Combining Gamma Knife and Linac radiosurgery for large brain tumors and metastases

Combined Gamma Knife/Linac Hypofractionated Stereotactic Radiosurgery for Large Intracranial VolumEs (GK-LIVE): A Prospective Phase II Single-Arm Trial

This will test whether using both Gamma Knife and Linac stereotactic radiosurgery in adults with large brain tumors or brain metastases can improve tumor control and reduce side effects.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07162246 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center interventional protocol at Sunnybrook uses a planned combination of Gamma Knife (GK) and linear accelerator (Linac) stereotactic radiosurgery to treat large intracranial lesions. Eligible adults with up to two large lesions among as many as ten total brain metastases receive focused treatments delivered by both machines, with fractionation and dosing chosen based on lesion size and location. Outcomes include tumor control, radiation necrosis rates, and other treatment-related adverse events monitored by MRI and clinical follow-up. The trial aims to characterize the safety and preliminary effectiveness of the combined approach compared with historical outcomes for fractionated Linac SRS.

Who should consider this trial

Good fit: Adults (≥18 years) with up to two large intracranial lesions and up to ten brain metastases total, ECOG 0–2, expected survival >3 months, judged suitable for both GK and Linac treatment, and able to pause systemic therapy around SRS are ideal candidates.

Not a fit: Patients with prior SRS to the target lesions, prior or planned whole-brain radiotherapy, leptomeningeal disease, ventricular or corpus callosum metastases, small cell/hematopoietic/germ cell primaries, MRI contraindications, or severe symptoms preventing MRI or treatment are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this combined approach could improve control of large brain lesions while lowering the risk of radiation damage to healthy brain tissue and related symptoms.

How similar studies have performed: Single- and hypofractionated SRS with either Linac or Gamma Knife have shown good control for many brain metastases, but combining GK and Linac specifically for large lesions is a relatively novel approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

* Presence of up to two large intracranial lesions
* Up to 10 (previously untreated, or progressing after previous treatment) brain metastases at the time of enrollment on the diagnostic MRI (which includes the ILLs) to be treated with SRS/HSRS
* Age =\> 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Expected survival \>3 months
* Patients that are deemed suitable for both GK and Linac based treatment
* Patients that are able to hold systemic cancer chemotherapy/immunotherapy at least 2 days prior and following an SRS fraction

Exclusion Criteria:

* Prior SRS to the ILLs
* Prior WBRT, or plan for concurrent WBRT with the protocol treatment
* Presence or history of any leptomeningeal/pachymeningeal disease
* Metastatic disease within the ventricles of the brain or corpus callosum
* Small cell, hematopoietic or germ cell primaries
* Patient with absolutely contraindications for MRI
* Severe symptoms that preclude MRI or treatment using standard procedures for Linac or GK
* Pregnant or lactating patient
* Inability or unwillingness to undergo informed consent or post-treatment follow-up

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Study coordinator: Hanbo Chan, MD

Conditions: Brain Cancers, Brain Metastasases, SRS