Stereotactic Radiosurgery for Brain Aneurysm

(BLAST Trial)

Overseen By David Mathieu, M.D. FRCS(C)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dr David Mathieu

Disqualifiers: Prior rupture, Symptoms, High-risk imaging, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether stereotactic radiosurgery, which uses focused radiation, is safe for individuals with small, unruptured brain aneurysms (bulging blood vessels in the brain that haven’t burst). Participants can choose to receive the treatment or be monitored without it. Researchers will assess if the treatment affects the risk of aneurysm rupture over three years. Doctors have advised potential participants to monitor their small, symptomless brain aneurysms instead of undergoing more invasive surgery. As an unphased trial, this study offers a unique opportunity for patients to contribute to understanding a non-invasive treatment option for brain aneurysms.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators or your doctor for guidance.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that stereotactic radiosurgery is safe for treating brain aneurysms?

Research shows that stereotactic radiosurgery (SRS) is a treatment that people generally tolerate well. It has safely addressed other brain issues like tumors and certain disorders. Studies have found that SRS precisely targets radiation to the problem area, protecting the surrounding healthy tissue. A review of different systems used for similar brain treatments found no major long-term safety concerns. This suggests that SRS can be a safe option for treating brain aneurysms, as it has been for other conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about stereotactic radiosurgery (SRS) for brain aneurysms because it offers a non-invasive alternative to traditional treatments like surgical clipping or endovascular coiling. Unlike these standard procedures, which require direct intervention within the brain, SRS uses targeted radiation (Gamma Knife radiosurgery) to stabilize aneurysms from outside the skull. This technique minimizes surgical risks and recovery time, potentially offering a safer option for patients who are at high risk from conventional surgery.

What evidence suggests that stereotactic radiosurgery is effective for brain aneurysms?

Research has shown that stereotactic radiosurgery (SRS) effectively treats various brain conditions, such as tumors and abnormal blood vessel formations. In this trial, participants in the SRS group will receive SRS, which uses precise radiation to treat brain aneurysms without open surgery. Early studies suggested that SRS can safely manage aneurysms without increasing the risk of rupture. Although data specifically on aneurysms is limited, SRS has demonstrated good results in treating other brain issues, indicating potential benefits here as well. Meanwhile, the control group will receive standard medical care, which includes monitoring for signs of increased risk, such as aneurysm growth or instability in shape. ^{1 2 3 6 7}

Who Is on the Research Team?

David Mathieu, MD FRCS(C)

Principal Investigator

Service de neurochirurgie, Département de chirurgie, Centre hospitalier universitaire de Sherbrooke

Are You a Good Fit for This Trial?

This trial is for people with small, unruptured brain aneurysms in the front part of the brain who've been advised to just watch it instead of getting surgery. They shouldn't have symptoms from the aneurysm, previous treatments on it, or conditions that make follow-ups hard.

Inclusion Criteria

I have a small, unruptured brain aneurysm detected by imaging.

My neurosurgeon recommended monitoring over surgery for my vascular condition.

Exclusion Criteria

The aneurysm is touching the optic pathways in the medical images.

You have had coils or clips placed in the aneurysm being studied, or in any other aneurysm.

Patient unable or unlikely to comply with the follow-up schedule

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Assessment and Treatment Decision

Participants choose between radiosurgery or observation. Initial assessments including CTA scan, MRI, and questionnaire are conducted.

1 day

1 visit (in-person)

Radiosurgery (for SRS group)

Radiosurgery is performed on participants who opt for the SRS group.

1 day

1 visit (in-person)

Follow-up

Participants undergo follow-up assessments including CTA scans and questionnaires at 6, 12, 24, and 36 months to monitor aneurysm status and safety.

36 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic RadioSurgery (SRS)

Trial Overview

The study tests if using Stereotactic RadioSurgery (SRS) on these low-risk aneurysms is safe and doesn't increase rupture risk compared to just watching them. Participants can choose SRS or observation and are followed up for three years with scans and questionnaires.

How Is the Trial Designed?

Group I: SRS group Experimental Treatment 1 Intervention

Participants in the SRS group will receive the intervention described earlier, consisting of a Gamma Knife radiosurgery, and undergo the same follow-up exams (radiological and clinical) as participants of the control group.

Group II: Control group Active Control 1 Intervention

The medical care will consist of observation for any element that may indicate an increased risk of rupture, like aneurysm growth or instability in shape.

Stereotactic RadioSurgery (SRS) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Stereotactic Radiosurgery for:

• Brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Unruptured brain aneurysms

Approved in European Union as Stereotactic Radiosurgery for:

• Brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Unruptured brain aneurysms

Approved in Canada as Stereotactic Radiosurgery for:

• Brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Unruptured brain aneurysms

Approved in Japan as Stereotactic Radiosurgery for:

• Brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Unruptured brain aneurysms

Who Is Running the Clinical Trial?

