Extensive brainstem infiltration, not mass effect, is a common feature of end-stage cerebral glioblastomas.
autopsy
brainstem
glioblastoma
medulla
midbrain
pons
postmortem
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
15 04 2020
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
470-479Subventions
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.
Références
Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):144-50
pubmed: 17306935
J Neurooncol. 2014 Dec;120(3):597-605
pubmed: 25168214
Cancer Cell. 2012 Jul 10;22(1):21-35
pubmed: 22789536
Radiat Oncol. 2013 Apr 23;8:97
pubmed: 24499582
N Engl J Med. 2005 Mar 10;352(10):997-1003
pubmed: 15758010
Neuro Oncol. 2010 Nov;12(11):1162-6
pubmed: 20511193
Acta Neuropathol. 2016 Dec;132(6):917-930
pubmed: 27664011
Eur J Cancer. 2012 Sep;48(14):2192-202
pubmed: 22608262
Cancer. 1979 Oct;44(4):1256-72
pubmed: 387205
J Neurooncol. 1991 Apr;10(2):179-85
pubmed: 1654403
N Engl J Med. 2017 Nov 16;377(20):1954-1963
pubmed: 29141164
Neuro Oncol. 2010 Mar;12(3):233-42
pubmed: 20167811
Clin Neuropathol. 2015 Nov-Dec;34(6):330-42
pubmed: 26308254
Neurosurgery. 1990 Oct;27(4):516-21; discussion 521-2
pubmed: 2172859
Cancer. 1983 Dec 15;52(12):2320-33
pubmed: 6315212
JAMA. 2017 Dec 19;318(23):2306-2316
pubmed: 29260225
Clin Cancer Res. 2018 Sep 1;24(17):4175-4186
pubmed: 29437767
MedGenMed. 2006 Sep 21;8(3):80
pubmed: 17406199
Neuro Oncol. 2016 Mar;18(3):379-87
pubmed: 26681766
J Neurosurg. 1987 Jun;66(6):865-74
pubmed: 3033172
Autops Case Rep. 2017 Dec 8;7(4):1-2
pubmed: 29259925
Acta Neuropathol. 2013 May;125(5):621-36
pubmed: 23512379
N Engl J Med. 2014 Feb 20;370(8):699-708
pubmed: 24552317
Int J Radiat Oncol Biol Phys. 1989 Dec;17(6):1347-50
pubmed: 2557310
Nat Med. 2018 Sep;24(9):1459-1468
pubmed: 30104766
J Magn Reson Imaging. 2010 Oct;32(4):809-17
pubmed: 20882611
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Neurosurgery. 1989 Oct;25(4):533-40
pubmed: 2797391
J Neurooncol. 2014 Jan;116(1):169-75
pubmed: 24135848
N Engl J Med. 2014 Feb 20;370(8):709-22
pubmed: 24552318