2024
Distinct epigenetic and transcriptional profiles of Epstein-Barr virus-positive and negative primary CNS lymphomas
Hai L, Friedel D, Hinz F, Hoffmann D, Doubrovinskaia S, Rohdjess H, Weidenauer K, Denisova E, Scheffler G, Kessler T, Kourtesakis A, Herold-Mende C, Henegariu O, Baehring J, Dietrich J, Brors B, Wick W, Sahm F, Kaulen L. Distinct epigenetic and transcriptional profiles of Epstein-Barr virus-positive and negative primary CNS lymphomas. Neuro-Oncology 2024, 27: 979-992. PMID: 39575767, PMCID: PMC12083237, DOI: 10.1093/neuonc/noae251.Peer-Reviewed Original ResearchPrimary CNS lymphomaEpstein-Barr virusB cell receptorCNS lymphomaTargeted therapyEpigenetic profilesB cellsDiffuse large B-cell lymphomaLarge B-cell lymphomaB-cell lymphomaPromoter region hypermethylationEBV oncogeneEBV lymphomasEBV- tumorsEPIC methylation arrayWnt/beta-catenin signalingEBV diseaseBiological subtypesUnsupervised cluster analysisInterleukin-10Promoter methylationLymphomaSyk kinase activityBrain tumorsMutational landscapePATH-35. INTEGRATED GENOMIC ANALYSES OF IMMUNODEFICIENCY-ASSOCIATED EPSTEIN-BARR VIRUS- (EBV) POSITIVE PRIMARY CNS LYMPHOMAS
Kaulen L, Denisova E, Hinz F, Hai L, Friedel D, Henegariu O, Hoffmann D, Ito J, Kourtesakis A, Lehnert P, Doubrovinskaia S, Karschnia P, von Baumgarten L, Kessler T, Baehring J, Brors B, Sahm F, Wick W. PATH-35. INTEGRATED GENOMIC ANALYSES OF IMMUNODEFICIENCY-ASSOCIATED EPSTEIN-BARR VIRUS- (EBV) POSITIVE PRIMARY CNS LYMPHOMAS. Neuro-Oncology 2024, 26: viii186-viii186. PMCID: PMC11553229, DOI: 10.1093/neuonc/noae165.0734.Peer-Reviewed Original ResearchPrimary CNS lymphomaEpstein-Barr virusRNAseq dataSingle nucleotide variantsCopy number variantsComprehensive genetic analysisRNA sequencing dataCopy number gainCNS lymphomaGermline controlTumor microenvironmentNucleotide variantsSequence dataTranscript groupsTargeting motifGenetic analysisGenetic landscapeJAK/STAT signalingCytotoxic T cell responsesRNA sequencingTolerogenic tumor microenvironmentAberrant somatic hypermutationExpression of CD70T regulatory cellsT cell responsesP20.12.B INTEGRATED GENETIC ANALYSES OF IMMUNODEFICIENCY-ASSOCIATED EPSTEIN-BARR VIRUS- (EBV) POSITIVE PRIMARY CNS LYMPHOMAS
Kaulen L, Denisova E, Hinz F, Hai L, Friedel D, Henegariu O, Hoffmann D, Ito J, Kourtesakis A, Lehnert P, Doubrovinskaia S, Karschnia P, von Baumgarten L, Kessler T, Baehring J, Brors B, Sahm F, Wick W. P20.12.B INTEGRATED GENETIC ANALYSES OF IMMUNODEFICIENCY-ASSOCIATED EPSTEIN-BARR VIRUS- (EBV) POSITIVE PRIMARY CNS LYMPHOMAS. Neuro-Oncology 2024, 26: v118-v118. PMCID: PMC11485591, DOI: 10.1093/neuonc/noae144.399.Peer-Reviewed Original ResearchPrimary CNS lymphomaEpstein-Barr virusRNAseq dataSingle nucleotide variantsCopy number variantsComprehensive genetic analysisRNA sequencing dataCNS lymphomaCopy number gainTumor microenvironmentGermline controlNucleotide variantsSequence dataTranscript groupsCytotoxic T cell responsesEpstein-Barr virus-positiveTargeting motifGenetic analysisGenetic landscapeJAK/STAT signalingTolerogenic tumor microenvironmentRNA sequencingAberrant somatic hypermutationExpression of CD70T regulatory cellsPatterns of CNS Failures in Relapse/Refractory Large B-Cell Lymphoma (LBCL) Patients with Secondary CNS Disease Following Chimeric Antigen Receptor T-Cell (CAR T) Therapy
