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

• Type of Material: Article
• Authors: Jonathan Beitler, Emory University; Qiang Zhang, Radiation Therapy Oncology Group; Karen K Fu, University of California San Francisco; Andy Trotti, University of South Florida; Sharon A Spencer, University of Alabama at Birmingham; Christopher U Jones, Radiological Associates of Sacramento; Adam S Garden, MD Anderson Cancer Center; George Shenouda, McGill University; Jonathan Harris, Radiation Therapy Oncology Group; Kian K Ang, MD Anderson Cancer Center
• Language: English
• Date: 2014-05-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ijrobp.2013.12.027
• Title of Journal or Parent Work: International Journal of Radiation Oncology - Biology - Physics
• ISSN: 0360-3016
• Volume: 89
• Issue: 1
• Start Page: 13
• End Page: 20
• Grant/Funding Information: This trial was conducted by the Radiation Therapy Oncology Group (RTOG), and was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI).
• Keywords: Science & Technology; SQUAMOUS-CELL CARCINOMA; THERAPY; Life Sciences & Biomedicine; ACCELERATED RADIOTHERAPY; ONCOLOGY; EFFICACY; HYPERFRACTIONATION; STRATEGIES; STANDARD FRACTIONATION; RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING; Oncology; Radiology, Nuclear Medicine & Medical Imaging; TERM-FOLLOW-UP; CHEMOTHERAPY; RISK
• Research Categories: Health Sciences, General; Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

Purpose 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 and Materials 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.