Elsevier

Radiotherapy and Oncology

Volume 50, Issue 1, 1 January 1999, Pages 25-28
Radiotherapy and Oncology

Overall treatment time and the conventional arm of the CHART trial in the radiotherapy of head and neck cancer

https://doi.org/10.1016/S0167-8140(98)00116-9Get rights and content

Abstract

Background and purpose: An analysis of the 366 patients treated with conventional radiotherapy in the CHART randomized trial was performed to determine whether prolongation of treatment time had any influence on tumour control or survival and to assess if this could have influenced the results of the randomized comparison of CHART against conventional radiotherapy.

Method: After a preliminary analysis the cases were divided into two groups according to duration of treatment.

Results: Survival and primary tumour control showed small margins of deterioration when the 232 patients who had been treated up to 48 days were compared with 127 patients who had been treated in 49 or more days. These differences were not large with an estimated difference in 2-year survival of 8% and not conventionally statistically significant (P=0.25); furthermore, the survival difference was considerably reduced when the prognostic factors were taken into consideration in a Cox model.

Conclusion: With a mean difference in treatment duration of 5.8 days, the marginal differences observed between patients treated for longer and shorter times are compatible with that which has been suggested in previous publications for the prolongation of treatment time in head and neck cancer. We conclude that the randomized comparison of CHART with conventional radiotherapy is unlikely to be affected by conventionally treated patients who took longer than 48 days to complete their treatment.

Introduction

Prolongation of a course of radiotherapy is considered an important cause of treatment failure in head and neck and especially laryngeal cancer. Rapid tumour cell repopulation is believed to be the underlying mechanism [1], [15]. Evidence to support this hypothesis has been gained from a comparison of split-course treatment, involving a rest period with conventional treatment [10]. Despite an increase in dose achieved with the split course, no benefit in tumour control was achieved, suggesting that the prolongation of treatment time negated the advantage expected from an elevation of total dose. Mathematical analyses of data from a large number of series reporting tumour control probabilities with a range of doses and planned overall times have also given support to this hypothesis [16]; however, the assumptions involved have been criticized [2], [4]. A large number of retrospective analyses of the effect of treatment prolongation in cases attending for routine radiotherapy have shown considerable increases in the rate of failure [5], [6], [7], [8], [9], [14]. However, those patients who require longer treatment times may be those who have the poorest prognosis. Thus, the prolongation of treatment time may not be the cause of treatment failure itself, but rather be related to patients having a poorer prognosis who in turn will have more chance of treatment failure. Roberts et al. [13] analyzed data from two randomized clinical trials conducted by the British Institute of Radiology in order to overcome the problems of this selection bias in retrospective data. They found that the overall time of treatment was an important prognostic factor but their data were very heterogeneous as each of 17 centres chose its own regime and overall treatment times ranged from 18 to 56 days.

In the randomized controlled trial in head and neck cancer of CHART versus conventional radiotherapy, all patients in the conventional radiotherapy arm were given a daily dose of 2 Gy 5 days a week to a total dose of 66 Gy in 33 fractions [3]. Strict entry criteria governed all cases submitted to the trial and all factors which were possibly related to the prognosis were recorded prior to start of treatment. Therefore, the 366 patients treated conventionally present a well documented group of similarly treated cases where the influence of prolongation of treatment time could be studied. In the patients treated with CHART, only 4% exceeded the planned duration of 12 days. Conventional treatment was planned to be completed in 45 days but 35% were treated in 49 or more days. Therefore, it is possible that prolongation of treatment time in the conventional arm could have influenced the result of the randomized comparison of CHART with conventional radiotherapy. An analysis of the influence of overall treatment time upon the local control and survival has now been performed in the cases randomized to the conventional radiotherapy arm.

Section snippets

Methods

The randomized controlled trial comparing CHART with conventional radiotherapy included 918 patients with squamous cell carcinoma of the head and neck region who were entered in the period April 1990 to March 1995. A 3:2 randomization in favour of CHART led to 366 patients being allocated to conventional radiotherapy. A daily dose of 2 Gy was given to these patients 5 days a week (44 Gy in 22 fractions was given to a large volume and 22 Gy in 11 fractions was given to a small volume). The total

Results

A total of 366 patients were included in the conventionally treated arm but seven patients who were all treated in less than 45 days were found to have received less than 90% of their planned radiotherapy and so were not included in the analysis, leaving 359 patients. There was a non-symmetric distribution of treatment times (Fig. 1) and this precluded the use of treatment time as a continuous variable. In order to divide the patients into three groups of approximately equal size, those treated

Discussion

Only modest differences in survival and local tumour control were observed in this analysis of treatment time in the 366 patients treated with conventional radiotherapy in the CHART trial. However, the hazard ratio for survival was reduced from 1.19 to 1.09 in the Cox analysis, suggesting that, at least in part, prognostic factors account for some of the modest differences seen in survival. It is probable that some of these factors may have been influential in leading to the prolongation of

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