Evidence map›Paper›PMID 33625503›Full record

ArticleNeuro-oncology2021

Tumor metabolism and neurocognition in CNS lymphoma.

Huimin Geng, Mazie Tsang, Lakshmipriya Subbaraj, Joseph Cleveland, Lingjing Chen, Ming Lu, Jigyasa Sharma, Daniel B Vigneron, John Kurhanewicz, Marisa LaFontaine and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Huimin GengDepartment of Laboratory Medicine, University of California, San Francisco (UCSF), San Francisco, California, USA.
Mazie TsangDivision of Hematology/Oncology, University of California, San Francisco (UCSF), San Francisco, California, USA.
Lakshmipriya SubbarajDepartment of Medicine, University of California, San Francisco (UCSF), San Francisco, California, USA.
Joseph ClevelandDepartment of Medicine, University of California, San Francisco (UCSF), San Francisco, California, USA.
Lingjing ChenDepartment of Medicine, University of California, San Francisco (UCSF), San Francisco, California, USA.
Ming LuDivision of Hematology/Oncology, University of California, San Francisco (UCSF), San Francisco, California, USA.
Jigyasa SharmaDepartment of Radiology and Biomedical Imaging, University of California, San Diego, San Diego, California, USA.
Daniel B VigneronDepartment of Radiology and Biomedical Imaging, University of California, San Diego, San Diego, California, USA.
John KurhanewiczDepartment of Radiology and Biomedical Imaging, University of California, San Diego, San Diego, California, USA.
Marisa LaFontaineDepartment of Radiology and Biomedical Imaging, University of California, San Diego, San Diego, California, USA.
Tracy LuksDepartment of Radiology and Biomedical Imaging, University of California, San Diego, San Diego, California, USA.
Bruce A BarshopDepartment of Genetics and Pediatrics, University of California, San Diego, San Diego, California, USA.
Jon GangoitiDepartment of Genetics and Pediatrics, University of California, San Diego, San Diego, California, USA.
Javier E Villanueva-MeyerHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, California, USA.
James L RubensteinHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco (UCSF), San Francisco, California, USA.
University of California, San Diego · USUniversity of California, San Francisco · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

TR&D3: Open-Source Tools for Processing Hyperpolarized MR DataP41EB013598 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Daniel B Vigneron · 2011 to 2026
$19.9M
RESEARCH TRAINING IN GERIATRIC MEDICINET32AG000212 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alexander Keliimoeanu Smith · 1991 to 2026
$7.7M
The Role of Interleukin-4 (IL-4) in the Pathogenesis of Non-Hodgkin's LymphomaR01CA139083 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUBENSTEIN, JAMES LOUIS · 2009 to 2018
$3.4M
Application of Hyperpolarized 13C Magnetic Resonance Imaging to Detect Target Inhibition of NF-kB Activation and Response in Primary CNS LymphomaR01CA239462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAUMEIL, MYRIAM MARIANNE, RUBENSTEIN, JAMES LOUIS · 2019 to 2023
$3.1M
NCI NIH HHS R01 CA139083NCI NIH HHS R01 CA239462NIA NIH HHS T32 AG000212NIBIB NIH HHS P41 EB013598
6 · The paper itself

Abstract

backgroundThe mechanistic basis for neurocognitive deficits in central nervous system (CNS) lymphoma and other brain tumors is incompletely understood. We tested the hypothesis that tumor metabolism impairs neurotransmitter pathways and neurocognitive function.

methodsWe performed serial cerebrospinal fluid (CSF) metabolomic analyses using liquid chromatography-electrospray tandem mass spectrometry to evaluate changes in the tumor microenvironment in 14 patients with recurrent CNS lymphoma, focusing on 18 metabolites involved in neurotransmission and bioenergetics. These were paired with serial mini-mental state examination (MMSE) and MRI studies for tumor volumetric analyses. Patients were analyzed in the setting of the phase I trial of lenalidomide/rituximab. Associations were assessed by Pearson and Spearman correlation coefficient. Generalized estimating equation (GEE) models were also established, adjusting for within-subject repeated measures.

resultsOf 18 metabolites, elevated CSF lactate correlated most strongly with lower MMSE score (P < 8E-8, ρ = -0.67). High lactate was associated with lower gamma-aminobutyric acid (GABA), higher glutamate/GABA ratio, and dopamine. Conversely, high succinate correlated with higher MMSE scores. Serial analysis demonstrated a reproducible, time-dependent, reciprocal correlation between changes in lactate and GABA concentrations. While high lactate and low GABA correlated with tumor contrast-enhancing volume, they correlated more significantly with lower MMSE scores than tumor volumes.

conclusionsWe provide evidence that lactate production and Warburg metabolism may impact neurotransmitter dysregulation and neurocognition in CNS lymphomas. We identify novel metabolomic biomarkers that may be applied in future studies of neurocognition in CNS lymphomas. Elucidation of mechanistic interactions between lymphoma metabolism, neurotransmitter imbalance, and neurocognition may promote interventions that preserve cognitive function.

Indexed as

Brain NeoplasmsCentral Nervous System NeoplasmsLymphomaLymphoma, Non-HodgkinHumansRituximabTumor MicroenvironmentRituximablymphoma metabolismneurocognitionneurotransmitter pathways

Identifiers

PMID33625503
PMCPMC8485453
OpenAlexW3129341959

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.