Seventh Interim Progress Report of The British Institute of Radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx

Wiernik, G.; Bates, Thelma D.; Berry, R. J.; Brindle, J.; Bullimore, J.; Dalby, J. E.; Flatman, G. E.; Fowler, Jack F.; Hadden, Rob; Haybittle, J. L.; Henk, J.M.; Howard, N.; Ledda, J.; Lindup, R.; Phillips, Derrick; Pointon, R. S.; Sambrook, D. K.; Skeggs, D.

doi:10.1259/0007-1285-55-655-505

Cited by 24 publications

(2 citation statements)

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“…Indeed, this undoubtedly has been the most frequent reason for altered fractionation. at least in the last 15 years. This is not sufficient justification, per se, to initiate clinical trials; however, the arbitrary decision to choose altered fractionation in clinical practice, even if justified on the basis of a formula of alleged isoeffectiveness, must be made with great caution.…”

Section: Discussionmentioning

confidence: 99%

Large-dose fractionation. (Hypofractionation)

Cox

1985

Cancer

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Fractionation is a radiotherapeutic “modality” that may be manipulated to attempt to improve control of malignant tumors or to decrease effects on normal tissues. In addition, some fractionation regimen must be selected as the basis for addition of any other modality such as radiosensitizers or hyperthermia. Considerable literature derived from clinical experiences with reduced numbers of large fractions has become available in the last 15 years. A review of this literature is focused on tumor control and effects on normal tissues resulting from hypofractionation (fewer than five fractions/week), rapid fractionation (large daily fractions treated five times/week), and rapid split‐course regimens that include a rest interval in the course of treatment. The evidence available indicates that a decrease in tumor control is associated with each of these large‐dose fractionation approaches. At the same time, late effects on normal tissues are increased as the result of the large‐sized fractions. The overall reduction in therapeutic ratio suggests that this avenue of clinical research should no longer be pursued and that such regimens should be adopted with caution for purposes of combining radiosensitizers or hyperthermia. Conversely, clinical research in radiotherapy justifiably can explore the effects of increased numbers of small fractions.

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Section: Discussionmentioning

confidence: 99%

Large-dose fractionation. (Hypofractionation)

Cox

1985

Cancer

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“…Several interim analyses were made and reported, the last of these being in the seventeenth year after the start of the trial (Wiernik et al, 1982). The first three analyses were made during the recruitment period and were comparatively simple.…”

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confidence: 99%

Recruitment, follow-up and analysis times in clinical trials of cancer treatment: a case study

Haybittle¹,

Alcock²,

Fowler³

et al. 1990

Br J Cancer

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Summary A study has been made of the way in which the number of events available for analysis in a clinical trial was dependent on the recruitment period, the maximum follow-up time on individual patients and the length of time between the start of the trial and its analysis. The events considered were deaths, local recurrences and late radiation effects on normal tissue in patients treated for cancer of the laryngo-pharynx by two different fractionation regimes. The The third time needing specification is that at which the results of the trial are to be analysed. While early interim analyses may be advisable to monitor the treatment effects, the use of any interim result to stop entry into the trial or to trigger early publication must take into account the effect of repeated analyses on apparent significance levels. This is a topic that has been discussed by many authors, e.g. Armitage et al. (1969), Haybittle (1971) We have recently studied the way in which events accumulated in a trial that began to be planned over 28 years ago. Our results show how, if we had, at the time of planning this trial, the requisite data concerning the time-course of occurrence of significant events, we could have saved ourselves and the trial participants considerable time and effort. Unfortunately there was a lack of suitable retrospective data on which to base such considerations and the trial design was very much influenced by the clinical concepts then current. Our experience may therefore be of value for others planning clinical trials of cancer treatment. Materials and methodsIn 1962 the planning of a multicentre trial began under the auspices of the British Institute of Radiology to compare two radiotherapy regimes in the treatment of cancer of the laryngopharynx. The two regimes differed in their fractionation schedules. One employed five fractions per week (one each weekday), which was common radiotherapy practice at that time. The other used three fractions per week (on Monday, Wednesday and Friday), which, provided any difference in its therapeutic effect was clinically unimportant, would be beneficial to the patient because of a reduced number of attendances, and would be more economical in the use of radiotherapy machines and associated staff. Because of the known radiobiological effects of changing fractionation, the total dose to patients treated with three fractions per week was set at 11 or 13% less than that given to patients treated with five fractions per week, for the longer or shorter schedules respectively. Recruitment started in 1966.The initial aim was to recruit about 900 patients, which would have given a 90% power of detecting a difference of about 10% in 5-year event-free rate, should such a difference really exist. As will be discussed later, this could have been too modest an ambition for a trial that was set up to show that one regime (three fractions/week) was no worse in therapeutic outcome than the other and could therefore be preferred on non-therapeutic grounds. However, the number of parti...

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