Jean-Pierre Pignon, MD
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 linked to the greatest benefit. 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 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 (for the most part, 66–70 Gy in 2-Gy fractions, for 5 days a week) 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 employing a variety of different regimens. The primary endpoint was 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. ■