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JOURNAL ARTICLE
Maria Diaz, Sofia Chudsky, Elena Pentsova, Alexandra M Miller
For patients with central nervous system (CNS) malignancies, liquid biopsies of the cerebrospinal fluid (CSF) may offer an unparalleled source of information about the tumor, with much less risk than traditional biopsies. Two techniques have been adapted to CSF in clinical settings: circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). CTCs have been employed mostly as a diagnostic tool for leptomeningeal metastases in epithelial tumors, although they may also have value in the prognostication and monitoring of this disease...
January 12, 2024: Translational Oncology
#2
JOURNAL ARTICLE
Maria Diaz, Satshil Rana, Carlos Eduardo Silva Correia, Anne S Reiner, Andrew L Lin, Alexandra M Miller, Maya S Graham, Sofia Chudsky, Tejus A Bale, Marc Rosenblum, Matthias A Karajannis, Elena Pentsova
BACKGROUND: The 2016 WHO classification described a subtype of midline gliomas harboring histone 3 (H3) K27M alterations, and the 2021 edition added a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. The incidence and clinical behavior of leptomeningeal disease (LMD) in these patients is not well defined. METHODS: Retrospective study of patients with H3-altered gliomas diagnosed from 01/2012 to 08/2021; histone mutations were identified through next-generation sequencing (NGS) of tumor biopsy and/or cerebrospinal fluid (CSF)...
2023: Neuro-oncology advances
#3
JOURNAL ARTICLE
Christian Grommes, Elena Pentsova, Lauren R Schaff, Craig P Nolan, Thomas Kaley, Anne S Reiner, Katherine S Panageas, Ingo K Mellinghoff
Central Nervous System (CNS) Lymphomas are aggressive brain tumors with limited treatment options. Targeting the phosphoinositide 3-kinase (PI3K) pathway yields promising responses across B-cell malignancies, but its therapeutic potential in CNS lymphomas remains unexplored. We present pre-clinical and clinical data on the pan-PI3K inhibitor Buparlisib in CNS lymphomas. In a primary CNS lymphoma-patient-derived cell line, we define the EC50. Four patients with recurrent CNS lymphoma were enrolled in a prospective trial...
June 15, 2023: Leukemia & Lymphoma
#4
JOURNAL ARTICLE
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
PURPOSE: Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response. EXPERIMENTAL DESIGN: We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel...
February 16, 2023: Clinical Cancer Research
#5
JOURNAL ARTICLE
Lauren R Schaff, Marina Kushnirsky, Andrew L Lin, Subhiksha Nandakumar, Christian Grommes, Alexandra Michelle Miller, Igor T Gavrilovic, Craig Nolan, Elena Pentsova, Ingo K Mellinghoff, Thomas J Kaley
OBJECTIVES: To report on the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma METHODS: Single-center retrospective series of glioma patients treated with olaparib/TMZ September 2018-December 2021 RESULTS: Twenty patients (median age: 42, median Karnofsky Performance Status: 90) received olaparib/TMZ for diagnoses of IDH -mutant oligodendroglioma (n=5), IDH- mutant astrocytoma grade 2-3 (n=4), IDH -mutant astrocytoma grade 4 (n=7), or IDH- wildtype glioma (n=4)...
August 10, 2022: Neurology
#6
JOURNAL ARTICLE
Priya U Kumthekar, Michael J Avram, Andrew B Lassman, Nancy U Lin, Eudocia Lee, Sean A Grimm, Margaret Schwartz, Kirsten L Bell Burdett, Rimas V Lukas, Karan Dixit, Isabella Perron, Hui Zhang, William J Gradishar, Elena I Pentsova, Suriya Jeyapalan, Morris D Groves, Michelle Melisko, Jeffrey J Raizer
BACKGROUND: Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive LMD. METHODS: This multicenter study enrolled 34 LMD patients in a combined Phase I/II study in treating patients with intrathecal trastuzumab...
August 10, 2022: Neuro-oncology
#7
RANDOMIZED CONTROLLED TRIAL
Jonathan T Yang, N Ari Wijetunga, Elena Pentsova, Suzanne Wolden, Robert J Young, Denise Correa, Zhigang Zhang, Junting Zheng, Alexa Steckler, Weronika Bucwinska, Ashley Bernstein, Allison Betof Warner, Helena Yu, Mark G Kris, Andrew D Seidman, Jessica A Wilcox, Rachna Malani, Andrew Lin, Lisa M DeAngelis, Nancy Y Lee, Simon N Powell, Adrienne Boire
PURPOSE: Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT. PATIENTS AND METHODS: We conducted a randomized, phase II trial of pCSI versus IFRT in patients with non-small-cell lung cancer and breast cancers with LM...