Dr David Mathieu

Lead Sponsor

Trials

1

Recruited

40+

Université de Sherbrooke

Collaborator

Trials

317

Recruited

79,300+

Centre de recherche du Centre hospitalier universitaire de Sherbrooke

Collaborator

Trials

64

Recruited

33,600+

Published Research Related to This Trial

The implementation of a safety checklist for Gamma Knife stereotactic radiosurgery (SRS) over 1500 procedures in 8 years has resulted in no reported human errors, highlighting its effectiveness in enhancing safety.

The checklist addresses specific indications for irradiating tissue volumes and functional disorders, promoting a zero-tolerance approach to errors and fostering multidisciplinary cooperation in neurosurgical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lausanne checklist for safe stereotactic radiosurgery. Tuleasca, C., Zeverino, M., Patin, D., et al.[2020]

Stereotactic radiosurgery (SRS) is a precise treatment that delivers a high dose of radiation to targeted areas in the brain, using advanced imaging techniques like CT and MRI for accuracy.

Recent innovations in SRS technologies are moving towards non-invasive methods, reducing the need for rigid head frames, which can enhance patient comfort and treatment efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in technology for intracranial stereotactic radiosurgery. Sahgal, A., Ma, L., Chang, E., et al.[2022]

In a study of 381 patients with cerebral arteriovenous malformations (AVMs) treated with stereotactic radiosurgery (SRS) over 20 years, the obliteration rates improved over time, with 85.1% at 8 years, but the newer treatment period showed fewer patients achieving obliteration compared to earlier years.

The risk of radiation-induced complications (RICs) decreased with advancements in SRS techniques, with rates of 4.4% at 4 years and 8.6% at 8 years, suggesting that while safety improved, strategies to enhance obliteration rates for larger AVMs are still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery for Arteriovenous Malformations: The Effect of Treatment Period on Patient Outcomes. Pollock, BE., Link, MJ., Stafford, SL., et al.[2018]

In a study of 180 patients with brain metastases, both preoperative stereotactic radiosurgery (Pre-SRS) and postoperative stereotactic radiosurgery (Post-SRS) showed similar outcomes in terms of overall survival and recurrence rates, indicating that either approach can be effective.

However, Pre-SRS was associated with significantly lower rates of complications such as symptomatic radiation necrosis and leptomeningeal disease compared to Post-SRS, suggesting it may be a safer option for patients undergoing surgery for brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Preoperative With Postoperative Stereotactic Radiosurgery for Resectable Brain Metastases: A Multi-institutional Analysis. Patel, KR., Burri, SH., Asher, AL., et al.[2022]

Out of 221 reported incidents related to CyberKnife™ SRS and SBRT from 2012 to 2019, the majority (205 incidents) had little to no clinical impact, indicating a high level of safety in the treatment process.

Human performance issues were the most common contributing factor (79% of incidents), with many errors occurring during pre-treatment phases, highlighting the need for improved training and protocols to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Error Pathways in CyberKnife™ Radiation Therapy. Mullins, BT., Mazur, L., Dance, M., et al.[2020]

A case study of a 21-year-old female who underwent stereotactic radiosurgery (SRS) for a ruptured arteriovenous malformation (AVM) revealed the development of a glioblastoma (GBM) six years post-treatment, highlighting a rare but serious potential long-term risk associated with SRS.

While SRS is generally considered safe, this case underscores the importance of informing patients about the potential risk of radiation-induced malignancies, particularly glioblastomas, which can occur even years after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma after AVM radiosurgery. Case report and review of the literature. Xhumari, A., Rroji, A., Enesi, E., et al.[2018]

Stereotactic radiosurgery (SRS) effectively controls small brain metastases from various cancers with minimal side effects on surrounding healthy brain tissue, making it a suitable option for patients with a limited number of tumors and a good prognosis.

While whole-brain radiation therapy (WBRT) can enhance local control and reduce the emergence of new lesions when used with SRS, it does not improve overall survival, suggesting that SRS alone may be sufficient for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgery for metastatic brain tumors. Serizawa, T.[2022]

Stereotactic radiosurgery (SRS) is an effective non-invasive technique for targeting deep brain lesions with high doses of radiation, but it does not provide benefits for newly diagnosed malignant gliomas.