Nakashima J, Khatri V, Cruz-Chamorro R, Zhou J, Patra P, Gaballa S, Khimani F, Mirza S, Shah B, Saeed H, Chavez J, Locke F, Nishihori T, Liu H, Dong N, Lazaryan A, Robinson T, Freeman C, Jain M, Figura N. Patterns of CNS Failures in Relapse/Refractory Large B-Cell Lymphoma (LBCL) Patients with Secondary CNS Disease Following Chimeric Antigen Receptor T-Cell (CAR T) Therapy. International Journal Of Radiation Oncology • Biology • Physics 2024, 120: e646-e647. DOI: 10.1016/j.ijrobp.2024.07.1421.Peer-Reviewed Original ResearchLarge B-cell lymphomaSecondary CNS lymphomaB-cell lymphomaCNS failureCNS recurrenceCNS diseaseCNS lymphomaCAR-TOverall survivalBridging therapyCNS diagnosisRelapsed/refractory large B-cell lymphomaChimeric antigen receptor T cellsCAR-T cell trialsPattern of failure analysisCAR-T cell therapyMedian age of patientsClinical outcomes of patientsCNS-only progressionSystemic disease recurrenceT-cell therapyCAR-T therapyCytokine-release syndromePatterns of recurrenceKaplan-Meier method
2023
Association of MTHFR Polymorphisms With Leukoencephalopathy Risk in Patients With Primary CNS Lymphoma Treated With Methotrexate-Based Regimens
Karschnia P, Kurz S, Brastianos P, Winter S, Gordon A, Jones S, Pisapia M, Nayyar N, Tonn J, Batchelor T, Plotkin S, Dietrich J. Association of MTHFR Polymorphisms With Leukoencephalopathy Risk in Patients With Primary CNS Lymphoma Treated With Methotrexate-Based Regimens. Neurology 2023, 101: e1741-e1746. PMID: 37527941, PMCID: PMC10624483, DOI: 10.1212/wnl.0000000000207670.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaCNS lymphomaHD-MTXMethylenetetrahydrofolate reductaseResponse to induction therapyAssociation of MTHFR polymorphismsMethotrexate-based regimensSeverity of leukoencephalopathyProgression-free survivalHigh-dose methotrexateRisk of leukoencephalopathyAssociated with increased frequencyAssociated with leukoencephalopathyInduction chemotherapyDecreased functional statusInduction therapyOverall survivalMassachusetts General HospitalMTX clearanceMTHFR polymorphismsFolate depletionLeukoencephalopathyPatientsElevated riskFunctional statusIntegrated genetic analyses of immunodeficiency-associated Epstein-Barr virus- (EBV) positive primary CNS lymphomas
Kaulen L, Denisova E, Hinz F, Hai L, Friedel D, Henegariu O, Hoffmann D, Ito J, Kourtesakis A, Lehnert P, Doubrovinskaia S, Karschnia P, von Baumgarten L, Kessler T, Baehring J, Brors B, Sahm F, Wick W. Integrated genetic analyses of immunodeficiency-associated Epstein-Barr virus- (EBV) positive primary CNS lymphomas. Acta Neuropathologica 2023, 146: 499-514. PMID: 37495858, PMCID: PMC10412493, DOI: 10.1007/s00401-023-02613-w.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaCNS lymphomaCytotoxic T cell responsesDistinct clinicopathological entityT cell responsesRegulatory cellsClinicopathological entityEpstein-BarrInferior prognosisMonocyte fractionM2 macrophagesJAK/STATMast cellsTumor microenvironmentAberrant somatic hypermutationMolecular classificationComprehensive genetic analysisBulk RNAseq dataStrong expressionChromosomal aberrationsGenetic alterationsPathological informationNumber gainCD70LymphomaMTHFR polymorphisms and neurotoxicity and overall survival after methotrexate-based therapy in primary CNS lymphoma.