November 20, 2022: Journal of Clinical Oncology
#8
JOURNAL ARTICLE
Maria Diaz, Priya Singh, Ivan S Kotchetkov, Anna Skakodub, Alicia Meng, Christel Tamer, Robert J Young, Anne S Reiner, Katherine S Panageas, Lakshmi V Ramanathan, Elena Pentsova
PURPOSE: Circulating tumor cells in cerebrospinal fluid are a quantitative diagnostic tool for leptomeningeal metastases from solid tumors, but their prognostic significance is unclear. Our objective was to evaluate CSF-CTC quantification in predicting outcomes in LM. METHODS: This is a single institution retrospective study of patients with solid tumors who underwent CSF-CTC quantification using the CellSearch® platform between 04/2016 and 06/2019. Information on neuroaxis imaging, CSF results, and survival was collected...
March 2022: Journal of Neuro-oncology
#9
JOURNAL ARTICLE
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
Cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) offers unique opportunities for genomic profiling of tumors involving the central nervous system but remains uncommonly used in clinical practice. We describe our clinical experience using cfDNA from CSF for routine molecular testing using Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (targeting 468 cancer-related genes). In all, 148 cfDNA samples were assessed, comparing results of cfDNA versus genomic DNA (gDNA; gDNA from cell pellets) derived from the same CSF sample and the primary tumor...
June 2021: Journal of Molecular Diagnostics: JMD
#10
JOURNAL ARTICLE
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
BACKGROUND: Leptomeningeal metastases (LM) are associated with limited survival and treatment options. While involved-field radiotherapy is effective for local palliation, it lacks durability. We evaluated the toxicities of proton craniospinal irradiation (CSI), a treatment encompassing the entire central nervous system (CNS) compartment, for patients with LM from solid tumors. METHODS: We enrolled patients with LM to receive hypofractionated proton CSI in this phase I prospective trial...
January 30, 2021: Neuro-oncology
#11
JOURNAL ARTICLE
Kathryn S Nevel, Natalie DiStefano, Xuling Lin, Anna Skakodub, Shahiba Q Ogilvie, Anne S Reiner, Elena Pentsova, Adrienne Boire
BACKGROUND: Improvements in detection and molecular characterization of leptomeningeal metastasis from lung cancer (LC-LM) coupled with cerebrospinal fluid (CSF)-penetrating targeted therapies have altered disease management. A barrier to formal study of these therapies in LM is quantification of disease burden. Also, outcomes of patients with targetable mutations in LC-LM are not well defined. This study employs molecular and radiographic measures of LM disease burden and correlates these with outcome...
May 15, 2020: Neuro-oncology
#12
JOURNAL ARTICLE
Thomas J Kaley, Katherine S Panageas, Elena I Pentsova, Ingo K Mellinghoff, Craig Nolan, Igor Gavrilovic, Lisa M DeAngelis, Lauren E Abrey, Eric C Holland, Antonio Omuro, Mario E Lacouture, Emmy Ludwig, Andrew B Lassman
PURPOSE: Malignant glioma (MG) is the most deadly primary brain cancer. Signaling though the PI3K/AKT/mTOR axis is activated in most MGs and therefore a potential therapeutic target. The mTOR inhibitor temsirolimus and the AKT inhibitor perifosine are each well-tolerated as single agents but with limited activity reclinical data demonstrate synergistic anti-tumor effects from combined treatment. Therefore, we initiated a phase I trial of combined therapy in recurrent MGs to determine safety and a recommended phase II dose...
April 2020: Annals of Clinical and Translational Neurology
#13
JOURNAL ARTICLE
Michael Offin, Daniel Feldman, Ai Ni, Mackenzie L Myers, W Victoria Lai, Elena Pentsova, Adrienne Boire, Mariza Daras, Emmet J Jordan, David B Solit, Maria E Arcila, David R Jones, James M Isbell, Kathryn Beal, Robert J Young, Charles M Rudin, Gregory J Riely, Alexander Drilon, Viviane Tabar, Lisa M DeAngelis, Helena A Yu, Mark G Kris, Bob T Li
BACKGROUND: Mutations in human epidermal growth factor receptor 2 (HER2; also known as ERBB2) are found in approximately 2% of lung adenocarcinomas. The frequency and clinical course of brain metastases in this oncogenic subset are ill defined. METHODS: Baseline and subsequent development of brain metastases was evaluated in consecutive patients with HER2-mutant (n = 98), epidermal growth factor receptor (EGFR)-mutant (n = 200), and KRAS-mutant lung cancers (n = 200)...
