Pre- vs Post-operative SRS for Brain Cancer

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AHS Cancer Control Alberta

Disqualifiers: Leptomeningeal disease, Germ cell tumor, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 3-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if administering radiotherapy (a type of targeted radiation treatment) before surgery benefits people with brain cancer more than performing surgery first. Brain metastases occur when cancer from another part of the body spreads to the brain, causing issues like headaches and confusion. The trial compares two groups: one undergoes brain surgery followed by stereotactic radiosurgery (SRS), while the other receives SRS first. Suitable candidates have cancer that has spread to the brain but have not undergone full brain radiation or radiation to the current tumor. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that using stereotactic radiosurgery (SRS) before surgery was safe and easy to manage. Research shows that it may lower certain risks, such as tissue damage from radiation and the spread of cancer in the brain. Another study confirmed that using SRS before surgery might target tumors more effectively, leading to fewer side effects.

Stereotactic radiosurgery is a type of radiation treatment that uses precise beams to treat tumors without cutting into the brain. This approach helps protect healthy brain tissue and can reduce side effects. Overall, current studies suggest that SRS is generally well-tolerated and safe for patients with cancer that has spread to the brain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about comparing the timing of stereotactic radiosurgery (SRS) and brain surgery for brain cancer because it could redefine treatment sequences. Unlike the standard approach where surgery is followed by SRS, one experimental method flips the order, starting with SRS. This could potentially shrink tumors more effectively before surgical removal, possibly leading to better outcomes and fewer complications. By exploring these different sequences, researchers hope to find the most effective strategy to improve recovery and survival rates for patients with brain cancer.

What evidence suggests that this trial's treatments could be effective for brain metastases?

This trial will compare the effects of stereotactic radiosurgery (SRS) administered before surgery with those administered after surgery for treating cancer that has spread to the brain. Research has shown that performing SRS before surgery is promising. Studies suggest that pre-operative SRS might lower the risk of harming healthy brain tissue and reduce the spread of cancer cells in the brain's protective layers, compared to post-operative SRS. Pre-operative SRS also allows for more precise targeting of tumors. This method is safe and could speed up treatment without affecting survival rates. Overall, pre-operative SRS could lead to better outcomes for patients with brain metastases. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with confirmed primary cancer who have brain metastases. They must be able to perform neurocognitive tests, not have had whole-brain radiotherapy or SRS on the lesion in question, and can't have specific cancers like germ cell tumors or small cell lung cancer.

Inclusion Criteria

I have had radiation therapy on cancer spots other than the one being removed.

Women who could become pregnant must have a negative pregnancy test within a week before joining the study.

I can complete brain function tests on my own.

Exclusion Criteria

I have had whole brain radiation or stereotactic radiosurgery on the tumor being removed.

You cannot have an MRI scan because you have a pacemaker.

My cancer has spread to the lining of my brain and spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either SRS followed by surgery or surgery followed by SRS

3-4 weeks

Multiple visits for surgery and SRS

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular assessments at 3, 6, 9, 12, 16, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Brain Surgery
• Stereotactic Radiosurgery

Trial Overview The study is testing if performing stereotactic radiosurgery (SRS) before surgery gives better outcomes than doing surgery first for patients with brain metastases. It aims to see which sequence improves quality of life and reduces side effects.

How Is the Trial Designed?

Group I: SRS followed by Surgical Resection (Experimental) Experimental Treatment 2 Interventions

SRS followed by surgery within 1 week of radiotherapy end date.

Group II: Surgical Resection followed by SRS (Non-Experimental) Active Control 2 Interventions

Surgical Resection followed by SRS within 3 weeks of surgery date.

Brain Surgery is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Vascular malformations

Approved in United States as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Epilepsy
• Trigeminal neuralgia

Approved in Canada as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Vascular malformations

Approved in Japan as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Epilepsy

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Published Research Related to This Trial

A national benchmarking program involving 68 treatment plans across multiple centers demonstrated that stereotactic radiosurgery (SRS) effectively prioritized target coverage for benign brain tumors, achieving ≥95% coverage for most cases.

However, significant variability in selectivity and normal tissue irradiation was observed, particularly with LINAC-based plans, indicating a need for improved standardization and collaboration among treatment centers to enhance safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for benign brain tumors: Results of multicenter benchmark planning studies. Eaton, DJ., Lee, J., Patel, R., et al.[2018]

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 130 patients treated with CyberKnife Radiosurgery for brain metastases, a cumulative tumor volume greater than 7cc was linked to worse outcomes, including higher rates of death and neurological defects.

The addition of whole brain radiation therapy (WBRT) was associated with improved survival rates in patients with a higher tumor burden, suggesting that WBRT may play a beneficial role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases. Kim, IK., Starke, RM., McRae, DA., et al.[2018]

This multicenter, randomized controlled trial aims to determine whether preoperative stereotactic radiosurgery (SRS) is more effective than postoperative SRS in managing resectable brain metastases, involving 88 patients over three years.

