Whole Brain vs Stereotactic Radiation for Brain Cancer

Recruiting at 1 trial location

Overseen By Ayal Aizer, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Chronic kidney disease, Leptomeningeal disease, Small cell lung cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 2-4 weeks

196 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of radiation treatments for individuals with brain metastases, tumors that have spread to the brain from other body parts. The study compares whole brain radiation, which targets the entire brain, with stereotactic radiation (SRS), a focused treatment aimed at specific tumor sites. It is designed for individuals with 5-20 brain tumors who have not yet received radiation therapy for them but may have undergone other treatments. Participants must be eligible for an MRI scan and cannot have certain kidney issues or other specific conditions. The trial aims to determine which radiation method better controls brain tumors. As an unphased trial, it offers a unique opportunity to contribute to research that could enhance future treatment options for brain metastases.

Will I have to stop taking my current medications?

The trial protocol 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.

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

Research has shown that stereotactic radiation (SRS) safely treats brain tumors. Studies have found that SRS generally does not harm brain function and offers survival rates similar to whole brain radiation therapy (WBRT), meaning patients live just as long with SRS as with WBRT.

SRS targets the tumor directly, reducing radiation exposure to the rest of the brain and potentially minimizing side effects compared to treating the entire brain. While SRS does not prevent new tumors from forming elsewhere in the brain, it effectively treats existing ones.

For whole brain radiation, a technique called hippocampal sparing often protects brain areas related to memory, helping to reduce side effects on thinking and memory. Whole brain radiation has been a standard treatment for brain tumors, with well-established safety.

In summary, both stereotactic radiation and whole brain radiation are considered safe and well-tolerated. Prospective clinical trial participants should know that these treatments have been successfully used in many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer distinct approaches to targeting brain cancer. Stereotactic radiation (SRS) is unique due to its precision, delivering high doses of radiation directly to the tumor in just 1-5 sessions, which minimizes damage to surrounding healthy tissue. This contrasts with whole brain radiation, which treats the entire brain and might be less precise but can target multiple cancer sites. Additionally, whole brain radiation in this trial uses a hippocampal sparing technique to preserve memory and cognitive function as much as possible, addressing one of the significant side effects of traditional whole brain radiation. These innovations offer hope for more effective and less harmful brain cancer treatments.

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

This trial will compare the effectiveness of stereotactic radiation (SRS) and whole brain radiation in treating brain cancer. Research has shown that SRS can effectively treat brain tumors, with studies indicating it matches whole brain radiation in survival rates for patients with up to 10 brain tumors. For tumors smaller than 3 cm, SRS has delivered promising results. Additionally, patients with multiple brain tumors treated with SRS may live longer, suggesting it is a strong option for targeting specific tumors without affecting the entire brain.

Whole brain radiation also effectively manages brain tumors and helps prevent cancer from spreading in the brain. It is particularly useful for treating cancer cells that might not be visible on scans. Both treatments in this trial aim to control cancer spread in the brain, each with its own strengths. ^{6 7 8 9 10}

Who Is on the Research Team?

Ayal Aizer, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with solid tumors that have spread to the brain, showing 5-20 metastases on MRI. They must be in good physical condition (Karnofsky score ≥70) and can have had previous systemic therapy. Excluded are those who've had brain radiation before, cannot get an MRI or gadolinium contrast, have severe kidney disease, certain cancers like small cell lung cancer, lymphoma or myeloma, or a very large tumor over 5 cm.

Inclusion Criteria

I am able to care for myself but cannot do normal activities without help.

I have a confirmed solid tumor with untreated brain metastases.

I have had treatment that affects my whole body.

Exclusion Criteria

I have had radiation treatment for cancer that spread to my brain.

I have small cell lung cancer, lymphoma, or myeloma.

I had surgery to remove one or more brain tumors but haven't started follow-up radiation therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either hippocampal sparing whole brain radiation or stereotactic radiation

2-4 weeks

1-5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Routine study visits

Quality of Life Assessment

Participants complete the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) questionnaire

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic radiation (SRS)
• Whole brain radiation

Trial Overview The study compares two radiation treatments for patients with multiple brain tumors from another cancer source: whole-brain radiation versus stereotactic radiation (SRS), which targets specific areas. It's designed to see which method is more effective at treating these types of brain metastases.

How Is the Trial Designed?

Group I: Stereotactic Radiation (SRS) Experimental Treatment 1 Intervention

* MRI will be performed prior to radiation is administered * Radiation will be given in 1-5 fractions (dose depends on the size of the tumor that will be treated)

Group II: Whole Brain Radiation Active Control 1 Intervention

* MRI will be performed prior to radiation is administered * A hippocampal sparing approach will be used when possible * Dose will be 30 Gy in 10 fractions

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

A case study of a 21-year-old female who underwent stereotactic radiosurgery (SRS) for a ruptured arteriovenous malformation (AVM) revealed the development of a glioblastoma (GBM) six years post-treatment, highlighting a rare but serious potential long-term risk associated with SRS.

While SRS is generally considered safe, this case underscores the importance of informing patients about the potential risk of radiation-induced malignancies, particularly glioblastomas, which can occur even years after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma after AVM radiosurgery. Case report and review of the literature. Xhumari, A., Rroji, A., Enesi, E., 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 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]

A review of 77 studies involving 6384 patients found that stereotactic radiosurgery (SRS) combined with systemic therapies (like chemotherapy and immunotherapy) is safe, showing no significant increase in skin toxicities, bleeding, or radiation necrosis.

The median SRS dose was 20 Gy, and the findings support the continuation of systemic treatments alongside SRS for patients with brain metastases, indicating that this combination does not adversely affect patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. Borius, PY., Régis, J., Carpentier, A., et al.[2021]

Fractionated stereotactic radiosurgery (SRS) for large brain metastases (over 3 cm) is both feasible and safe, with no reported acute or late complications in a study of 36 patients.

The treatment showed improved local control rates, with 73% progression-free survival at 6 months and 63% at 12 months, suggesting it may be more effective than single fraction SRS for these larger tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic radiosurgery for large brain metastases. Wegner, RE., Leeman, JE., Kabolizadeh, P., et al.[2018]

The study analyzed 435 patients with brain metastases treated with Gamma Knife stereotactic radiosurgery (SRS) and found that the overall incidence of adverse radiation effects (ARE) was low at 5.4%, but increased significantly with lesion size and volume, reaching a 1-year cumulative incidence of 13%-14% for larger lesions.

Approximately 60% of the 118 cases of ARE were symptomatic, with most occurring between 3 to 18 months post-treatment, highlighting the importance of monitoring patients during this time frame for potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. Sneed, PK., Mendez, J., Vemer-van den Hoek, JG., et al.[2022]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11049204/

Prognosis versus Actual Outcomes in Stereotactic ... Recent data increasingly show that survival after SRS as an initial treatment for up to 10 brain metastases is non-inferior compared to 2–4 BMs ...

2. 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

3. 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.

4. advancesradonc.org advancesradonc.org/article/S2452-1094(23)00230-0/fulltext

Stereotactic Radiosurgery in the Management of Brain ... Therefore, prospective evidence supports treatment of up to 15 lesions with SRS, although many centers consistently treat larger numbers of ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11452-7

Overall survival following stereotactic radiosurgery for ten or ... Patients with 10 or more brain metastases treated with stereotactic radiosurgery can have prolonged survival outcomes.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38799108/

Safety and Feasibility of Stereotactic Radiosurgery for ... SRS was safe, had favorable cognitive outcomes, and had comparable survival outcomes to contemporary studies evaluating WBRT in this population.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625028032

Stereotactic Radiosurgery for 15 or More Brain Metastases ... The mean summed dose to the whole brain after all SRS courses was 5.28 Gy. Median and 1-year OS was 27.8 months and 63.2%, respectively. 1-year FFN was 87.3%.

8. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2835449

Therapy, Safety, and Logistics of Preoperative vs ... Even with the success of postoperative SRS, patients with brain metastases are still susceptible to distant recurrence outside the surgical ...

9. advancesradonc.org advancesradonc.org/article/S2452-1094(24)00072-1/fulltext

Safety and Feasibility of Stereotactic Radiosurgery for ... ... brain metastases, demonstrating no difference in OS in patients who had 2 to 4 brain metastases versus 5 or more brain metastases when treated with SRS alone.

10. academic.oup.com academic.oup.com/neuro-oncology/article/27/2/479/7787241

Results of the CYBER-SPACE randomized phase 2 trial Repeated stereotactic radiosurgery (SRS) for multiple brain metastases avoids whole-brain radiotherapy (WBRT) and neurologic death. The more ...