Extensive brainstem infiltration, not mass effect, is a common feature of end-stage cerebral glioblastomas.


Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
15 04 2020
Historique:
pubmed: 12 11 2019
medline: 28 4 2021
entrez: 12 11 2019
Statut: ppublish

Résumé

Progress in extending the survival of glioblastoma (GBM) patients has been slow. A better understanding of why patient survival remains poor is critical to developing new strategies. Postmortem studies on GBM can shed light on why patients are dying. The brains of 33 GBM patients were autopsied and examined for gross and microscopic abnormalities. Clinical-pathologic correlations were accomplished through detailed chart reviews. Data were compared with older published autopsy GBM studies that predated newer treatment strategies, such as more extensive surgical resection and adjuvant temozolomide. In older GBM autopsy series, mass effect was observed in 72% of brains, with herniation in 50% of all cases. Infiltration of tumor into the brainstem was noted in only 21% of those older cases. In the current series, only 10 of 33 (30%) GBMs showed mass effect (P = 0.0003), and only 1 (3%) showed herniation (P < 0.0001). However, extensive GBM infiltration of the brainstem was present in 22 cases (67%, P < 0.0001), with accompanying destruction of the pons and white matter tracts. There was a direct correlation between longer median patient survival and the presence of brainstem infiltration (16.1 mo in brainstem-invaded cases vs 9.0 mo in cases lacking extensive brainstem involvement; P = 0.0003). With improving care, severe mass effect appears to be less common in GBM patients today, whereas dissemination, including life-threatening brainstem invasion, is now more pronounced. This has major implications regarding preclinical GBM models, as well as the design of clinical trials aimed at further improving patient survival.

Sections du résumé

BACKGROUND
Progress in extending the survival of glioblastoma (GBM) patients has been slow. A better understanding of why patient survival remains poor is critical to developing new strategies. Postmortem studies on GBM can shed light on why patients are dying.
METHODS
The brains of 33 GBM patients were autopsied and examined for gross and microscopic abnormalities. Clinical-pathologic correlations were accomplished through detailed chart reviews. Data were compared with older published autopsy GBM studies that predated newer treatment strategies, such as more extensive surgical resection and adjuvant temozolomide.
RESULTS
In older GBM autopsy series, mass effect was observed in 72% of brains, with herniation in 50% of all cases. Infiltration of tumor into the brainstem was noted in only 21% of those older cases. In the current series, only 10 of 33 (30%) GBMs showed mass effect (P = 0.0003), and only 1 (3%) showed herniation (P < 0.0001). However, extensive GBM infiltration of the brainstem was present in 22 cases (67%, P < 0.0001), with accompanying destruction of the pons and white matter tracts. There was a direct correlation between longer median patient survival and the presence of brainstem infiltration (16.1 mo in brainstem-invaded cases vs 9.0 mo in cases lacking extensive brainstem involvement; P = 0.0003).
CONCLUSIONS
With improving care, severe mass effect appears to be less common in GBM patients today, whereas dissemination, including life-threatening brainstem invasion, is now more pronounced. This has major implications regarding preclinical GBM models, as well as the design of clinical trials aimed at further improving patient survival.

Identifiants

pubmed: 31711239
pii: 5618827
doi: 10.1093/neuonc/noz216
pmc: PMC7158646
doi:

Substances chimiques

Temozolomide YF1K15M17Y

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

470-479

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS102669
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS107833
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221747
Pays : United States

Commentaires et corrections

Type : ErratumIn
Type : CommentIn

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Michael R Drumm (MR)

Department of Neurological Surgery, Northwestern University, Chicago, Illinois.

Karan S Dixit (KS)

Department of Neurology, Northwestern University, Chicago, Illinois.

Sean Grimm (S)

Department of Neurology, Northwestern University, Chicago, Illinois.

Priya Kumthekar (P)

Department of Neurology, Northwestern University, Chicago, Illinois.

Rimas V Lukas (RV)

Department of Neurology, Northwestern University, Chicago, Illinois.

Jeffrey J Raizer (JJ)

Department of Neurology, Northwestern University, Chicago, Illinois.

Roger Stupp (R)

Department of Neurology, Northwestern University, Chicago, Illinois.

Milan G Chheda (MG)

Department of Medicine, Washington University School of Medicine, St Louis, Missouri.

Kwok-Ling Kam (KL)

Department of Pathology, Northwestern University, Chicago, Illinois.

Matthew McCord (M)

Department of Pathology, Northwestern University, Chicago, Illinois.

Sean Sachdev (S)

Department of Radiation Oncology, Northwestern University, Chicago, Illinois.

Timothy Kruser (T)

Department of Radiation Oncology, Northwestern University, Chicago, Illinois.

Alicia Steffens (A)

Department of Neurological Surgery, Northwestern University, Chicago, Illinois.

Rodrigo Javier (R)

Department of Neurological Surgery, Northwestern University, Chicago, Illinois.

Kathleen McCortney (K)

Department of Neurological Surgery, Northwestern University, Chicago, Illinois.

Craig Horbinski (C)

Department of Neurological Surgery, Northwestern University, Chicago, Illinois.
Department of Pathology, Northwestern University, Chicago, Illinois.

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