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Hypofractionation: Lessons from complications
Radiotherapy and Oncology, 21 (1991) 286 © 1991 Elsevier Science Publishers B.V. 0167-8140/91/$03.50
286 R A D I O N 00873
Letter to the Editors HYPOFRACTIONATION:
LESSONS TIONS
FROM
COMPLICA-
To the Editors, In his enthusiasm to castigate hypofractionation, Fletcher [1] seems to have misinterpreted the clinical trials of fractionation in head and neck cancer conducted in the U.K. The first BIR trial in larynx and hypopharynx did indeed consider the end points of local tumour control and late morbidity in addition to survival [5]. 734 patients were followed for 10 years and no difference between 3 fractions per week and 5 fractions per week could be detected for any of these end points. The second BIR trial [4] compared short (3-4 weeks) with long (6-7 weeks) treatment. Again, no difference in local control was found, but the short treatment time group in which the fraction size averaged 3 Gy had a lower late morbidity rate which is now statistically significant [5]. The Cardiff trial [2] was conducted on patients with poor performance status who were unfit for treatment in hyperbaric oxygen. The original aim of this was to test the hypothesis that the results of the first M R C hyperbaric oxygen trial [3] were invalid, because the 10 fraction regime given to the control group would give poorer results than the more conventional 5 times per week treatment over 6 weeks. The patient material was indeed heterogenous, but the patients were matched into pairs by site and stage of disease, one of each pair being randomly allocated to 10 fractions and the other
to 30 fractions. All that can be said of this trial is that it failed to provide evidence in favour of the original hypothesis tested; however, a rather similar trial at Yale produced the same result [7]. It is certainly true that some treatment with large fractions has caused severe late sequelae. Nevertheless, the necessity to keep fraction sizes to a maximum of 2 Gy has never been confirmed in randomised controlled clinical trials. Comparison of fractionation schemes requires adjustment of total dose so that late normal tissue effects are the same. In randomised trials in which this has been achieved, conventional radiotherapy with 2 Gy per day fractions has so far not been demonstrated to yield better tumour control than shorter courses of treatment using larger fraction sizes in either breast or head and neck cancer. Sincerely, J. M. Henk (received 20 March 1991, accepted 11 June 1991) On behalf of the
The Royal Marsden Hospital Downs Road, Sutton, Surrey SM2 5PT, U.K.
References 1 Fletcher, G.H. Hypofractionation: lessons from complications. Radiother. Oncol. 20: 10-15, 1991. 2 Henk, J.M. and James, K.W. Comparative trial of large and small fractions in the radiotherapy of head and neck cancer. Clin. Radiol. 29: 611-616, 1978. 3 Henk, J. M., Kunkler, P. B., Shah, N. K., Smith, C. W., Sutherland, W. H, and Wassif, S.B. Hyperbaric oxygen in radiotherapy of head and neck carcinoma. Interim report of a controlled clinical trial. Clin. Radiol. 21: 223-231, 1970. 4 Wiernik, G., Alcock, C. J., Bates, T. D., Berry, R. J., Brindle, J. M., Dalby, J. E., Fowler, J. F., Gajek, W.R., Goodman, S., Haybittle, J. L., Henk, J. M., Hopewell, J. W., Howard, N., Lindup, R., Phillips, D. L., Pointon, R. S., Rezvani, M. and Tobias, T.S. First interim progress report on the second British Institute of Radiology fractionation study. Br. J. Radiol. 62: 450-456, 1989. 5 Wiernik, G., Alcock, C. J., Bates, T. D., Brindle, J. M., Fowler, J. F., Gajek,
W. R., Goodman, S., Haybittle, J. L., Henk, J. M., Hopewell, J. W., Hunter, R. D., Lindup, R., Phillips, D. L. and Rezvani, M. Final report on the second British Institute of Radiology Fractionation Study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngopharynx. Br. J. Radiol. 64, 1991 (in press). 6 Wiernik, G., Bates, T.D., Bleehen, N.M., Brindle, J.M., Bullimore, J., Fowler, J.F., Haybittle, J.L., Howard, N., Laing, A.H., Lindup, R., McGurk, F., Phillips, D. L. and Rezvani, M. Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx. Br. J. Radiol. 63: 169-180. 7 Weissberg, J. B., Son, Y. H., Percarpio, B. and Fischer, J.J. Randomised trial of conventional versus high fractional dose radiation therapy in the treatment of advanced head and neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 8: 179-185, 1982.
