Outcomes of Sinonasal Cancer Treated With Proton Therapy

Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):377-385. doi: 10.1016/j.ijrobp.2016.02.019. Epub 2016 Feb 12.


Purpose: To report disease outcomes after proton therapy (PT) for sinonasal cancer.

Methods and materials: Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients.

Results: The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with grade 3 or higher unilateral vision loss in 2%).

Conclusions: Dose-intensified, hyperfractionated PT with or without concurrent chemotherapy results in excellent LC after gross total resection, and results in patients with gross disease are encouraging. Patients with high-grade histology are at greater risk of death from distant dissemination. Continuous LC is a major determinant of survival justifying aggressive local therapy in nearly all cases.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Adenoid Cystic / drug therapy
  • Carcinoma, Adenoid Cystic / pathology
  • Carcinoma, Adenoid Cystic / radiotherapy*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Esthesioneuroblastoma, Olfactory / drug therapy
  • Esthesioneuroblastoma, Olfactory / pathology
  • Esthesioneuroblastoma, Olfactory / radiotherapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm, Residual
  • Nose Neoplasms / drug therapy
  • Nose Neoplasms / pathology
  • Nose Neoplasms / radiotherapy*
  • Paranasal Sinus Neoplasms / drug therapy
  • Paranasal Sinus Neoplasms / pathology
  • Paranasal Sinus Neoplasms / radiotherapy
  • Proton Therapy / methods*
  • Radiotherapy, Adjuvant
  • Relative Biological Effectiveness
  • Survival Rate
  • Treatment Outcome