Article
Oncology
T. Jonathan Yang, Neil A. Wijetunga, Josh Yamada, Suzanne Wolden, Michelle Mehallow, Debra A. Goldman, Zhigang Zhang, Robert J. Young, Mark G. Kris, Helena A. Yu, Andrew D. Seidman, Igor T. Gavrilovic, Andrew Lin, Bianca Santomasso, Christian Grommes, Anna F. Piotrowski, Lauren Schaff, Jacqueline B. Stone, Lisa M. DeAngelis, Adrienne Boire, Elena Pentsova
Summary: Proton craniospinal irradiation is a safe treatment for patients with leptomeningeal metastases from solid tumors, with durable disease control observed in some patients.
Article
Oncology
Jan Remsik, Jessica A. Wilcox, N. Esther Babady, Tracy A. McMillen, Behroze A. Vachha, Neil A. Halpern, Vikram Dhawan, Marc Rosenblum, Christine A. Iacobuzio-Donahue, Edward K. Avila, Bianca Santomasso, Adrienne Boire
Summary: Cancer patients with neurologic sequelae of COVID-19 have meningeal inflammatory cytokines without viral neuroinvasion, mainly driven by type II interferon and correlated with the degree of neurological dysfunction. The neuroinflammatory process persists weeks after recovery from acute respiratory infection, leading to long-term neurocognitive dysfunction. Anti-inflammatory treatments may play a role in managing neurological complications of COVID-19 infection.
Article
Medicine, General & Internal
Mei-Mei Zheng, Yang-Si Li, Hai-Yan Tu, Hao Sun, Kai Yin, Ben-Yuan Jiang, Jin-Ji Yang, Xu-Chao Zhang, Qing Zhou, Chong-Rui Xu, Zhen Wang, Hua-Jun Chen, De-Xiang Zhou, Yi-Long Wu
Summary: This study revealed site-specific resistant mechanisms to osimertinib and investigated subsequent treatments for leptomeningeal metastases (LM) in EGFR-mutated NSCLC patients. Private resistant mechanisms in cerebrospinal fluid (CSF) might match osimertinib-resistant LM for targeted therapy. Continuing osimertinib with intensification strategy might prolong survival, especially for those with CNS-only progression.
Review
Oncology
Stefania Morganti, Heather A. Parsons, Nancy U. Lin, Albert Grinshpun
Summary: A subset of metastatic breast cancer patients develop brain metastasis, and as systemic therapies have improved, the incidence of breast cancer brain metastases has increased. Brain metastases pose challenges in diagnosis, treatment, and monitoring in all subtypes of breast cancer, and liquid biopsy offers a potential solution. This review focuses on the clinical validity of liquid biopsy, specifically circulating tumor cells and circulating tumor DNA, in patients with breast cancer brain metastases.
Article
Medicine, Research & Experimental
Xin Chen, Kaixuan Bai, Yu Zhang, Yang Xu, Yinghao Huo, Sha Wang, Yueli Zou, Xuejiao Qi, Rongyun Guo, Qiuxiang Ou, Dengxiang Liu, Shaohua Yin, Shubo Chen, Hui Bu
Summary: In this study, it was found that cerebrospinal fluid circulating tumor DNA could sensitively detect molecular markers and metastasis-related mechanisms in gastric cancer patients with leptomeningeal metastases, providing new clues for prognosis estimation and clinical assessment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
N. Ari Wijetunga, Alexander G. Goglia, Nils Weinhold, Michael F. Berger, Michael Cislo, Daniel S. Higginson, Kiana Chabot, Ahmed M. Osman, Lauren Schaff, Elena Pentsova, Alexandra M. Miller, Simon N. Powell, Adrienne Boire, Jonathan T. Yang
Summary: This study analyzed the genetic characteristics and changes before and after proton craniospinal irradiation (pCSI) in patients with solid tumor leptomeningeal metastasis (LM) to explore their relationship with clinical response. The results showed unique mutations in the cell-free DNA of cerebrospinal fluid (CSF) before and after pCSI, and lower genomic diversity was associated with extended survival after pCSI.
