Proton Beam Therapy for Early Breast Cancer: A Systematic Review and Meta-analysis of Clinical Outcomes

BACKGROUND: Adjuvant proton beam therapy (PBT) is increasingly available to patients with breast cancer. It achieves better planned dose distributions than standard photon radiotherapy and therefore may reduce the risks. However, clinical evidence is lacking. METHODS: A systematic review of clinical outcomes from studies of adjuvant PBT for early breast cancer published 2000-2022 was undertaken. Early breast cancer was defined as when all detected invasive cancer cells are in the breast or nearby lymph nodes and can be removed surgically. Adverse outcomes were summarized quantitatively, and the prevalence of the most common ones estimated using meta-analysis. RESULTS: Thirty-two studies (1452 patients) reported clinical outcomes after adjuvant PBT for early breast cancer. Median follow up ranged from 2-59 months. There were no published randomized trials comparing PBT with photon radiotherapy. Scattering PBT was delivered in seven studies (258 patients) starting 2003-2015 and scanning PBT in 22 studies (1041 patients) starting 2000-2019. Two studies (123 patients) starting 2011 used both PBT types. For one study (30 patients) PBT type was unspecified. Adverse events were less severe after scanning than after scattering PBT. They also varied by clinical target. For partial breast PBT, 498 adverse events were reported (8 studies, 358 patients). None were categorized as severe after scanning PBT. For whole breast or chest wall +/- regional lymph nodes PBT, 1344 adverse events were reported (19 studies, 933 patients). After scanning PBT, 4% (44/1026) of events were severe. The most prevalent severe outcome after scanning PBT was dermatitis which occurred in 5.7% (95% CI 4.2-7.6) of patients. Other severe adverse outcomes included infection, pain and pneumonitis (each ≤1%). Of the 141 reconstruction events reported (13 studies, 459 patients), the most prevalent after scanning PBT was prosthetic implant removal (34/181, 19%). CONCLUSIONS: This is a quantitative summary of all published clinical outcomes after adjuvant PBT for early breast cancer. Ongoing randomized trials will provide information on its longer-term safety compared with standard photon radiotherapy.