Long-Term Follow-Up Of Primary And Adjuvant Proton Therapy For Sinonasal Cancer

Abstract

To report long-term disease control, patterns of recurrence, survival, and toxicity after proton therapy (PT) for sinonasal cancer. We reviewed the records of 143 adult, non-metastatic patients treated with primary (18%) or adjuvant (82%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). The most common histologies were squamous carcinoma (29%), olfactory neuroblastoma (23%), and adenoid cystic carcinoma (16%). Most patients had advanced stage disease (T3, 24%; T4, 66%), 11% were N+, and 52% were high grade. Surgical management included endoscopic resection alone (50%), with craniotomy (10%), or open procedures (40%). At the time of PT, 31% had gross disease at the primary site. Most patients received hyperfractionation (1.2 GyRBE twice daily, 91%) and chemotherapy (70%, most commonly low-dose weekly cisplatin). Median RT dose was 73.6 GyRBE and 84% received > 70 GyRBE. Kaplan-Meier method was used to estimate disease control and survival endpoints and log-rank and cox-proportion hazard models were used to for univariate and multivariate models were used to assess prognostic factors. Serious, late G3+ toxicities were reported per CTCAE v4. The median follow-up was 4.4 years (range, 0.1 – 12.5) for all patients and 4.9 years (range, 0.9 – 12.5) for living patients. The local control (LC), neck control, disease-free, cause-specific, and overall survival (OS) rates were 80%, 96% 62%, 64%, and 59% at 5 years. Surgery improved local control; however, the benefit of surgery was only apparent after gross total resection. At 5 years, LC was 90% for patients without gross disease at PT, compared with 62.9% after subtotal resection, and 55% after biopsy alone (p < 0.001). Gross residual disease at the time of PT was the only significant prognostic factor for LC on multivariate analysis. High-grade, T4, and local-recurrence after therapy were associated with decreased OS. Serious late toxicity occurred in 22% (G3, 16%; G4, 3%; and G5, 3%). G3+ toxicity occurred in 22% of patients. CNS necrosis and vision loss occurred in 6% and 3.5%, and 2 patients (1%) had radiation-associated 2nd tumors (meningioma). PT after gross-total resection results in excellent long-term local control, which is a strong predictor of long-term survival. About 50-60% of patients will still achieve long-term LC even with gross disease. Balancing the benefits of LC against significant toxicity remains a challenge. High-grade histology was strongly associated with distant dissemination, and surgery should be avoided in such patients when non-morbid gross-total resection is unlikely.