title: Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.
abstract: OBJECTIVE
  To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC).
  
  
  METHODS
  TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR).
  
  
  RESULTS
  A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR.
  
  
  CONCLUSIONS
  In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA 02115, USA. dsher@partners.org
authors.forename: David J
authors.initials: DJ
authors.lastname: Sher
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
authors.forename: Roy B
authors.initials: RB
authors.lastname: Tishler
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Sarlis
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Holupka
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Devlin
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012720:Severity of Illness Index; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil