 treated breasts, randomized to proton therapy (84 patients) or photon RT (83 patients) after breast-conserving surgery or mastectomy.
- Trial eligibility enriched for patients most likely to derive a dosimetric proton benefit: their photon plan had to predict mean heart dose ≥4 Gy and/or ipsilateral lung V17/V20 ≥37%. Patients could have invasive breast cancer or DCIS and receive whole-breast/chest-wall irradiation with or without regional nodal treatment.
- Contemporary treatment was predominantly moderately hypofractionated. From July 2021, 40 Gy in 15 fractions became the Danish standard including for regional nodal irradiation; earlier patients requiring nodal RT could receive 50 Gy in 25 fractions. Photon treatment used 3D-CRT, VMAT or tomotherapy, while proton plans used 2–3 single-field optimized pencil-beam scanning fields with 3.5% range and 5-mm setup robustness.
- Acute skin toxicity clearly favored photons. At the week-five peak, grade 2–3 dermatitis occurred in 71% with protons versus 20% with photons. Pruritus was also more frequent (20% vs 5%) as was local pain (17% vs 4%).
- Importantly, the excess toxicity was transient: all grade 2–3 skin events returned to grade 0–1 within 2–4 weeks. No patient discontinued radiotherapy because of acute toxicity.
- The difference was predominantly cutaneous rather than systemic. Respiratory symptoms, dysphagia and fatigue were generally mild and similar between groups, while clinically meaningful arm/shoulder impairment and lymphedema were uncommon.
- This substudy was designed around acute morbidity, not the principal reason proton therapy is being tested in breast cancer. It therefore cannot determine whether reducing heart and lung dose ultimately lowers cardiovascular disease, second cancers or other late effects; those questions require longer follow-up from the main phase III trial.
CLINICAL TAKEAWAY
For selected breast cancer patients receiving modern adjuvant RT, protons did not make acute treatment easier: skin toxicity was substantially greater than with photons. The important trade-off is therefore becoming clearer—more short-lived dermatitis in exchange for lower heart/lung exposure whose long-term clinical value remains under study.
SOURCE
International Journal of Radiation Oncology, Biology, Physics