title: Proton therapy for pediatric and adolescent esthesioneuroblastoma.
abstract: BACKGROUND
  Esthesioneuroblastoma (EN) of the paranasal sinus comprises less than 3% of tumors of in pediatric and adolescent patients [1]. The collective adult literature indicates a critical role for radiotherapy in attaining cure [2], yet pediatric outcome data is limited. Radiation in pediatric patients with EN can cause significant morbidity due to the proximity of critical structures. Proton radiotherapy offers a potential dosimetric benefit that may improve long-term survival and toxicity outcomes in the pediatric population [3].
  
  
  METHODS
  We retrospectively identified eight patients treated for EN with proton radiotherapy from 2000-2013. Times to event clinical endpoints are summarized using the Kaplan-Meier methods and are from the date of radiotherapy completion. Toxicities are reviewed and graded according to CTCAE v. 4.0.
  
  
  RESULTS
  Median follow up was 4.6 years for survivors (range 0.8-9.4 years). The 4 year overall survival was 87.5%. Four of eight patients (one elective) had comprehensive neck radiotherapy. No local or regional failures were observed. Two patients failed distantly with diffuse leptomeningeal disease and intraparenchymal brain metastases, at 0.6 and 1.3 months respectively. Four patients developed radiation related late toxicities including endocrine dysfunction, two cases of grade 2 retinopathy and one case of grade 3 optic neuropathy.
  
  
  CONCLUSIONS
  In a limited cohort, proton radiotherapy appears to provide excellent locoregional disease control even in those patients with locally advanced disease and intracranial extension. Distant failure determined overall survival in our cohort. Toxicities were acceptable given disease location and extent.
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: John T
authors.initials: JT
authors.lastname: Lucas
authors.affiliation: Provision Center for Proton Therapy, Knoxville, Tennessee.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Ladra
authors.affiliation: Department of Radiation Oncology, Boston, Massachusetts.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: MacDonald
authors.affiliation: Department of Radiation Oncology, Boston, Massachusetts.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Busse
authors.affiliation: Pediatrics at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Friedmann
authors.affiliation: Pediatrics at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: David H
authors.initials: DH
authors.lastname: Ebb
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Marcus
authors.affiliation: Department of Radiation Oncology, Boston, Massachusetts.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Tarbell
authors.affiliation: Department of Radiation Oncology, Boston, Massachusetts.
authors.forename: Torunn I
authors.initials: TI
authors.lastname: Yock
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D018304:Esthesioneuroblastoma, Olfactory / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008577:Meningeal Neoplasms / Q000556:secondary; D009296:Nasal Cavity / Q000473:pathology*; D009669:Nose Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D061766:Proton Therapy / Q000009:adverse effects; D011832:Radiation Injuries / Q000209:etiology; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014750:Vincristine; D005047:Etoposide; D019772:Topotecan; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin
keywords: esthesioneuroblastoma; olfactory neuroblastoma; proton radiotherapy
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