Radiosurgery vs Whole Brain Radiation for Brain Metastasis

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants

Disqualifiers: Melanoma, Small cell carcinoma, 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

Compensation: Varies

Number of Visits: 6

Duration: 1 day for SRS or 2 weeks for WBRT

88 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you may need to pause anti-coagulation medications for a short time around the radiosurgery treatment. You can continue other systemic therapies like temozolomide if your oncologist agrees.

What data supports the effectiveness of the treatment Radiosurgery vs Whole Brain Radiation for Brain Metastasis?

Research suggests that Stereotactic Radiosurgery (SRS) can deliver higher radiation doses directly to brain metastases, leading to better control of the tumors compared to Whole-Brain Radiation Therapy (WBRT), which can result in diminished cognitive function and no overall survival benefit when used as an addition to SRS. ^{1 2 3 4 5}

Is radiosurgery safe for treating brain metastases?

Research indicates that stereotactic radiosurgery (SRS) is generally safe for treating brain metastases, with studies showing it as an effective initial management strategy and an alternative to whole-brain radiation therapy (WBRT) to reduce neurotoxicity (damage to the nervous system). ^{1 3 6 7 8}

How does the treatment of radiosurgery compare to whole brain radiation for brain metastasis?

Radiosurgery (SRS) is unique because it delivers high-dose focused radiation directly to the tumor, minimizing damage to surrounding healthy brain tissue, unlike whole brain radiation therapy (WBRT) which affects the entire brain. This focused approach can be beneficial for patients with fewer brain metastases, but the advantage of combining SRS with WBRT is still unclear. ^{3 4 9 10 11}

What is the purpose of this trial?

This trial compares two radiation treatments for brain tumors from non-melanoma cancers. One treatment is a focused, high-dose method, while the other treats the entire brain over several sessions. The goal is to determine which method controls tumors better and has fewer side effects on thinking and memory. The focused, high-dose method has been increasingly used over the past years as an effective treatment for brain metastases, often replacing the whole brain treatment due to its ability to improve outcomes and reduce side effects.

Research Team

Jing Li

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with non-melanoma cancer that has spread to the brain, with 3-15 detectable lesions on MRI. Participants must have proof of malignant cancer and be able to undergo all treatments proposed. They should not have had prior brain surgery or whole-brain radiation, no melanoma or certain other cancers, and women of childbearing age must not be pregnant.

Inclusion Criteria

My blood clotting levels are normal, and I can stop blood thinners for radiosurgery.

My cancer is confirmed to be spreading, based on a tissue sample.

I have 3 to 15, possibly up to 20, brain tumors visible on a recent MRI.

Exclusion Criteria

I have not had surgery to remove cancer from my brain.

Female patients of childbearing age will be excluded if they are pregnant as assessed by serum b-HCG or urine pregnancy test. A serum b-HCG test or urine pregnancy test will be performed no greater than 14 days prior to study registration

Patients will be excluded if they are unable to obtain an MRI scan

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either stereotactic radiosurgery (SRS) on day 1 or whole brain radiation therapy (WBRT) 5 days per week for 2 weeks

1 day for SRS or 2 weeks for WBRT

1 visit for SRS, 10 visits for WBRT

Follow-up

Participants are monitored for local tumor control and cognitive decline at 1, 4, 6, 9, and 12 months post-treatment

12 months

5 visits (in-person)

Treatment Details

Interventions

• Stereotactic Radiosurgery
• Whole-Brain Radiotherapy

Trial Overview The study compares stereotactic radiosurgery (SRS), which targets tumors directly in a single high dose, against whole-brain radiotherapy (WBRT) that treats the entire brain over multiple sessions. The goal is to determine which method is more effective for treating brain metastases from non-melanoma cancers and causes fewer cognitive side effects.

Participant Groups

Group I: Arm II (WBRT) Experimental Treatment 3 Interventions

Patients undergo WBRT 5 days per week (7 days per week for inpatients) for 2 weeks.

Group II: Arm I (SRS) Experimental Treatment 3 Interventions

Patients undergo SRS on day 1.

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

The novel Spatially Partitioned Adaptive Radiosurgery (SPARE) technique significantly reduces radiation exposure to the hippocampus and normal brain tissue compared to traditional hippocampal-avoidance whole brain radiation therapy (HA-WBRT), with reductions of up to 93% in dose metrics.

