title: High survival and organ function rates after primary chemoradiotherapy for intermediate-stage squamous cell carcinoma of the head and neck treated in a multicenter phase II trial.
abstract: OBJECTIVE
  Patients with intermediate-stage squamous cell carcinoma of the head and neck traditionally have been treated with initial surgical resection followed by radiotherapy (RT) alone or chemoradiotherapy. A previous study in this patient population reported a 91% locoregional control rate and 65% overall survival (OS) rate at 5 years, with chemoradiotherapy used as primary treatment. This study was undertaken to assess whether shortening treatment duration with hyperfractionated RT would be feasible and improve locoregional control, organ preservation, and progression-free survival.
  
  
  METHODS
  Eligible patients with stage II or III disease received fluorouracil, hydroxyurea, and RT given twice daily on a week-on/week-off schedule. Quality-of-life scores were measured using three validated indexes.
  
  
  RESULTS
  All 53 patients enrolled are included in the analysis, with a median follow-up of 42 months (range, 5 to 98 months). Grade 3 or 4 in-field mucositis was observed in 77% and 9%, respectively. No patients required surgical salvage at the primary tumor site (pathological complete response rate, 100%). The 3-year progression-free and OS rates are 67% and 78%, respectively. The 3-year disease-specific mortality rate is 7%. At the time of analysis, 87% of surviving patients do not require enteral feeding support. Quality-of-life and performance assessment indicated that, although acute treatment toxicities were severe, most patients returned to pretreatment function by 12 months.
  
  
  CONCLUSIONS
  Concurrent chemoradiotherapy with hyperfractionated RT is feasible in this patient population and yields high local control and cure rates. Compared with our historical control using once-daily fractionation, hyperfractionation is accompanied by increased acute in-field toxicity.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, 60637, USA. ecohen@medicine.bsd.uchicago.edu
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: Marcy A
authors.initials: MA
authors.lastname: List
authors.forename: Masha
authors.initials: M
authors.lastname: Kocherginsky
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Mittal
authors.forename: Fred
authors.initials: F
authors.lastname: Rosen
authors.forename: Bruce
authors.initials: B
authors.lastname: Brockstein
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Williams
authors.forename: Mary Ellyn
authors.initials: ME
authors.lastname: Witt
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Stenson
authors.forename: Merrill S
authors.initials: MS
authors.lastname: Kies
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000175:diagnosis; D011788:Quality of Life; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005472:Fluorouracil; D006918:Hydroxyurea