Accelerated Versus Conventional Fractionated Radiotherapy in Squamous Cell Carcinoma of the Head and Neck (SCCHN: A Randomized International Multicenter Trial with 908 Patients Conducted by the IAEA-ACC Study Group

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 13, 2006

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Presenter: J. Overgaard
Presenter's Affiliation: Aarhus University Hospital, Denmark
Type of Session: Scientific

Background

  • Multiple prospective randomized trials have suggested that accelerated fractionation schedules may increase the efficacy of radiation therapy for SCCHN
  • Because these trials have been performed in Europe and the United States where tumor burden may be lower and treatment resources more plentiful, it is unclear whether any benefit of accelerated treatment would translate to countries with higher tumor burden and more limited resources
  • For this reason, the International Atomic Energy Agency (IAEA) sought to evaluate accelerated treatment in a more generalized setting, and undertook this prospective, randomized, multi-country trial comparing the efficacy, toxicity, and feasibility of accelerated versus conventional radiation

Materials and Methods

  • Between 1999 and 2004, 908 patients with non-metastatic SCCHN were enrolled to receive external beam radiotherapy to doses of 66-70 Gy in 2 Gy daily fractions (fx) and were randomized to either 5 or 6 (fx) per week
  • Centers participated from locations in Asia, Europe, the Middle East, Africa, and South America
  • Patients with carcinoma of the oral cavity (N=212), oropharynx (N=318), hypopharynx (N=162), and larynx (N=216) were eligible, and the number of patients by stage is as follows:
    • stage I: 28
    • stage II: 229
    • stage III: 337
    • stage IV: 314

Results

  • 900 of the 908 enrolled patients met the eligibility requirements and were evaluable for analysis
  • Patient and tumor-associated characteristics were similar between the 2 arms
  • Median treatment duration was 40 days in the 6 fx arm and 47 days in the 5 fx arm
  • There was no significant difference between the 2 arms with respect to 5-year overall survival
  • The 6 fx arm demonstrated significantly increased 5-year disease-specific survival vs. the 5 fx arm (53% vs. 39%, p=0.02)
  • The 6 fx arm demonstrated significantly increased 5-year local control vs. the 5 fx arm (41% vs. 28%, p=0.01)
    • The 6 fx arm demonstrated significantly increased 5-year local control of the primary site vs. the 5 fx arm (47% vs. 34%, p=0.01)
    • There was no significant difference between the 2 arms with respect to 5-year local control of the neck
  • The 6 fx arm demonstrated significantly increased acute mucositis vs. the 5 fx arm, though there were no differences between the 2 groups with respect to late toxicity

Author's Conclusions

The 6 fraction per week arm demonstrated significant improvements in disease-specific survival and local control versus the 5 fraction per week arm with no increases in late toxicity, and may represent a new standard of care for primary radiotherapy treatment of SCCHN that is feasible on a global scale.

Clinical/Scientific Implications

This large, randomized, multi-national, prospective study of accelerated radiotherapy in head and neck cancer is somewhat novel in that it seeks to provide an efficacious and tolerable radiation regimen, one that offers potential improvements in outcome over conventional treatment while being realistically available for implementation by centers around the globe. The role of such an accelerated schedule in the setting of multimodal therapy involving systemic and/or targeted agents remains largely undefined, and may represent an important question for future research initiatives.