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

40 Participants Needed

Trial Summary

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 data supports the idea that Stereotactic Radiosurgery for Brain Aneurysm is an effective treatment?

The available research shows that Stereotactic Radiosurgery (SRS) is effective for treating brain conditions like metastases, which are cancerous growths that spread to the brain. SRS delivers precise, high-dose radiation to small areas, helping control tumors and maintain daily life activities with minimal side effects. It is often compared to whole-brain radiation therapy (WBRT), and studies suggest that SRS can improve local control of tumors and reduce the emergence of new ones. While SRS is not specifically mentioned for brain aneurysms in the provided data, its success in treating other brain conditions suggests it could be a promising option. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Stereotactic Radiosurgery (SRS) for brain aneurysms?

Stereotactic radiosurgery (SRS) has been shown to effectively control small brain tumors and prevent neurological death, as it delivers precise high-dose radiation to targeted areas with minimal impact on surrounding healthy brain tissue. While this data is specific to brain tumors, it suggests that SRS could potentially be effective for other brain conditions, like aneurysms, due to its precision and ability to target specific areas in the brain. ^{1 2 3 4 5}

What safety data is available for stereotactic radiosurgery for brain aneurysms?

Stereotactic radiosurgery (SRS) is generally considered a safe procedure for various neurosurgical conditions, including brain aneurysms. The Lausanne checklist emphasizes the importance of safety guidelines to prevent errors and complications in Gamma Knife procedures. While SRS is relatively safe, there are rare reports of malignancies associated with its use. A meta-analysis comparing Gamma Knife and linear accelerator systems for vestibular schwannoma found no clear differences in long-term safety outcomes. Advances in SRS technology, such as non-invasive frame systems, continue to improve safety and efficacy. ^{5 6 7 8 9}

Is stereotactic radiosurgery generally safe for humans?

Stereotactic radiosurgery (SRS), including Gamma Knife and CyberKnife, is generally considered safe for humans, with most incidents leading to little or no patient harm. There are very few reported cases of serious complications, such as malignancies, and most issues are related to human errors or administrative problems rather than the procedure itself. ^{5 6 7 8 10}

Is Stereotactic Radiosurgery (SRS) a promising treatment for brain aneurysms?

Yes, Stereotactic Radiosurgery (SRS) is a promising treatment. It is a precise method that uses focused radiation to treat brain conditions like arteriovenous malformations and brain metastases. SRS can be an effective alternative to more invasive procedures, offering targeted treatment with potentially fewer side effects. ^{1 3 11 12 13}

How is the treatment Stereotactic Radiosurgery (SRS) unique for brain aneurysms?

Stereotactic Radiosurgery (SRS) is unique because it uses a high dose of focused radiation in a single session to treat brain conditions, offering a non-invasive alternative to traditional surgery. This precision allows it to target specific areas in the brain, minimizing damage to surrounding healthy tissue, which is different from more invasive surgical options. ^{1 3 11 12 13}

What is the purpose of this trial?

The goal of this clinical trial is to confirm the feasibility and safety of performing radiosurgery on unruptured, low-risk aneurysms in humans. Participants will choose if they want to undergo radiosurgery or not. Participants who choose not to have radiosurgery will be assigned to the observational group. Participants who choose to have radiosurgery performed will be assigned to the radiosurgery group. Participants in both groups will attend an initial exam session as well as four follow-up sessions: Day 0 * Initial questionnaire * CTA scan * MRI * Radiosurgery performed on patients in the radiosurgery group 6 months * CTA scan * Follow-up questionnaire 12 months * CTA scan * MRI * Follow-up questionnaire 24 months * CTA scan * Follow-up questionnaire 36 months * CTA scan * MRI * Follow-up questionnaire Researchers will compare the observational group and the radiosurgery group to see if there is a difference in the incidence of aneurysm rupture during the study period (3 years). The hypothesis is that radiosurgery should not increase the risk of aneurysm rupture.

Research Team

David Mathieu, MD FRCS(C)

Principal Investigator

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

Eligibility Criteria

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.

I am unable to give consent for medical procedures.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

ABC/2 Method Does not Accurately Predict Cerebral Arteriovenous Malformation Volume. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

Radiosurgery for metastatic brain tumors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

The role of radiosurgery in the management of malignant brain tumors. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases. [2022]

6. Austria pubmed.ncbi.nlm.nih.gov

Lausanne checklist for safe stereotactic radiosurgery. [2020]

7. Austria pubmed.ncbi.nlm.nih.gov

Glioblastoma after AVM radiosurgery. Case report and review of the literature. [2018]

8. England 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Advances in technology for intracranial stereotactic radiosurgery. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Common Error Pathways in CyberKnife™ Radiation Therapy. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery for Arteriovenous Malformations: The Effect of Treatment Period on Patient Outcomes. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Single-fraction stereotactic radiosurgery for intracranial targets. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Comparing Preoperative With Postoperative Stereotactic Radiosurgery for Resectable Brain Metastases: A Multi-institutional Analysis. [2022]