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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two radiation treatments to determine which is more effective for non-melanoma cancer that has spread to the brain. Stereotactic radiosurgery, a precise form of radiation therapy, targets the tumor with a single, high dose to kill more cancer cells while sparing healthy tissue. In contrast, whole brain radiation treats the entire brain over several sessions and may lead to more thinking and memory issues. Individuals with 4 to 15 brain tumors from cancer that did not originate in the brain may be suitable for this trial. As a Phase 3 trial, this research represents the final step before FDA approval, offering patients a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that stereotactic radiosurgery (SRS) is generally well-tolerated. Research indicates that patients who received SRS experienced fewer issues with thinking and memory compared to other treatments. For instance, one study found that patients had fewer problems with memory and thinking skills. Another study showed that SRS can effectively control brain tumors for several years, suggesting it is a safe option.

Whole brain radiation therapy (WBRT) is another method used to treat brain metastases. It involves delivering radiation to the entire brain over multiple sessions. While effective, it can sometimes lead to more side effects, such as memory problems, because the whole brain is exposed to radiation.

In summary, both treatments are effective, but SRS might cause fewer side effects related to memory and thinking. Discussing options with healthcare providers is important to determine the best approach for individual needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about comparing Stereotactic Radiosurgery (SRS) and Whole-Brain Radiotherapy (WBRT) for brain metastasis because these approaches offer distinct benefits. SRS is unique because it delivers highly targeted radiation in a single session, minimizing damage to surrounding healthy brain tissue and potentially reducing side effects. On the other hand, WBRT treats the entire brain over multiple sessions, which can address both visible and microscopic tumors but may lead to more widespread cognitive effects. This trial aims to determine which method provides better outcomes for patients, balancing effectiveness with quality of life.

What evidence suggests that this trial's treatments could be effective for brain metastasis?

This trial will compare the effectiveness of stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) for treating brain metastasis. Research has shown that SRS can effectively treat cancer that has spread to the brain, with studies finding that patients receiving SRS tend to live about 11 to 16 months after treatment. SRS also typically causes fewer issues with thinking and memory compared to WBRT. WBRT treats the entire brain and is known for addressing multiple cancer spots but may affect cognitive functions more. While both treatments aim to shrink tumors, SRS is more targeted and precise, potentially leading to better cancer control and less harm to healthy brain tissue. Participants in this trial will be assigned to either the SRS arm or the WBRT arm to evaluate these outcomes. ^{1 4 6 7 8}

Who Is on the Research Team?

Jing Li

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

All patients must sign informed consent verifying that they are aware of the investigational nature of this study in keeping with the rules and policies of M.D. Anderson Cancer Center. The only acceptable consent form is the one attached at the end of this protocol, and it must have been approved and amended by the M.D. Anderson IRB

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

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

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

Outcomes of single brain metastasis treated with gamma ... Gamma Knife Stereotactic radiosurgery(GKSR) achieved good outcomes in terms of OS with fewer neurocognitive disorders.

2. advancesradonc.org advancesradonc.org/article/S2452-1094(23)00132-X/fulltext

Cystic Brain Metastasis Outcomes After Gamma Knife ... With a median follow-up of 8.9 months, the median survival time (MST) was 11.1 months, and the 1-year local control rate was 75.9%. Gamma Knife ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4630352/

Efficacy and Safety of Fractionated Stereotactic Radiosurgery ... The median OS was 16 months, and the estimated OS rates at 6, 12 and 18 months were 81.1%, 56.8%, and 40.7%, respectively. Of 21 patients who died, 10 (47.6%) ...

5. research.va.gov research.va.gov/resources/pubs/docs/gamma.pdf

Stereotactic Radiosurgery for Metastases to the Brain Comparison data to assess the effectiveness of stereotactic radiosurgery for the treatment of multiple metastases are absent, or of such poor quality as to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34952524/

Survival and outcomes in patients with ≥ 25 cumulative ... The authors examined the survival outcomes and dosimetry to critical structures in patients treated with Gamma Knife radiosurgery (GKRS) for ≥ 25 metastases.

7. investors.accuray.com investors.accuray.com/news-releases/news-release-details/new-data-indicates-cyberknifer-system-can-provide-safe-and?mobile=1

New Data Indicates the CyberKnife® System Can Provide ... The results showed one-year, two-year, and three-year local BSM control rates were 82.9 percent, 71.4 percent, and 61.2 percent. This study ...

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

Safety and Feasibility of Stereotactic Radiosurgery for ... Treatment-naïve patients had a median survival of >6 months, long enough to benefit from cognitive sparing with SRS. Our study supports randomized studies ...