For decades, radiation therapy has been one of the central pillars of glioma treatment. After surgery, many patients were told that radiation, often combined with chemotherapy, was the next unavoidable step. For some, that approach was lifesaving. For others, it came with long-term costs that followed them for years.
Now, for the first time in a generation, that paradigm is beginning to shift.
Read MoreWhy Radiation Has Always Been a Double-Edged Sword
Radiation therapy has long been considered one of the most effective tools against gliomas. It works quickly. It reduces tumor burden. It helps control disease that surgery alone cannot eliminate, as surgery alone cannot eliminate microscopic disease.But radiation is also, by nature, unforgiving.
“Radiation is really the cornerstone of glioma treatment,” Dr. Alnahhas explains. “But it is a double-edged sword.”
Even when radiation is precisely targeted, the brain itself is still being exposed. Over time, that exposure can lead to changes in memory, attention, processing speed, and executive function. These effects may not appear immediately. They often develop slowly, years later… which makes the tradeoff especially difficult for younger patients.
Grade 2 gliomas are frequently diagnosed in people in their 30s or 40s. These are patients who may live for many years, even decades, after diagnosis. Preserving cognitive function isn’t a luxury for them — it’s essential.
This is why neuro-oncologists have spent years asking the same question: What if we could safely delay radiation without sacrificing tumor control?
What Is Vorasidenib and Why It’s Different
“I will say for the last year and a half in the neuro-oncology field that we’ve had two FDA approved drugs after years of hiatus. So we’re lucky to have vorasidenib as an FDA approved option for patients with grade two gliomas that have an IDH mutation.” – says Alnahhas
“Vorasidenib is what we call an IDH1 and IDH2 inhibitor. It’s not chemotherapy, it belongs to what called targeted therapy, which is now more specific.” adds Dr. Alnahhas.
It inhibits mutated forms of an enzyme called IDH (isocitrate dehydrogenase), a mutation found in many Grade 2 gliomas. IDH mutations disrupt normal cellular metabolism and contribute to tumor growth. Vorasidenib works upstream, targeting one of the earliest drivers of tumor formation rather than damaging DNA indiscriminately.
“We’re trying to tackle the cellular mechanisms that triggered the cells to grow.” Dr. Alnahhas explains.
This approach is fundamentally different from chemotherapy, which damages DNA in rapidly dividing cells — cancerous or not. Chemotherapy damages DNA in all rapidly dividing cells in the body whether cancerous or not. Targeted therapy targets a specific target, like IDH mutation, in a tumor. That means it’s more precise and usually causes fewer side effects in healthy cells.
What Vorasidenib Actually Does
Vorasidenib does not “melt” tumors away overnight. Instead, it slows tumor growth, helping keep remaining cancer cells in check after surgery.
“The idea is that vorasidenib is going to slow down the tumor cells. It’s going to slow down how rapidly they divide and it will make sure that the tumors do not grow after surgery, hopefully for a long period of time. And then when they do, that’s when we would rely to the more traditional treatments there are the radiation and chemotherapy.” – says Alnahhas
By slowing cell division and altering the tumor’s metabolic machinery, the drug can delay progression — sometimes for years.
And that delay matters.
“The huge advantage is that it’s delaying patient’s need to radiation chemotherapy. So it’s helping us with avoiding, at least for a good period of time, hopefully the radiation effects” – Dr. Alnahhas says
Why Delaying Radiation Matters So Much
Radiation-related cognitive effects are cumulative. The younger the patient, the more years they must live with those effects.
If radiation can be postponed safely:
- memory may be preserved longer
- work and daily functioning may remain intact
- quality of life may be significantly better
“Radiation is not without side effects at the end of the day.”
“There is concern, of course about the cognitive effects because we’re radiating the brain. And again, all that depends on the patient’s age and on the location of the tumor. There are locations that are more forgiving when it comes to say cognitive effects than others.”
“However, it is believed that radiation therapy can induce some volume decrease inside the normal brain, and that in turn with time can lead to cognitive effects.” says Dr Alnahhas.
Importantly, delaying radiation does not mean abandoning it forever. Radiation remains available and effective when and if it’s needed later.
Vorasidenib simply changes when that moment arrives.
“So in our field, if hopefully we ever get to a point where we can eliminate radiation therapy for patients, and we are getting closer, I wouldn’t say eliminate… but at least now we’re able to delay the need of radiation therapy for certain patients with certain brain tumors.”
“And that is really huge for us. Because we can again, reduce a lot of the cognitive effects, especially for younger patients” – adds Dr Alnahhas.
Who Is a Candidate for Vorasidenib?
Vorasidenib is oral, convenient, and taken at home. Some patients are excellent candidates for vorasidenib, especially younger adults with residual or subtly growing IDH-mutant tumors who want to delay radiation because of long-term cognitive concerns.
Right now, vorasidenib is FDA approved for:
- Grade 2 gliomas
- With an IDH mutation
- After surgery
This includes both:
- IDH-mutant astrocytomas
- IDH-mutant oligodendrogliomas
But patients should also understand that the treatment is a life-long commitment, long-term side effects are not yet known, and there may be a significant financial burden. Factors like emotional readiness, ability to commit to a daily medication, insurance stability, and access to monitoring all matter.
Molecular Testing & Precision Medicine
With molecular testing, doctors are no longer treating gliomas as a one-size-fits-all disease. They now know that a glioma with an IDH mutation, for example, behaves very differently from one without it, and this difference can completely change the approach to treatment.
Gliomas are a diverse group of tumors. Some grow slowly and respond well to certain treatments, while others are more aggressive and require a different approach.
Molecular testing provides doctors with the information to correctly diagnose which type of glioma the patient has and choose the best treatment moving forward.
Make sure to ask your doctor if your tumor has been tested for IDH mutation.
Questions To Ask Your Doctor
If you have been diagnosed with glioma, here are some questions to guide your conversation with your doctor:
- Have I/can I undergo molecular testing?
- What specific mutations will you be testing for in my tumor?
- How will the results of this testing affect my treatment options?
- Am I eligible for any targeted therapies or clinical trials based on my molecular testing results?
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