Reflecting recent significant classification changes and new data on the use of biomarkers to inform treatment for central nervous system tumors, a new guideline offers oncologists up-to-date recommendations for managing gliomas in adults with neurologic cancer.1
“Over the past decade, there have been several trials in gliomas that have been practice-changing—and in particular, they have demonstrated a role for chemotherapy across many glioma subtypes,” said expert Panel Co-Chair Nimish A. Mohile, MD, of the University of Rochester Medical Center. “At the same time, two significant revisions to the World Health Organization classification of brain tumors—in 2016 and July 2021—inform clinicians [on] how to identify glioma subtypes that are most likely to benefit from chemotherapy.”
Nimish A. Mohile, MD
Jaishri Blakeley, MD
The guideline represents an effort to ensure community and specialty oncologists understand these and other recent changes in the field of neuro-oncology—particularly the new taxonomy, which represents a significant departure from how these tumor types were previously organized and labeled. Expert Panel Co-Chair Jaishri Blakeley, MD, of Johns Hopkins University, also emphasized emerging data on predictive and prognostic molecular biomarkers as a driving factor behind the guideline’s development.
“Unfortunately, most adults with gliomas have terrible outcomes,” she said. “But there are rare exceptions where someone does really well, and we didn’t know why. In the past several years, with emerging molecular data in gliomas, we have been able to say, ‘This person did well because of X, and this person did well because of Y.’ Now that some key predictive and prognostic factors have been established, we needed to provide clinicians with information for practical treatment and management decision-making.”
The guideline was developed in partnership between ASCO and the Society for Neuro-Oncology (SNO) to ensure it speaks to both community oncologists and neuro-oncology specialists.
Fine-Tuning Treatment Decisions
The guideline underscores the importance of access to molecular testing for isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations and O6-methylguanine-DNA methyl-transferase (MGMT) for any patient with a new glioma diagnosis, as their presence (or absence) can influence treatment choice. Other relevant biomarkers should be assessed as well.
“A specific subtype of glioma that’s very rare is oligodendroglioma, and there’s a specific marker for it called 1p/19q codeletion,” Dr. Blakeley said. “It’s absolutely critical for management that if there’s any question of an oligodendroglioma diagnosis that the codeletion testing be done, because it changes how you counsel patients and their family about prognosis and how you approach management.”
Similarly, she added, it is important to recognize that the absence of certain markers such as IDH1/2 mutations or 1p/19q codeletions have prognostic and predictive meaning, including new evidence that some classically used aggressive treatments may not improve outcomes and expose patients without these markers to toxicity unnecessarily.
“We were able to incorporate evidence from a recent study evaluating non-codeleted anaplastic astrocytomas [the CATNON study; ClinicalTrials.gov identifier NCT00626990], and one of the key findings in that study was that concurrent temozolomide was not beneficial for nonglioblastoma high-grade gliomas,” Dr. Mohile added. “That may be a change for many U.S. clinicians.”
However, he also noted that although the guideline is written to reflect the latest evidence, it also gives oncologists latitude to make treatment decisions based on each patient’s unique circumstances. For instance, the guideline addresses specific chemotherapy and radiotherapy for both diffuse astrocytic and oligodendroglial tumors but suggests clinicians consider factors like tumor stage, patient functional status, and toxicity of chemotherapy in weighing the potential harms vs benefits of these treatments.
Emerging Research Gaps
One of the biggest challenges the expert panel faced was translating the results of trials that enrolled patients based on previous classifications to the newer classification system, Dr. Mohile said. And because some of the studies took 10 years to accrue plus another decade to be published, redoing those studies to match the new nomenclature would be difficult.
“I think the solution is to invest the money and time and do a complete characterization of tumor samples when enrolling patients in clinical trials, which is not really done now because it’s not the standard of care and it’s costly,” he said. “But if we had all of that information in the database, in 10 years, when we learn this marker or that marker is important, we can look back and see how it impacts survival.”
Moreover, because of a lack of data for some tumor subtypes, the guideline also stresses the importance of improving clinical trial enrollments for patients with central nervous system tumors in general but especially for recurrent gliomas and the rare subtypes like midline gliomas.
“We also need to redouble our efforts on research for patients without IDH1/2 mutations or 1p/19q codeletions, as they have the least number of effective therapies available,” Dr. Blakeley added. “We have to keep the pressure on for federal funding for clinical trials and keep encouraging the pharmaceutical industry to support clinical trials for these tumors.”
REFERENCE
1. Mohile NA, Messersmith H, Gatson NT, et al: Therapy for diffuse astrocytic and oligodendroglial tumors in adults: ASCO-SNO guideline. J Clin Oncol 40:403-426, 2022.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, December 15, 2021. All rights reserved.
