WE-AB-202-11: Radiobiological Modeling of Tumor Response During Radiotherapy Based On Pre-Treatment Dynamic PET Imaging Data.

PURPOSE: To evaluate the ability of a multiscale radiobiological model of tumor response to predict mid-treatment hypoxia images, based on pretreatment imaging of perfusion and hypoxia with [18-F]FMISO dynamic PET and glucose metabolism with [18-F]FDG PET.

METHODS: A mechanistic tumor control probability (TCP) radiobiological model describing the interplay between tumor cell proliferation and hypoxia (Jeong et al., PMB 2013) was extended to account for intra-tumor nutrient heterogeneity, dynamic cell migration due to nutrient gradients, and stromal cells. This extended model was tested on 10 head and neck cancer patients treated with chemoradiotherapy, randomly drawn from a larger MSKCC protocol involving baseline and mid-therapy dynamic PET scans. For each voxel, initial fractions of proliferative and hypoxic tumor cells were obtained by finding an approximate solution to a system of linear equations relating cell fractions to voxel-level FDG uptake, perfusion (FMISO K1 ) and hypoxia (FMISO k3 ). The TCP model then predicted their evolution over time up until the mid treatment scan. Finally, the linear model was reapplied to predict each lesion's median hypoxia level (k3 [med,sim]) which in turn was compared to the FMISO k3 [med] measured at mid-therapy.

RESULTS: The average k3[med] of the tumors in pre-treatment scans was 0.0035 min(-1) , with an inter-tumor standard deviation of σ[pre]=0.0034 min(-1) . The initial simulated k3 [med,sim] of each tumor agreed with the corresponding measurements within 0.1σ[pre]. In 7 out of 10 lesions, the mid-treatment k3 [med,sim] prediction agreed with the data within 0.3σ[pre]. The remaining cases corresponded to the most extreme relative changes in k3 [med].

CONCLUSION: This work presents a method to personalize the prediction of a TCP model using pre-treatment kinetic imaging data, and validates the modeling of radiotherapy response by predicting changes in median hypoxia values during treatment. Variations from predicted response may be a useful biomarker, which should be further explored. Partially supported by NIH grant #1 R01 CA157770-01A1 and a grant from Varian Corporation.