Abstract
PurposeTo report long-term disease control, survival, and toxicity after proton therapy for sinonasal cancer.Patients and MethodsWe 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.ResultsThe 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.ConclusionProton 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.
Highlights
Sinonasal cancers are some of the rarest and most diverse head and neck malignancies with an annual incidence in the United States of approximately 1 in 180 000 distributed among dozens of histologic subtypes [1,2,3,4]
Under an institutional review board–approved study, we reviewed the medical records of patients with sinonasal cancers treated with curative-intent primary or postoperative proton radiotherapy at our institution between 2007 and 2018
Most were male with advanced (T4, 66%) tumors of the nasal cavity/ethmoid sinus (78%), and the most common histology was squamous cell carcinoma (29%), followed by olfactory neuroblastoma (23%), adenoid cystic carcinoma (16%), and sinonasal undifferentiated carcinoma. aAnaplastic carcinoma (SNUC) (11%)
Summary
Sinonasal cancers are some of the rarest and most diverse head and neck malignancies with an annual incidence in the United States of approximately 1 in 180 000 distributed among dozens of histologic subtypes [1,2,3,4]. Proton therapy for sinonasal cancer and chemotherapy, despite the lack of prospective clinical trial data to guide therapy [3, 4]. The proximity of these tumor to (or invasion of) vital structures, including the orbits, skull base, cranial nerves, central nervous system (CNS), and visual pathways, presents a formidable challenge to aggressive local therapy. We undertook this study to update our initial experience with proton therapy for sinonasal cancers [4], and here, we report long-term disease control, survival rates, major toxicities, and prognostic factors among nearly double the patients, with double the follow-up, of our previous analysis [4]
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