Altered fractionated radiotherapy in head and neck cancer

Abstract

We believe that a few important observations are worth considering when interpreting the results of the MARCH meta-analysis of hyperfractionated or accelerated radiotherapy in head and neck cancer (Sept 2, p 843).1Bourhis J Overgaard J Audry H et al.Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.Lancet. 2006; 368: 843-854Summary Full Text Full Text PDF PubMed Scopus (828) Google Scholar First, patients with stage I–II cancers, who comprised 26% of the total, benefited minimally from altered fractionation (hazard ratio close to unity). The greatest benefit was for those with stage III, for whom the relative risk of death was reduced by more than 20%. Hence, to generalise the benefit of altered fractionation across all stages might not be entirely correct. Second, age and performance status had a substantial effect on outcome in patients younger than 50 years, with good performance status deriving maximum benefit from altered fractionation. However, this group of patients can also tolerate aggressive chemoradiotherapy, and in view of the comparable benefits,1Bourhis J Overgaard J Audry H et al.Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.Lancet. 2006; 368: 843-854Summary Full Text Full Text PDF PubMed Scopus (828) Google Scholar, 2Bourhis J Amand C Pignon JP on behalf of the MACH-NC collaborative groupUpdate of MACH-NC (Meta-analysis of Chemotherapy in Head and Neck Cancer) database focused on concomitant chemo-radiotherapy.Proc Am Soc Clin Oncol. 2004; 22 (abstr 5505): 488sGoogle Scholar whether it is best to offer them chemoradiation or altered fractionation remains unclear. The only published trial3Olmi P Crispino S Fallai C et al.Locoregionally advanced carcinoma of oropharynx: conventional radiotherapy versus hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy: a multicenter randomized trial.Int J Radiat Biol Phys. 2003; 55: 78-92Summary Full Text Full Text PDF PubMed Scopus (105) Google Scholar to compare the two showed no clear benefit of one over the other. There is also a case for cost-benefit analysis, particularly in resource-limited settings. In this context we are trying to explore the possibility of an indirect comparison between the two approaches from the respective meta-analyses. Finally, altered fractionation was more efficient in reducing local failures (hazard ratio 0·77, p<0·001), than nodal failures (0·87, p<0·01), as also seen in the MACH-NC analysis.2Bourhis J Amand C Pignon JP on behalf of the MACH-NC collaborative groupUpdate of MACH-NC (Meta-analysis of Chemotherapy in Head and Neck Cancer) database focused on concomitant chemo-radiotherapy.Proc Am Soc Clin Oncol. 2004; 22 (abstr 5505): 488sGoogle Scholar Biological factors such as clonogen density, hypoxic fraction, labelling index, potential doubling time, and survival fraction at 2 Gy affect radiocurability. Since large nodes are likely to harbour more radioresistant clones, radiobiological modelling should also include nodal tissues rather than being restricted to primary tumour. We declare that we have no conflict of interest. Altered fractionated radiotherapy in head and neck cancer – Authors' replyWe agree with C Srinivas and colleagues that it is difficult to extrapolate the results of the Meta-Analysis of Radiotherapy in Carcinoma of Head and Neck (MARCH) to stage I and II, because 99% of stage I and 58% of stage II patients were included in the group given accelerated fractionation without total dose reduction. This group represents 54% of the MARCH population (see webtable 4 of original report). Full-Text PDF