CLINICAL CANCER RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
Xiyue Huang, Shanshan Ying, Lan Luo, Lixin Li, Dongdong Li, Yi Xie
Summary: This study quantitatively assessed intrathecal protein synthesis in patients with neurosyphilis and found an association between different stages of neurosyphilis and intrathecal synthesis of IgM and IgG. The use of specific antibody indices may also serve as a new tool for neurosyphilis diagnosis.
FRONTIERS IN PUBLIC HEALTH
(2022)
Review
Clinical Neurology
Jessica A. Wilcox, Adrienne A. Boire
Summary: Leptomeningeal metastases are a difficult stage of cancer to treat effectively. The use of small molecule inhibitors and immune checkpoint inhibitors has shown promise in treating various types of cancer, but their effectiveness in treating leptomeningeal metastases is still unclear. Further research is needed to understand how these drugs penetrate the blood-cerebrospinal fluid barrier and to develop better therapeutic options for patients with leptomeningeal disease.
Review
Pharmacology & Pharmacy
Minsoo Khang, Ranjit S. Bindra, W. Mark Saltzman
Summary: Intrathecal delivery has been clinically used for anesthesia and pain relief, and it also shows potential in treating certain cancers. However, the dynamics and clearance pathways of cerebrospinal fluid pose challenges for predicting drug distribution, and new approaches are needed to overcome these obstacles.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Ji-Woong Kwon, Ji Hye Im, Kyue-Yim Lee, Byong Chul Yoo, Jun Hwa Lee, Kyung-Hee Kim, Jong Heon Kim, Sang Hoon Shin, Heon Yoo, Ho-Shin Gwak
Summary: We analyzed the metabolomic and proteomic profiles of cerebrospinal fluid (CSF) samples from patients with leptomeningeal metastasis (LM) in different compartments (ventricular and lumbar). Our findings suggest that the metabolite and protein profiles of CSF differ between paired lumbar and ventricular samples, and that the CSF from spinal LM-positive patients shows more similarity to the lumbar CSF. This indicates that CSF metabolites and proteins could reflect LM disease activity and that LM-associated differences in CSF are more likely to be present in the lumbar compartment.
Letter
Oncology
Jianing Chen, Hainan Yang, Chao Zhao, Tao Lin, Da Liu, Weiping Hong, Changguo Shan, Cheng Zhou, Ling Bao, Caicun Zhou, Linbo Cai, Chunxia Su, Zhaoming Zhou, Lei Wen
Summary: Brain metastasis is a major cause of cancer-related death. Some patients are diagnosed with brain metastases at their first visit without prior treatment, while others develop brain metastases during systemic therapies. The genomic differences between these two groups are unclear. In this study, we analyzed the genomic features of synchronous and metachronous brain metastases in lung adenocarcinoma patients using panel-targeted gene sequencing of cerebrospinal fluid and plasma samples. CSF liquid biopsies were found to be superior in detecting gene alterations. EGFR and TP53 were the most frequently altered genes in both groups, but with different exon point mutations. The RTK-RAS and TP53 pathways were identified as the most affected pathways.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Giuseppe Minniti, Gaetano Lanzetta, Luca Capone, Martina Giraffa, Ivana Russo, Francesco Cicone, Alessandro Bozzao, Filippo Alongi, Luca Nicosia, Gioia Fineschi, Luca Marchetti, Tommaso Tufo, Federico Bianciardi, Vincenzo Esposito, PierCarlo Gentile, Sergio Paolini
Summary: The study evaluated the effects of postoperative stereotactic radiosurgery (SRS) with immunotherapy compared to SRS alone in patients with resected brain metastases (BM). The combination therapy showed a lower rate of leptomeningeal disease (LMD) and distant brain parenchymal failure (DBF), leading to reduced neurological death and prolonged survival.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Medicine, General & Internal
Ji Hye Im, Tae Hoon Kim, Kyue-Yim Lee, Ho-Shin Gwak, Weiwei Lin, Jong Bae Park, Jong Heon Kim, Byong Chul Yoo, Seong-Min Park, Ji-Woong Kwon, Sang Hoon Shin, Heon Yoo
Summary: The study demonstrated the potential of extracellular microRNAs in cerebrospinal fluid as biomarkers for the diagnosis and pathogenesis study of leptomeningeal metastasis (LM). The unique miRNA profile in LM compared to brain metastasis (BM) suggests the importance of miRNAs in understanding LM pathogenesis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Hainan Yang, Lei Wen, Chao Zhao, Jianing Chen, Zhaoming Zhou, Cheng Zhou, Linbo Cai, Caicun Zhou
Summary: For non-small cell lung cancer patients with leptomeningeal metastases (NSCLC-LM), cerebrospinal fluid (CSF) is superior to plasma (PLA) as a liquid biopsy medium, providing a more comprehensive representation of genomic alterations and higher clinical value.
