title: Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma.
abstract: OBJECTIVE
  Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy.
  
  
  METHODS
  Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0.
  
  
  RESULTS
  With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity.
  
  
  CONCLUSIONS
  Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton therapy in the treatment of sinonasal malignancy.
authors.affiliation: Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Russo
authors.affiliation: Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Adams
authors.affiliation: Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Weyman
authors.affiliation: Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Busse
authors.affiliation: Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Saveli I
authors.initials: SI
authors.lastname: Goldberg
authors.affiliation: Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary; Harvard Medical School, Boston, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Varvares
authors.affiliation: Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary; Harvard Medical School, Boston, Massachusetts.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Deschler
authors.affiliation: Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary; Harvard Medical School, Boston, Massachusetts.
authors.forename: Derrick T
authors.initials: DT
authors.lastname: Lin
authors.affiliation: Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Delaney
authors.affiliation: Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: awchan@partners.org.
authors.forename: Annie W
authors.initials: AW
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D009669:Nose Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D010255:Paranasal Sinus Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D016016:Proportional Hazards Models; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011832:Radiation Injuries / Q000473:pathology; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012907:Smoking / Q000009:adverse effects; D015996:Survival Rate