PET-guided short-course higher-dose radiotherapy with temozolomide for poor-prognosis glioblastoma

BIOlogically-guided Short-course HypOfractionatedRadiation Therapy in Poor-prognosis GBM (BIO-SHORT): A Prospective Phase 2 Randomised Control Trial

This trial will try a shorter, higher-dose PET-guided radiotherapy schedule plus temozolomide in people aged 50 and older with poor-prognosis, IDH‑wildtype glioblastoma who are not candidates for surgery to see if it helps them live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 108 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Tata Memorial Centre (Academic / other)
• Drugs / interventions: Bevacizumab, chemotherapy, Radiation
• Locations: 1 site (Mumbai, Maharashtra)
• Trial ID: NCT07338539 on ClinicalTrials.gov

What this trial studies

This randomized phase 2 trial will enroll 116 patients with biopsy-proven or imaging-defined IDH‑wildtype glioblastoma who are unfit for surgery. Participants will be randomized to standard hypofractionated radiotherapy with temozolomide or to a shorter (1–2 week), higher-dose hypofractionated radiotherapy plan that is guided by PET imaging plus temozolomide, with PET used to identify the most metabolically active tumor regions for focused dosing. The trial will track overall survival, safety, treatment tolerance, and effects on healthy brain tissue. Follow-up includes serial imaging, clinical exams, and standardized performance scales.

Who should consider this trial

Good fit: Ideal candidates are adults aged 50 or older with biopsy-proven or imaging-defined IDH‑wildtype glioblastoma who are unfit for surgery, have a Neurological Predictor Scale (NPS) of 2–3, a Karnofsky Performance Status of at least 50, and no prior systemic glioma therapy.

Not a fit: Patients with IDH‑mutant or histone‑altered gliomas, multifocal or disseminated disease requiring whole‑brain radiation, very poor performance (KPS <50) or NPS scores of 0–1 or 4, prior systemic glioma therapy, or inability to attend the Mumbai treatment site are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could extend survival while shortening treatment time and limiting damage to healthy brain tissue by focusing higher doses on the most active tumor areas.

How similar studies have performed: Short-course hypofractionated radiotherapy with temozolomide has shown comparable survival to longer schedules in elderly and poor‑prognosis patients, but PET‑guided focal dose escalation is a newer strategy with limited prior evidence.

Eligibility criteria

Inclusion Criteria:

* Patients with biopsy proven IDH- wild type GBM or imaging defined GBM
* Neurological Predictor Scale (NPS) = 2-3
* Unfit for surgery and referred for direct RT
* Age \>/= 50 years

Exclusion Criteria:

* IDH mutant glioma
* Histone altered glioma
* Multifocal disease or Gliomatosis like appearance which necessitates whole brain RT
* Disseminated disease in brain or spine
* NPS = 0-1 or = 4
* Karnofsky Performance Status score less than 50(Patient requires considerable assistance and frequent medical care)
* Prior administration of any systemic therapy directed against glioma (eg.Temozolomide, CCNU, Bevacizumab)

Where this trial is running

Mumbai, Maharashtra

• Tata Memorial Hospital — Mumbai, Maharashtra, India (Recruiting)

Study contacts

• Study coordinator: Abhishek Chatterjee, MD

Conditions Glioma