August 30, 2019: Cancer
#14
Correction to: Sequencing and curation strategies for identifying candidate glioblastoma treatments.
Mayu O Frank, Takahiko Koyama, Kahn Rhrissorrakrai, Nicolas Robine, Filippo Utro, Anne-Katrin Emde, Bo-Juen Chen, Kanika Arora, Minita Shah, Heather Geiger, Vanessa Felice, Esra Dikoglu, Sadia Rahman, Xiaolan Fang, Vladimir Vacic, Ewa A Bergmann, Julia L Moore Vogel, Catherine Reeves, Depinder Khaira, Anthony Calabro, Duyang Kim, Michelle F Lamendola-Essel, Cecilia Esteves, Phaedra Agius, Christian Stolte, John Boockvar, Alexis Demopoulos, Dimitris G Placantonakis, John G Golfinos, Cameron Brennan, Jeffrey Bruce, Andrew B Lassman, Peter Canoll, Christian Grommes, Mariza Daras, Eli Diamond, Antonio Omuro, Elena Pentsova, Dana E Orange, Stephen J Harvey, Jerome B Posner, Vanessa V Michelini, Vaidehi Jobanputra, Michael C Zody, John Kelly, Laxmi Parida, Kazimierz O Wrzeszczynski, Ajay K Royyuru, Robert B Darnell
Following publication of the original article [1], it was reported that the given name of the fourteenth author was incorrectly published. The incorrect and the correct names are given below.
August 2, 2019: BMC Medical Genomics
#15
JOURNAL ARTICLE
Philip Jonsson, Andrew L Lin, Robert J Young, Natalie M DiStefano, David M Hyman, Bob T Li, Michael F Berger, Ahmet Zehir, Marc Ladanyi, David B Solit, Angela G Arnold, Zsofia K Stadler, Diana Mandelker, Michael E Goldberg, Juliann Chmielecki, Maryam Pourmaleki, Shahiba Q Ogilvie, Shweta S Chavan, Andrew T McKeown, Malbora Manne, Allison Hyde, Kathryn Beal, T Jonathan Yang, Craig P Nolan, Elena Pentsova, Antonio Omuro, Igor T Gavrilovic, Thomas J Kaley, Eli L Diamond, Jacqueline B Stone, Christian Grommes, Adrienne Boire, Mariza Daras, Anna F Piotrowski, Alexandra M Miller, Philip H Gutin, Timothy A Chan, Viviane S Tabar, Cameron W Brennan, Marc Rosenblum, Lisa M DeAngelis, Ingo K Mellinghoff, Barry S Taylor
PURPOSE: The genomic landscape of gliomas has been characterized and now contributes to disease classification, yet the relationship between molecular profile and disease progression and treatment response remain poorly understood. Experimental Design: We integrated prospective clinical sequencing of 1,004 primary and recurrent tumors from 923 glioma patients with clinical and treatment phenotypes. RESULTS: Thirteen percent of glioma patients harbored a pathogenic germline variant, including a subset associated with heritable genetic syndromes and variants mediating DNA repair dysfunctions (29% of the total) that were associated with somatic biallelic inactivation and mechanism-specific somatic phenotypes...
September 15, 2019: Clinical Cancer Research
#16
JOURNAL ARTICLE
Hui Chen, Cheddhi Thomas, Felipe Andres Munoz, Sanda Alexandrescu, Craig M Horbinski, Adriana Olar, Declan McGuone, Sandra Camelo-Piragua, Lu Wang, Elena Pentsova, Joanna Phillips, Kenneth Aldape, Wen Chen, A John Iafrate, Andrew S Chi, David Zagzag, John G Golfinos, Dimitris G Placantonakis, Marc Rosenblum, Pamela Ohman-Strickland, Meera Hameed, Matija Snuderl
BACKGROUND: Chromosomal instability is associated with earlier progression in isocitrate dehydrogenase (IDH)-mutated astrocytomas. Here we evaluated the prognostic significance of polysomy in gliomas tested for 1p/19q status. METHODS: We analyzed 412 histologic oligodendroglial tumors with use of 1p/19q testing at 8 institutions from 1996 to 2013; fluorescence in situ hybridization (FISH) for 1p/19q was performed. Polysomy was defined as more than two 1q and 19p signals in cells...