286 R A D I O N 00873
Letter to the Editors HYPOFRACTIONATION:
LESSONS TIONS
FROM
COMPLICA-
To the Editors, In his enthusiasm to castigate hypofractionation, Fletcher [1] seems to have misinterpreted the clinical trials of fractionation in head and neck cancer conducted in the U.K. The first BIR trial in larynx and hypopharynx did indeed consider the end points of local tumour control and late morbidity in addition to survival [5]. 734 patients were followed for 10 years and no difference between 3 fractions per week and 5 fractions per week could be detected for any of these end points. The second BIR trial [4] compared short (3-4 weeks) with long (6-7 weeks) treatment. Again, no difference in local control was found, but the short treatment time group in which the fraction size averaged 3 Gy had a lower late morbidity rate which is now statistically significant [5]. The Cardiff trial [2] was conducted on patients with poor performance status who were unfit for treatment in hyperbaric oxygen. The original aim of this was to test the hypothesis that the results of the first M R C hyperbaric oxygen trial [3] were invalid, because the 10 fraction regime given to the control group would give poorer results than the more conventional 5 times per week treatment over 6 weeks. The patient material was indeed heterogenous, but the patients were matched into pairs by site and stage of disease, one of each pair being randomly allocated to 10 fractions and the other
to 30 fractions. All that can be said of this trial is that it failed to provide evidence in favour of the original hypothesis tested; however, a rather similar trial at Yale produced the same result [7]. It is certainly true that some treatment with large fractions has caused severe late sequelae. Nevertheless, the necessity to keep fraction sizes to a maximum of 2 Gy has never been confirmed in randomised controlled clinical trials. Comparison of fractionation schemes requires adjustment of total dose so that late normal tissue effects are the same. In randomised trials in which this has been achieved, conventional radiotherapy with 2 Gy per day fractions has so far not been demonstrated to yield better tumour control than shorter courses of treatment using larger fraction sizes in either breast or head and neck cancer. Sincerely, J. M. Henk (received 20 March 1991, accepted 11 June 1991) On behalf of the
The Royal Marsden Hospital Downs Road, Sutton, Surrey SM2 5PT, U.K.
References 1 Fletcher, G.H. Hypofractionation: lessons from complications. Radiother. Oncol. 20: 10-15, 1991. 2 Henk, J.M. and James, K.W. Comparative trial of large and small fractions in the radiotherapy of head and neck cancer. Clin. Radiol. 29: 611-616, 1978. 3 Henk, J. M., Kunkler, P. B., Shah, N. K., Smith, C. W., Sutherland, W. H, and Wassif, S.B. Hyperbaric oxygen in radiotherapy of head and neck carcinoma. Interim report of a controlled clinical trial. Clin. Radiol. 21: 223-231, 1970. 4 Wiernik, G., Alcock, C. J., Bates, T. D., Berry, R. J., Brindle, J. M., Dalby, J. E., Fowler, J. F., Gajek, W.R., Goodman, S., Haybittle, J. L., Henk, J. M., Hopewell, J. W., Howard, N., Lindup, R., Phillips, D. L., Pointon, R. S., Rezvani, M. and Tobias, T.S. First interim progress report on the second British Institute of Radiology fractionation study. Br. J. Radiol. 62: 450-456, 1989. 5 Wiernik, G., Alcock, C. J., Bates, T. D., Brindle, J. M., Fowler, J. F., Gajek,
W. R., Goodman, S., Haybittle, J. L., Henk, J. M., Hopewell, J. W., Hunter, R. D., Lindup, R., Phillips, D. L. and Rezvani, M. Final report on the second British Institute of Radiology Fractionation Study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngopharynx. Br. J. Radiol. 64, 1991 (in press). 6 Wiernik, G., Bates, T.D., Bleehen, N.M., Brindle, J.M., Bullimore, J., Fowler, J.F., Haybittle, J.L., Howard, N., Laing, A.H., Lindup, R., McGurk, F., Phillips, D. L. and Rezvani, M. Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx. Br. J. Radiol. 63: 169-180. 7 Weissberg, J. B., Son, Y. H., Percarpio, B. and Fischer, J.J. Randomised trial of conventional versus high fractional dose radiation therapy in the treatment of advanced head and neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 8: 179-185, 1982.