Article
Oncology
Haoyu Ruan, Zhe Wang, Ziwei Sun, Jia Wei, Lei Zhang, Huanyu Ju, Ting Wang, Chao Zhang, Ming Guan, Shiyang Pan
Summary: This study examined the cerebrospinal fluid (CSF) tumor microenvironment (TME) of patients with leptomeningeal metastases (LM) using single-cell RNA sequencing (scRNA-seq). The analysis revealed the presence of M2-subtype macrophages and regulatory T cells, indicating an immunosuppressive tumor immunity direction in LM patients. Furthermore, the CSF circulating tumor cells (CTCs) of breast cancer LM patients were classified into five molecular subtypes and showed heterogeneity in cell proliferation and cancer-testis antigen expression. The study provides insights into the mechanism research, diagnosis, and therapy of LM.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Pathology
Tejus A. Bale, Soo-Ryum Yang, James P. Solomon, Khedoudja Nafa, Sumit Middha, Jacklyn Casanova, Justyna Sadowska, Anna Skakodub, Hamza Ahmad, Helena A. Yu, Greg J. Riely, Mark G. Kris, Sarat Chandarlapaty, Marc K. Rosenblum, Igor Gavrilovic, Matthias A. Karajannis, Elena Pentsova, Alexandra Miller, Adrienne Boire, Ingo Mellinghoff, Michael F. Berger, Ahmet Zehir, Marc Ladanyi, Ryma Benayed, Maria E. Arcila
Summary: This study demonstrates that routine molecular profiling of cfDNA from cerebrospinal fluid is superior to gDNA, enabling the capture of mutations with high variant allele frequency even in cases with negative cytology results.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2021)
Review
Oncology
Aaron Kaplan, Min Jun Li, Rachna Malani
Summary: This paper provides a review of emerging management strategies for breast cancer and central nervous system metastases. It discusses the evolution from standard chemotherapy to more targeted approaches, drug delivery methodologies, immunotherapeutics, and radiotherapeutic approaches. The future therapeutics may improve patients' quality of life and survival by bypassing the limitations of standard therapies.
CURRENT ONCOLOGY REPORTS
(2022)
Article
Oncology
Sara Haddock, Tyler J. Alban, Sevin Turcan, Hana Husic, Eric Rosiek, Xiaoxiao Ma, Yuxiang Wang, Tejus Bale, Alexis Desrichard, Vladimir Makarov, Sebastien Monette, Wei Wu, Rui Gardner, Katia Manova, Adrienne Boire, Timothy A. Chan
Summary: Mutations in IDH1 and IDH2 drive the development of gliomas by inducing phenotypic reprogramming and stem-like properties. The CD24-positive cell population in IDH-mutant tumors possesses remarkable stem-like characteristics and shows enhanced tumor initiating potency. The induction of a CD24-positive population is one mechanism by which IDH-mutant tumors acquire stem-like properties.
Article
Oncology
Emanuela Ferraro, Jasmeet Singh, Sujata Patil, Pedram Razavi, Shanu Modi, Sarat Chandarlapaty, Andrea Barrio, Rachna Malani, Ingo K. Mellinghoff, Adrienne Boire, Hannah Y. Wen, Edi Brogi, Andrew D. Seidman, Larry Norton, Mark E. Robson, Chau T. Dang
Summary: The study aimed to investigate the incidence of brain metastases in early stage HER2-positive breast cancer patients receiving HP-based neoadjuvant chemotherapy as well as survival outcomes. While patients in the pCR group had better survival outcomes, there was no significant difference in brain metastases incidence between pCR and non-pCR patients.
