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

Trial Summary

What is the purpose of this trial?

The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.

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 data supports the idea that Radiosurgery for Brain Metastases is an effective treatment?

The available research shows that stereotactic radiosurgery (SRS) is an effective treatment for brain metastases. It is often used instead of whole-brain radiation therapy (WBRT) because it improves outcomes and reduces side effects. For example, guidelines suggest that SRS is effective for patients with multiple brain metastases, and it is commonly used to treat 10 or more tumors in a single session. Additionally, SRS can be used after surgery to target large brain metastases, providing good control over the disease. In some cases, SRS alone is preferred over WBRT, as it does not decrease survival time and can be reserved for later use if needed. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Stereotactic Radiosurgery (SRS) for brain metastases?

Research shows that Stereotactic Radiosurgery (SRS) is effective for treating multiple brain metastases, improving outcomes and reducing side effects compared to whole-brain radiation therapy (WBRT). It is particularly beneficial for patients with a high number of tumors, as it can treat up to 10 or more tumors in a single session, focusing on the total tumor volume rather than the number of metastases. ^{1 2 3 4 5}

What safety data is available for radiosurgery treatments like SRS and SBRT?

Safety data for radiosurgery treatments such as SRS and SBRT indicate that these procedures are generally safe with advancements in technology improving accuracy and reducing risks. The ASTRO Safety White Paper highlights the importance of quality and patient safety considerations due to the complexity and high doses involved. A study on CyberKnife radiosurgery for brain metastases in elderly patients shows it is effective and reduces neurotoxicity compared to whole brain radiation therapy. An analysis of CyberKnife incidents found that most led to little or no patient harm, with human performance being a common contributing factor. Overall, while there are risks, the safety profile of these treatments is favorable with ongoing efforts to improve safety practices. ^{3 6 7 8 9}

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

Stereotactic radiosurgery (SRS) is generally considered safe for treating brain metastases, with most incidents related to the procedure causing little or no harm to patients. Safety measures and best practices are emphasized to ensure patient safety, and most errors are related to administrative issues rather than the treatment itself. ^{3 6 7 8 9}

Is Stereotactic Radiosurgery a promising treatment for brain metastases?

Yes, Stereotactic Radiosurgery (SRS) is a promising treatment for brain metastases. It is a focused radiation therapy that can be used instead of more invasive surgery or whole brain radiation. SRS is effective in controlling the growth of brain tumors and can be used as a primary treatment or alongside surgery. It has been shown to help improve survival and manage brain metastases from various cancers, including breast cancer. ^{2 10 11 12 13}

How is the treatment Stereotactic Radiosurgery (SRS) unique for brain metastases?

Stereotactic Radiosurgery (SRS) is unique because it delivers a highly focused dose of radiation in a single session, targeting brain metastases precisely without affecting surrounding healthy tissue. This makes it an alternative to whole brain radiation therapy, especially for patients with large or multiple brain metastases. ^{1 2 10 11 12}

Research Team

Zabi Wardak

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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) 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]

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) 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) 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]

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]

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 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]

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]

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]

References

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

Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases. [2018]

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

Predictors of linear accelerator versus Gamma Knife stereotactic radiosurgery use for brain metastases in the United States. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Guidelines for Multiple Brain Metastases Radiosurgery. [2019]

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

The role of radiosurgery in the management of malignant brain tumors. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

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

Quality and Safety Considerations in Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy: An ASTRO Safety White Paper Update. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Common Error Pathways in CyberKnife™ Radiation Therapy. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. [2021]

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

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

12. Poland pubmed.ncbi.nlm.nih.gov

CyberKnife Stereotactic Radiosurgery in brain metastases: A report from Latin America with literature review. [2022]

13. Italy 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. [2021]