Stereotactic Radiosurgery for Brain Cancer

(SRS Trial)

Overseen By Jonathan VanPelt, MHA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Leptomeningeal metastasis, Life expectancy < 3 months, Uncontrolled illness, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 90 days

135 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose of stereotactic radiosurgery, a precise radiation therapy, for treating brain cancer that has metastasized. Researchers aim to assess whether higher doses can better control cancer, extend life, or improve quality of life. The trial is recruiting individuals with up to 10 brain tumors that have not received prior radiation treatment. Candidates should have non-blood-related cancers, such as those excluding small cell lung cancer, and must be able to undergo an MRI or CT scan. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance future treatment options.

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 is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that Stereotactic Radiosurgery is safe for brain cancer patients?

Research has shown that stereotactic radiosurgery (SRS) is generally safe for treating brain conditions, including brain metastases. Studies have found that SRS effectively targets the treatment area and is well-tolerated by patients. A review of 32 studies involving 1,446 patients linked SRS to high local control rates, effectively stopping tumor growth in the treated area.

Patients in these studies reported a high therapeutic ratio with SRS, indicating that the benefits of treatment often outweigh the potential risks. While some side effects, such as headaches or nausea, can occur, they are usually mild and temporary. Overall, SRS is considered a safe treatment option for brain cancer patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Stereotactic Radiosurgery is unique because it offers a highly precise way to target brain cancer cells with radiation. Unlike traditional radiation therapy, which can impact surrounding healthy tissue, this method delivers focused beams of radiation directly to the tumor. This precision minimizes damage to nearby healthy brain tissue and may reduce side effects. Researchers are excited about this treatment because it has the potential to escalate the radiation dose safely, potentially improving outcomes for patients with brain cancer.

What evidence suggests that Stereotactic Radiosurgery might be an effective treatment for brain cancer?

Studies have shown that stereotactic radiosurgery (SRS), the treatment tested in this trial, effectively treats brain metastases, which are cancer cells that have spread to the brain. This noninvasive treatment uses focused radiation to precisely target tumors, potentially improving cancer control. Research indicates that SRS can offer survival rates similar to whole-brain radiotherapy (WBRT) while reducing side effects. However, some studies suggest that tumors larger than 3 cm might not respond as well to SRS alone. Overall, strong evidence supports SRS as a promising option for managing brain metastases. ^{1 2 3 4 6}

Who Is on the Research Team?

Robert Timmerman, MD

Principal Investigator

UTSW

Are You a Good Fit for This Trial?

This trial is for adults with non-hematopoietic cancer and up to 10 brain metastases, none larger than 3.0 cm or in the brain stem. Participants must not be pregnant, agree to use contraception, have an ECOG score of ≤2 or Karnofsky score ≥50, and can have had prior treatments except recent brain surgery or radiation.

Inclusion Criteria

I have 10 or fewer brain tumors.

My cancer is not related to blood, small cell lung, germ cell, or an unknown primary.

I have brain metastasis visible on MRI or CT scans.

Exclusion Criteria

Patients with life expectancy < 3 months

I do not have any severe illnesses that could interfere with the study.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic radiosurgery (SRS) with dose escalation to determine maximal tolerated doses

90 days

1 visit (in-person) for SRS procedure

Follow-up

Participants are monitored for safety, overall survival, time to progression, and local progression rate after treatment

3 years

Regular follow-up visits with imaging as per protocol

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic Radiosurgery

Trial Overview The study tests increasing doses of Stereotactic Radiosurgery (SRS) on patients who haven't received previous brain radiation. The goal is to find higher tolerable doses that could improve treatment outcomes like tumor control and patient survival.

How Is the Trial Designed?

Group I: Stereotactic Radiosurgery Experimental Treatment 1 Intervention

Radiation, Stereotactic Radiosurgery Dose-Escalation

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

Approved in European Union as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in United States as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas
• Liver tumors
• Lung tumors
• Spinal cord tumors

Approved in Canada as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in Japan as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in China as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in Switzerland as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Stereotactic radiosurgery, particularly using high-energy X-rays and the gamma-knife technique, has become a promising treatment for conditions like arteriovenous malformations and certain slow-growing brain tumors, thanks to advancements in neuro-imaging and radiation delivery methods.

This treatment can be used alone or in combination with other therapies, such as surgery and embolization, and is effective for well-defined, deep-seated tumors, making it a valuable option for carefully selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactically guided radiosurgery using the linear accelerator. Blond, S., Coche-Dequeant, B., Castelain, B.[2020]

Stereotactic radiosurgery (SRS) for patients with 5 or more melanoma brain metastases showed a high local control rate of 91.3% at 6 months and 82.2% at 12 months, indicating its effectiveness as a treatment option.

