What is the dose-limiting for altered radiotherapy for head and neck cancers - facts and doubts

Altered fractionation radiotherapy for head and neck produces locoregional benefit at the expence of an increased incidence and greater severity of acute reactions. This paper presents analysis of 21 data sets (2859 cases) including our own data of escalated and accelerated irradiation and aims to assess to what extent H & N mucosa is limiting to dose intensification by altered regimes. The rate and speed of dose accumulation is the most important determinant for early reactions. The analysis shows that there is no single predictor for severity of acute mucosal reactions, and among many fractionation parameters maximal relative Accumulated Normalized Dose (rAND max ) for week in which acute reaction reaches the peak of severity gives the best fit to all data, especially if α/β ratio is lower than 10 Gy. It may suggest that H & N mucosa is more sensitive to change in dose per fraction as it is generally accepted. Although mucosal reactions are more severe for altered fractionation regimes and troublesome for patients usually they are not beyond the limit of tolerance. After all, they are transient. It seems that the real dose-limiting factor is consequential late effects (CLE) which occur relatively early during follow-up and they may progress into permanent severe damage which significantly decreases the comfort and quality of life of the patients. For hybrids of accelerated – hyperfractionated regimes risk of CLE is low (<3.5%), however it increases to 15-20% for purely accelerated schedules. In order to avoid the risk of CLE, acute reactions should be regularly monitored during the treatment by precise and frequent scoring and recording of morphological changes and its severity.