Estimate of the impact of FDG-avidity on the dose required for head and neck radiotherapy local control.

BACKGROUND AND PURPOSE Although FDG-avid tumors are recognized as a potential target for dose escalation, there is no clear basis for selecting a boost dose to counter this apparent radioresistance. Using a novel analysis method, based on the new concept of an outcome-equivalent dose, we estimate the extra dose required to equalize local control between FDG-avid and non-avid head and neck tumors. MATERIALS AND METHODS Based on a literature review, five reports of head and neck cancer (423 patients in total), along with an internal validation dataset from our institution (135 oropharynx patients), were used in this analysis. To compensate for the heterogeneity among multi-institutional patient cohorts and corresponding treatment techniques, local control data of the cohorts were fit to a single dose-response curve with a clinically representative steepness (γ50=2), thereby defining an 'outcome-equivalent dose' (OED) for each institutional cohort. Separate dose-response curves were then determined for the FDG-avid and FDG-non-avid patient cohorts, and the ratio of TD50 (tumor dose required for 50% of control) values between the high- and low-FDG-uptake groups (TD50,high/TD50,low) was estimated, resulting in an estimated metabolic dose-modifying factor (mDMF) due to FDG-avidity. RESULTS For individual datasets, the estimated mDMFs were found to be in the range of 1.07-1.62, decreasing if the assumed slope (γ50) increased. Weighted logistic regression for the six datasets resulted in a mDMF of 1.19 [95% CI: 1.04-1.34] for a γ50 value of 2, which translates to a needed dose increase of about 1.5Gy per unit increase in the maximum standardized uptake value (SUVm) of FDG-PET [95% CI: 0.3-2.7]. Assumptions of lower or higher γ50 values (1.5 or 2.5) resulted in slightly different mDMFs: 1.26 or 1.15, respectively. A validation analysis with seven additional datasets, based on relaxed criteria, was consistent with the estimated mDMF. CONCLUSIONS We introduced a novel outcome-equivalent dose analysis method to estimate the dose-response modifying effect of FDG uptake variation. To reach equal response rates, FDG-avid tumors are likely to require 10% to 30% more dose than FDG-non-avid tumors. These estimates provide a rational starting point for selecting IMRT boosts for FDG-avid tumors. However, independent tests and refinements of the estimated dose-modifying effect, using high-quality prospective clinical trial data, are needed.