Prognostic and Predictive Effect of Age in Molecularly Defined Lower-Grade Gliomas
Abstract
PURPOSE Age ≥40 years is regarded as a high-risk feature and an indication for adjuvant chemoradiotherapy for patients with lower-grade glioma in clinical practice guidelines. It is unclear whether age remains a relevant prognostic factor for contemporary definitions of lower-grade gliomas in the molecular era. METHODS The Prospective Gliomas Research (PROGRES) database contains individual patient-level data from 11 prospective clinical trials or observational registries of histologically defined lower-grade 2-3 oligodendroglioma or astrocytoma. We determined the association of age (18-39 years v ≥40 years) with progression-free survival (PFS) stratified by isocitrate dehydrogenase 1 or 2 ( IDH1/2 ) status, using log-rank tests and Cox regression models. We validated our findings in a separate multi-institutional retrospective cohort (Retrospective Glioma Research [REGRES] database). RESULTS We identified 1,619 and 1,292 eligible patients in the PROGRES and REGRES cohorts, respectively. IDH -wildtype tumors were more common in patients 40 years and older (38% v 5%, odds ratio: 11.3 [95% CI, 6.5 to 19.7]). Age was associated with PFS in IDH -wildtype (5-year PFS for ≥40 v 18-39 years: 6% v 24%, hazard ratio [HR], 1.74 [95% CI, 1.21 to 2.50]) but not in IDH -mutant glioma (60% v 59%, HR, 0.89 [95% CI, 0.76 to 1.05], P interaction < .001). In IDH -wildtype tumors, older age predicted aggressive molecular features, including TERT promoter mutation (65% v 28%), EGFR amplification (41% v 15%), and chromosome +7/–10 alteration (57% v 25%). In a pooled analysis of four clinical trials, age was not predictive of a benefit from chemoradiotherapy versus radiotherapy alone for IDH -mutant glioma. CONCLUSION In the absence of additional clinical or molecular risk factors, age alone should not be considered an indication for administration or deferral of adjuvant treatment. Practice guidelines should be revised to reflect contemporary prognostic factors in the molecular era.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (37)
Connor J. Kinslow
Giuseppe Minniti
Paul D. Brown
Michael A. Vogelbaum
Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Karla V. Ballman
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Ann Mercurio
1Icahn School of Medicine at Mount Sinai Morningside/West, Department of Medicine, New York, United States
Markus D. Siegelin
Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY
Emre Kocakavuk
Kyle Tuohy
Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, PA
Alireza Mansouri
Mehdi Touat
François Ducray
Neuro-Oncology Department, Hospices Civils de Lyon, Cancer Research Center of Lyon, Université Lyon 1, Lyon, France
Caroline Dehais
Service de Neuro-oncologie, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, Paris Brain Institute, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière—Charles Foix, Paris, France
Angelo Dipasquale
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
Matteo Simonelli
David M. DeStephano
Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY
Jack Grinband
Department of Radiology, Columbia University Irving Medical Center, New York, NY
James B. Yu
Department of Radiation Oncology and Applied Sciences, Dartmouth Hitchcock Medical Center, Lebanon, NH
Henry Walch
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
Mitchell I. Parker
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Igor Shuryak
Soumyajit Roy
Shawn L. Hervey-Jumper
Matthew Gallitto
Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY
David P. Horowitz
Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY
Guy M. McKhann
Department of Neurosurgery, Columbia University
Michael B. Sisti
Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY
Jeffrey N. Bruce
Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY
Peter Canoll
Quinn T. Ostrom
Alfred I. Neugut
Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY
Luke R.G. Pike
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Fabio M. Iwamoto
10Department of Neuro-Oncology, Columbia University Irving Medical Center, New York, NY
Simon K. Cheng
Lisa A. Kachnic
Minesh P. Mehta
Tony J.C. Wang
Department of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, NY