title: Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States.
abstract: OBJECTIVE
  To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Using the National Cancer Data Base (NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds.
  
  
  RESULTS
  A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio [HR], 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P < .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P < .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days.
  
  
  CONCLUSIONS
  TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival.
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Colin T
authors.initials: CT
authors.lastname: Murphy
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA. thomas.galloway@fccc.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Galloway
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Handorf
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Egleston
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Lora S
authors.initials: LS
authors.lastname: Wang
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Ranee
authors.initials: R
authors.lastname: Mehra
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Flieder
authors.affiliation: All authors: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: John A
authors.initials: JA
authors.lastname: Ridge
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D061665:Time-to-Treatment; D014481:United States