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Association between systemic treatment with immune checkpoint inhibitor therapy in renal cell carcinoma and reduced risk of brain metastasis development

Mark Damante, Kristin Huntoon, David Gibbs, Dante Pezzutti, Thomas Olencki, and J. Bradley Elder

OBJECTIVE

Immune checkpoint inhibitor (ICI) efficacy in the treatment of metastatic renal cell carcinoma (RCC) without brain metastases (BMs) is well established in several clinical trials; however, patients with BMs were typically excluded from these trials. Therefore, the efficacy of ICI in the treatment or prevention of BM remains unclear. The primary aim of the study was to address the efficacy of ICI in treatment of patients with RCC BMs compared with patients receiving targeted therapies. A secondary aim was to evaluate the risk of RCC BM development among patients who received ICI versus targeted therapies early in their treatment course.

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A retrospective single-center review between 2011 and 2018 identified 425 patients treated for metastatic RCC. The study group included patients who received ICI and/or targeted therapies during their disease. Data analyzed included demographic information, systemic treatments, overall survival from RCC diagnosis (OSRCC) and from BM diagnosis (OSBM), and BM development. Fisher’s exact test was used to evaluate the frequency of BM occurrence. Survival was assessed using Kaplan-Meier curves and log-rank tests.

RESULTS

Of the 425 patients, 125 received ICI and 300 were treated with molecular targeted agents only during their clinical course. BMs occurred in 113 (9.5%) of the 425 patients. Among patients with BMs, OSRCCwas improved with the use of ICI (77.2 vs 25.2 months, p < 0.001), with 1-, 2-, and 5-year survival rates of 93.9%, 81.8%, and 62.6%, respectively. The use of ICI was associated with increased OSBM(21.7 vs 8.9 months, p = 0.001). The rate of BM development was lower when patients were treated with ICI (8/100 [8.0%]) compared with targeted therapy (47/267 [17.6%]) (OR 0.41, 95% CI 0.18–0.89; p = 0.021).

CONCLUSIONS

ICI was associated with improved OSRCCand OSBMin patients with BMs and decreased the probability of BM development in patients with metastatic RCC. Prospective trials are needed to further evaluate optimal use of ICI in treatment of RCC BMs.

InNeurosurgical Focus Volume 55 (2023): Issue 2 (Aug 2023): Update on Brain Metastases

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Epileptic versus neuro-oncological focus of management in pediatric patients with concurrent primary brain lesion and seizures: a systematic review

Maxwell D. Gruber, Jonathan Pindrik, Mark Damante, Lauren Schulz, Ammar Shaikhouni, and Jeffrey R. Leonard

OBJECTIVE

Seizures can be a debilitating manifestation of underlying neoplastic intracranial pathology. Existing literature offers a paucity of scientific consensus regarding risk factors, seizure semiology, operative techniques, and tumor characteristics in pediatric patients with a concurrent diagnosis of primary intracranial neoplasm and seizures. To address the limited evidence in current literature, the authors systematically reviewed published literature on current clinical characteristics and management strategies for patients presenting concurrently with seizures and a newly diagnosed brain lesion, while aiming to synthesize a potential management protocol or set of recommendations for these patients.

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An initial search revealed 792 papers, of which 196 studies were excluded, leaving 596 studies available for abstract review. After further stratification, 546 studies were eliminated, leaving 50 studies for eligibility assessment. Of the 50 studies, 12 met the criteria for outcome extraction.

RESULTS

The results indicate that patients with a mean age of 9 years with a newly diagnosed brain tumor and presenting symptoms of seizure are likely to present with daily seizures of the complex partial subtype, with the most likely primary epileptogenic and neoplastic foci occurring in the temporal lobe. The most common tumor subtypes were low-grade gliomas, ganglioglioma, dysembryoplastic neuroepithelial tumor, or astrocytoma. With the aim of gross-total resection, 77.54% of patients are likely to achieve seizure freedom.

CONCLUSIONS

This study highlights the demographic, clinical, seizure, tumor, and postoperative outcomes for pediatric patients presenting with a primary brain tumor and concurrent seizures. Further prospective multicenter studies are necessary to understand and compare varying treatment approaches and to develop standardized guidelines for these patients, with the goal of optimizing neuro-oncological and seizure-related outcomes.

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