September 6, 2019: Neuro-oncology
#17
JOURNAL ARTICLE
Mayu O Frank, Takahiko Koyama, Kahn Rhrissorrakrai, Nicolas Robine, Filippo Utro, Anne-Katrin Emde, Bo-Juen Chen, Kanika Arora, Minita Shah, Heather Geiger, Vanessa Felice, Esra Dikoglu, Sadia Rahman, Alice Fang, Vladimir Vacic, Ewa A Bergmann, Julia L Moore Vogel, Catherine Reeves, Depinder Khaira, Anthony Calabro, Duyang Kim, Michelle F Lamendola-Essel, Cecilia Esteves, Phaedra Agius, Christian Stolte, John Boockvar, Alexis Demopoulos, Dimitris G Placantonakis, John G Golfinos, Cameron Brennan, Jeffrey Bruce, Andrew B Lassman, Peter Canoll, Christian Grommes, Mariza Daras, Eli Diamond, Antonio Omuro, Elena Pentsova, Dana E Orange, Stephen J Harvey, Jerome B Posner, Vanessa V Michelini, Vaidehi Jobanputra, Michael C Zody, John Kelly, Laxmi Parida, Kazimierz O Wrzeszczynski, Ajay K Royyuru, Robert B Darnell
BACKGROUND: Prompted by the revolution in high-throughput sequencing and its potential impact for treating cancer patients, we initiated a clinical research study to compare the ability of different sequencing assays and analysis methods to analyze glioblastoma tumors and generate real-time potential treatment options for physicians. METHODS: A consortium of seven institutions in New York City enrolled 30 patients with glioblastoma and performed tumor whole genome sequencing (WGS) and RNA sequencing (RNA-seq; collectively WGS/RNA-seq); 20 of these patients were also analyzed with independent targeted panel sequencing...
April 25, 2019: BMC Medical Genomics
#18
JOURNAL ARTICLE
Aki Morikawa, Elisa de Stanchina, Elena Pentsova, Margaret M Kemeny, Bob T Li, Kendrick Tang, Sujata Patil, Martin Fleisher, Catherine Van Poznak, Larry Norton, Andrew D Seidman
PURPOSE: Lapatinib and capecitabine cross the blood tumor-barrier in breast cancer brain metastasis but have modest clinical efficacy. Administration of high dose tyrosine kinase inhibitor (TKI) has been evaluated in brain metastases and primary brain tumors as a strategy to improve drug exposure in the central nervous system (CNS).We derived a rational drug scheduling of intermittent high dose lapatinib alternating with capecitabine-basedon our preclinical data and Norton-Simon mathematical modeling...
April 15, 2019: Clinical Cancer Research
#19
JOURNAL ARTICLE
Alexandra M Miller, Ronak H Shah, Elena I Pentsova, Maryam Pourmaleki, Samuel Briggs, Natalie Distefano, Youyun Zheng, Anna Skakodub, Smrutiben A Mehta, Carl Campos, Wan-Ying Hsieh, S Duygu Selcuklu, Lilan Ling, Fanli Meng, Xiaohong Jing, Aliaksandra Samoila, Tejus A Bale, Dana W Y Tsui, Christian Grommes, Agnes Viale, Mark M Souweidane, Viviane Tabar, Cameron W Brennan, Anne S Reiner, Marc Rosenblum, Katherine S Panageas, Lisa M DeAngelis, Robert J Young, Michael F Berger, Ingo K Mellinghoff
Diffuse gliomas are the most common malignant brain tumours in adults and include glioblastomas and World Health Organization (WHO) grade II and grade III tumours (sometimes referred to as lower-grade gliomas). Genetic tumour profiling is used to classify disease and guide therapy1,2 , but involves brain surgery for tissue collection; repeated tumour biopsies may be necessary for accurate genotyping over the course of the disease3-10 . While the detection of circulating tumour DNA (ctDNA) in the blood of patients with primary brain tumours remains challenging11,12 , sequencing of ctDNA from the cerebrospinal fluid (CSF) may provide an alternative way to genotype gliomas with lower morbidity and cost13,14 ...
January 2019: Nature
#20
JOURNAL ARTICLE
Kathryn S Nevel, Elena Pentsova, Mariza Daras
Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is a rare type of Non-Hodgkin's lymphoma which rarely metastasizes to the central nervous system (CNS). Ten of 60 patients (16.7%) with ENKTCL followed at Memorial Sloan Kettering Cancer Center (MSKCC) were diagnosed with CNS involvement between 1995 and 2016. Eight patients had systemic disease at the time of CNS diagnosis; one patient never developed systemic disease and another was in remission at the time of CNS relapse. Median overall survival was 3...
July 2019: Leukemia & Lymphoma
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