Glioma Recurrence: What Comes Next?

“If the patient had been watched over time, which is an approach sometimes in place in patients that have been treated, we discuss what could be the next steps,” Dr. Nick Gonzalez Castro, a neuro-oncologist at Dana-Farber Cancer Institute and assistant professor at Harvard Medical School, tells SurvivorNet. “And oftentimes, we revisit all available options. Sometimes patients will go for additional surgery … We can re-characterize the tumor and understand if there are any new molecular changes, some of which we might be able to target.”

How Common Is Recurrence in Grade 2 Glioma?

Even with excellent surgery and careful follow-up, most IDH-mutant grade 2 gliomas eventually grow again. Recent studies indicate people with this disease often live longer than 10 years on average. That’s the good news, but the trade-off is that tumor regrowth may happen throughout those years, and many patients need more than one type of treatment over time.

In one study, the 1-year progression-free survival (meaning no growth at one year) in IDH-mutant gliomas was about 90%, compared with about 40% in IDH-wildtype disease. These differences in biology matter when it comes to treatment planning.

When your doctor says, “The tumor is growing again,” it doesn’t mean treatment has “failed” or that there are no options. It means you’re entering the next chapter, one that can now include targeted drugs like vorasidenib, alongside familiar tools such as surgery, radiation, and chemotherapy.

The Vorasidenib Era: A New Option After Surgery

Until recently, systemic treatment for grade 2 glioma was limited to radiation therapy or temozolomide or PCV (procarbazine, lomustine, vincristine) chemotherapy.

That changed with the INDIGO trial, which studied a targeted drug called vorasidenib, an oral IDH1/2 inhibitor, in people with IDH-mutant grade 2 gliomas after surgery. Patients were randomly assigned to vorasidenib or placebo and followed over time.

The trial’s key findings included:

• Median progression-free survival (meaning no growth at one year) was 27.7 months on vorasidenib vs 11.1 months on placebo. In plain language, that means a 61% reduction in the risk of progression or death (hazard ratio 0.39).

• Vorasidenib delayed the need for more aggressive treatments like radiation or chemotherapy.

In August 2024, the FDA approved vorasidenib (brand name: Voranigo) for adults and children 12+ with IDH-mutant grade 2 astrocytoma or oligodendroglioma after surgery. It became the first targeted therapy specifically approved for this group.

Vorasidenib For Recurrence

If you haven’t yet received vorasidenib and your tumor regrows, your team may now consider it as a way to slow growth and defer radiation or more chemotherapy.

If you have already been on vorasidenib and the tumor progresses, your options may shift toward radiation, chemotherapy, clinical trials, or a combination.

We don’t yet have “real-world” registry data showing that recurrence rates across the entire population have decreased since the approval of vorasidenib; such long-term data typically takes years. But we do know, from INDIGO, that for people similar to the trial population, the risk of progression can be cut dramatically when this drug is used.

The data on vorasidenib are game-changing, and experts in the field continue to work towards more effective disease management.

“Myself and many colleagues throughout the country and throughout the world are working on trying to bring new treatments to patients,” Dr. Castro explains. “And we do this in the context of what we call a clinical trial, which is an experiment essentially where we offer patients a new treatment and we look to see if this is safe and if it’s effective.”

The Main Paths After Recurrence

When a scan shows progression, neuro-oncologists usually think through a familiar set of questions.

Can we operate again and safely?

A second surgery can remove tumor bulk, improve symptoms (such as seizures), and provide fresh tissue to reconfirm the diagnosis and rule out transformation to a higher-grade tumor.

“This is helpful because, in addition to removing some potential new areas of growth, we can re-characterize the tumor,” Dr. Castro explains.

Is this the moment to start or change systemic therapy?

Depending on what you’ve already received, your team might consider vorasidenib, if you’re eligible and haven’t used it yet.

Chemotherapy, with temozolomide or PCV, are also options, especially if your tumor has features that predict responsiveness.

Has the tumor transformed or remained low-grade?

A small, slow change in a grade 2 glioma may be handled differently than a sudden, more aggressive shift toward grade 3 or 4. Transformation often prompts a more intensive approach (radiation + chemotherapy) rather than a targeted drug alone.

For some patients, especially those with mild growth and few symptoms, the discussion may center on how to balance tumor control with preserving cognition, work, and daily life.

“Programs like this [SurvivorNet] are helpful to educate patients about their disease because an educated patient, an informed patient, is a patient who can make better decisions. And we providers, we don’t make decisions for patients,” Dr. Castro notes.

“We make decisions with patients, and the more patients are informed and educated about their disease and potential treatments, the better that, as a team, we can arrive at the best treatment plan,” he adds.

Questions To Ask Your Doctor

• How will I be monitored for recurrence?
• Is there any treatment that offers less chance of recurrence?
• When does the recurrence generally happen after the primary treatment?
• Can I have a second surgery if the tumor regrows?
• If I choose to wait or watch a bit longer, how will you monitor me so that we don’t miss a critical window?

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