title: Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer.
abstract: BACKGROUND
  Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy.
  
  
  METHODS
  A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m2 on Day 1 and 5-FU 1,000 mg/m2/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m2 on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease.
  
  
  METHODS
  Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months.
  
  
  RESULTS
  Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09).
  
  
  CONCLUSIONS
  Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.
authors.affiliation: Head and Neck Oncology Program, Department of Otolaryngology--Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA. kevin.fung@lhsc.on.ca
authors.forename: Kevin
authors.initials: K
authors.lastname: Fung
authors.forename: Teresa H
authors.initials: TH
authors.lastname: Lyden
authors.forename: Julia
authors.initials: J
authors.lastname: Lee
authors.forename: Susan G
authors.initials: SG
authors.lastname: Urba
authors.forename: Frank
authors.initials: F
authors.lastname: Worden
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.forename: Christina
authors.initials: C
authors.lastname: Tsien
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Norman D
authors.initials: ND
authors.lastname: Hogikyan
authors.forename: Mark E P
authors.initials: ME
authors.lastname: Prince
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003679:Deglutition; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D011788:Quality of Life; D013065:Speech Intelligibility; D014833:Voice Quality
chemical_list: D002945:Cisplatin; D005472:Fluorouracil