title: Intensive chemoradiotherapy as a primary treatment for organ preservation in patients with advanced cancer of the head and neck: efficacy, toxic effects, and limitations.
abstract: OBJECTIVE
  To evaluate the efficacy and toxic effects of intensive chemoradiotherapy as a primary modality for organ preservation in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and to define the patterns of treatment failure associated with this therapy.
  
  
  METHODS
  Retrospective review.
  
  
  METHODS
  Tertiary care referral center.
  
  
  METHODS
  A total of 127 consecutive patients with advanced SCCHN treated with primary concurrent chemoradiotherapy.
  
  
  METHODS
  Efficacy data included the rates of tumor response to therapy, organ preservation, disease recurrence, overall and disease-specific survival, and patterns of treatment failure. Toxic effect data included the rate and grade of treatment-related complications and the rate of unscheduled hospital admissions for managing treatment-related toxic effects.
  
  
  RESULTS
  Ninety-six patients (76%) were men and 31 (24%) were women. Average age at diagnosis was 62 years (range, 37-85 years). The primary tumor site was the oropharynx in 58 patients (46%), the larynx in 36 (28%), the hypopharynx in 20 (16%), the oral cavity in 10 (8%), and another site in 3 (2%). Most patients (91%) had stage III or IV disease. Average follow-up was 36 months. Primary chemoradiotherapy achieved complete response at the primary tumor site in 109 patients (86%). Patients with partial response, stable or progressive disease, or recurrence at the primary site underwent salvage surgery. Overall, at mean follow-up of 3 years, local disease control was achieved in 113 patients (89%), and organ preservation was possible in 102 patients (80%). Two thirds of all patients (n = 83) had clinical N+ disease. Complete clinical response to chemoradiotherapy in the neck was achieved in 57 of these patients (69%). However, complete response to chemoradiotherapy was 93%, 62%, and 47% for N1, N2, and N3 disease, respectively (P <.001). Patients achieving less than complete clinical response underwent salvage neck dissection. Overall, at an average follow-up of 36 months, regional disease control was achieved in 76 (92%) of the 83 patients with neck metastasis. Despite this high locoregional control rate, distant metastasis occurred in 18 patients (14%), was the most common site of disease recurrence (53%), and accounted for almost 40% of all treatment failures. Severe (grade 3 or 4) mucositis and neutropenia occurred in 33% and 25% of patients, respectively. Two patients (2%) died of treatment-related toxic effects. At 3-year mean follow-up, disease-specific and overall survival were 72% and 57%, respectively. Most deaths were due to distant metastasis, comorbidity, and second primary tumors.
  
  
  CONCLUSIONS
  High rates of locoregional disease control and organ preservation are achievable with primary chemoradiotherapy in patients with advanced SCCHN, but they are associated with severe treatment-related toxic effects. Despite this effective local and regional disease control, improved survival is hampered by the relatively high incidence of distant metastasis, second primary tumors, and comorbidity.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, USA. eyhanna@mdanderson.org
authors.forename: Ehab
authors.initials: E
authors.lastname: Hanna
authors.forename: Michael
authors.initials: M
authors.lastname: Alexiou
authors.forename: Justin
authors.initials: J
authors.lastname: Morgan
authors.forename: Jenny
authors.initials: J
authors.lastname: Badley
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Maddox
authors.forename: Jose
authors.initials: J
authors.lastname: Penagaricano
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Fan
authors.forename: Randall
authors.initials: R
authors.lastname: Breau
authors.forename: James
authors.initials: J
authors.lastname: Suen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001131:Arkansas / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil