Proliferation Saturation Index to Simulate Adaptive Radiation Fractionation in HPV-Associated Oropharyngeal Cancer
Year: 2023
Type: article
Abstract: Purpose/Objective(s) In current clinical practice for fractionated radiotherapy (RT) patients receive a fixed fractionation protocol throughout radiation course. Radiation oncology has not yet moved toward adaptive fractionation to change RT fractionation based on individual patients' response dynamics. We have previously introduced a novel mathematical and imaging biomarker, proliferation saturation index (PSI), to simulate and evaluate tumor volume dynamics during therapy. Robust tumor volume reduction was associated with lower PSI, and PSI has been utilized to select fractionation schedules for the first mathematical model informed clinical trial. Here we simulate the possibility of adapting the selection of RT fractionation on a week-by-week basis by utilizing a dynamic weekly estimation of PSI. Materials/Methods We generated a cohort of in silico patients by sampling from distributions of PSI, radiosensitivity, and growth rate parameters. These distributions were by pre-treatment and on-treatment tumor volume dynamics from a prospective clinical trial (NCT03656133), where 49 HPV+ OPC patients were treated with either 2 Gy daily fractions up to a total of 70 Gy if PS<0.75, or hyperfractionation at 1.2 Gy b.i.d. up to a total of 66 Gy for patients with PSI ≥ 0.75. We then simulated standard (2 Gy q.d.) and hyperfractionated (1.2 Gy b.i.d) for 1-8 weeks of RT to build a library of response dynamics for the different parameter combinations and treatment durations. This library was then used to estimate optimal adaptive fractionation schedules for the in silico patients that maximized tumor volume reduction and minimized total RT dose. Results We found that PSI evolved towards lower values (i.e., higher proliferative fractions) over the fractionation RT treatment course. For patients that began treatment with standard fractionation, no adaption was found to be superior to uniform fractionation. For selected patients who began treatment with hyperfractionation, however, the optimal fractionation schedule included a period of upfront hyperfractionated RT followed by a switch to standard fractionation at different times during their treatment course. Conclusion The results of this study suggest that in addition to selecting the best initial fractionation schedule, a novel approach to personalize RT for OPC patients may include adapting the fractionation based on early treatment response dynamics. These results motivate validation in prospective clinical trials.
Institution: Moffitt Cancer Center
Language: English
Subfield: Radiation
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,900
OpenAlex ID: W4387206735