Radiobiological considerations in the design of fractionation strategies for intensity-modulated radiation therapy of head and neck cancers

Purpose: The dose distributions of intensity-modulated radiotherapy (IMRT) treatment plans can be shown to be significantly superior in terms of highe r conformality if designed to simultaneously deliver high dose to the prima ry disease and lower dose to the subclinical disease or electively treated regions. We use the term "simultaneous integrated boost" (SIB) to define su ch a treatment. The purpose of this paper is to develop suitable fractionat ion strategies based on radiobiological principles for clinical trials and routine use of IMRT of head and neck (HN) cancers. The fractionation strate gies are intended to allow escalation of tumor dose while adequately sparin g normal tissues outside the target volume and considering the tolerances o f normal tissues embedded within the primary target volume. Methods and Materials: IMRT fractionation regimens are specified in terms o f "normalized total dose" (NTD), i.e.,the biologically equivalent dose give n in 2 Gy/fx. A linear-quadratic isoeffect formula is applied to convert NT Ds into "nominal" prescription doses. Nominal prescription doses for a high dose to the primary disease, an intermediate dose to regional microscopic disease, and lower dose to electively treated nodes are used for optimizing IMRT plans. The resulting nominal dose distributions are converted back in to NTD distributions for the evaluation of treatment plans. Similar calcula tions for critical normal tissues are also performed. Methods developed wer e applied for the intercomparison of several HN treatment regimens, includi ng conventional regimens used currently and in the past, as well as SIE str ategies, This was accomplished by comparing the biologically equivalent NTD values for the gross tumor and regional disease, and bone, muscle, and muc osa embedded in the gross tumor volume. Results: (1) A schematic HN example was used to demonstrate that dose distr ibutions for SIB IMRT are more conformal compared to dose distributions whe n IMRT is divided into a large-field phase and a boost phase, Both were sho wn to be significantly superior compared to dose distributions obtained usi ng conventional beams for the large-field phase followed by IMRT for the bo ost phase, (2) The relationship between NTD and nominal dose for HN tumors was found to be quite sensitive to the choice of tumor clonogen doubling ti me but relatively insensitive to other parameters. (3) For late effect norm al tissues embedded in the tumor volume and assumed to receive the same dos e as the tumor, the biologically equivalent NTD for the SIE IMRT may be sig nificantly higher. (4) Normal tissues outside the target volume receive low er dose due to the higher conformality of the IMRT plans, The biologically equivalent NTDs are even lower due to the lower dose per fraction in the SI E strategy. Conclusions: IMRT dose distributions are most conformal when designed to be delivered as SIE. Using isoeffect radiobiological relationships and publis hed HN data, fractionation strategies can be designed in which the nominal dose levels to the primary, regional disease and electively treated volumes are appropriately adjusted, each receiving different dose/fx, Normal tissu es outside the treated volumes are at reduced risk in such strategies since they receive lower total dose as well as lower dose/fx. However, the late effect toxicities of tissues embedded within the primary target volume and assumed to receive the same dose as the primary may pose a problem. The eff icacy and safety of the proposed fractionation strategies mill need to be e valuated with careful clinical trials, (C) 2000 Elsevier Science Inc.