Abstract
Simple SummaryIn the multi-modal treatment of brain metastasis (BM), the role of systemic therapy has undergone a recent revolution. Due to the development of multiple agents with modest central nervous system penetration of the blood-brain barrier, targeted therapies and immune checkpoint inhibitors are increasingly being utilized alone or in combination with radiation therapy. However, the adoption of sequential or concurrent strategies varies considerably, and treatment strategies employed in clinical practice have rapidly outpaced evidence development. Therefore, this review critically analyzes the data regarding combinatorial approaches for a variety of systemic therapeutics with stereotactic radiosurgery and provides an overview of ongoing clinical trials.Brain metastasis (BM) represents a common complication of cancer, and in the modern era requires multi-modal management approaches and multi-disciplinary care. Traditionally, due to the limited efficacy of cytotoxic chemotherapy, treatment strategies are focused on local treatments alone, such as whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and resection. However, the increased availability of molecular-based therapies with central nervous system (CNS) penetration now permits the individualized selection of tailored systemic therapies to be used alongside local treatments. Moreover, the introduction of immune checkpoint inhibitors (ICIs), with demonstrated CNS activity has further revolutionized the management of BM patients. The rapid introduction of these cancer therapeutics into clinical practice, however, has led to a significant dearth in the published literature about the optimal timing, sequencing, and combination of these systemic therapies along with SRS. This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis.
Highlights
Brain metastases (BM) represent the most common intracranial neoplasm in adults and occur in approximately 20–40% of all cancer patients [1]
Cagney et al reported the outcomes of patients treated with pemetrexed and stereotactic radiosurgery (SRS) for lung cancer BM, and found that the combination was associated with a r and SRS for lung cancer BM, and found that the combination was associated with a reduced duced likelihood of developing new brain metastases (p = 0.006) and a reduced need f likelihood of developing new brain metastases (p = 0.006) and a reduced need for brainbrain-directed salvage Radiation therapy (RT) (p = 0.005) [32]
There needs to be a standardized inclusion of patients with BM on clinical trials testing novel agents, with a key effort to include those with treated or stable disease, active BM, and leptomeningeal disease
Summary
Brain metastases (BM) represent the most common intracranial neoplasm in adults and occur in approximately 20–40% of all cancer patients [1]. BM can be managed with systemic therapy either prior to, concomitantly, or after RT, and various combinations of RT with systemic therapies are being explored to improve both local and extracranial disease control, as well as overall survival (OS). This necessitates effective management strategies from multidisciplinary teams, as treatment decisions must balance the risk of recurrence/progression with treatment-related side effects. In this review, we summarize the data from recent studies and clinical trials supporting the use of BM-directed systemic therapies, such as chemotherapy, targeted therapy, and immunotherapy, that have been completed or are currently being investigated, and their integration with SRS for the treatment of BM
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