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Session: Pre-Clinical Modeling [Return to Session]

A Mechanistic Radiotherapy Tumor Response Model Predicts Primer Fractions Would Significantly Improve Local Control

J. Jeong1*, Z.A.R. Gouw2, J.-J. Sonke2, J.O. Deasy1, (1) Memorial Sloan Kettering Cancer Center, New York, NY, (2) Netherlands Cancer Institute, Amsterdam, NL


TU-D1030-IePD-F4-3 (Tuesday, 7/12/2022) 10:30 AM - 11:00 AM [Eastern Time (GMT-4)]

Exhibit Hall | Forum 4

Purpose: Conventional radiotherapy practice assumes that fractions should be delivered over fixed, or nearly fixed intervals (e.g. ‘daily Fx with weekend breaks’). The underlying assumption that this is the best way to maximize TCP has not been thoroughly tested. Here, we use a validated mechanistic tumor simulation program to investigate various temporally varying fractionation schedules, searching for an optimal schedule.

Methods: Using a previously developed tumor response model that was validated for early stage lung cancer for all published fractionation results (Jeong et al., Clin Cancer Res 2017), 8 different clinically feasible fraction/dose combinations (2Gyx35, 3Gyx20, 4Gyx15, 5Gyx10, 7Gyx6, 8Gyx5, 10Gyx4, and 12Gyx5) were tested with differing time delays between fractions and compared to the standard 5fx/weekday schedule; the best fractionation schedule was found for each fractionation. For 6fx or less schedules, all possible combinations of weekday schedules within 10 weeks were simulated; for longer fractionations (10fx or more), the best schedules were found through random search, due to the enormous number of total possible combinations.

Results: For 2Gy fractionation consistent weekday fractionation was found to be optimal. However, for other fraction/dose combinations, optimal schedules were found that predict an increase in TCP, related to the reoxygenation process. For 6fx or less, the best schedules were found with one initial fraction (termed a “primer shot”) followed by a 2-week gap (during which full reoxygenation occurs), with remaining fractions delivered daily, resulting in a significant 1.27-1.75 times increase of TCP. For 10-20fx, initial two to five sparsely spaced fractions before reoxygenation following rest of fractions delivered daily lead to the highest TCPs.

Conclusion: The results suggest that there are improved fractionation schedules depending on fraction size, except for conventional 2Gy per weekday deliveries. With an increased use of hypofractionation treatment, this effect should be tested in preclinical and potentially clinical settings.


Not Applicable / None Entered.


TH- Radiobiology(RBio)/Biology(Bio): RBio- LQ/TCP/NTCP/outcome modeling

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