Stereotactic Radiosurgery Timing for Brain Metastasis

Overseen By Debra Yeboa

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Prior brain radiation, Small-cell lung cancer, Lymphoma, Leukemia, Multiple myeloma, 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: Unknown

Duration: Up to 4 weeks

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial studies stereotactic radiosurgery (SRS) before surgery to see how well it works compared with SRS after surgery in treating patients with cancer that has spread to the brain (brain metastases). SRS is the delivery of focused, high-dose radiation given in a single session to the tumors, with a minimal dose given to uninvolved areas of the brain.

Do I need to stop my current medications for 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 trial coordinators or your doctor.

What data supports the effectiveness of the treatment Stereotactic Radiosurgery for brain metastasis?

Research shows that Stereotactic Radiosurgery (SRS) can prolong survival in patients with a single brain metastasis and maintain functional independence in those with up to three brain metastases. Additionally, SRS is effective in treating multiple brain metastases without the cognitive decline associated with whole brain radiation therapy. ^{1 2 3 4 5}

Is stereotactic radiosurgery generally safe for humans?

Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) are generally considered safe for humans, with studies showing their use in treating various conditions like brain metastases and prostate cancer. Safety guidelines and checklists are in place to minimize errors and complications, and advancements in technology have improved their safety and accuracy. ^{6 7 8 9 10}

How is stereotactic radiosurgery (SRS) different from other treatments for brain metastasis?

Stereotactic radiosurgery (SRS) is unique because it delivers a single, highly focused dose of radiation directly to the brain metastasis, minimizing damage to surrounding healthy tissue. Unlike whole brain radiation therapy (WBRT), SRS is associated with better cognitive outcomes and quality of life, as it targets only the tumor and not the entire brain. ^{4 11 12 13 14}

Research Team

Debra N. Yeboa

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for cancer patients with brain metastases who can undergo surgery and stereotactic radiosurgery (SRS). They should have a primary lesion size within specified limits, be in good enough health as measured by performance scores, and not have had previous brain radiation. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

I am mostly able to care for myself and carry out daily activities.

My main cancer area is 4 cm or less for one treatment, or 7 cm or less for multiple treatments.

I am a candidate for focused radiation therapy soon after my brain surgery.

Exclusion Criteria

I have had radiation therapy to my brain before.

For females, if they are pregnant or breast-feeding (The exclusion is made because gadolinium may be teratogenic in pregnancy)

My primary cancer is either small-cell lung cancer, lymphoma, leukemia, or multiple myeloma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo SRS and surgery based on randomization to pre-operative or post-operative SRS

Up to 4 weeks

Multiple visits for SRS and surgery

Follow-up

Participants are monitored for safety, effectiveness, and neurocognitive function after treatment

Up to 1 year

Periodic visits

Long-term follow-up

Participants are monitored for long-term outcomes such as local control, distant brain control, and overall survival

Up to 4 years

Treatment Details

Interventions

• Stereotactic Radiosurgery

Trial Overview The study compares the effectiveness of SRS when done before surgery versus after surgery in treating brain tumors from metastasized cancer. It's a phase III trial to determine which timing works best for high-dose radiation focused on the tumors.

Participant Groups

Group I: Group I (pre-operative SRS) Experimental Treatment 3 Interventions

Patients undergo SRS within 30 days of randomization followed by surgery within 30 days. Patients may undergo additional SRS if disease returns after treatment.

Group II: Group II (post-operative SRS) Active Control 3 Interventions

Patients undergo surgery within 30 days of randomization followed by standard of care SRS within 30 days. Patients may undergo additional SRS if disease returns after treatment.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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 radiosurgery (SRS) is an effective treatment for patients with brain metastases, particularly prolonging survival for those with a single metastasis and maintaining functional independence for patients with up to three metastases.

As SRS technology becomes more widely used, careful patient selection and treatment planning are essential to maximize its benefits and integrate it safely with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in intracranial stereotactic radiotherapy for metastases. Pinkham, MB., Whitfield, GA., Brada, M.[2022]

In a study of 130 patients treated with CyberKnife Radiosurgery for brain metastases, a cumulative tumor volume greater than 7cc was linked to worse outcomes, including higher rates of death and neurological defects.

The addition of whole brain radiation therapy (WBRT) was associated with improved survival rates in patients with a higher tumor burden, suggesting that WBRT may play a beneficial role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases. Kim, IK., Starke, RM., McRae, DA., et al.[2018]

In a study of 898 patients with brain metastases who received whole-brain radiation therapy (WBRT), only 7.8% were treated with stereotactic radiosurgery (SRS), highlighting its limited use despite established guidelines.

The presence of an on-site SRS program significantly increased the likelihood of patients receiving SRS, with 40.3% of eligible patients treated at hospitals with SRS compared to just 3.0% at those without, indicating that access to technology greatly influences treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-institutional study of factors influencing the use of stereotactic radiosurgery for brain metastases. Hodgson, DC., Charpentier, AM., Cigsar, C., et al.[2018]

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]

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]

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 body radiation therapy (SBRT) using CyberKnife for localized prostate cancer was found to be safe, with no severe treatment-related toxicities (grade 3 or higher) reported among 44 patients over a median follow-up of 40 months.

The treatment showed excellent efficacy, with a 100% cause-specific survival rate and progression-free survival rate, and a high biochemical failure-free rate of 90.8% for high-risk patients, particularly with the 34 Gy in 4 fractions regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided stereotactic body radiation therapy for localized prostate cancer. Kang, JK., Cho, CK., Choi, CW., 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 (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]

Stereotactic brachytherapy (SBT) is a safe and effective treatment for singular cerebral metastases, showing comparable survival rates and disease control to stereotactic radiosurgery (SRS) in a study of 219 patients (142 SRS, 77 SBT).

SBT allows for the possibility of histological evaluation and treatment in one procedure, and it can treat larger tumors than SRS, making it a valuable alternative for selected cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of stereotactic brachytherapy (125 iodine seeds) with stereotactic radiosurgery (LINAC) for the treatment of singular cerebral metastases. Ruge, MI., Kocher, M., Maarouf, M., et al.[2021]

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]

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

Linear accelerator radiosurgery in the treatment of brain metastases. [2022]

3. England pubmed.ncbi.nlm.nih.gov

New developments in intracranial stereotactic radiotherapy for metastases. [2022]

4. Scotland pubmed.ncbi.nlm.nih.gov

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases. [2018]

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

A multi-institutional study of factors influencing the use of stereotactic radiosurgery for brain metastases. [2018]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Austria pubmed.ncbi.nlm.nih.gov

Lausanne checklist for safe stereotactic radiosurgery. [2020]

8. Greece pubmed.ncbi.nlm.nih.gov

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

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

Image-guided stereotactic body radiation therapy for localized prostate cancer. [2022]

10. 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]

11. Germany pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

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

13. Germany pubmed.ncbi.nlm.nih.gov

Comparison of stereotactic brachytherapy (125 iodine seeds) with stereotactic radiosurgery (LINAC) for the treatment of singular cerebral metastases. [2021]

14. 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]