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

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

Trial Summary

What is the purpose of this trial?

This research study is studying two different types of radiation as treatment for brain metastases (tumors in the brain that spread from a cancer that originated elsewhere in the body)

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.

What data supports the effectiveness of the treatment Stereotactic radiation (SRS) and Whole brain radiation for brain cancer?

Research shows that Stereotactic Radiosurgery (SRS) can improve survival and control cancer spread in the brain when used with Whole Brain Radiation Therapy (WBRT) for patients with a limited number of brain metastases. SRS is effective in treating multiple brain tumors and is often preferred over WBRT due to better outcomes and fewer side effects. ^{1 2 3 4 5}

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

Stereotactic radiosurgery (SRS) is generally considered safe for treating brain conditions, including brain metastases. Studies show that it does not significantly increase the risk of skin problems, bleeding, or severe tissue damage when used alone or with other treatments like chemotherapy. ^{6 7 8 9 10}

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

Whole brain radiation (WBRT) treats the entire brain and has been the traditional approach for brain metastases, while stereotactic radiosurgery (SRS) targets high-dose radiation precisely to the tumor, sparing healthy brain tissue. SRS is increasingly used due to its focused approach, which may reduce side effects associated with WBRT. ^{11 12 13 14 15}

Research Team

Ayal Aizer, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Guidelines for Multiple Brain Metastases Radiosurgery. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

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

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

Role of stereotactic radiosurgery in the treatment of brain metastases. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

The effect of low-dose radiation spillage during stereotactic radiosurgery for brain metastases on the development of de novo metastases. [2022]

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

Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastases. [2022]

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

Fractionated stereotactic radiosurgery for large brain metastases. [2018]

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

Glioblastoma after AVM radiosurgery. Case report and review of the literature. [2018]

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

Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors. [2022]

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

Biological implications of whole-brain radiotherapy versus stereotactic radiosurgery of multiple brain metastases. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. [2021]

11. Ireland pubmed.ncbi.nlm.nih.gov

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

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

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

13. 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]

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

Patients with Long-Term Control of Systemic Disease Are a Favorable Prognostic Group for Treatment of Brain Metastases with Stereotactic Radiosurgery Alone. [2017]

15. England pubmed.ncbi.nlm.nih.gov

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