Does fractionation in radiotherapy of head and neck cancer reach a summit or is there still a room for novel therapeutic strategies?

Abstract

The aim of this paper is to answer to the question whether various dose fractionation regimens are highly effective up to the summit of normal tissue tolerance. Data from 45 trials on altered fractionation, radio-response of the HPV(+) oropharyngeal cancer (OPC) and concurrent chemoradiation (11 533 data) have been selected from the published papers and re-analysed. Altered fractionation regimens showed an average therapeutic gain (TG) of local tumour control (LTC) of about 2.7% per each 1 izoGy2.0 above 65 Gy. For HPV(+) OPC, TG increased by 3–3.5%/1izoGy2.0. Concurrent chemoradiation for locally advanced H&N cancer produced about 60% LTC using 65 Gy (about 20% more than altered RT). Despite randomization, data sets in the trials remain clinically and biologically heterogeneous. It is not possible to separate the TG rate as the result of change in dose per fraction from that caused by changing the overall treatment time. This is major weakness of the trials. Moreover, the results are presented as an average value of the LTC or survival. The overstepped tolerance summit is very rarely precisely presented. It likely seems that the tolerance summit is not a single value and is only partly related to dose fractionation intensity, it mainly depends on radiosensitivity and the irradiation volume of normal tissue(s) and their potential repair capacity, and an activation of immunological defense. Finally, it is difficult to accept average trial’ results as evidence based guidelines for personalized radiotherapy for individual patients; what is more the individual tolerance summit is not universal and well quantified.