Radiosurgery for Brain Metastases

Overseen By Sarah Neufeld, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Leptomeningeal metastasis, Life expectancy < 4 months, Psychiatric 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: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a type of targeted radiation treatment called stereotactic radiosurgery to determine the optimal dose and its effects on thinking and memory. It targets adults with at least six brain cancer spots, each no larger than 4 cm. Participants must not have previously received this treatment and should not have certain types of brain or spinal cancer spread. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that stereotactic radiosurgery (SRS) is generally well-tolerated for treating brain metastases. This noninvasive treatment uses focused radiation to target tumors precisely. Studies have found that SRS effectively manages brain tumors and other brain conditions without requiring more invasive surgery.

SRS is considered a safe option for many patients. Some studies indicate that it can lead to similar survival rates as whole-brain radiation therapy (WBRT), but with potentially fewer side effects. The procedure's precision helps protect healthy brain tissue, reducing the chance of unwanted effects.

While SRS is not a new treatment and has been used successfully for various brain conditions, this trial is in its early stages. These stages mainly focus on assessing safety and dosage levels. Ongoing research aims to find the best and safest ways to use SRS for brain metastases.

Overall, existing data suggest that SRS is a safe and effective treatment with a good track record. However, as with any treatment, discussing potential risks and benefits with healthcare professionals is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Stereotactic Radiosurgery (SRS) is unique because it delivers precise, high-dose radiation to brain metastases in a single session, minimizing damage to surrounding healthy tissue. Unlike traditional whole-brain radiation therapy, which can impact cognitive function due to its broader exposure, SRS specifically targets the tumor, offering a more focused approach. Researchers are excited about SRS because it has the potential to effectively control tumor growth while reducing side effects, leading to better overall outcomes for patients with brain metastases.

What evidence suggests that stereotactic radiosurgery might be an effective treatment for brain metastases?

Studies have shown that stereotactic radiosurgery, the treatment tested in this trial, can effectively control brain tumors. One study found that the treatment stopped tumor growth in about 70% of cases. This method works especially well for smaller brain tumors that have spread from other parts of the body. It is recommended for tumors less than 2 cm in size, with treatment doses typically ranging from 2000 to 2400 cGy. Although not all tumors respond the same way, this treatment offers a focused approach that can benefit certain patients. ^{2 5 6 7 8}

Who Is on the Research Team?

Zabi Wardak

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with non-blood related cancers, like small cell lung carcinoma, who have six or more brain metastases but no larger than 4 cm. They should be relatively active (able to care for themselves) and not pregnant. They must agree to use birth control during the study. People with prior whole-brain radiation, leptomeningeal metastasis, a life expectancy under four months, or certain psychiatric conditions can't join.

Inclusion Criteria

The biggest tumor is no larger than 4 centimeters.

You have not received a specific type of radiation treatment to the areas that will be treated in this study.

You are able to perform daily activities without help or only need a little help.

Exclusion Criteria

You have received radiation treatment to your entire brain in the past.

You have cancer that has spread to the tissues surrounding the brain and spinal cord.

You are not expected to live for more than 4 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Determine the maximal tolerated dose (MTD) of stereotactic radiosurgery for patients with multiple brain metastases

60 days

Multiple visits for dose escalation and monitoring

Phase II Treatment

Evaluate neurocognitive decline in patients treated with the determined MTD of stereotactic radiosurgery

3 years

Regular follow-up visits for neurocognitive assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on neurocognitive outcomes

4 months

Follow-up visits for neurocognitive testing

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic Radiosurgery

Trial Overview The trial is testing Stereotactic Radiosurgery (SRS), a precise form of radiation therapy aimed at brain tumors. The first phase determines the highest dose patients can take without serious side effects; the second phase looks at how this treatment affects patients' thinking and memory skills over time.

How Is the Trial Designed?

Group I: Radiation Experimental Treatment 1 Intervention

Stereotactic Radiosurgery

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

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) 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]

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 (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]

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]

In a study of 4,327 patients with brain metastases from non-small cell lung cancer, it was found that treatment at non-academic facilities significantly increased the likelihood of receiving LINAC SRS over Gamma Knife SRS, especially in the Midwestern, Northeastern, and Southern US regions.

Patients receiving higher doses of radiation (18-24 Gy) were also more likely to receive LINAC SRS, and those living within 20 miles of a treatment facility had a 27% higher chance of receiving LINAC, suggesting that geographic accessibility plays a role in treatment modality choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of linear accelerator versus Gamma Knife stereotactic radiosurgery use for brain metastases in the United States. McClelland Iii, S., Degnin, C., Chen, Y., et al.[2022]

Radiosurgery (SRS) using a mono-isocentric, non-coplanar technique effectively treated 172 patients with multiple brain metastases, achieving a 2-year local progression-free survival (LPFS) rate of 71.6%.

The study indicates that higher biological effective doses (BED) correlate with better local control, and the technique allows for safe treatment of patients with many metastases while delaying the need for whole-brain radiation therapy (WBRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique. Alongi, F., Nicosia, L., Figlia, V., et al.[2021]

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]

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) 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]

In a study of 49 patients with brain metastases treated with CyberKnife Stereotactic Radiosurgery (CKRS), the median overall survival was 15.5 months, indicating effective long-term outcomes.

CKRS demonstrated high local control rates of 98% at 3 months and 90% at 1 year, with no late complications such as radiation necrosis, highlighting its safety and efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CyberKnife Stereotactic Radiosurgery in brain metastases: A report from Latin America with literature review. de la Peña, C., Guajardo, JH., Gonzalez, MF., et al.[2022]

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 (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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9931898/

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 ...

2. 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.

3. 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

4. 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.

5. practicalradonc.org practicalradonc.org/article/S1879-8500(22)00054-6/fulltext

Radiation Therapy for Brain Metastases: An ASTRO ... For patients with intact brain metastases measuring <2 cm in diameter, single-fraction SRS with a dose of 2000-2400 cGy is recommended.

6. 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 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2452109424000721;

Safety and Feasibility of Stereotactic Radiosurgery for ... 1, 2, 3 Traditionally, patients with multiple brain metastases have a poor median survival of <6 months and often require whole brain radiation therapy (WBRT).

8. 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.