In a study of 10 cases, the GKI-Spr method not only outperformed HA-WBRT but also showed superior dosimetry compared to single-fraction single-day SRS, indicating it may be a safer and more effective option for treating multiple brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Fraction Stereotactic Radiosurgery Versus Hippocampal-Avoidance Whole Brain Radiation Therapy for Patients With 10 to 30 Brain Metastases: A Dosimetric Analysis. Nguyen, TK., Sahgal, A., Detsky, J., et al.[2020]

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 involving 40 patients treated with stereotactic radiosurgery (SRS) and a historical control group of 70 patients receiving whole-brain radiotherapy (WBRT), SRS showed a median overall survival (OS) of 10.4 months compared to 6.5 months for WBRT, although the difference was not statistically significant.

SRS was associated with no grade III toxicities, suggesting it may be a safer option compared to WBRT, which indicates the need for further randomized trials to explore its efficacy and safety in the context of modern cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4-10 brain metastases: A nonrandomized controlled trial. Bodensohn, R., Kaempfel, AL., Boulesteix, AL., et al.[2023]

The study proposes a new treatment approach called HA-SIB-WBRT, which combines hippocampal avoidance with a simultaneous integrated boost of radiation to improve tumor control in patients with multiple brain metastases, aiming to recruit 100 patients over 2 years.

The primary goal of the trial is to assess whether this technique leads to better target lesion control and improved cognitive outcomes compared to traditional HA-WBRT, highlighting the importance of maintaining quality of life for patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised prospective phase II trial in multiple brain metastases comparing outcomes between hippocampal avoidance whole brain radiotherapy with or without simultaneous integrated boost: HA-SIB-WBRT study protocol. Chia, BSH., Leong, JY., Ong, ALK., 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]

A meta-analysis of two trials involving 358 participants found that adding stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) did not significantly improve overall survival compared to WBRT alone, although it did show benefits for specific patient groups.

Patients receiving the combination of WBRT and SRS experienced better local control of brain metastases, improved performance status, and reduced need for steroids, indicating that while overall survival may not differ, the quality of life and treatment effectiveness could be enhanced with the combined approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Patil, CG., Pricola, K., Garg, SK., et al.[2018]

A meta-analysis of two trials involving 358 participants found that adding stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) did not significantly improve overall survival compared to WBRT alone, although it did show better local control of brain metastases.

Patients receiving the combination of WBRT and SRS had improved performance status and reduced need for steroids, with a notable increase in the percentage of patients maintaining or improving their Karnofsky Performance Scale scores at 6 months (43% vs. 28% for WBRT alone).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Patil, CG., Pricola, K., Sarmiento, JM., et al.[2022]

Combining stereotactic radiosurgery (SRS) with whole brain radiation therapy (WBRT) does not significantly improve overall survival for patients with brain metastases compared to WBRT alone, based on a meta-analysis of two studies involving 358 participants.

However, patients receiving the combined treatment of SRS and WBRT showed better local control of the disease and improved performance status, particularly those with a single brain metastasis, indicating that while survival may not be extended, quality of life and disease management can be enhanced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Patil, CG., Pricola, K., Sarmiento, JM., et al.[2020]

References

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

Single-Fraction Stereotactic Radiosurgery Versus Hippocampal-Avoidance Whole Brain Radiation Therapy for Patients With 10 to 30 Brain Metastases: A Dosimetric Analysis. [2020]

2. Scotland pubmed.ncbi.nlm.nih.gov

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

3. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4-10 brain metastases: A nonrandomized controlled trial. [2023]

4. India pubmed.ncbi.nlm.nih.gov

Whole brain radiotherapy and stereotactic radiosurgery for patients with recursive partitioning analysis I and lesions [2017]

5. England pubmed.ncbi.nlm.nih.gov

Randomised prospective phase II trial in multiple brain metastases comparing outcomes between hippocampal avoidance whole brain radiotherapy with or without simultaneous integrated boost: HA-SIB-WBRT study protocol. [2021]

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

Radiotherapy: Neurocognitive considerations in the treatment of brain metastases. [2021]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cumulative Doses to Brain and Other Critical Structures After Multisession Gamma Knife Stereotactic Radiosurgery for Treatment of Multiple Metastatic Tumors. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. [2020]