Radiobiological Evaluation of Combined Gamma Knife Radiosurgery and Hyperthermia for Pediatric Neuro-Oncology

SIMPLE SUMMARY: This study proposes a novel strategy in brain cancer management. Stereotactic radiosurgery delivered by the Gamma Knife was combined with hyperthermia. For the radiobiological modelling of this synergistic treatment modality, we used the linear-quadratic model with temperature-dependent parameters to assess the potential enhancement of the therapeutic outcome. The results indicate that focused intracranial heating can be used to boost the dose to the target. Alternatively, one can conclude that for the same therapeutic effect, hyperthermia can help to minimize the dose undesirably delivered to healthy tissues. This study is also the first to advocate a combination of stereotactic radiosurgery with focused heating and motivates the future development of hyperthermia systems for brain cancer treatment. ABSTRACT: Combining radiotherapy (RT) with hyperthermia (HT) has been proven effective in the treatment of a wide range of tumours, but the combination of externally delivered, focused heat and stereotactic radiosurgery has never been investigated. We explore the potential of such treatment enhancement via radiobiological modelling, specifically via the linear-quadratic (LQ) model adapted to thermoradiotherapy through modulating the radiosensitivity of temperature-dependent parameters. We extend this well-established model by incorporating oxygenation effects. To illustrate the methodology, we present a clinically relevant application in pediatric oncology, which is novel in two ways. First, it deals with medulloblastoma, the most common malignant brain tumour in children, a type of brain tumour not previously reported in the literature of thermoradiotherapy studies. Second, it makes use of the Gamma Knife for the radiotherapy part, thereby being the first of its kind in this context. Quantitative metrics like the biologically effective dose (BED) and the tumour control probability (TCP) are used to assess the efficacy of the combined plan.