Leptomeningeal metastasis is an uncommon and typically late complication of cancer with a poor prognosis and limited treatment options. Diagnosis is often challenging, with nonspecific presenting symptoms ranging from headache and confusion to focal neurologic deficits, such as cranial nerve palsies. Standard diagnostic evaluation involves a neurologic examination, magnetic resonance imaging of the brain and spine with gadolinium, and cytologic evaluation of the cerebral spinal fluid. Therapy entails a multimodal approach focused on palliation with surgery, radiation, and/or chemotherapy, which may be administered systemically or directly into the cerebral spinal fluid. Limited trial data exist to guide treatment, and current regimens are based primarily on expert opinion. Although newer targeted and immunotherapeutic agents are under investigation and have shown promise, an improved understanding of the biology of leptomeningeal metastasis and treatment resistance as well as additional randomized controlled studies are needed to guide the optimal treatment of this devastating disease. Cancer 2018;124:21-35. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.30911 | DOI Listing |
Cancer Metab
January 2025
InnoBation Bio, Seoul, Republic of Korea.
Background: Leptomeningeal metastasis (LM) is a devastating complication of cancer that is difficult to treat. Thus, early diagnosis is essential for LM patients. However, cerebrospinal fluid (CSF) cytology has low sensitivity, and imaging approaches are ineffective.
View Article and Find Full Text PDFJ Natl Cancer Inst
January 2025
Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA.
Background: Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor.
Methods: A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM.
Acta Neuropathol Commun
January 2025
Department of Neurosurgery, University of California, Los Angeles, CA, USA.
The incidence of brain metastases (BrM) in patients with metastatic melanoma is reported to be 30-50% and constitutes the third most frequent BrM after breast and renal cancers. Treatment strategies including surgical resection, stereotactic radiation, and immunotherapy have improved clinical response rates and overall survival, but the changes that occur in circulating melanoma cells to promote invasion of the brain are not fully understood. To investigate brain tropism, we generated new variants of the B16 mouse melanoma model by serially passaging B16 cells through the brain of immune competent syngeneic C57BL/6 mice.
View Article and Find Full Text PDFEcancermedicalscience
October 2024
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, India.
Spread of lung cancer to the leptomeninges is rare and difficult to treat. Standard therapy comprises CNS-penetrant targeted agents with or without intrathecal chemotherapy. We performed a retrospective analysis of 16 patients with advanced NSCLC and leptomeningeal disease treated with intrathecal pemetrexed 50 mg.
View Article and Find Full Text PDFHeliyon
January 2025
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Bevacizumab is widely used in various clinical indications, but investigations into its optimal dosage for treating CNS metastases remain limited. The BEEP regimen, comprising bevacizumab, etoposide, and cisplatin, has recently demonstrated promising clinical outcomes for patients with breast cancer brain metastasis (BCBM) or leptomeningeal metastasis (LM). This study aimed to evaluate the exposure-response relationship of bevacizumab in BCBM patients and to explore the improved CNS penetration of chemotherapy by bevacizumab with LM patients.
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