title: Randomized trial of hyperfractionation versus conventional fractionation in T2 squamous cell carcinoma of the vocal cord (RTOG 9512).
abstract: OBJECTIVE
  To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial.
  
  
  METHODS
  Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power.
  
  
  RESULTS
  Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239 patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX.
  
  
  CONCLUSIONS
  The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.
authors.affiliation: Department of Radiation Oncology, University of South Florida H. Lee Moffittt Cancer Center, Tampa, Florida. Electronic address: andy.trotti@moffitt.org.
authors.forename: Andy
authors.initials: A
authors.lastname: Trotti
authors.affiliation: RTOG Statistical Center, Philadelphia, Pennsylvania.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Human Oncology, University of Wisconsin School of Medicine, Madison, Wisconsin.
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Department of Radiation Therapy, Loyola University Medical Center, Maywood, Illinois.
authors.forename: Bahman
authors.initials: B
authors.lastname: Emami
authors.affiliation: Department of Pathology, LDS Hospital, Salt Lake City, Utah.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Hammond
authors.affiliation: Radiological Associates of Sacramento, Sacramento, California.
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: William H
authors.initials: WH
authors.lastname: Morrison
authors.affiliation: McMaster University, Juravinski Cancer Centre, Hamilton, Ontario, Canada.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Sagar
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: John A
authors.initials: JA
authors.lastname: Ridge
authors.affiliation: Department of Radiation Oncology, University of California (emeritus), San Francisco, California.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Fu
authors.affiliation: Department of Radiotherapy, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011832:Radiation Injuries / Q000473:pathology; D014827:Vocal Cords