Long-term Outcomes from Proton Therapy for Sinonasal Cancers

Abstract

Purpose: To report long-term disease control, survival, and toxicity after proton therapy for sinonasal cancer.

Patients and methods: We reviewed 143 cases of adults with nonmetastatic sinonasal cancers treated with primary (18%; n = 26) or adjuvant (82%; n = 117) proton therapy. The most common histologies were squamous cell carcinoma (29%; n = 42), olfactory neuroblastoma (23%; n = 33), and adenoid cystic carcinoma (16%; n = 23). Patients had predominantly advanced-stage disease (T3, 24%, n = 35; T4, 66%, n = 94) and high-grade histology (52%; n = 74). Surgery included endoscopic resection alone (50%) with craniotomy (10%) or open resection (40%), and 31% had gross disease present at radiotherapy. Most (91%) received high-dose (median, 73.6 Gy radiobiological equivalent [GyRBE]; 84% >70 GyRBE) passive-scatter proton therapy using accelerated hyperfractionation (1.2 GyRBE twice daily) and concurrent chemotherapy (70%). Univariate and multivariate models assessed prognostic factors. Grade 3⁺ toxicities were recorded per Common Terminology Criteria, version 4. Median follow-up was 3.4 years (range, 0.1-12.5 years) overall and 4.9 years (range, 0.9-12.5 years) for living patients.

Results: The 5-year outcomes were as follows: local control (LC), 80%; neck control, 96%; local-regional control, 78%; freedom from distant metastases, 71%; and disease-free survival, 62%; cause-specific survival, 64%; and overall survival, 59%. Surgery improved LC, but only with gross total resection (5-year LC 87% versus subtotal resection 62.9%, and biopsy alone 55% (P < 0.001). Gross residual disease was the only significant prognostic factor for local-regional control on multivariate analysis. High-grade, T4, and local recurrence were associated with decreased overall survival. Late (G3⁺) toxicity occurred in 22% (32 of 143), including central nervous system necrosis and vision loss in 6% (9 of 143) and 3.5% (5 of 143), respectively.

Conclusion: Proton therapy after gross-total resection provides excellent long-term LC in patients with locally advanced, high-grade sinonasal cancer. Moreover, LC remains strongly associated with long-term survival. With gross disease, about 60% of patients had long-term LC with proton therapy and induction or concurrent chemotherapy.

Keywords: head and neck; outcomes; particle therapy; proton therapy; sinonasal tumors.

Figure 1.

Kaplan-Meier estimates for survival (a) and disease control (b) among the 143 patients included in the analysis.

Figure 2.

Pattern of progression among the patient population.

Figure 3.

Kaplan-Meier estimates for overall survival with or without local control among the 143 patients included in the analysis.

Figure 4.

Kaplan-Meier estimates for local control based on extent of surgery (A) and the presence or absence of gross disease (B) at initiation of radiotherapy among the 143 patients included in the analysis. GTR, gross total resection; STR, subtotal resection.