Survival, Tumor Control, and Safety Outcomes of Proton Therapy in Sinonasal Cancer Population: A Systematic Review and Meta‐Analysis

ABSTRACT Background In sinonasal cancer (SNC), treatment with proton therapy (PT) provides excellent local control, especially after gross total resection. Because of the heterogeneity and rarity of this disease site, a comprehensive assessment of toxicity, survival, and control rates is lacking. Our primary objective was to assess the toxicity outcomes of PT in SNC patients, with a secondary aim of assessing survival and tumor control after PT. Methods PubMed, Embase, EBSCO, Scopus, Science Direct, Web of Science, Ovid, Proquest, and Cochrane Library were searched from inception to August 2024 reporting PT acute and late toxicity, survival, and tumor control outcomes in SNC patients. A random‐effect meta‐analysis was used to assess the pooled safety, survival, and tumor control outcomes. The primary analysis was to report acute and late toxicity. The secondary aims included overall survival (OS), disease‐free survival (DFS), local control (LC), regional control (RC), and distant metastasis control (DMC) rate. Results Fourteen studies were included for qualitative analysis. We pooled data from 756 patients who received PT for SNC. Among acute toxicity (AT), there was a 31.9% occurrence rate of grade ≥ 3 events, whereas within late toxicity (LT), grade ≥ 3 events occurred at a rate of 35.3%. Most LT (62.1%) were classified as grade 2, with the most frequent being ocular (24.8%) or neurological (18.4%) toxicities. The most common grade ≥ 3 toxicities were mucositis (15.3%) in AT and ocular toxicity (9.6%) in LT. The pooled 5‐year OS, DFS, LC, RC, and DMC were 36.8%, 34.2%, 35.6%, 28.6%, and 54.3%, respectively. Conclusion Our analysis demonstrates that PT‐treated SNC patients experience acceptable rates of acute and LT consistent with other published outcomes with highly conformal radiation techniques. PT demonstrates favorable OS and DFS. Further prospective and comparative effectiveness research is needed to better quantify the magnitude of the benefit of PT or other forms of radiation modalities.