title: Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.
abstract: OBJECTIVE
  The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy.
  
  
  METHODS
  We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis.
  
  
  RESULTS
  Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2)
  
  
  CONCLUSIONS
  Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.
authors.affiliation: The Feinberg School of Medicine and the Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA. a-argiris@northwestern.edu
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Brockstein
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haraf
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Stenson
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Mittal
authors.forename: Merrill S
authors.initials: MS
authors.lastname: Kies
authors.forename: Fred R
authors.initials: FR
authors.lastname: Rosen
authors.forename: Borko
authors.initials: B
authors.lastname: Jovanovic
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D015897:Comorbidity; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D012189:Retrospective Studies; D013997:Time Factors