title: Outcomes of Sinonasal Cancer Treated With Proton Therapy.
abstract: OBJECTIVE
  To report disease outcomes after proton therapy (PT) for sinonasal cancer.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiation Oncology, University of Florida, Gainesville, Florida; Department of Radiation Oncology, University of Florida, Jacksonville, Florida. Electronic address: rdagan@floridaproton.org.
authors.forename: Roi
authors.initials: R
authors.lastname: Dagan
authors.affiliation: Department of Radiation Oncology, University of Florida, Gainesville, Florida; Department of Radiation Oncology, University of Florida, Jacksonville, Florida.
authors.forename: Curtis
authors.initials: C
authors.lastname: Bryant
authors.affiliation: Department of Radiation Oncology, University of Florida, Gainesville, Florida; Department of Radiation Oncology, University of Florida, Jacksonville, Florida.
authors.forename: Zuofeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, University of Florida, Gainesville, Florida; Department of Radiation Oncology, University of Florida, Jacksonville, Florida.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yeung
authors.affiliation: Department of Otolaryngology, University of Florida, Gainesville, Florida.
authors.forename: Jeb
authors.initials: J
authors.lastname: Justice
authors.affiliation: Department of Otolaryngology, University of Florida, Gainesville, Florida.
authors.forename: Peter
authors.initials: P
authors.lastname: Dzieglewiski
authors.affiliation: Department of Otolaryngology, University of Florida, Gainesville, Florida.
authors.forename: John
authors.initials: J
authors.lastname: Werning
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Florida, Jacksonville, Florida.
authors.forename: Rui
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Florida, Jacksonville, Florida.
authors.forename: Phil
authors.initials: P
authors.lastname: Pirgousis
authors.affiliation: Sinus & Nasal Institute of Florida, St. Petersburg, Florida.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Lanza
authors.affiliation: Department of Radiation Oncology, University of Florida, Gainesville, Florida; Department of Radiation Oncology, University of Florida, Jacksonville, Florida.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.affiliation: Department of Radiation Oncology, University of Florida, Gainesville, Florida; Department of Radiation Oncology, University of Florida, Jacksonville, Florida.
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D018304:Esthesioneuroblastoma, Olfactory / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D009669:Nose Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D010255:Paranasal Sinus Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D061766:Proton Therapy / Q000379:methods*; D018714:Radiotherapy, Adjuvant; D012062:Relative Biological Effectiveness; D015996:Survival Rate; D016896:Treatment Outcome