Radiosurgery for Brain Cancer

Overseen By John Fiveash, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Cytotoxic chemotherapy, TKIs

Disqualifiers: Pregnancy, Tumor > 4 cm, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1-3 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores radiosurgery, a precise, high-dose radiation treatment, to address brain tumors that have spread from other parts of the body. Researchers compare two targeting methods: one with no margin and another with a small 2mm margin around the tumor, to determine which is more effective. It suits individuals diagnosed with brain metastases (tumors that have spread to the brain) measuring 4 cm or less, provided they are not undergoing certain other treatments, such as recent chemotherapy. As an unphased trial, this study allows patients to contribute to innovative research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial requires that you stop taking cytotoxic chemotherapy within 3 days of treatment and hold certain TKIs (a type of cancer medication) at least 24 hours before treatment. There are no restrictions on the use of immunotherapy during treatment.

What prior data suggests that radiosurgery is safe for treating brain cancer?

Research has shown that radiosurgery for brain cancer is generally well-tolerated by patients, whether using a 0mm or a 2mm margin. Studies comparing these margins found no significant difference in tumor control or rates of pseudoprogression, a temporary increase in tumor size that resembles growth but is not. This suggests both methods are similarly effective and safe.

For the 0mm margin, studies indicate it is commonly used and does not compromise safety. Many centers prefer it because it precisely targets tumors without affecting nearby healthy brain tissue.

Regarding the 2mm margin, research shows it is safe and effective. Using a small margin like 1mm to 2mm helps account for uncertainties during treatment while protecting healthy brain areas. Patients have reported good cognitive outcomes and survival rates similar to other standard treatments.

Overall, radiosurgery with either a 0mm or 2mm margin is a safe option for treating brain metastases, tumors that have spread to the brain. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the radiosurgery technique for brain cancer because it offers a highly precise way to target tumors while sparing surrounding healthy tissue. Unlike traditional methods, this approach uses advanced imaging to deliver radiation with pinpoint accuracy, minimizing damage to normal brain structures. Additionally, the trial investigates two different margin settings—0mm and 2mm—for planning target volumes, which could lead to insights on optimizing treatment effectiveness and reducing side effects. By refining how radiation is delivered, this technique has the potential to improve outcomes and quality of life for patients with brain cancer.

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

This trial will compare two radiosurgery techniques for treating brain metastases: one with no extra space (0mm margin) around the tumor and another with a small extra space (2mm margin). Previous studies have shown that a 0mm margin can control tumors as effectively as a 2mm margin. Specifically, the 2mm margin managed 92% of tumors effectively over 12 months, demonstrating strong control in most cases. Both techniques use precise radiation to target the tumor while avoiding healthy brain tissue, which is crucial for reducing side effects and protecting brain function. Overall, the trial aims to evaluate the effectiveness of both margin strategies in treating brain cancer with focused radiation. ^{1 4 5 6 7}

Who Is on the Research Team?

John A Fiveash, MD

Principal Investigator

The University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for individuals with brain tumors that have spread (metastases) and are no larger than 4 cm. Specific eligibility details aren't provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

My brain cancer has not needed more treatment.

I am 19 years old or older.

Exclusion Criteria

My treatment plan may target more than 20 cancer areas after review.

I've had focused radiation before and may need it again.

Inability to have MRI imaging

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive radiosurgery treatment with either a 0mm or 2mm margin for brain metastases

1-3 weeks

1 visit (in-person)

Follow-up

Participants are monitored for tumor control and toxicity over a 12-month period

12 months

Regular visits (frequency not specified)

What Are the Treatments Tested in This Trial?

Interventions

• Radiosurgery

Trial Overview

The trial is testing the effectiveness of radiosurgery, a high-dose radiation treatment aimed at destroying tumors in the brain. It compares two approaches: one uses no extra space around the tumor (0mm margin), while the other includes a small buffer zone (2mm margin).

How Is the Trial Designed?

