Radiotherapy Fractionation for Head and Neck Cancers

Key Points

  • In patients with head and neck cancers, hyperfractionated radiotherapy was associated with a survival advantage vs conventional fractionation.
  • Survival was worse with altered fractionation vs conventional fractionation and concurrent chemotherapy.

An update of the Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck (MARCH) showed that hyperfractionated radiotherapy maintained a survival advantage over conventional radiotherapy in head and neck cancers. The findings were reported in The Lancet Oncology by Lacas et al. A prior report from MARCH showed that altered fractionation radiotherapy was associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy being associated with the greatest benefit.

Study Details

The updated analysis incorporated new individual patient data from randomized trials performed between January 2009 and July 2015 that compared primary or postoperative conventional fractionation radiotherapy vs altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy vs altered fractionation radiotherapy alone (comparison 2). Altered fractionation included hyperfractionated, moderately accelerated, and very accelerated approaches. The primary endpoint was overall survival.

Overall Survival

In comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy), including 33 trials and 11,423 patients, altered fractionation radiotherapy was associated with a significant benefit in overall survival (hazard ratio [HR] = 0.94, P = .0033), with absolute benefits of 3.1% at 5 years and 1.2% at 10 years. A significant interaction (P = .051) was found between fractionation type and treatment effect, with the survival benefit being limited to hyperfractionation (HR = 0.83, 95% confidence interval [CI] = 0.74–0.92), with absolute benefits of 8.1% at 5 years and 3.9% at 10 years vs conventional fractionation.

In comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy vs altered fractionation radiotherapy alone), including 5 trials and 986 patients, altered fractionation radiotherapy was associated with worse overall survival (HR = 1.22, P = .0098), with absolute deficits of –5.8% at 5 years and –5.1% at 10 years.

The investigators concluded: “This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested.”

The study was funded by the Institut National du Cancer and Ligue Nationale Contre le Cancer.

Jean-Pierre Pignon, MD, of Gustave Roussy Cancer Campus, Universite Paris-Sud, Universite Paris-Saclay, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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