The aim of our study was to evaluate the value of two different altered fractionation schedules - hyperfractionation and accelerated fractionation with concomitant boost - in comparison with conventional fractionation in primary definitive radiotherapy for squamous cell carcinomas of the larynx, oropharynx or hypopharynx. The study began and was conducted while the only teletherapy unit in our department was the cobalt-60 machine. During that period we were expecting the installation of new sophisticated equipment. We assumed that the results of this study would be also able to show whether or not it would be rational to use the altered fractionation regimens on the new machines.

Eligible patients admitted from March 1999 to December 2000 were treated with conventionally fractionated radiotherapy. These patients represented the retrospective part of the study. Patients admitted between January 2001 and June 2004 were included in the prospective part of the study. Following the confirmation of their eligibility, altered fractionation schedule assignment was made after stratifying by site of origin (larynx vs oropharynx vs hypopharynx), Karnofsky performance score (60%-70% vs 80%-100%), and stage of disease (I and II vs III and IV). Patients were randomized to receive radiotherapy delivered using either hyperfractionation or accelerated fractionation with concomitant boost as a late accelerating component. Exceptions occurred when patients either refused treatment with two daily fractions or were not offered twice-a-day irradiation because of lack of machine time.

Radiotherapy Scheduling and Technique The conventionally fractionated radiotherapy schedule was 66-70 Gy in 6½ -7 weeks (one fraction of 2 Gy per day, 5 fractions per week), whereas the hyperfractionation treatment schedule was 74.4-79.2 Gy in 6.2-7 weeks (two fractions of 1.2 Gy per day, 10 fractions per week with interfraction interval of at least 6 hours; Figure 1). The treatment schedule in accelerated fractionation using concomitant boost consisted of daily fraction of 1.8 Gy, 5 days a week, up to 32.4 Gy including all sites of disease and electively irradiated areas of the neck, followed by two daily fractions for the last 11-12 days. The first daily fraction encompassed all sites of the disease and electively irradiated neck nodes using a dose of 1.8 Gy, and the second daily fraction was the concomitant boost delivered through reduced fields to encompass the gross disease only, using a fraction of 1.5 Gy up to total doses of 68.7-72 Gy in 6 weeks (Figure 1). The interval between the two daily fractions was at least 6 hours.

Inclusion Criteria:The inclusion criteria were age 18-75 years, Karnofsky performance score equal or more then 60%, and all stages of disease except stage IVC (TNM classification according to International Union Against Cancer and American Joint Committee of Cancer (UICC and AJCC) from 1997). -

Exclusion Criteria:Patients with previous or concurrent malignancy other then basal cell carcinoma were excluded.

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