Outcomes of Intensity Modulated Irradiation for Sinonasal Cancers: The MD Anderson Experience

Purpose: To report our institutional outcomes and toxicities in patients treated with intensity modulated irradiation for sinonasal cancers and to identify prognostic variables impacting survival.

Methods and Materials: A retrospective analysis of patients with sinonasal tumors treated with either intensity modulated radiotherapy (IMRT) or intensity modulated proton therapy (IMPT) from 2000 to 2016 was conducted. Patients with prior radiotherapy (RT), treated with palliative intent and/or with lymphoma histologies were excluded. The Kaplan–Meier method was used for estimation of local control (LC), regional control (RC), distant metastasis-free survival (DMFS), progression free survival (PFS) and overall survival (OS). Toxicity was assessed using the Common Terminology Criteria for Adverse Events (version 4.0). Cox proportional hazard ratio models were used for univariate and multivariate analysis of predictive variables of survival. Variables associated with survival were entered in a recursive partitioning analysis (RPA) to identify appropriate cut-off points.

Results: A total of 366 patients were included in the analysis, with a median age of 57 years at the time of treatment (range, 20–90). The most common primary sites were nasal cavity (41%), maxillary sinus (29%) and ethmoid sinus (15%); the most common histologies were squamous cell carcinoma (37%), adenoid cystic (13%), sinonasal undifferentiated carcinoma (13%) and esthesioneuroblastoma (11%). Sixty-eight percent of patients received surgery and adjuvant RT ± chemotherapy (CT) while 32% received definitive RT ± CT. Induction CT was given to 46% of patients and 41% were treated with concurrent chemoradiation. Median follow-up was 43 months (range: 1–186). Five year LC, RC, DMFS, PFS and OS rates were 81, 92, 58, 51, and 63%, respectively. Outcomes were similar between the adjuvant RT versus definitive RT groups, as well as across histologies. On multivariate analysis, age (0.04), T stage (p < 0.0001) and N stage (p = 0.04) were predictive of PFS. RPA identified age ≥ 43 years, T4 stage, N stage ≥ 2 as significant cut-offs predicting adverse PFS. Acute grade 3 mucositis, dermatitis and dysphagia developed in 7%, 4% and 3% of patients respectively; 11% of patients required a feeding tube during treatment. Late grade 3 toxicities included cerebral necrosis (2%), osteoradionecrosis (3%), keratopathies (8%), and retinopathies (2%).

Conclusion: Results from this large cohort of sinonasal cancer patients treated with IMRT or IMPT demonstrate good disease control rates, excellent acute treatment tolerance and rare occurrence of severe late toxicities. Older age and more advanced T- and N-stages are associated with worse PFS.