title: Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis.
abstract: BACKGROUND
  Malignant tumours arising within the nasal cavity and paranasal sinuses are rare and composed of several histological types, rendering controlled clinical trials to establish the best treatment impractical. We undertook a systematic review and meta-analysis to compare the clinical outcomes of patients treated with charged particle therapy with those of individuals receiving photon therapy.
  
  
  METHODS
  We identified studies of nasal cavity and paranasal sinus tumours through searches of databases including Embase, Medline, Scopus, and the Cochrane Collaboration. We included treatment-naive cohorts (both primary and adjuvant radiation therapy) and those with recurrent disease. Primary outcomes of interest were overall survival, disease-free survival, and locoregional control, at 5 years and at longest follow-up. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for charged particle therapy and photon therapy using an interaction test.
  
  
  RESULTS
  43 cohorts from 41 non-comparative observational studies were included. Median follow-up for the charged particle therapy group was 38 months (range 5-73) and for the photon therapy group was 40 months (14-97). Pooled overall survival was significantly higher at 5 years for charged particle therapy than for photon therapy (relative risk 1·51, 95% CI 1·14-1·99; p=0·0038) and at longest follow-up (1·27, 1·01-1·59; p=0·037). At 5 years, disease-free survival was significantly higher for charged particle therapy than for photon therapy (1·93, 1·36-2·75, p=0·0003) but, at longest follow-up, this event rate did not differ between groups (1·51, 1·00-2·30; p=0·052). Locoregional control did not differ between treatment groups at 5 years (1·06, 0·68-1·67; p=0·79) but it was higher for charged particle therapy than for photon therapy at longest follow-up (1·18, 1·01-1·37; p=0·031). A subgroup analysis comparing proton beam therapy with intensity-modulated radiation therapy showed significantly higher disease-free survival at 5 years (relative risk 1·44, 95% CI 1·01-2·05; p=0·045) and locoregional control at longest follow-up (1·26, 1·05-1·51; p=0·011).
  
  
  CONCLUSIONS
  Compared with photon therapy, charged particle therapy could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses. Prospective studies emphasising collection of patient-reported and functional outcomes are strongly encouraged.
  
  
  BACKGROUND
  Mayo Foundation for Medical Education and Research.
authors: Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, USA. Electronic address: patel.samir@mayo.edu.
authors: Samir H
authors: SH
authors: Patel
authors: Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors: Zhen
authors: Z
authors: Wang
authors: Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, USA.
authors: William W
authors: WW
authors: Wong
authors: Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors: Mohammad Hassan
authors: MH
authors: Murad
authors: Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, USA.
authors: Courtney R
authors: CR
authors: Buckey
authors: Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors: Khaled
authors: K
authors: Mohammed
authors: Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors: Fares
authors: F
authors: Alahdab
authors: Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors: Osama
authors: O
authors: Altayar
authors: Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors: Mohammed
authors: M
authors: Nabhan
authors: Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, USA.
authors: Steven E
authors: SE
authors: Schild
authors: Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
authors: Robert L
authors: RL
authors: Foote
mesh_terms: D000328:Adult; D000368:Aged; D000512:Alpha Particles / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods*; D015331:Cohort Studies; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009669:Nose Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D010255:Paranasal Sinus Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D017785:Photons / Q000627:therapeutic use*; D011379:Prognosis; D011829:Radiation Dosage; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome