Stereotactic Radiosurgery Before or After Surgery for Brain Metastasis

Recruiting at 3 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals, Steroids

Disqualifiers: Pregnancy, HIV, Heart failure, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

140 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial studies the side effects and how well stereotactic radiosurgery (SRS) works before or after surgery in patients with tumors that has spread to the brain or that can be removed by surgery. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on antiretroviral therapy for HIV, you may not be eligible to participate.

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

Research shows that stereotactic radiosurgery (a precise form of radiation therapy) after surgery for brain metastases can reduce the risk of cancer returning in the treated area and improve quality of life compared to whole-brain radiotherapy. It is considered a standard treatment option for patients with brain metastases, offering effective control with fewer side effects. ^{1 2 3 4 5}

Is preoperative stereotactic radiosurgery (SRS) safe for treating brain metastases?

Preoperative stereotactic radiosurgery (SRS) is generally considered safe for treating brain metastases, with studies showing a low risk of adverse effects like radiation necrosis (damage to brain tissue from radiation) and leptomeningeal disease (cancer spread to the lining of the brain). It may offer safety advantages over postoperative SRS by reducing the volume of healthy brain exposed to radiation. ^{6 7 8 9 10}

How does the treatment of stereotactic radiosurgery before or after surgery for brain metastasis differ from other treatments?

Stereotactic radiosurgery (SRS) is unique because it can be used either before or after surgery to target brain metastases with high precision, reducing the risk of local recurrence and potentially offering a better quality of life compared to whole-brain radiotherapy. Preoperative SRS may also have advantages like less uncertainty in targeting the tumor and a lower risk of radiation-related side effects. ^{2 3 4 5 11}

Research Team

Elizabeth Yan, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults over 18 with certain types of cancer that have spread to the brain and are candidates for surgery. They must be able to consent, have a performance status indicating they can handle daily activities, agree to follow-up visits, and not be pregnant or nursing. Those unwilling to use contraception or who are immunocompromised due to HIV treatment are excluded.

Inclusion Criteria

I agree to follow-up visits or to send in MRI images and notes as required.

I can take care of myself but might not be able to do heavy physical work.

I am recommended for brain surgery to remove a tumor based on a neurosurgeon's advice.

Exclusion Criteria

My cancer is suspected to be a germ cell tumor, small cell carcinoma, or lymphoma.

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

Known allergy to gadolinium, pacemaker, or other contraindication such as metal implant that is not safe for MRI. Patients with MRI-compatible implants including MRI compatible pacemakers are eligible

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative SRS

Patients undergo stereotactic radiosurgery before surgery

1 day

1 visit (in-person)

Surgery

Patients undergo surgery following stereotactic radiosurgery

Within 4 weeks after SRS

1 visit (in-person)

Post-operative SRS

Patients undergo stereotactic radiosurgery after surgery

Within 2 weeks after surgery

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3-4 months for up to 2 years, then periodically for up to 3 years

Treatment Details

Interventions

• Conventional Surgery
• Stereotactic Radiosurgery

Trial Overview The study is testing whether stereotactic radiosurgery (SRS), a precise high-dose radiation therapy, is more effective before or after surgical removal of brain tumors in patients with metastatic cancer. It aims to see if SRS results in less damage to healthy tissue compared to traditional methods.

Participant Groups

Group I: Arm B (Pre-operative SRS) Experimental Treatment 6 Interventions

Patients undergo stereotactic radiosurgery on day 1. Within 4 weeks, patients undergo surgery. Patients also undergo a planning CT or MRI before radiation and tissue and CSF sample collection at time of surgery and MRI throughout the study. Additionally, patients undergo MRI and option blood sample collection throughout the study.

Group II: Arm A (Post-operative SRS) Active Control 6 Interventions

Patients undergo surgery on day 1. Within 2 weeks, patients undergo stereotactic radiosurgery. Patients also undergo a planning CT or MRI before radiation and tissue and CSF sample collection at time of surgery. Additionally, patients undergo MRI and option blood sample collection throughout the study.

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

Approved in European Union as Conventional Surgery for:

• Various surgical conditions

Approved in United States as Conventional Surgery for:

• Various surgical conditions

Approved in Canada as Conventional Surgery for:

• Various surgical conditions

Approved in Japan as Conventional Surgery for:

• Various surgical conditions

Approved in China as Conventional Surgery for:

• Various surgical conditions

Approved in Switzerland as Conventional Surgery for:

• Various surgical conditions

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 58 patients who underwent resection of brain metastases after stereotactic radiosurgery (SRS), the median survival after resection was 7.7 months, with survival rates of 65%, 30%, and 16% at 6, 12, and 24 months, respectively.