Karschnia P, Kurz S, Brastianos P, Winter S, Gordon A, Jones S, Pisapia M, Nayyar N, Tonn J, Batchelor T, Plotkin S, Dietrich J. MTHFR polymorphisms and neurotoxicity and overall survival after methotrexate-based therapy in primary CNS lymphoma. Journal Of Clinical Oncology 2023, 41: 2079-2079. DOI: 10.1200/jco.2023.41.16_suppl.2079.Peer-Reviewed Original ResearchPrimary CNS lymphomaMethylenetetrahydrofolate reductase polymorphismPrimary CNS lymphoma patientsHD-MTXMethylenetetrahydrofolate reductaseOverall survivalC genotypeCNS lymphomaPatients treated with HD-MTXEffect of HD-MTXHD-MTX-based therapyAssociated with reduced overall survivalAssociation of MTHFR polymorphismsSeverity of leukoencephalopathyKaplan-Meier survival analysisProgression-free survivalLog-rank testMethylenetetrahydrofolate reductase genotypeAssociated with increased frequencyIntracellular folate metabolismAssociated with toxicityCerebral white matterInduction chemotherapyDecreased functional statusMassachusetts General HospitalTop advances of the year: Neuro‐oncology
Barden M, Omuro A. Top advances of the year: Neuro‐oncology. Cancer 2023, 129: 1467-1472. PMID: 36825454, DOI: 10.1002/cncr.34711.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBrain tumorsRecent phase 3 trialAnti-PD-1 immunotherapyCentral nervous system dysfunctionSingle-agent pembrolizumabHigh-dose chemotherapyPhase 3 trialPrimary CNS lymphomaStem cell transplantationLong-term outcomesLimited therapeutic optionsNervous system dysfunctionOngoing clinical trialsClinical trial landscapeDrug Administration approvalBRAF V600E mutationExcellent disease controlConsolidation therapyCNS lymphomaImproved survivalLeptomeningeal metastasesTherapeutic optionsCell transplantationCraniospinal irradiationPatient populationNCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022.
Horbinski C, Nabors L, Portnow J, Baehring J, Bhatia A, Bloch O, Brem S, Butowski N, Cannon D, Chao S, Chheda M, Fabiano A, Forsyth P, Gigilio P, Hattangadi-Gluth J, Holdhoff M, Junck L, Kaley T, Merrell R, Mrugala M, Nagpal S, Nedzi L, Nevel K, Nghiemphu P, Parney I, Patel T, Peters K, Puduvalli V, Rockhill J, Rusthoven C, Shonka N, Swinnen L, Weiss S, Wen P, Willmarth N, Bergman M, Darlow S. NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022. Journal Of The National Comprehensive Cancer Network 2023, 21: 12-20. PMID: 36634606, DOI: 10.6004/jnccn.2023.0002.Peer-Reviewed Original ResearchConceptsCentral nervous system cancerNervous system cancersNCCN guidelinesCNS cancersSystem cancersPrimary spinal cord tumorsExtensive brain metastasesNCCN Guidelines InsightsMetastatic spine tumorsPrimary CNS lymphomaSpinal cord tumorsBrain metastasesCNS lymphomaSystemic therapyCord tumorsSpine tumorsLeptomeningeal metastasesSurgical managementCNS tumorsRelevant new dataSpinal ependymomasBrain tumorsCancer panelTumorsCancer
2022
P11.46.A Whole exome sequencing identifies novel SLIT2 mutations in primary CNS lymphoma