For patients with brain metastases, SRS can improve median survival when combined with whole-brain radiation therapy (WBRT), and in some cases, SRS alone may be a viable treatment option without compromising survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of radiosurgery in the management of malignant brain tumors. Stieber, VW., Ellis, TL.[2019]

Stereotactic radiosurgery (SRS) using CyberKnife for large brain metastasis cavities (≥2 cm) showed a local failure rate of 24%, indicating it can effectively control local disease after surgery.

Patients with synchronous metastases had a higher risk of distant brain failure, suggesting that while SRS can delay the need for whole brain radiation therapy (WBRT), careful monitoring is needed for those with multiple metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases. Vogel, J., Ojerholm, E., Hollander, A., et al.[2018]

Both gamma knife (GK) and linear accelerator (LINAC) systems provide comparable tumor control rates for vestibular schwannoma, with rates of 93% for GK and 94% for LINAC based on a meta-analysis of 39 studies involving 6516 patients.

GK may better preserve trigeminal nerve function, while LINAC is associated with a lower incidence of tinnitus, suggesting that each method has unique benefits regarding side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the long-term safety and efficacy of gamma knife and linear accelerator radiosurgery for vestibular schwannoma: A systematic review and meta-analysis. Guadix, SW., Tao, AJ., An, A., et al.[2022]

The ABC/2 method for calculating the volume of cerebral arteriovenous malformations (AVMs) significantly overestimates their size compared to the more accurate volumetric analysis used in stereotactic radiosurgery (SRS) planning, with a median volume of 6.07 cm³ versus 4.96 cm³ respectively in a study of 90 AVMs.

This overestimation is particularly pronounced for larger AVMs (greater than 7 cm³), which could impact treatment decisions and patient counseling regarding the risks of intracranial hemorrhage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABC/2 Method Does not Accurately Predict Cerebral Arteriovenous Malformation Volume. Roark, C., Vadlamudi, V., Chaudhary, N., et al.[2019]

In a study of 30 patients receiving Gamma Knife stereotactic radiosurgery for 10 or more brain metastases, the mean dose to the whole brain was low at 1.8 Gy, indicating a potentially safe treatment approach.

The treatment allowed nearly half of the patients to avoid additional whole-brain radiotherapy, with only a 6.6% incidence of grade 2 radionecrosis, suggesting that Gamma Knife SRS can effectively manage multiple brain metastases with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases. Sita, TL., Gopalakrishnan, M., Rooney, MK., et al.[2022]

Stereotactic radiosurgery (SRS) delivers a high dose of ionizing radiation in a single session, allowing for precise treatment of intracranial lesions.

The technique utilizes a stereotactic apparatus for accurate localization and patient immobilization, enhancing the safety and efficacy of targeting tumors or other lesions in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-fraction stereotactic radiosurgery for intracranial targets. Verhey, LJ., Chen, CC., Chapman, P., et al.[2018]

Citations

1.

mayoclinic.org

mayoclinic.org/tests-procedures/brain-stereotactic-radiosurgery/about/pac-20384679

Brain stereotactic radiosurgery

This procedure delivers precise radiation therapy to treat brain tumors and other brain conditions.

2.

withpower.com

withpower.com/trial/phase-aneurysm-2023-94fae

Stereotactic Radiosurgery for Brain Aneurysm (BLAST Trial)

A meta-analysis comparing Gamma Knife and linear accelerator systems for vestibular schwannoma found no clear differences in long-term safety outcomes.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4152711/

Cranial Stereotactic Radiosurgery: Current Status of the Initial ...

SRS has altered the treatment paradigms for benign and malignant intracranial tumors, functional disorders, and vascular malformations.

4.

thejns.org

thejns.org/view/journals/j-neurosurg/142/6/article-p1763.xml

Outcomes following stereotactic radiosurgery for high-grade ...

SRS for high-grade AVMs is associated with a modest rate of obliteration and is complicated by AREs in 9% of cases.

5.

journals.lww.com

journals.lww.com/tcmj/fulltext/2022/34040/clinical_outcomes_of_benign_brain_tumors_treated.17.aspx

Clinical outcomes of benign brain tumors treated with...

Among symptomatic patients, post-SRS symptom(s) was improved, stable, and worse in 68.2%, 24.3%, and 3.6%, respectively. Radiological response rate for 111 ...

6.

mayoclinic.org

mayoclinic.org/tests-procedures/stereotactic-radiosurgery/about/pac-20384526

Stereotactic radiosurgery

Stereotactic radiosurgery (SRS) uses many precisely focused radiation beams to treat tumors and other problems in the brain, neck, lungs, liver, spine and ...

7.

cco.amegroups.org

cco.amegroups.org/article/view/16081/html

Stereotactic radiosurgery of the brain: a review of common ...

SRS is a powerful tool in the treatment of intracranial disease spanning the spectrum of malignant, benign, and functional disorders of the brain.