Outcomes of different treatment patterns for adenoid cystic carcinoma of the anterior craniofacial area: A multi-institutional study on 578 patients

Background Adenoid cystic carcinoma of the anterior craniofacial region (ACF-ACC) is challenging to treat due to extensive subclinical spread and proximity to critical structures. Although surgery followed by radiotherapy (RT) is the current standard, real-world outcomes with modern photon and particle therapy remain insufficiently characterized. Methods We retrospectively analyzed 578 patients with ACF-ACC treated at eight international centers (1984–2023). Clinicopathologic features, treatment patterns, and outcomes were assessed. Anatomical extension was classified using hierarchical clustering. Comparative analyses of gross total resection (GTR) and non-surgical treatment (NST) were adjusted using propensity score matching and multivariable Cox and Fine-Gray models. Primary endpoints were local recurrence-free survival (LRFS) and cumulative incidence of local recurrence (LRCI). Results Most tumors arose in the sinonasal tract (75.8%) and were low/intermediate grade (68.6%). Long-term outcomes showed high local and distant recurrence (20-year LRCI: 74.1%; cumulative incidence of distant metastasis: 55.6%). GTR followed by adjuvant RT, especially with proton therapy (PT), achieved the best local control. R2 resections provided no advantage over NST. Within the NST cohort (n = 110), PT yielded higher complete response rates than photon RT, while responders demonstrated local control comparable to surgically treated patients. Ten-year ≥G3 toxicity incidence was 36%. Conclusions For ACF-ACC, GTR plus modern RT provides the strongest local control, and R2 surgery should be avoided. PT is an effective definitive option for selected patients, supporting future response-guided treatment strategies.