Kaulen L, Erson-Omay E, Henegariu O, Karschnia P, Huttner A, Günel M, Baehring J. P11.46.A Whole exome sequencing identifies novel SLIT2 mutations in primary CNS lymphoma. Neuro-Oncology 2022, 24: ii68-ii68. PMCID: PMC9443199, DOI: 10.1093/neuonc/noac174.235.Peer-Reviewed Original ResearchPrimary CNS lymphomaCNS lymphomaOverall survivalExtension cohortEpstein-Barr virus statusKaplan-Meier methodLog-rank testCBio Cancer Genomics PortalReporter luciferase assaysFree survivalShorter OSTumor DNA samplesPCNSL patientsClinical outcomesShorter PFSSomatic insertions/deletionsVirus statusFavorable outcomeLymphoid malignanciesClinical observationsTumor tissuePersonalized careCDKN2A lossCopy number alterationsCohortMachine Learning in Differentiating Gliomas from Primary CNS Lymphomas: A Systematic Review, Reporting Quality, and Risk of Bias Assessment
Petersen G, Shatalov J, Verma T, Brim WR, Subramanian H, Brackett A, Bahar RC, Merkaj S, Zeevi T, Staib LH, Cui J, Omuro A, Bronen RA, Malhotra A, Aboian MS. Machine Learning in Differentiating Gliomas from Primary CNS Lymphomas: A Systematic Review, Reporting Quality, and Risk of Bias Assessment. American Journal Of Neuroradiology 2022, 43: 526-533. PMID: 35361577, PMCID: PMC8993193, DOI: 10.3174/ajnr.a7473.Peer-Reviewed Original ResearchConceptsMachine learning-based methodsLearning-based methodsBalanced data setData setsVector machine modelMachine learningClassification algorithmsMachine modelMachineAlgorithmData basesPrediction modelPromising resultsPrimary CNS lymphomaPrediction model study RiskRisk of biasRadiomic featuresClassifierSetCNS lymphomaWebLearningFeaturesQualitySystematic review
2021
Exome sequencing identifies SLIT2 variants in primary CNS lymphoma
Kaulen LD, Erson‐Omay E, Henegariu O, Karschnia P, Huttner A, Günel M, Baehring JM. Exome sequencing identifies SLIT2 variants in primary CNS lymphoma. British Journal Of Haematology 2021, 193: 375-379. PMID: 33481259, DOI: 10.1111/bjh.17319.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaShorter progression-free survivalCentral nervous system lymphomaRole of SLIT2Primary CNS lymphomaProgression-free survivalLarger validation cohortNervous system lymphomaShorter overall survivalPossible prognostic implicationsWarrants further investigationCNS lymphomaTumor DNA samplesOverall survivalPCNSL patientsSystem lymphomaPrognostic implicationsValidation cohortPCNSL pathogenesisLymphoid malignanciesFunction variantsTumor suppressor geneExome sequencingLuciferase assayLymphoma
2020
Clinical neuro-oncology for the neurologist.
Lukas R, Taylor J, Kurz S, Mohile N. Clinical neuro-oncology for the neurologist. Neurology Clinical Practice 2020, 10: 458-465. PMID: 33299675, PMCID: PMC7717629, DOI: 10.1212/cpj.0000000000000765.Peer-Reviewed Original ResearchNeuro-oncologyReclassification of tumorsClinical neuro-oncologyClinical practiceClinically relevant pointsCNS lymphomaNeuro-oncology patientsBrain metastasesInfiltrating gliomasBrain tumorsStandard managementAdult neurologistsTumorPatient carePatientsMolecular characteristicsEvolving fieldNeurologistsBrainLymphomaMetastasisMeningiomasGliomaCNSClinicDiagnosis of leptomeningeal metastasis (LM) through identification of circulating tumor cells (CTCs) in cerebrospinal fluid (CSF).