Factors such as preoperative classification, performance status, systemic disease status, and the time interval between SRS and resection were found to significantly influence patient survival, with better outcomes observed in patients with delayed local progression after SRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The results of resection after stereotactic radiosurgery for brain metastases. Kano, H., Kondziolka, D., Zorro, O., et al.[2010]

Stereotactic radiosurgery after the surgical removal of brain metastases significantly reduces the risk of local recurrence of cancer, based on findings from two clinical trials presented in 2016.

This treatment approach also improves the quality of life for patients compared to traditional whole-brain radiotherapy, suggesting it should be adopted as a new standard of care for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery Keeps Brain Metastases at Bay. [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 is highly effective in managing both newly diagnosed and recurrent brain metastases, making it a preferred treatment option.

This method is particularly beneficial for patients with small, solitary brain metastases due to its low risk of complications, high effectiveness, and cost efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgery: its role in brain metastasis management. Flickinger, JC., Lunsford, LD., Somaza, S., et al.[2005]

Stereotactic radiosurgery for brain metastases from breast cancer showed a high tumor control rate of 93% and a median survival of 13 months post-treatment, indicating its efficacy as a treatment option.

The absence of multiple brain metastases was the only significant factor associated with longer survival, while the treatment had a low complication rate, with only a few cases of radiation-induced edema that did not require further surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for brain metastases from breast cancer. Firlik, KS., Kondziolka, D., Flickinger, JC., et al.[2019]

Preoperative stereotactic radiosurgery (SRS) in 117 patients with brain metastases showed excellent local control of tumor cavities with a low risk of radiation necrosis (4.8%) and leptomeningeal disease recurrence (4.3%), suggesting it is a safe and effective treatment option.

The study found that subtotal resection of tumors significantly increased the risk of local recurrence and worsened overall survival, highlighting the importance of achieving gross total resection for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm. Prabhu, RS., Miller, KR., Asher, AL., et al.[2021]

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 study analyzed 435 patients with brain metastases treated with Gamma Knife stereotactic radiosurgery (SRS) and found that the overall incidence of adverse radiation effects (ARE) was low at 5.4%, but increased significantly with lesion size and volume, reaching a 1-year cumulative incidence of 13%-14% for larger lesions.

Approximately 60% of the 118 cases of ARE were symptomatic, with most occurring between 3 to 18 months post-treatment, highlighting the importance of monitoring patients during this time frame for potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. Sneed, PK., Mendez, J., Vemer-van den Hoek, JG., et al.[2022]

Postoperative stereotactic radiosurgery (SRS) improves local control of brain metastases and preserves neurocognitive function compared to whole brain radiation therapy, but local recurrence rates can still be as high as 40% within a year.

Preoperative SRS may enhance tumor control by targeting intact metastases, potentially reducing the risk of intra-operative tumor cell seeding and leptomeningeal disease, while also lowering the likelihood of symptomatic radiation necrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Stereotactic Radiosurgery for Brain Metastases. Routman, DM., Yan, E., Vora, S., et al.[2020]

In a study of 174 patients treated with stereotactic radiosurgery (SRS) for brain metastases, those who underwent surgery after SRS experienced significant improvements in quality of life, with 50% showing better performance scores post-surgery.

Patients who had surgery after SRS had a median overall survival of 11 months, with longer survival observed in those with radiation necrosis, suggesting that SRS can effectively manage symptoms and improve outcomes when followed by surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative Resection of Metastatic Brain Tumors Previously Treated by Stereotactic Radiosurgery. Jeon, YS., Koh, YC., Song, SW., et al.[2020]

References

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

The results of resection after stereotactic radiosurgery for brain metastases. [2010]

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

Stereotactic Radiosurgery Keeps Brain Metastases at Bay. [2018]

3. 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]

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

Radiosurgery: its role in brain metastasis management. [2005]

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

Stereotactic radiosurgery for brain metastases from breast cancer. [2019]

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

Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm. [2021]

7. 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]

8. 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]

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

Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. [2022]

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

Preoperative Stereotactic Radiosurgery for Brain Metastases. [2020]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Palliative Resection of Metastatic Brain Tumors Previously Treated by Stereotactic Radiosurgery. [2020]