**Background:** Sinonasal malignancies (SNMs) are rare head and neck cancers (<3% of cases) that often present at advanced stages. Management typically involves surgery, radiotherapy (RT), and/or chemoradiotherapy (CRT). Despite multimodal therapy improving prognosis, treatment-related long-term complications are poorly documented. This study aimed to characterize long-term complications and identify risk factors in a cohort of SNM patients.
**Methods:** A retrospective analysis was conducted at a single tertiary center including all patients treated for primary SNMs from 2001 to 2018, with a minimum follow-up of 6 months. Seventy-seven patients were included (median age 65.2 years, 57% male, mean follow-up 48.5 months). Data on demographics, tumor characteristics, treatment details, and complications were collected. Long-term complications were defined as those persisting >6 months or appearing ≥6 months post-treatment. Chronic rhinosinusitis (CRS) was defined per international consensus, and radiation toxicity was graded using CTCAE v5.0. Statistical analyses included chi-square, Fisher's exact, Mann-Whitney tests, and logistic regression.
**Key Results:** Overall, 41 patients (53%) developed long-term complications. The most common were sinonasal (22 patients, 29%)—including CRS (16 patients, 21%) and intranasal synechiae (10 patients, 13%)—and orbital/ocular (18 patients, 23%)—including orbital-related issues (16 patients, 21%) such as epiphora (12 patients) and ocular complications (8 patients, 10%) such as grade ≥3 visual acuity impairment (VAI) (5 patients). Other complications included dysphagia (7 patients, 9%), osteoradionecrosis (5 patients, 6.5%), trismus (4 patients, 5%), hyposmia (4 patients, 5%), cranial nerve neuropathy (3 patients, 4%), dermatitis/hyperpigmentation (3 patients, 4%), and hypothyroidism (2 patients, 3%).
Complications were significantly more frequent in patients receiving RT/CRT (adjuvant or definitive) compared to surgery alone (65% vs. 12%, p<0.001). In multivariate regression, radiation therapy was the only significant predictor of long-term complications (p=0.001, OR=18.86, CI=3.31-107.6). No significant associations were found with tumor stage, surgical modality (open vs. endoscopic vs. combined), radiation modality (IMRT vs. external beam), or radiation dose (<60 Gy vs. ≥60 Gy). However, mean radiation dose ≥50 Gy to the optic nerve was strongly associated with grade ≥3 VAI (100% vs. 3%, p=0.006).
Disease recurrence occurred in 24 patients (31%). Among those, 9 (37.5%) developed new long-term complications from salvage treatment, with a higher rate in irradiated vs. non-irradiated patients (56% vs. 11%, p=0.04).
**Clinical Implications:** This study demonstrates that long-term complications after SNM treatment are substantial (53%), with radiation therapy as the dominant risk factor. The dose-response relationship for optic nerve toxicity (≥50 Gy) underscores the importance of radiation planning to minimize visual impairment. The lack of association between surgical approach and complications suggests that adjuvant RT/CRT may overshadow surgical effects. These findings can guide patient counseling and treatment decisions, emphasizing the need for strategies to reduce radiation-related morbidity, such as proton beam therapy or careful dose constraints. The high complication rate with salvage radiation for recurrence further highlights the importance of optimizing initial treatment.