WATCH: Tweaks to Stupp Protocol May Extend Survival for Glioblastoma Patients

Two decades after the Stupp protocol redefined treatment for glioblastoma, Houston Methodist Hospital researchers have found that subtle but targeted modifications can yield striking gains in survival, sometimes doubling or even tripling life expectancy for select patients.

Dr. David Baskin, director of the Kenneth R. Peak Brain & Pituitary Tumor Center at Houston Methodist, outlines the findings in a new whiteboard video aimed at improving management of glioblastoma, one of the most aggressive and fatal brain tumors.

The Stupp regimen — surgery followed by chemoradiation with temozolomide and adjuvant chemotherapy — increased median survival from nine to 15 months, but progress has since stalled.

"We wondered if there was anything we could do to make this better," Dr. Baskin explains. "Could we 'hack' the protocol — tweak it or twist it — to improve outcomes and survival?"

Completing treatment

One of the strongest predictors of survival was simply finishing the six prescribed cycles of adjuvant temozolomide. Patients with methylated tumors who completed therapy had a median survival of 30 months, compared with 13 months in those who stopped early. Even in unmethylated tumors, completing treatment provided an additional six months of survival.

"Whatever it takes, press on and finish the protocol," Dr. Baskin says. "Give transfusions, use growth factors, because the difference in outcomes is dramatic."

Timing is everything

The Houston Methodist team also found that delaying radiation until approximately 31 days after surgery improved outcomes significantly for methylated patients. Starting too soon compounds inflammation from surgery and may blunt the effectiveness of therapy.

A similar principle applies to adjuvant chemotherapy: Waiting 75–90 days after radiation before beginning the six cycles of temozolomide nearly doubles survival in both methylated and unmethylated tumors.

Precision and restraint

New technology also allows for refinements in radiation delivery. Adding a stereotactic radiation boost to residual tumors after standard treatment extends median survival from 21 to 36 months in methylated patients.

Conversely, traditional reliance on high-dose steroids can be detrimental. "Our initial instincts about dexamethasone were wrong," Dr. Baskin admits. "Steroids reduce the immune response at the very moment radiation and chemotherapy are breaking down tumor defenses."

Patients kept on low doses — less than 1.2 mg/m² in the last week of radiation — lived 16 months longer on average than those given higher doses.

Small changes add up

Even inexpensive supplements may make a difference. The researchers found that patients who took a daily vitamin D dose survived an additional 10 months in methylated patients and nearly seven months in unmethylated cases. "That's better than what temozolomide alone accomplished," notes Dr. Baskin.

For a disease where incremental gains matter, Dr. Baskin said the impact of these "hacks" surprised even his team.

"We were astonished at the power of these simple changes and how much difference they made in survival and quality of life," he said. "I feel confident that if you do this, you will find the same thing."

Houston Methodist now incorporates these modifications into its clinical practice, underscoring the institution's commitment to providing the best brain tumor care.