Pre- vs Post-operative SRS for Brain Cancer

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

88 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if performing radiotherapy (SRS) prior to surgery results in better treatment outcomes than performing surgery before radiotherapy for patients with brain metastases. Brain metastases occur when cancer cells from a primary cancer (e.g. lung, breast, colon) travel through the bloodstream and spread (metastasize) to the brain. As these new tumors grow they apply pressure and change how healthy brain tissue works. This can lead to a loss of brain function and worsening quality of life. Treatments for patients whose cancer has spread to the brain is often surgery, radiation therapy (radiotherapy) or a combination of both. Surgery is one the main treatments for brain tumors. To remove the tumor, a neurosurgeon makes an opening in the skull and attempts to the remove the entire tumor. If the tumor is too close to important brain tissue, the surgeon may attempt to remove part of the tumor. Removal of the tumor from the brain tissue is called resection. The complete or partial removal of tumor helps to relieve symptoms by reducing pressure on healthy tissues and reduces the amount of tumor that needs to be treated by radiotherapy. One type of radiotherapy used to treat brain metastases is stereotactic radiosurgery (SRS). SRS uses many focused radiation beams to treat tumors within the brain. Unlike surgery, there is no incision or cut being made. Instead, SRS uses an accurate map of your brain to deliver a precise beam of radiation to the tumors. The radiation damages the tumor cells forcing them to shrink and die off. The focused radiation beams also limit damage to healthy brain tissue minimizing side effects. Surgery followed by radiotherapy is a standard treatment for brain metastases. However, there are still risks associated with the combination of treatments. This study plans to investigate whether performing surgery prior to SRS results in improved quality of life and decreased side effects.

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.

What data supports the effectiveness of this treatment for brain cancer?

Research shows that stereotactic radiosurgery (SRS), like CyberKnife, can effectively treat brain metastases by targeting specific areas with high doses of radiation, potentially improving survival without the need for whole brain radiation therapy (WBRT). SRS is also used for treating benign brain tumors and can be an alternative to invasive surgery for deep-seated brain tumors. ^{1 2 3 4 5}

Is stereotactic radiosurgery (SRS) generally safe for humans?

Stereotactic radiosurgery (SRS) is considered generally safe for treating various brain conditions, including tumors and vascular issues, with strict safety guidelines in place to minimize risks. Studies have shown its safety in both short- and long-term follow-ups, although the safety for larger tumors is less understood. ^{2 6 7 8 9}

How does pre- and post-operative stereotactic radiosurgery (SRS) for brain cancer differ from other treatments?

Pre-operative SRS for brain cancer may offer advantages over post-operative SRS, such as better targeting of the tumor before surgery, potentially reducing the spread of cancer cells and lowering the risk of radiation damage to healthy brain tissue. This approach contrasts with whole brain radiation therapy, which can affect cognitive function and quality of life without improving survival. ^{1 2 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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) 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]

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 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]

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]

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]

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]

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]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases. [2018]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Mexico pubmed.ncbi.nlm.nih.gov

[Stereotactic radiosurgery]. [2018]

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

Stereotactic radiosurgery for benign brain tumors: Results of multicenter benchmark planning studies. [2018]

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

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

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

Lausanne checklist for safe stereotactic radiosurgery. [2020]

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

Radiosurgery for large-volume (> 10 cm3) benign meningiomas. [2022]

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

Quality and Safety Considerations in Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy: An ASTRO Safety White Paper Update. [2022]

9. Germany 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. [2022]

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

Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases-Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept. [2020]

11. England 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. [2023]

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

Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases. [2023]