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Accelerated radiation therapy improves outcomes of head and neck cancers

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Accelerated radiation therapy is more effective than conventional fractionation for squamous cell carcinoma of the head and neck (HNSCC), but complications of treatment are more common, investigators report.

The success of radiotherapy for these cancers depends on the extent of tumor stem cell proliferation during radiation. For this reason, shortening the treatment time without reducing the dose is an attractive option, the authors explain in their April 9th online report in The Lancet Oncology. Studies have already affirmed that this approach may be beneficial in industrial nations.

But the goal of this trial was to examine accelerated fractionation for patients with HNSCC in resource-limited settings, “where there are fewer therapeutic resources and where tumor burdens can be heavier,” note lead author Dr. Jens Overgaard, from Aarhus University Hospital, Denmark, and associates. Seventy percent of these cancers occur in developing countries, they say.

The 900 patients — from Asia, eastern Europe, the Middle East, Africa and South America – all had stage 1-4 invasive squamous-cell carcinoma of the larynx, pharynx, or oral cavity, with no distant spread.

Between 1999 and 2004, the researchers randomly assigned them to five (n = 448) or six (n = 452) fractions per week of 2 Gy (median treatment time 40 and 47 days, respectively). Tumors were treated with doses of 66-70 Gy in 33-35 fractions.

The 5-year actuarial rate of locoregional control was 42% in the accelerated group vs 30% in the conventional group. There was no difference in the effect on lymph nodes. In subgroup analyses, accelerated fractionation had the most benefit in laryngeal tumors and less benefit in advanced tumors at any site with a large nodal burden.

At 5 years, the actuarial rate of disease-free survival was 50% in the accelerated group and 40% in the conventional group (p = 0.03). Corresponding overall survival was 35% and 28% (p = 0.07).

In multivariate analysis, negative neck nodes, smaller tumor size (T1-T2), and six fractions per week were significant independent predictors of a good prognosis.

Severe skin reactions (20% vs 11%), confluent mucositis (10% vs 5%), and mucosal reaction requiring tube feeding (52% vs 45%) occurred significantly more often with accelerated treatment.

Late morbidity, however – moderate or severe fibrosis, laryngeal edema, or xerostomia – did not differ significantly by treatment schedule.

Dr. Overgaard’s group concludes that the accelerated regimen is more effective than conventional fractionation, “and since it does not require additional resources it might be a suitable new international standard of treatment.”

Lancet Oncol 2010.