Final report on the second British Institute of Radiology fractionation study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngo-pharynx

Abstract

The second British Institute of Radiology trial of dose fractionation in radiotherapy compared two groups of prospectively randomized patients with squamous carcinoma of the laryngo-pharynx; one group was treated in a short (less than or equal to 4 weeks) and the other in a long (greater than 4 weeks) overall time. Treatment in any one centre could be given, with no planned gap in the course of treatment, either as a conventional, daily (5 fractions per week regime) or as 3 fractions per week. A total of 611 patients were allocated to treatment, of whom nine have had to be excluded from the analysis for a lack of information. Patients were admitted to the trial from January 1976 to December 1985 and were followed up for a maximum of 10 years and a minimum of 3 years. A reduction in total dose was made for use in the short compared with the long treatment regime. This reduction in total dose varied between 18% and 22% depending on whether 5 fractions or 3 fractions per week regimes were used. Overall, no statistically significant differences have been found between the two arms of the trial. The patients treated with 5 fractions per week in a short overall treatment time showed fewer late normal tissue effects. An analysis based on stratification by age, stage and anatomical site gave a relative risk (short/long overall treatment time) for deaths of 1.23 with a 95% confidence interval from 0.96 to 1.59. Analyses stratified for stage and site gave relative risks with 95% confidence intervals of 1 x 10 (0.84-1.44) for local recurrences/tumour persistence, and 1.01 (0.70-1.45) for laryngectomies.

Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden Hospital Experience

“…However, the opposite was found in the BIR trial [52]. In our series, using fraction sizes ranging from 3.12 to 3.28 Gy, there was only one late serious complication, a patient who underwent laryngectomy for persistent pain and histology showed chondronecrosis.…”

“…6-week treatment times. There was no significant difference in local control between the two arms of the study, but, surprisingly to some, the short treatment times gave significantly less severe late normal tissue radiation effects [52]. The Royal Marsden Hospital took part in the trial; when the results were known they adopted a 3-week treatment time for T1 glottic cancer.…”

Jack Fowler's 90th Birthday and Contributions to Fractionation

“…He helped Frank Ellis in the 1960se1970s to set up two British Institute of Radiology clinical trials, one on three versus five fractions a week, the other on overall times of less than or more than 4 weeks, which each ran for 10 years at a time when no other clinical trials in radiotherapy were running in the UK. The planned reductions in dose by 11e13% for treatments in 3 rather than 5 weeks and 18e22% with three rather than five fractions per week, each gave broadly similar results for the two arms [4,5]. This not only gave clinical confidence in continuing to use such different schedules, but also it helped pave the way for more adventurous schedules that exploited the accruing clinical radiobiology knowledge.…”

Online dosimetric evaluation of larynx SBRT: A pilot study to assess the necessity of adaptive replanning

“…Despite conventional radiation techniques, there was no difference in cure rates when reducing radiation therapy from a 5‐week course down to 3 weeks 7. Later, a British Institute of Radiology study showed equivalent survival rates and no significant differences in toxicity with either a 3‐week or 6‐week radiation course 6. More recently, the Royal Marsden Hospital treated 200 patients with T1 glottic cancer to a dose of 50–52.5 Gy in 16 daily fractions,5 matching outcomes from historical studies.…”

“…Accelerated hypofractionated irradiation of early‐stage larynx cancer originated in Europe, with early results mirroring those achieved with conventional therapy 5, 6. Despite conventional radiation techniques, there was no difference in cure rates when reducing radiation therapy from a 5‐week course down to 3 weeks 7.…”