Revisiting proton therapy for adenoid cystic carcinoma: a case worth making

Background Adenoid cystic carcinoma (ACC) is a rare malignancy characterized by indolent growth, frequent perineural invasion, and a propensity for locally advanced disease involving the skull base. High-dose radiation to complex target volumes must be balanced with minimizing exposure to adjacent organs at risk, making particle therapy attractive. Proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) provide favorable dose distributions compared with photon-based radiotherapy, while CIRT offers additional theoretical radiobiologic advantages through its higher linear energy transfer and relative biological effectiveness. However, whether these properties translate into superior clinical outcomes remains uncertain. Methods This perspective reviews physical and radiobiologic characteristics of PBT and CIRT and evaluates contemporary clinical evidence supporting their use in ACC. Available studies demonstrate favorable local control, overall survival, and toxicity outcomes with both modalities but have not established a clear clinical advantage of CIRT over modern PBT. Interpretation is limited by heterogeneous patient populations, treatment techniques, fractionation schedules, institutional practices, follow-up, and the absence of prospective data. Additionally, differences in infrastructure, cost, geographic availability, and reimbursement influence treatment selection and patient access. Results Current evidence supports PBT as an efficacious and broadly applicable treatment option for ACC, particularly for complex skull base and perineural target volumes. Future research should prioritize comparative dosimetry, refinement of biologic dose modeling, multicenter clinical outcomes, contemporary cost-effectiveness analyses, and patient selection. Expanding equitable access to particle therapy should remain a parallel objective. Conclusion Current literature supports PBT in the treatment of ACC. Reported treatment outcomes are comparable to CIRT.