Fenn K, Singh V, Lee S, Cieremans D, Lassman A, Hershman D, Crew K, Accordino M, Trivedi M, Iwamoto F, Schultz R, Huynh L, Sales E, Fisher D, Mayer J, Kreisl T, Kalinsky K. Diagnosis of leptomeningeal metastasis (LM) through identification of circulating tumor cells (CTCs) in cerebrospinal fluid (CSF). Journal Of Clinical Oncology 2020, 38: 3567-3567. DOI: 10.1200/jco.2020.38.15_suppl.3567.Peer-Reviewed Original ResearchDiagnosis of LMLeptomeningeal metastasesCerebrospinal fluidLumbar punctureCSF cytologyNext-generation sequencingMedian age 56 yearsTime of LPSolid tumor diagnosisAge 56 yearsMetastatic breast cancerBreast cancer CTCsPeripheral blood samplesBreast cancer-related genesSomatic mutationsEvaluable ptsCNS lymphomaER statusHER2 statusBreast cancerStandard cytologyMetastatic therapyBlood samplesCSF samplesActionable mutationsPrimary dural lymphomas: Clinical presentation, management, and outcome
Karschnia P, Batchelor TT, Jordan JT, Shaw B, Winter SF, Barbiero FJ, Kaulen LD, Thon N, Tonn J, Huttner AJ, Fulbright RK, Loeffler J, Dietrich J, Baehring JM. Primary dural lymphomas: Clinical presentation, management, and outcome. Cancer 2020, 126: 2811-2820. PMID: 32176324, DOI: 10.1002/cncr.32834.Peer-Reviewed Original ResearchConceptsPrimary dural lymphomaPrimary CNS lymphomaNon-Hodgkin lymphomaCNS lymphomaOverall survivalDural lymphomaPrimary central nervous system lymphomaT-cell non-Hodgkin lymphomaB-cell non-Hodgkin lymphomaCentral nervous system lymphomaLarge B-cell lymphomaMedian apparent diffusion coefficient (ADC) valuesAvid contrast enhancementMedian overall survivalCerebrospinal fluid analysisNervous system lymphomaMarginal zone lymphomaB-cell lymphomaExtra-axial massApparent diffusion coefficient (ADC) valuesMassachusetts General HospitalAggressive surgeryMultimodality treatmentSystem lymphomaSystemic involvement
2017
CNS Leukemia
An Y, Roberts K. CNS Leukemia. 2017, 311-333. DOI: 10.1007/978-3-319-55430-3_17.Peer-Reviewed Original ResearchAcute myeloid leukemiaAcute lymphoblastic leukemiaAllogeneic stem cell transplantCentral nervous system involvementPediatric acute lymphoblastic leukemiaInduction systemic therapyHigh-risk patientsNervous system involvementTotal body irradiationStem cell transplantUse of radiotherapyHigh cure ratesIntensity of therapyBlood-brain barrierCNS leukemiaCNS relapseCNS lymphomaPalliative therapySystemic therapyPrognostic factorsBody irradiationCell transplantRisk stratificationCure rateCommon cancerUsefulness of enhancement-perfusion mismatch in differentiation of CNS lymphomas from other enhancing malignant tumors of the brain
Goyal P, Kumar Y, Gupta N, Malhotra A, Gupta S, Gupta S, Mangla M, Mangla R. Usefulness of enhancement-perfusion mismatch in differentiation of CNS lymphomas from other enhancing malignant tumors of the brain. Quantitative Imaging In Medicine And Surgery 2017, 7: 511-519. PMID: 29184763, PMCID: PMC5682400, DOI: 10.21037/qims.2017.09.03.Peer-Reviewed Original ResearchCNS lymphomaGlioblastoma multiformeMalignant lesionsMean rCBVSecondary central nervous system lymphomaCentral nervous system lymphomaDifferentiation of CNSMagnetic resonance perfusion imagingNervous system lymphomaRelative cerebral blood volumePerfusion imagesDSC perfusion MRCerebral blood volumeRelative CBV valuesMann-Whitney testEnhancing partSystem lymphomaLymphoma patientsTreatment optionsAnaplastic gliomasTumor differentiationMalignant tumorsPerfusion