The study found that a larger planning target volume (PTV) was a significant predictor of local failure, highlighting the importance of careful treatment planning in achieving better outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases. Frakes, JM., Figura, NB., Ahmed, KA., et al.[2016]

Both stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) achieved similar local control rates for vestibular schwannomas, with SRS showing 100% and fSRS showing 94.2%.

However, fSRS was associated with a significantly higher risk of toxicities (42.3% vs. 8.3% for SRS), indicating that while both treatments are effective, fSRS may pose greater safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery and fractionated stereotactic radiosurgery for vestibular schwannomas: A comparison of clinical outcomes from the RSSearch patient registry. Singh, R., Ansinelli, H., Jenkins, J., et al.[2022]

A retrospective analysis of 383 patients treated with stereotactic radiosurgery (SRS) for brain metastases showed a median survival of 9 months, indicating that SRS can be an effective treatment option.

The study found a 75% local control rate at one year, suggesting that SRS is a safe and effective method for managing brain metastases, particularly in selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear accelerator radiosurgery in the treatment of brain metastases. Ulm, AJ., Friedman, WA., Bova, FJ., et al.[2022]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

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]

Out of 221 reported incidents related to CyberKnife™ SRS and SBRT from 2012 to 2019, the majority (205 incidents) had little to no clinical impact, indicating a high level of safety in the treatment process.

Human performance issues were the most common contributing factor (79% of incidents), with many errors occurring during pre-treatment phases, highlighting the need for improved training and protocols to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Error Pathways in CyberKnife™ Radiation Therapy. Mullins, BT., Mazur, L., Dance, M., et al.[2020]

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]

Both gamma knife (GK) and linear accelerator (LINAC) systems provide comparable tumor control rates for vestibular schwannoma, with rates of 93% for GK and 94% for LINAC based on a meta-analysis of 39 studies involving 6516 patients.

GK may better preserve trigeminal nerve function, while LINAC is associated with a lower incidence of tinnitus, suggesting that each method has unique benefits regarding side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the long-term safety and efficacy of gamma knife and linear accelerator radiosurgery for vestibular schwannoma: A systematic review and meta-analysis. Guadix, SW., Tao, AJ., An, A., 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]

The combination of stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) improves local tumor control and neurological function in patients with brain metastases, particularly benefiting those with a single metastasis, as it is associated with better survival compared to WBRT alone.

Current studies on SRS compared to other treatments like WBRT or neurosurgery show limited quality and inconclusive evidence, highlighting the need for more rigorous research to assess the effectiveness and safety of these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. Müller-Riemenschneider, F., Schwarzbach, C., Bockelbrink, A., et al.[2021]

Stereotactic radiosurgery is an innovative technique that delivers a high dose of radiation to specific areas in the brain in just one session, allowing for effective treatment of various intracranial lesions.

In a study involving 24 patients treated since June 1992, the procedure has been well tolerated, indicating a favorable safety profile for this method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of intracranial lesions with stereotactic radiosurgery. Sinha, PP., Bloomfield, S., Smith, GK.[2004]

Stereotactic radiosurgery (SRS) has been shown to improve patient outcomes and reduce toxicity compared to whole-brain radiation therapy (WBRT) for treating multiple brain metastases, based on three decades of research.

Current practices allow for the treatment of patients with 10 or more brain metastases using SRS alone, even with cumulative tumor volumes of up to 25 cm³, reflecting a shift in clinical approach due to advancements in cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for Multiple Brain Metastases Radiosurgery. Niranjan, A., Monaco, E., Flickinger, J., et al.[2019]

Stereotactic radiosurgery (SRS) using CyberKnife is a safe and effective treatment for elderly patients (≥65 years) with brain metastases, achieving high local control rates and maintaining a stable quality of life in 97.9% of patients.

In a study of 97 patients, SRS demonstrated a 79% overall survival rate at 3 months and a 99.2% local tumor progression-free rate at 6 months, indicating its efficacy compared to traditional whole brain radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation. Acker, G., Hashemi, SM., Fuellhase, J., et al.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK542166/

Stereotactic Radiosurgery (SRS) and Stereotactic Body ... - NCBI These noninvasive modalities offer effective management for a range of conditions, including brain metastases, benign brain tumors (such as ...

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

Brain stereotactic radiosurgery This procedure delivers precise radiation therapy to treat brain tumors and other brain conditions.

3. advancesradonc.org advancesradonc.org/article/S2452-1094(23)00230-0/fulltext

Stereotactic Radiosurgery in the Management of Brain ... Stereotactic radiosurgery in the management of brain metastases: a case-based radiosurgery society practice guideline.

4. nature.com nature.com/articles/s41467-024-47998-8

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

5. surgicalneurologyint.com surgicalneurologyint.com/surgicalint-articles/stereotactic-radiosurgery-versus-whole-brain-radiotherapy-for-intracranial-metastases-a-systematic-review-and-meta-analysis/

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. 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 ...