title: Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy.
abstract: BACKGROUND
  The authors report the results of a prospective study of patients with malignant neuroendocrine tumors of the sinonasal tract who received multimodality treatment incorporating high-dose proton-photon radiotherapy.
  
  
  METHODS
  Nineteen patients with olfactory neuroblastoma (ONB) or neuroendocrine carcinoma (NEC) were treated between 1992 and 1998 on a prospective study. Four patients had Kadish Stage B disease, and 15 patients had Kadish Stage C disease. The median patient age was 44 years. Patients received chemotherapy with 2 courses of cisplatin and etoposide followed by high-dose proton-photon radiotherapy to 69.2 cobalt-Gray equivalents (CGE) using 1.6-1.8 CGE per fraction twice daily in a concomitant boost schedule. Two further courses of chemotherapy were given to responders.
  
  
  RESULTS
  Of 19 patients, 15 patients were alive at the time of this report with a median follow-up of 45 months (range, 20-92 months). Four patients died from disseminated disease 8-47 months after their original diagnosis. The 5-year survival rate was 74%. There were two local recurrences, and both patients underwent salvage surgery. The 5-year local control rate of initial treatment was 88%. Acute toxicity of chemotherapy was tolerable, with no patient sustaining more than Grade 3 hematologic toxicity. Thirteen patients showed a partial or complete response to chemotherapy. One patient developed unilateral visual loss after the first course of chemotherapy; otherwise, visual preservation was achieved in all patients. Four patients who were clinically intact developed radiation-induced damage to the frontal or temporal lobe by magnetic resonance imaging criteria. Two patients showed soft tissue and/or bone necrosis, and one of these patients required surgical repair of a cerebrospinal fluid leak.
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy and high-dose proton-photon radiotherapy is a successful treatment approach for patients with ONB and NEC. Radical surgery is reserved for nonresponders. Due to the precision of delivery of radiation with stereotactic setup and protons, no radiation-induced visual loss was observed.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. markus.fitzek@uni-essen.de
authors.forename: Markus M
authors.initials: MM
authors.lastname: Fitzek
authors.forename: Allan F
authors.initials: AF
authors.lastname: Thornton
authors.forename: Marc
authors.initials: M
authors.lastname: Varvares
authors.forename: Marek
authors.initials: M
authors.lastname: Ancukiewicz
authors.forename: James
authors.initials: J
authors.lastname: Mcintyre
authors.forename: Judy
authors.initials: J
authors.lastname: Adams
authors.forename: Stanley
authors.initials: S
authors.lastname: Rosenthal
authors.forename: Michael
authors.initials: M
authors.lastname: Joseph
authors.forename: Philip
authors.initials: P
authors.lastname: Amrein
mesh_terms: D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000628:therapy*; D009669:Nose Neoplasms / Q000628:therapy*; D013517:Otorhinolaryngologic Surgical Procedures; D010255:Paranasal Sinus Neoplasms / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D011882:Radiotherapy, High-Energy; D016879:Salvage Therapy
chemical_list: D005047:Etoposide; D002945:Cisplatin