Prospective Patient-Reported Outcomes, Physician-Assessed Toxicities, and Treatment Outcomes in Sinonasal Malignancies Following Proton Beam Therapy

Abstract

Historically, sinonasal cancer outcomes have had minimal improvement in the photon radiotherapy (XRT) treatment eras, with 3-year overall survival (OS) of 40-70% and grade 3+ (G3) physician-assessed toxicities (PATs) of 15-35%. Proton beam therapy (PBT) has the potential to improve outcomes but prospective data is scarce, particularly PATs and patient-reported outcomes (PROs). To report on the outcomes and toxicities for a prospective patient cohort with sinonasal malignancies treated using PBT. From 2011-2019, PBT treated patients with a sinonasal malignancy were enrolled with a primary endpoint of toxicity assessment. PATs and PROs were assessed at baseline, acute (during PBT), subacute (90 days after PBT), and chronic time-points. PATs were graded using CTCAE. PROs were assessed using the Xerostomia-Related Quality of Life Scale (XeQoLS), MD Anderson Dysphagia Inventory (MDADI), and Functional Assessment of Cancer Therapy (FACT). PATs and PROs were analyzed with a paired t-test. Kaplan-Meier and log-rank tests were used to analyze local control (LC), local-regional control (LRC), disease-free survival (DFS), and OS. Sixty-four patients had a median follow-up of 33 months (range: 2-129). The most common histologies included olfactory neuroblastoma (28%), sinonasal undifferentiated carcinoma (22%), squamous cell carcinoma (20%), and adenoid cystic carcinoma (15.6%). The majority of patients had T3-T4 (52%) disease and were treated with surgery followed by adjuvant chemo-PBT (33%) or PBT (23%). The most common acute G3 PATs were radiation dermatitis (20%), oral mucositis (11%), and pain (6%); there were no acute G4-5 toxicities. The only acute G3 neurologic PAT was blurred vision (2%) which resolved. There were no G3-4 late PATs. Feeding tube placement occurred in 6% (4/64; 1 permanent in re-irradiation case, 1 lost to follow-up, 1 death with tube, 1 removed after 4 months). On XeQoLS, physical function was significantly worse from baseline (median score of 0; range: 0-3.5) to the acute (delta of +0.75; P<0.01), subacute (delta of +0.5; P<0.01), and chronic (delta of +0.25; P=0.01) follow-up. Similarly, MDADI physical was significantly worse from baseline (median score: 90.6; range: 37.5-100) to the acute (delta of -11.4; P<0.01), subacute (delta of -10.1; P<0.01), and chronic (delta of -3.2; P=0.02) follow-up. Unlike MDADI, there was significant improvement in the FACT-HN global from baseline (median of 2.1; range: 1.6-2.5) to chronic follow-up (delta of +0.2; P=0.001). The 3-year LC, LRC, DFS, and OS was 88%, 82%, 76%, and 82%, respectively. In a predominantly locally advanced, recurrent, or heavily pre-treated patient cohort with sinonasal cancer, we demonstrate some of the most encouraging LC, DFS, and OS rates following PBT. PATs favor PBT compared to historically reported XRT data. PROs suggest significant changes in the acute/subacute period with gradual recovery to baseline.