CHICAGO — The 2016 World Health Organization (WHO) Classification of Infiltrating Gliomas alters diagnostic criteria, providing the basis for clinical trial inclusion or exclusion based on an integrated diagnosis and setting the stage for all future research, according to a summary of 4 posters related to CNS biomarkers presented at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.
Poster discussion session discussant Howard Colman, MD, PhD, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, said that “to optimize patient treatment going forward,” the field needs “to extract as much information as possible using the new classification from prior retrospective data sets.”
Three studies by Tabouret et al1 and Bell et al2,3 “demonstrated the utility of applying new markers and classification to large retrospective cohorts and prior prospective studies,” he said. However, “it will be interesting to see whether full WHO reclassification indicates any differential effects of prior treatment arms or approaches within new diagnostic groups in retrospective and prospective cohorts.
For example, prior studies were not powered for identification of treatment effects in molecular subgroups, which were not known at the time of study initiation; therefore, perhaps there is a “need to combine multiple retrospective and prospective data sets for sufficient power,” Dr. Colman said.
Tabouret and colleagues evaluated the diagnostic and prognostic effects of reclassifying 1041 high-grade gliomas from the French POLA network using molecular data according to the new WHO classification. They performed testing for IDH1 R132H and ATRX by immunohistochemistry (IHC); 1p/19q deletion, 7p gain, and 10q loss by DNA array; and IDH 1 and 2 and H3.3 K27M by sequencing. Also available was age, gender, Karnofsky performance status, cognitive status, extent of resection, and first-line treatment; histopathology information included mitoses, necrosis, and microvascular proliferation.
Dr. Colman said this study validated the prognostic associations of the new WHO classification and “nicely demonstrates effects of reclassification using new diagnostic criteria.”
The first study by Bell and colleagues re-analyzed outcomes from a prior phase 3 study of anaplastic gliomas using a subset of molecular markers. These included IDH 1 and 2 by IHC and sequencing; TERT promoter by sequencing; and ATRX, CIC, and FUBP1 by sequencing panel. The investigators looked at the prognostic association of individual alterations within both treatment arms and found that IDH and ATRX “showed significant association” with progression-free survival and overall survival in multivariate analysis.
The second study from Bell’s team was a retrospective validation of key molecular markers in a prospective phase 3 trial of high-risk, low-grade gliomas of various histologies. Results showed only IDH status showed significant association with progression-free survival in multivariate analysis.
Finally, the study by Vera et al4 “demonstrates the power of combining clinical and molecular assessments in glioma studies to identify novel mechanisms underlying patient symptoms and toxicities for risk-stratification and interventions to improve patient outcomes.”
The study combined clinical assessment of fatigue and predetermined biomarker hypotheses for single nucleotide polymorphism (SNP) predisposition and identified clinical factors and SNPs associated with risk and severity of fatigue. In multivariate analysis, they found 2 SNPs related to circadian rhythm pathways to be significant.
These results show it is possible to expand biomarker analysis in brain tumor trials and retrospective analyses beyond tumor efficacy end points, Dr. Colman said.
1. Tabouret E, Nguyen AT, Dehais C, et al. Validation of the new glioma WHO classification in the French POLA network: Analysis of 1041 cases. Poster presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.
2. Bell EH, McElroy JP, Fleming J, et al. Comprehensive mutation analysis in NRG Oncology/RTOG 9813: a phase III trial of RT + TMZ vs RT + nu for anaplastic astrocytoma and mixed anaplastic oligoastrocytoma (Astrocytoma Dominant). Poster presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.
3. Bell EH, McElroy JP, Fleming J, et al. Comprehensive mutation analysis in NRG Oncology/RTOG 9802: a phase III study of RT vs RT + PCV in high-risk low-grade gliomas (LGGs). Poster presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.
4. Vera E, Scheurer ME, Zhou R, et al. Investigation of risk factors associated with fatigue in glioma patients. Poster presentation at: ASCO 2016 Annual Meeting; June 3-7, 2016; Chicago, IL.