Article
Oncology
Ayal A. Aizer, Nayan Lamba, Manmeet S. Ahluwalia, Kenneth Aldape, Adrienne Boire, Priscilla K. Brastianos, Paul D. Brown, D. Ross Camidge, Veronica L. Chiang, Michael A. Davies, Leland S. Hu, Raymond Y. Huang, Timothy Kaufmann, Priya Kumthekar, Keng Lam, Eudocia Q. Lee, Nancy U. Lin, Minesh Mehta, Michael Parsons, David A. Reardon, Jason Sheehan, Riccardo Soffietti, Hussein Tawbi, Michael Weller, Patrick Y. Wen
Summary: This consensus review provides a comprehensive overview of brain metastases, with a focus on management approaches and ongoing efforts to shape future paradigms of care. The hope is that these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and drive advancements in the field.
Article
Clinical Neurology
Yoshie Umemura, Baber Khan, Benjamin J. Weill, Justin J. Buthorn, Anna Skakodub, Andrew J. Ridder, Kathryn S. Nevel, Yilun Sun, Adrienne Boire
Summary: Novel diagnostic techniques and neurologic biomarkers have expanded indications for cerebrospinal fluid (CSF) studies. Lumbar puncture (LP) is the most common method for obtaining CSF. Patients typically anticipate LP to be painful, but this study found that the majority of patients actually experience minimal pain. Anticipation of pain was correlated with feeling anxious and experiencing pain during LP.
NEUROLOGY-CLINICAL PRACTICE
(2022)
Review
Clinical Neurology
Jessica A. Wilcox, Adrienne A. Boire
Summary: Leptomeningeal metastases are a difficult stage of cancer to treat effectively. The use of small molecule inhibitors and immune checkpoint inhibitors has shown promise in treating various types of cancer, but their effectiveness in treating leptomeningeal metastases is still unclear. Further research is needed to understand how these drugs penetrate the blood-cerebrospinal fluid barrier and to develop better therapeutic options for patients with leptomeningeal disease.
Editorial Material
Genetics & Heredity
Ana Rita Nobre, Adrienne Boire
Summary: Mutations in the sodium channel NALCN can cause epithelial cell shedding and dissemination before oncogenic transformation, suggesting that metastasis may occur independently of the end stage of carcinogenesis.
Review
Clinical Neurology
Jessica A. Wilcox, Rachel Estrera, Adrienne Boire
Summary: This article provides a thorough review of five observed headache sub-classifications in patients with leptomeningeal metastases, including necessary diagnostic testing, recommended first-line treatments, and prevention strategies.
CURRENT PAIN AND HEADACHE REPORTS
(2023)
Article
Oncology
Archit B. Baskaran, Ankush Bhatia, Priya Kumthekar, Adrienne Boire, Rimas Lukas
Summary: This paper summarizes the findings from 48 clinical trials conducted since the 1970s about the treatment of leptomeningeal metastases through an intrathecal approach. The results of these studies suggest that although these therapies show promise for the future, they currently do not clearly and consistently report a benefit. Further work is needed to explore the possible use of these treatments.
Meeting Abstract
Oncology
Jonathan T. Yang, N. Ari Wijetunga, Elena Pentsova, Suzanne L. Wolden, Robert J. Young, Denise Correa, Zhigang Zhang, Junting Zheng, Allison Betof Warner, Helena Alexandra Yu, Mark G. Kris, Andrew David Seidman, Rachna Malani, Andrew Lin, Lisa Marie DeAngelis, Nancy Y. Lee, Simon N. Powell, Adrienne Ann Boire
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Jessica Wilcox, Lisa R. Modelevsky, Tiffany Thomas, Serge Cremers, Robert J. Young, Anne S. Reiner, Katherine Panageas, Helena Alexandra Yu, Adrienne Ann Boire
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Jan Remsik, Yudan Chi, Xinran Tong, Ugur Sener, Camille Derderian, Abigail Park, Fadi Saadeh, Tejus Bale, Adrienne Boire
Summary: By studying leptomeningeal derivatives of breast and lung cancer cell lines, researchers have found that floating cancer cells cultured in vitro have different proliferation rates, ATP content, and metabolic signatures. These floating cells are more likely to colonize the mouse leptomeninges and contribute to shortened survival. Additionally, patients with CSF disease only have a shorter life expectancy compared to patients with adherent disease.