Surgically targeted radiation therapy (STaRT) trials for brain neoplasms: A comprehensive review

Abstract

The mainstays of radiation therapy include external beam radiation therapy (EBRT) and internally implanted radiation, or brachytherapy (BT), all with distinct benefits and risks in terms of local or distant tumor control and normal brain toxicities, respectively. GammaTile® Surgically Targeted Radiation Therapy (STaRT) attempts to limit the drawbacks of other BT paradigms via a permanently implanted, bioresorbable, conformable, collagen tile containing four uniform intensity radiation sources, thus preventing deleterious direct contact with the brain and optimizing interseed spacing to homogenous radiation exposure. The safety and feasibility of GammaTile® STaRT therapy was established by multiple clinical trials encompassing the spectrum of primary and secondary brain neoplasms, both recurrent and newly-diagnosed. Implantable GT tiles were FDA approved in 2018 for use in recurrent intracranial neoplasms, expanded to newly-diagnosed malignant intracranial neoplasms by 2020. The current spectrum of trials focuses on better defining the relative efficacy and safety of non-GT standard-of-care radiation strategies for intracranial brain neoplasm. We summarize the key design and eligibility criteria for open and future trials of GT therapy, including registries and randomized trials for newly-diagnosed and recurrent brain metastases as well as recurrent and newly-diagnosed glioblastoma in combination with approved therapies.

Keywords: brachytherapy; brain metastases; gamma tile; gliomas; meningiomas.

Fig. 1

GT STaRT seed placement and resulting Isodose distribution. Patient with a recurrent left parietal brain metastasis after prior whole-brain radiotherapy treated with resection and GT Cs-131 brachytherapy: The figure illustrates the placement of 6 seeds, each with an individual source strength of 3.5U (5.49mCi), to a cumulative seed strength of 21U (32.94mCi). Axial, sagittal, and coronal images of the postimplant CT of the brain demonstrate the resulting isodose distribution of this implant to a prescription dose of 60 Gy.

Fig. 2

Comparison of GT STaRT to other radiation modalities. Isodose distribution for a recurrent right parietal brain metastasis treated with resection and GT Cs-131 brachytherapy: Alternative external beam radiotherapy approaches, such as Gamma Knife radiosurgery, CyberKnife radiosurgery, and intensity-modulated proton therapy are illustrated to demonstrate the differences in isodose distribution amongst the radiotherapy modalities. All plans were normalized to cover the same target volume with an EQD₂ of 60Gy. A prospective comparative study is critical to understanding the clinical outcomes with each of these approaches.