title: Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer.
abstract: OBJECTIVE
  To test whether altered radiation fractionation schemes (hyperfractionation [HFX], accelerated fractionation, continuous [AFX-C], and accelerated fractionation with split [AFX-S]) improved local-regional control (LRC) rates for patients with squamous cell cancers (SCC) of the head and neck when compared with standard fractionation (SFX) of 70 Gy.
  
  
  METHODS
  Patients with stage III or IV (or stage II base of tongue) SCC (n=1076) were randomized to 4 treatment arms: (1) SFX, 70 Gy/35 daily fractions/7 weeks; (2) HFX, 81.6 Gy/68 twice-daily fractions/7 weeks; (3) AFX-S, 67.2 Gy/42 fractions/6 weeks with a 2-week rest after 38.4 Gy; and (4) AFX-C, 72 Gy/42 fractions/6 weeks. The 3 experimental arms were to be compared with SFX.
  
  
  RESULTS
  With patients censored for LRC at 5 years, only the comparison of HFX with SFX was significantly different: HFX, hazard ratio (HR) 0.79 (95% confidence interval 0.62-1.00), P=.05; AFX-C, 0.82 (95% confidence interval 0.65-1.05), P=.11. With patients censored at 5 years, HFX improved overall survival (HR 0.81, P=.05). Prevalence of any grade 3, 4, or 5 toxicity at 5 years; any feeding tube use after 180 days; or feeding tube use at 1 year did not differ significantly when the experimental arms were compared with SFX. When 7-week treatments were compared with 6-week treatments, accelerated fractionation appeared to increase grade 3, 4 or 5 toxicity at 5 years (P=.06). When the worst toxicity per patient was considered by treatment only, the AFX-C arm seemed to trend worse than the SFX arm when grade 0-2 was compared with grade 3-5 toxicity (P=.09).
  
  
  CONCLUSIONS
  At 5 years, only HFX improved LRC and overall survival for patients with locally advanced SCC without increasing late toxicity.
authors.affiliation: Winship Cancer Institute of Emory University School of Medicine, Atlanta, Georgia. Electronic address: jjbeitl@emory.edu.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Beitler
authors.affiliation: Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: University of California San Francisco, San Francisco, California.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Fu
authors.affiliation: H. Lee Moffitt Cancer Center at the University of South Florida, Tampa, Florida.
authors.forename: Andy
authors.initials: A
authors.lastname: Trotti
authors.affiliation: University of Alabama at Birmingham Medical Center, Birmingham, Alabama.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Spencer
authors.affiliation: Radiological Associates of Sacramento, Sacramento, California.
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.affiliation: MD Anderson Cancer Center, University of Texas, Houston, Texas.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Garden
authors.affiliation: McGill University, Montréal, Quebec.
authors.forename: George
authors.initials: G
authors.lastname: Shenouda
authors.affiliation: Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Harris
authors.affiliation: MD Anderson Cancer Center, University of Texas, Houston, Texas.
authors.forename: Kian K
authors.initials: KK
authors.lastname: Ang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002423:Cause of Death; D016001:Confidence Intervals; D019583:Dose Fractionation, Radiation; D004750:Enteral Nutrition / Q000706:statistics & numerical data; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy; D009062:Mouth Neoplasms / Q000473:pathology / Q000532:radiotherapy; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000532:radiotherapy; D011832:Radiation Injuries / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014062:Tongue Neoplasms / Q000473:pathology / Q000532:radiotherapy; D017211:Treatment Failure