Purpose: Stereotactic radiosurgery (SRS) is a standard treatment modality for intracranial metastases. While small lesions are preferably treated in a single fraction, large metastases must be temporally fractionated to reduce dose toxicities in normal tissues. In this work, an algorithm for determining the best trade-off between single-fraction and hypofractionated SRS for the treatment of multiple brain metastases is developed and demonstrated.
Methods: Non-coplanar IMRT plans are created to obtain spatial dose distributions for the treatment of each metastasis. We then assume that each metastasis is either treated to the full dose in one of the fractions (spatial fractionation) or is fractionated uniformly over all fractions (temporal fractionation). The optimal fractionation scheme is obtained by solving a binary quadratic optimization problem, which, for a fixed tumor BED, minimizes an equally weighted sum of the mean cumulative biologically effective doses (BEDα/β) to the whole brain and to a 5 mm-thick rim structure around the metastases. The algorithm is demonstrated for a clinical case consisting of twenty-nine brain metastases of varying sizes to be treated with a BED10Gy of 45 Gy.
Results: A four-fraction SRS plan is computed with the proposed fractionation optimization algorithm and compared to two SRS plans treating all metastases with one and four uniform fractions, respectively. The optimal fractionation scheme suggests the temporal fractionation of large metastases and the spatial fractionation of smaller lesions, leading to mean BED2Gy of 14.90 Gy and 74.96 Gy in the healthy brain and rim structure, respectively. Single-fraction and hypofractionated SRS plans achieve mean BED2Gy in the healthy brain and rim structure of 20.18 Gy and 90.59 Gy, and 18.48 Gy and 72.17 Gy, respectively.
Conclusion: The proposed algorithm allows to optimally combine spatial and temporal fractionation for different lesions, potentially outperforming current state-of-the-art uniform fractionation schemes for the treatment of multiple intracranial metastases.
Funding Support, Disclosures, and Conflict of Interest: This work was supported by grant Spatiotemporal fractionation in radiotherapy (310030_189285/1) of the Swiss National Science Foundation. This material is based upon work supported by the National Science Foundation under Grant No. DMN-1847865.