Group I: 0mm margin Active Control 1 Intervention

For each patient two radiation treatment plans will be created. One will have 0 mm margin for the planning target volume. Tumors will be prescribed based upon the maximum diameter of the largest tumor and location at the discretion of the treating radiation oncologist with the following guidance: \< 2.0 cm diameter 16-20 Gy 2.0-4.0 cm diameter 3 fractions of 9 Gy for total 27 Gy.

Group II: 2mm margin Active Control 1 Intervention

For each patient two radiation treatment plans will be created. One will be 2 mm margin for the planning target volume. Tumors will be prescribed based upon the maximum diameter of the largest tumor and location at the discretion of the treating radiation oncologist with the following guidance: \< 2.0 cm diameter 16-20 Gy 2.0-4.0 cm diameter 3 fractions of 9 Gy for total 27 Gy.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Stereotactic radiosurgery (SRS) was safely administered to 30 patients with malignant gliomas after standard radiotherapy, showing no significant acute or late toxicity, which suggests it is a feasible option for dose escalation in treatment.

The study reported a median survival of 13.9 months, with 1- and 2-year disease-specific survival rates of 57% and 25%, respectively, indicating that while SRS can be effective, further research is needed to fully understand its impact on long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery as an adjunct to surgery and external beam radiotherapy in the treatment of patients with malignant gliomas. Gannett, D., Stea, B., Lulu, B., et al.[2022]

Moderately dosed stereotactic radiosurgery (SRS) for one to four brain metastases showed a median overall survival of 7.5 months, with high local brain control rates of 87% at 6 months and 79% at 12 months, indicating its efficacy in treating limited brain metastases.

The study suggests that initial SRS alone can be a safe treatment option, as only 22% of patients required additional whole-brain radiotherapy, and significant predictors of survival included the time between the primary diagnosis and brain metastases, as well as the volume of the treated metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. Meisner, J., Meyer, A., Polivka, B., et al.[2021]

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]

Radiosurgery effectively treats small intracranial tumors and arteriovenous malformations (AVMs) using precise radiation delivery, with applications for both malignant tumors (like brain metastases and gliomas) and benign tumors (such as meningiomas and acoustic neuromas).

Most patients experience clinical improvement with radiosurgery, and it generally results in less morbidity compared to traditional surgical resection, despite the potential for complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical uses of radiosurgery. Chang, SD., Adler, JR., Hancock, SL.[2006]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8111033/

Impact of PTV margin reduction (2 mm to 0 ... - PubMed Central

There was no difference in local tumour control and pseudoprogression rates between 0-mm and 2-mm PTV-margin. The results from our study were ...

2.

withpower.com

withpower.com/trial/phase-brain-neoplasms-3-2025-b7874

Radiosurgery for Brain Cancer

Moderately dosed stereotactic radiosurgery (SRS) for one to four brain metastases showed a median overall survival of 7.5 months, with high local brain control ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0360301614000698

Impact of Millimeter-Level Margins on Peripheral Normal ...

Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution.

4.

cancer.gov

cancer.gov/clinicaltrials/NCI-2025-07480

Comparing Stereotactic Radiosurgery Margin Treatment ...

This clinical trial compares stereotactic radiosurgery (SRS) using a 0mm margin treatment approach to SRS using a 2mm margin treatment approach for treating ...

5.

academic.oup.com

academic.oup.com/neuro-oncology/article/26/Supplement_1/S3/7618749

Evolving concepts in margin strategies and adaptive ...

The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6226261/

Stereotactic radiosurgery practice patterns for brain ...

The most common margin for SRS was 0 mm (49.1%; p = 0.0021), with 38.6 and 12.3% prescribing a 1- and 2-mm margin, respectively. The most ...

7.

practicalradonc.org

practicalradonc.org/article/S1879-8500(25)00016-5/abstract

The Impact of Margin Expansions on Local Control and ...

Across 17 studies, we identified 5015 lesions treated with SRS (1360 lesions with no margin and 3684 with a margin). The median total margin was 1.5 (range, 1-3) ...