For decades, treatment options for glioma changed very little. Neuro-oncologists largely relied on surgery, radiation, and a handful of established drugs to manage these complex brain tumors.

Today, advances in molecular diagnostics, imaging technology, and targeted therapies are reshaping how clinicians diagnose and treat glioma.

According to Dr. Michael Youssef, a neuro-oncologist at Houston Methodist, three developments have had the greatest impact on his practice in recent years:

• The emergence of IDH inhibitors
• The availability of advanced PET imaging
• The expansion of targeted therapies tailored to specific genetic alterations

“We don’t just go on the MRIs alone. We don’t just go on histology alone. All of the diagnosis now goes through molecular and through histology and through imaging combined to give a good comprehensive diagnosis,” Dr. Youssef tells SurvivorNet Connect.

This shift toward precision medicine has opened the door to more personalized treatment strategies and fueled several major advances.

Advance #1: IDH Inhibitors for Low-Grade Glioma

Dr. Youssef considers the development of IDH inhibitors the most important recent breakthrough in glioma treatment.

“Over the last few years, I think [among] the advances or changes that we’ve had, number one by far is the development of vorasidenib, the IDH inhibitor drug. That’s really changed the way we practice in the low-grade glioma population,” he explains.

Vorasidenib targets mutations in the IDH1 and IDH2 genes, which are commonly found in low-grade gliomas and help drive tumor growth. Before targeted therapies were available, many patients relied on chemotherapy agents such as temozolomide and lomustine or underwent prolonged observation before requiring additional treatment.

Clinical data from the phase 3 INDIGO trial, published in The New England Journal of Medicine, demonstrated that vorasidenib significantly delayed disease progression in patients with grade 2 IDH-mutant gliomas following surgery.

The study found that treatment more than doubled progression-free survival compared with placebo, helping establish a new treatment option for eligible patients.

Advance #2: FET-PET Imaging 

Another important development is the growing availability of FET-PET imaging in the United States.

“Number two would be the development of the FET-PET. It’s been used in Europe for years, and they’ve had a tool that we haven’t had. And now that it’s available, it’s helped us know what is tumor and what’s a post-treatment effect,” Dr. Youssef explains.

One of the most challenging aspects of glioma management is determining whether changes seen on imaging represent active tumor growth or treatment-related effects such as inflammation, radiation injury, or scar tissue.

Making this call is “…something that every patient who gets treated for a brain tumor will have to deal with at some point,” Dr. Youssef says. “Now we have a new resource to help us diagnose that.”

By improving diagnostic confidence, FET-PET imaging may help physicians make more informed treatment decisions and potentially avoid unnecessary interventions.

Advance #3: More Targeted Therapy Options

The third major shift involves the development of targeted therapies aimed at specific molecular alterations found in certain gliomas.

The new therapies include:

• ONC201 (dordaviprone), which has shown promise in patients with H3K27M-mutant diffuse midline gliomas
• Tovorafenib, a targeted therapy designed for tumors driven by BRAF alterations

“We have two other drugs that we use. ONC201 is a drug that targets midline glioma and H3K27M mutations. And then we have a drug, tovorafenib. It targets a BRAF fusion,” Dr. Youssef explains. “So, a lot of these patients who previously would’ve been treated with chemotherapy that may or may not work are now being treated with targeted therapy.”

Both therapies have received regulatory attention based on encouraging response rates, while confirmatory studies continue to evaluate their long-term benefit.

These treatments reflect a broader trend in neuro-oncology: moving away from one-size-fits-all treatment approaches and toward therapies matched to a tumor’s unique genetic profile.

The Future of Glioma Treatment

Although surgery, radiation, and chemotherapy remain foundational components of care, molecular testing and targeted therapies are increasingly shaping treatment decisions. Advances such as vorasidenib, FET-PET imaging, and mutation-specific therapies are helping doctors better classify tumors, monitor treatment response, and personalize care.

A key takeaway for clinicians and patients: understanding a tumor’s molecular characteristics is becoming as important as understanding what appears on an MRI scan.

As precision medicine continues to evolve, experts expect these innovations to further transform glioma care and create new opportunities for patients facing a disease that historically had few therapeutic advances.