MRGlioma patientsBlood volumeIbrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Grommes C, Pastore A, Palaskas N, Tang SS, Campos C, Schartz D, Codega P, Nichol D, Clark O, Hsieh WY, Rohle D, Rosenblum M, Viale A, Tabar VS, Brennan CW, Gavrilovic IT, Kaley TJ, Nolan CP, Omuro A, Pentsova E, Thomas AA, Tsyvkin E, Noy A, Palomba ML, Hamlin P, Sauter CS, Moskowitz CH, Wolfe J, Dogan A, Won M, Glass J, Peak S, Lallana EC, Hatzoglou V, Reiner AS, Gutin PH, Huse JT, Panageas KS, Graeber TG, Schultz N, DeAngelis LM, Mellinghoff IK. Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discovery 2017, 7: 1018-1029. PMID: 28619981, PMCID: PMC5581705, DOI: 10.1158/2159-8290.cd-17-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntineoplastic AgentsCARD Signaling Adaptor ProteinsCentral Nervous System NeoplasmsDrug Resistance, NeoplasmFemaleGuanylate CyclaseHumansLymphoma, B-CellMaleMaximum Tolerated DoseMiddle AgedMutationPiperidinesProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidinesTreatment OutcomeYoung AdultConceptsPrimary central nervous system lymphomaBruton's tyrosine kinaseB-cell lymphomaRefractory B-cell lymphomaB cell antigen receptorCentral nervous system lymphomaRole of BTKDiffuse large B-cell lymphomaLarge B-cell lymphomaPhase I clinical trialClass BTK inhibitorIncomplete tumor responseNervous system lymphomaToll-like receptorsPI3K/mTORIbrutinib responseCNS lymphomaClinical responseComplete responseReceptor-associated proteinSystem lymphomaActivation markersTumor responseClinical trialsPCNSL cellsUpdated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).
Grommes C, Gavrilovic I, Kaley T, Nolan C, Omuro A, Wolfe J, Pentsova E, Hatzoglou V, Mellinghoff I, DeAngelis L. Updated results of single-agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL). Journal Of Clinical Oncology 2017, 35: 7515-7515. DOI: 10.1200/jco.2017.35.15_suppl.7515.Peer-Reviewed Original ResearchSecondary CNS lymphomaProgression-free survivalMedian progression-free survivalALT elevationCNS lymphomaAdverse eventsClinical responseGrade 4 adverse eventsRecurrent/refractory diseaseAggressive primary brain tumorCerebrospinal fluid involvementCNS lymphoma patientsGrade 5 eventsManageable adverse eventsGrade 3 toxicityMedian overall survivalMethotrexate-based chemotherapyEnd-organ functionNormal end-organ functionSingle-agent ibrutinibUrinary tract infectionPrimary brain tumorsPromising clinical responsesMantle cell lymphomaCommon toxicitiesPhase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).
Tun H, Johnston P, Grommes C, Reeder C, Omuro A, Menke D, Copland J, DeAngelis L, Witzig T. Phase I clinical trial on pomalidomide and dexamethasone in treating patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL). Journal Of Clinical Oncology 2017, 35: 7516-7516. DOI: 10.1200/jco.2017.35.15_suppl.7516.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaOverall response rateRefractory primary central nervous system lymphomaPhase I clinical trialPrimary vitreoretinal lymphomaMTD cohortStable diseaseClinical trialsCentral nervous system lymphomaTherapeutic activityDiffuse large B-cell lymphomaLarge B-cell lymphomaDose level 3Grade 3/4 toxicitiesNovel immunomodulatory agentsNervous system lymphomaCycles of treatmentDose escalation levelsCSF/blood ratioB-cell lymphomaExcellent CNS penetrationPO weeklyPomalidomide treatmentPseudo progressionCNS lymphoma
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