DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management.
meningioma
methylation
nomogram
predictor
recurrence
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
11 07 2019
11 07 2019
Historique:
pubmed:
4
6
2019
medline:
6
8
2020
entrez:
4
6
2019
Statut:
ppublish
Résumé
Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma. DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts. The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03-0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8-7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22-0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3-11.1, P < 0.001) with clinical implications. The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.
Sections du résumé
BACKGROUND
Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma.
METHODS
DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts.
RESULTS
The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03-0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8-7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22-0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3-11.1, P < 0.001) with clinical implications.
CONCLUSIONS
The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.
Identifiants
pubmed: 31158293
pii: 5510481
doi: 10.1093/neuonc/noz061
pmc: PMC6620635
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
901-910Subventions
Organisme : NCI NIH HHS
ID : P50 CA221747
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Investigateurs
Kenneth Aldape
(K)
Karolyn Au
(K)
Jill Barnhartz-Sloan
(J)
Wenya Linda Bi
(WL)
Priscilla K Brastianos
(PK)
Nicholas Butowski
(N)
Carlos Carlotti
(C)
Michael D Cusimano
(MD)
Francesco DiMeco
(F)
Katharine Drummond
(K)
Ian F Dunn
(IF)
Evanthia Galanis
(E)
Caterina Giannini
(C)
Roland Goldbrunner
(R)
Brent Griffith
(B)
Rintaro Hashizume
(R)
C Oliver Hanemann
(CO)
Christel Herold-Mende
(C)
Craig Horbinski
(C)
Raymond Y Huang
(RY)
David James
(D)
Michael D Jenkinson
(MD)
Christine Jungk
(C)
Timothy J Kaufman
(TJ)
Boris Krischek
(B)
Daniel Lachance
(D)
Christian Lafougère
(C)
Ian Lee
(I)
Jeff C Liu
(JC)
Yasin Mamatjan
(Y)
Tathiane M Malta
(TM)
Christian Mawrin
(C)
Michael McDermott
(M)
David Munoz
(D)
Farshad Nassiri
(F)
Houtan Noushmehr
(H)
Ho-Keung Ng
(HK)
Arie Perry
(A)
Farhad Pirouzmand
(F)
Laila M Poisson
(LM)
Bianca Pollo
(B)
David Raleigh
(D)
Felix Sahm
(F)
Andrea Saladino
(A)
Thomas Santarius
(T)
Christian Schichor
(C)
David Schultz
(D)
Nils O Schmidt
(NO)
Warren Selman
(W)
Andrew Sloan
(A)
Julian Spears
(J)
James Snyder
(J)
Suganth Suppiah
(S)
Ghazaleh Tabatabai
(G)
Marcos Tatagiba
(M)
Daniela Tirapelli
(D)
Joerg C Tonn
(JC)
Derek Tsang
(D)
Michael A Vogelbaum
(MA)
Andreas von Deimling
(A)
Patrick Y Wen
(PY)
Tobias Walbert
(T)
Manfred Westphal
(M)
Adriana M Workewych
(AM)
Gelareh Zadeh
(G)
Informations de copyright
Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2019.
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