Spatiotemporal fractionation schemes for stereotactic radiosurgery of multiple brain metastases

Abstract

BackgroundStereotactic radiosurgery (SRS) is an established treatment for patients with brain metastases (BMs). However, damage to the healthy brain may limit the tumor dose for patients with multiple lesions.PurposeIn this study, we investigate the potential of spatiotemporal fractionation schemes to reduce the biological dose received by the healthy brain in SRS of multiple BMs, and also demonstrate a novel concept of spatiotemporal fractionation for polymetastatic cancer patients that faces less hurdles for clinical implementation.MethodsSpatiotemporal fractionation (STF) schemes aim at partial hypofractionation in the metastases along with more uniform fractionation in the healthy brain. This is achieved by delivering distinct dose distributions in different fractions, which are designed based on their cumulative biologically effective dose () such that each fraction contributes with high doses to complementary parts of the target volume, while similar dose baths are delivered to the normal tissue. For patients with multiple brain metastases, a novel constrained approach to spatiotemporal fractionation (cSTF) is proposed, which is more robust against setup and biological uncertainties. The approach aims at irradiating entire metastases with possibly different doses, but spatially similar dose distributions in every fraction, where the optimal dose contribution of every fraction to each metastasis is determined using a new planning objective to be added to the BED‐based treatment plan optimization problem. The benefits of spatiotemporal fractionation schemes are evaluated for three patients, each with >25 BMs.ResultsFor the same tumor BED10 and the same brain volume exposed to high doses in all plans, the mean brain BED2 can be reduced compared to uniformly fractionated plans by 9%–12% with the cSTF plans and by 13%–19% with the STF plans. In contrast to the STF plans, the cSTF plans avoid partial irradiation of the individual metastases and are less sensitive to misalignments of the fractional dose distributions when setup errors occur.ConclusionSpatiotemporal fractionation schemes represent an approach to lower the biological dose to the healthy brain in SRS‐based treatments of multiple BMs. Although cSTF cannot achieve the full BED reduction of STF, it improves on uniform fractionation and is more robust against both setup errors and biological uncertainties related to partial tumor irradiation.

A new approach to combined proton-photon therapy for metastatic cancer patients

“…Compared to the work of Gao (2019), the simultaneous optimization of IMPT and IMRT plans is performed based on the cumulative BED, thereby explicitly considering also the fractionation effect. Finally, this study also extends on the work of Torelli et al (2023), including the combination of multiple particle types.…”

“…In this way, better trade-offs can be achieved between increasing the proton dose contribution to reduce the integral dose to critical organs, and using photon beams to fractionate the dose in the normal tissue in between the metastases. In addition, compared to the work of Unkelbach et al (2018), the proposed approach is potentially more robust against misalignments of the proton and photon dose distributions, as dose gradients within the individual metastases are avoided and inter-fraction setup errors can be accounted for by using a safety margin (Torelli et al 2023). Although similar results could be obtained using previously suggested stochastic optimization methods for CPPT that consider multiple errors scenarios for setup and range errors (Fabiano et al 2020b, Torelli 2024, using the proposed approach robustness is achieved by the evaluation of a single additional planning objective and is therefore computationally more efficient.…”

“…However, the absolute dose contribution of each fraction to every individual metastasis is allowed to vary in between the photon and proton fractions, to best achieve the desired dosimetric goals. This is achieved by introducing the following additional planning objective, which has previously been proposed by Torelli et al (2023) for photon-only treatments:…”

“…In this way, in fact, it is possible to reduce the physical dose needed to achieve tumor control, while still achieving some degree of fractionation in the normal tissue in between the metastases. To relate the current work to the study of Torelli et al (2023), an additional CPPT plan was generated for all patients with the following characteristics:…”

“…For this reason, in this study we consider a novel approach to CPPT for metastatic cancer patients, which expands on the work of ten Eikelder et al (2019) by jointly optimizing IMRT and IMPT plans, while being more robust against setup uncertainties compared to the method of Unkelbach et al (2018). This approach, which has first been proposed by Torelli et al (2023) for photon-based SRS of multiple brain metastases, consists of treating different metastases to possibly different doses in the IMRT and IMPT fractions, while constraining the spatial dose distribution within each individual metastatic lesion to be similar in every fraction. In this way, some of the metastases can be treated with a high dose in a single proton fraction, what allows exploiting the superior dosimetric properties of proton beams and achieving the desired level of tumor control with a lower physical dose.…”