Evaluation of indirect damage and damage saturation effects in dose-response curves of hypofractionated radiotherapy of early-stage NSCLC and brain metastases

Abstract

Background: In this work we aim to investigate the possible contribution of indirect damage and damage saturation to tumor control probabilities (TCP) obtained with SBRT/SRS treatments for early-stage NSCLC and brain metastases. Methods: We have constructed a dataset of early-stage NSCLC and brain metastases response to different fractionations. Dose-response curves were fitted to models based on the linear-quadratic (LQ), the linear-quadratic-linear (LQL), and phenomenological modifications of the LQ model to account for indirect cell damage. We used the Akaike-Information-Criterion formalism to compare performance, and studied the stability of the results with changes in fitting parameters and perturbations on dose/TCP values. Results: In NSCLC, a modified LQ model with a beta-term increasing with dose yields better results than the LQ model. This rank remains consistent when different fitting parameters are changed, and only the inclusion of very fast accelerated proliferation can eliminate the superiority of the modified LQ. In brain, the LQL model yields the best-fits, and the ranking is not affected by variations of fitting parameters or dose/TCP perturbations. Conclusions: A modification of the LQ model with a beta-term increasing with dose provides better fits to NSCLC dose-response curves. For brain metastases, the LQL provides the best fit. This may be interpreted as a net contribution of indirect damage in NSCLC, and damage saturation in brain metastases. The results for NSCLC are borderline significant, while those for brain are clearly significant. Our results can assist on the design of optimal radiotherapy for NSCLC and brain metastases, aiming at avoiding over/under-treatment. Dose prescription to such tumors may be re-evaluated according to the reported evidence.

Evaluation of indirect damage and damage saturation effects in dose–response curves of hypofractionated radiotherapy of early-stage NSCLC and brain metastases

“…Information about each treatment schedule is summarised in Tables SM1 and SM2. Further information is provided in a datasheet available from [33].…”