title: Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time.
abstract: OBJECTIVE
  To test the hypothesis that (1) the distinction between intermediate- and high-risk patients by clustering different prognostic factors results in a significant difference in treatment outcome and (2) a shorter interval between surgery and radiotherapy and shorter overall treatment times of radiation (OTTRT) result in higher rates of locoregional control (LRC).
  
  
  METHODS
  Included were patients (n = 217) with previously untreated squamous cell carcinoma of the oral cavity treated with radical surgery and postoperative radiotherapy. Patients with extranodal spread or microscopic residual disease and patients with two or more other risk factors (i.e., N2b-N3, >1 nodal level involved, perineural growth, or stage T3-T4) were classified as high-risk patients. Patients with only one other risk factor were classified as intermediate risk.
  
  
  RESULTS
  In the intermediate-risk group, the 3-year LRC was 87% as compared with 66% in the high-risk group (p = 0.0005). No association was found between interval and LRC. However, the OTTRT was significantly associated with LRC. The 3-year LRC was 87%, 75%, 69%, and 51% when the OTT was <6 weeks, 6-7 weeks, 7-8 weeks, and >8 weeks, respectively (p = 0.0004). The 3-year overall survival (OS) in the intermediate risk patients was 74% compared with 50% in the high-risk group (p = 0.0014). A significant association was also found between the OS and OTTRT. The OS increased from 50% when the OTTRT was >8 weeks to 74% when the OTT was <6 weeks (p = 0.006). Similar results were found with regard to the disease-free survival (DFS). In the multivariate analysis, both risk group and OTT were significantly associated with LRC, DFS, and OS. No significant interaction term was present between these two factors, which means that the OTT was of importance both for the high-risk and the intermediate-risk patients.
  
  
  CONCLUSIONS
  In the subset of patients with carcinoma of the oral cavity, the classification of high- and intermediate-risk patients by clustering a number of prognostic factors provides important prognostic information regarding LRC, DFS, and OS. The OTT was the most important prognostic factor both in the high-risk and intermediate-risk patients. Reducing the OTT to 6 weeks or less is a rather simple measure to achieve a considerable improvement of the outcome of treatment in this category of patients.
authors.affiliation: Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlands. ja.langendijk@vumc.nl
authors.forename: J A
authors.initials: JA
authors.lastname: Langendijk
authors.forename: M A
authors.initials: MA
authors.lastname: de Jong
authors.forename: C R
authors.initials: CR
authors.lastname: Leemans
authors.forename: R
authors.initials: R
authors.lastname: de Bree
authors.forename: L E
authors.initials: LE
authors.lastname: Smeele
authors.forename: P
authors.initials: P
authors.lastname: Doornaert
authors.forename: B J
authors.initials: BJ
authors.lastname: Slotman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D011184:Postoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors