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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of stereotactic radiosurgery, a precise form of radiation therapy, when administered before or after surgery for patients with brain tumors that have metastasized. The goal is to determine which timing results in fewer side effects and better outcomes. Participants are divided into two groups: one receives radiosurgery after surgery, and the other before surgery. This study may suit individuals with a single brain tumor recommended for surgical removal (conventional surgery) who are already planning to undergo this type of radiation treatment. As a Phase 3 trial, it 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 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.

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

Research has shown that stereotactic radiosurgery (SRS) is a safe treatment for brain tumors. In a large study, SRS produced good results for patients with brain metastases. Patients tolerated the treatment well, and it even improved cognitive health. Another study found that SRS effectively targeted the tumor without harming nearby areas.

This treatment is known for its precision, delivering a high dose of radiation directly to the tumor, which helps protect normal tissue. While every treatment can have side effects, these studies indicate that SRS is generally well-tolerated.

For those considering a trial involving SRS, these findings suggest it is a safe option based on past research. Always consult a healthcare professional to understand personal risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about comparing the timing of stereotactic radiosurgery (SRS) with surgery for brain metastasis. Unlike the standard approach, which typically involves surgery followed by radiation, this trial explores the effects of performing SRS either before or after surgery. The excitement stems from the potential to better preserve healthy brain tissue and minimize side effects by optimizing the sequence of these treatments. This could lead to improved outcomes and quality of life for patients with brain metastases.

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

Studies have shown that stereotactic radiosurgery (SRS) effectively treats brain metastases, which are tumors that have spread to the brain. Research indicates that SRS leads to good results, with patients often experiencing fewer issues with thinking and memory. A review of multiple studies has found SRS to be both effective and safe for treating brain tumors. Additionally, SRS offers survival rates similar to other radiation treatments, such as whole-brain radiotherapy. In this trial, participants will receive SRS either before or after conventional surgery to evaluate the timing's impact on treatment outcomes. However, not all brain tumors respond the same way to SRS, especially those larger than 3 cm. ^{6 7 8 9 10}

Who Is on the Research Team?

Elizabeth Yan, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

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pmc.ncbi.nlm.nih.gov

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Gamma Knife Stereotactic radiosurgery(GKSR) achieved good outcomes in terms of OS with fewer neurocognitive disorders.

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Response of treatment-naive brain metastases to ...

Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone

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surgicalneurologyint.com

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Stereotactic radiosurgery versus whole-brain radiotherapy ...

SRS and WBRT exhibited similar recurrence rates and overall survival (OS) at 1 and 5 years, with WBRT being more effective in managing post-radiation LMD.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12248859/

Stereotactic Radiosurgery for Patients with Brain Metastases ...

Results: Median patient overall survival (OS) after SRS was 7 (range: 0–155) months. Local tumor control (LTC) was achieved in 105 out of 113 ...

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advancesradonc.org

advancesradonc.org/article/S2452-1094(24)00072-1/fulltext

Safety and Feasibility of Stereotactic Radiosurgery for ...

We present here one of the largest studies evaluating SRS for patients with ≥15 BMs. SRS was safe, had favorable cognitive outcomes, and had comparable survival ...

8.

nature.com

nature.com/articles/s41598-022-13853-3

Clinical outcomes of patients with multiple courses ...

Actuarial post-GKRS survival rates at 1, 2, 3, 4, and 5 years following initial GKRS were 88.1%, 79.5%, 65.3%, 51.4%, and 37.3%, respectively.

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S2667242123000064

Outcomes of single brain metastasis treated with gamma ...

The median percentage of tumor control after radiosurgery treatment was 70% (IQR: 65–78) and only 26.2% (n = 27) of patients had > 80% tumor control and ...

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jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2780031

Efficacy and Safety of Stereotactic Radiosurgery for ...

This systematic review and meta-analysis of 32 studies comprising 1446 patients found associations with high local control (86%), high therapeutic ratio of ...