The primary goal is to assess local control of the tumors at 12 months, while secondary outcomes will evaluate overall survival, recurrence rates, neurocognitive effects, and adverse events like radiation necrosis, addressing a significant gap in current treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, multicenter, randomized controlled trial of preoperative versus postoperative stereotactic radiosurgery for patients with surgically resectable brain metastases. Das, S., Faruqi, S., Nordal, R., et al.[2023]

Stereotactic radiosurgery (SRS) is an effective treatment for brain disorders, delivering a precise, high dose of radiation in a single session to target tumors and abnormalities.

Currently, SRS is limited to the head and neck due to the need for immobilization, while body stereotactic radiosurgery is not feasible in one session, requiring fractionated treatments over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stereotactic radiosurgery]. Madrazo-Navarro, I., Aldana-Herrero, A.[2018]

In a study of 404 patients with brain metastases, preoperative stereotactic radiosurgery (SRS) showed low rates of cavity local recurrence (13.7%) and adverse radiation effects (7.4%), indicating it is a safe option before surgical resection.

The median overall survival for patients receiving preoperative SRS was 17.2 months, with factors like systemic disease status and extent of resection significantly influencing survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases. Prabhu, RS., Akinyelu, T., Vaslow, ZK., et al.[2023]

Pre-operative stereotactic radiosurgery (SRS) for brain metastases significantly reduces dose exposure to healthy brain tissue compared to post-operative SRS, with a median volume receiving 28 Gy being lower in the pre-operative setting (6.79 ccm) than in the extended field post-operative setting (10.79 ccm).

The study found that the morphology of the resection cavity post-surgery differs significantly from the original lesion, which could complicate treatment planning; thus, pre-operative SRS may provide better delineation and treatment planning advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases-Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept. El Shafie, RA., Tonndorf-Martini, E., Schmitt, D., et al.[2020]

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) and stereotactic body radiation therapy (SBRT) have advanced significantly, necessitating updated best practices for safety and quality assurance due to their complexity and precision in delivering high doses of radiation.

A team-based approach with trained specialists and a comprehensive quality assurance program is essential for the safe and effective implementation of SRS and SBRT, emphasizing that patient safety is a collective responsibility among all stakeholders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy: An ASTRO Safety White Paper Update. Das, IJ., Dawes, SL., Dominello, MM., et al.[2022]

In a study of 148 patients treated with stereotactic LINAC radiosurgery for intracranial meningiomas, the long-term tumor control rate was high at 93.6% after 5, 10, and 15 years, indicating effective management of these tumors.

The treatment also led to improvement in neurological symptoms for nearly 60% of patients, with a low rate of local tumor progression (4.8%), suggesting that LINAC-SRS is a safe and effective option for both primary and recurrent meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and safety after a follow-up of over 12 years. El-Khatib, M., El Majdoub, F., Hunsche, S., et al.[2022]

Stereotactic radiosurgery (SRS) is highly effective for treating large intracranial meningiomas, achieving a tumor control rate of 99% at 3 years and 92% at 7 years in a study of 116 patients with tumors larger than 10 cm³.

However, the complication rate is notably higher for supratentorial tumors (44%) compared to skull base tumors (18%), suggesting that while SRS is safe for skull base meningiomas, surgical resection may be a better option for larger supratentorial meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgery for large-volume (> 10 cm3) benign meningiomas. Bledsoe, JM., Link, MJ., Stafford, SL., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39743641/

a systematic review and meta-analysis of comparative ... This review reveals pre- and post-SRS for BM have similar outcomes for LF, DF, and OS. Pre-SRS potentially lowers RN and LMD risks, with better tumor targeting.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11909010/

Transforming Brain Tumor Care: The Global Impact of ... This study corroborates the clinical efficacy of SRS and reinforces its critical role in the multidisciplinary treatment of patients with brain tumors and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001691

Preoperative Stereotactic Radiosurgery for Brain Metastases This study aimed to determine the safety of preoperative SRS via a phase 1 dose escalation trial and compare outcomes—including nLMD, classical ...

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2835449

Therapy, Safety, and Logistics of Preoperative vs ... Preoperative SRT was safe and logistically feasible with the potential benefit of expediting treatment.

5. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00169-1/fulltext

Preoperative Stereotactic Radiosurgery for Brain Metastases Preoperative SRS to 15 Gy is safe for tumors 2 to 6 cm and significantly reduces nLMD without compromising local control or OS. These findings support ...

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

Brain stereotactic radiosurgery Brain tumor before and after Gamma Knife treatment · Benign tumors may shrink over a period of months to years. · Malignant tumors may shrink ...