“Over the last two years or so, there have been advances for the first time in the management of glioma, in which we have new treatments called targeted therapies that target the mutation,” Dr. Esquenazi tells SurvivorNet.

“Many of these patients can live for decades,” he adds. “I generally tell them sometimes that they’ll be able to see their kids grow — and I hope we have more advances in the future.”

How Is Glioma Graded?

Gliomas arise from glial cells or their precursors, the supporting cells of the central nervous system. Unlike most solid tumors, they are not staged by how far they have spread. They are classified and graded on the World Health Organization’s Classification of Tumors of the Central Nervous System (CNS) grades 1 through 4.

The disease is also classified by type and molecular markers.

Adult-type diffuse gliomas fall into three types, based on IDH mutation and 1p/19q codeletion status. IDH-mutant tumors are no longer called glioblastoma, even at grade 4.

WATCH: IDH Mutations and Inhibitors in Gliomas

• Grade 1 gliomas are the least aggressive and typically occur in children. They grow slowly, and pilocytic astrocytomas fall into this category. When surgeons can fully remove the tumor, surgery is often curative and long‑term outcomes are excellent.
• Grade 2 gliomas are still low‑grade but more biologically complex. They grow slowly yet can progress to higher‑grade disease. Surgery is the cornerstone of care, with some patients requiring radiation, chemotherapy, or newer targeted options such as vorasidenib.
• Grade 3 gliomas are high‑grade and malignant. They grow more rapidly and almost always require multimodal treatment — surgery followed by radiation and chemotherapy. Recurrence is common, and therapy focuses on slowing progression.
• Grade 4 gliomas (glioblastomas) are the most aggressive. These fast‑growing tumors infiltrate surrounding brain tissue and demand intensive treatment with surgery, radiation, and chemotherapy. Clinical trials and experimental therapies are often considered, as research continues to push for better survival outcomes.

The distinction matters clinically. A grade 4 IDH-mutant astrocytoma and an IDH-wildtype glioblastoma share a grade but differ in biology and prognosis.

IDH-wildtype diffuse astrocytic tumors with certain molecular features can be classified as glioblastoma even when they look lower-grade under the microscope.

Surgery: Safer and More Complete

Surgery is usually the first and most important step in treating lower‑grade glioma. Dr. Esquenazi explains that today’s techniques are far safer and more effective than they were decades ago, giving many patients a much better outlook.

“There has certainly been a lot of advances in the surgical field because we can do these surgeries very safely and very successfully. And that was not the case many decades ago,” he says.

His own practice integrates brain mapping for awake craniotomy, stereotactic navigation, fluorescence-guided microscopy, laser ablation, and intraventricular endoscopy to improve safety and maximize resection.

For lower-grade patients, he stresses early and aggressive treatment, followed by long-term surveillance.

“They can live many years if we are aggressive and if we treat them early,” Dr. Esquenazi says.

He adds that his team monitors patients closely after surgery, and that some patients may not need additional treatment when a complete resection of the visible tumor on imaging is achieved.

Targeted Therapy: IDH Inhibition

Some gliomas — including astrocytoma and oligodendroglioma — have changes in genes called IDH1 or IDH2. When these mutations are present, the tumor makes a substance called 2‑hydroxyglutarate that helps it grow. That’s why doctors are now using new treatments designed to specifically target this mutation.

“This is a somatic mutation that leads to those tumors, particularly the [IDH-]mutant astrocytoma … and the [oligodendroglioma],” Dr. Esquenazi says. “And these patients can take a pill that is taken once a day.”

In August 2024, the FDA approved vorasidenib (Voranigo, Servier) for adult and pediatric patients 12 and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, following surgery including biopsy, subtotal resection, or gross total resection.

It was the first FDA approval of a systemic therapy for this population of patients.

Vorasidenib was approved based on a large study called the INDIGO trial, published in the New England Journal of Medicine in 2023. In this trial, 331 people with grade 2 IDH‑mutant glioma — who had only undergone surgery — were assigned to take either vorasidenib once a day or a placebo.

In the study, the group taking vorasidenib had significantly better progression-free survival (27.7 months vs. 11.1 months for the placebo).

It’s also important to know that the medication can affect the liver in some people, so doctors check liver function regularly during treatment to make sure it stays safe.

Dr. Esquenazi says the practical benefit is substantial for appropriately selected patients.

“Some of the novel studies have shown that in patients with the lower grade tumors, this therapy, which is noninvasive and the side effects are actually very limited and much easier to take than chemotherapy or radiation, can potentially delay the tumor progression and in addition, can delay the necessity to do radiation therapy,” he says.

“So there has certainly been a lot of excitement in that field.”

The Future of Glioma Care

Despite ongoing progress, open questions remain: how to sequence vorasidenib with radiation and chemotherapy, its long-term effects on survival and malignant transformation, and how to select patients for early IDH inhibition versus surveillance.

Vorasidenib is also being studied in combination with pembrolizumab in an early-phase trial in grade 2/3 glioma.

Dr. Esquenazi sees the targeted-therapy era as one front among several, alongside precision medicine and artificial intelligence.

“We’ve had good advances and very exciting advances in the lower [grade] glioma population, and certainly with precision therapies with AI and a lot of the new technologies,” he says.

“I do believe that there is hope for patients, and our job is to give them the best quality of life.”

Questions To Ask Your Doctor

• What grade/type of glioma do I have?
• Am I a candidate for surgery and if so, how will I be monitored after?
• Am I a candidate for targeted therapy with vorasidenib?
• Are there any clinical trials I should consider?

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