Carcinomatous meningitis: Leptomeningeal metastases in solid tumors
TLDR
Novel agents including targeted therapies, that may be promising in the future management of LM are discussed, which include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, and anti-HER2 monoclonal antibody trastuzumab in breast cancer.Abstract:
Leptomeningeal metastasis (LM) results from metastatic spread of cancer to the leptomeninges, giving rise to central nervous system dysfunction. Breast cancer, lung cancer, and melanoma are the most frequent causes of LM among solid tumors in adults. An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected. Apart from a clinical suspicion of LM, diagnosis is dependent upon demonstration of cancer in cerebrospinal fluid (CSF) or radiographic manifestations as revealed by neuraxis imaging. Potentially of use, though not commonly employed, today are use of biomarkers and protein profiling in the CSF. Symptomatic treatment is directed at pain including headache, nausea, and vomiting, whereas more specific LM-directed therapies include intra-CSF chemotherapy, systemic chemotherapy, and site-specific radiotherapy. A special emphasis in the review discusses novel agents including targeted therapies, that may be promising in the future management of LM. These new therapies include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, anti-HER2 monoclonal antibody trastuzumab in breast cancer, anti-CTLA4 ipilimumab and anti-BRAF tyrosine kinase inhibitors such as vermurafenib in melanoma, and the antivascular endothelial growth factor monoclonal antibody bevacizumab are currently under investigation in patients with LM. Challenges of managing patients with LM are manifold and include determining the appropriate patients for treatment as well as the optimal route of administration of intra-CSF drug therapy.read more
Citations
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Leptomeningeal Metastases in Patients with NSCLC with EGFR Mutations
Yang-Si Li,Ben-Yuan Jiang,Jin-Ji Yang,Hai-Yan Tu,Qing Zhou,Wei-Bang Guo,Hong-Hong Yan,Yi-Long Wu +7 more
TL;DR: Leptomeningeal metastases were much more frequent in patients with NSCLC harboring EGFR mutations, and EGFR TKIs were the optimal treatment for LM, and active treatment with WBRT did not prolong OS for EGFR‐mutated patients.
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Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era
TL;DR: New therapies with improved cerebral-spinal fluid penetration have been developed for subgroups of molecular selected patients indicating they could be promising therapeutic options for managing leptomeningeal disease.
Journal ArticleDOI
Leptomeningeal disease: current diagnostic and therapeutic strategies.
Gautam Nayar,Tiffany Ejikeme,Pakawat Chongsathidkiet,Aladine A. Elsamadicy,Kimberly L. Blackwell,Jeffrey M. Clarke,Shivanand P. Lad,Peter E. Fecci +7 more
TL;DR: While leptomeningeal disease is still a terminal, late-stage complication, a variety of treatment modalities, such as intrathecal chemotherapeutics and radiation therapy, have improved median survival from 4–6 weeks to 3–6 months.
Journal ArticleDOI
Therapy of leptomeningeal metastasis in solid tumors
Frederic Mack,Brigitta G. Baumert,Niklas Schäfer,Elke Hattingen,Björn Scheffler,Ulrich Herrlinger,Martin Glas +6 more
TL;DR: The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy for leptomeningeal metastasis, which is a devastating and mostly late-stage complication of various solid tumors.
Journal ArticleDOI
ANG1005, a brain penetrating peptide-drug conjugate, shows activity in patients with breast cancer with leptomeningeal carcinomatosis and recurrent brain metastases.
Priya Kumthekar,Shou-Ching Tang,Andrew Brenner,Santosh Kesari,David Piccioni,Carey K. Anders,Jose Carrillo,Pavani Chalasani,Peter Kabos,Shannon Puhalla,Katherine Tkaczuk,Agustin A. Garcia,Manmeet Ahluwalia,Jeffrey S. Wefel,Nehal Lakhani,Nuhad K. Ibrahim +15 more
TL;DR: Even though the study preset rule for iORR per IRF was not met in this heavily pretreated population, a notable CNS and systemic treatment effect was seen in all patients including symptom improvement and prolonged overall survival compared to historical control for the subset of patients with leptomeningeal carcinomatosis.
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