Stereotactic Radiosurgery for Brain Cancer

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Prior brain radiation, Leptomeningeal disease, Small-cell lung cancer, 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: 5

Duration: 4 weeks

132 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies stereotactic radiosurgery to see how well it works compared to clinical observation after surgery in treating patients with brain metastases. Stereotactic radiosurgery, a type of radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue.

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.

What data supports the effectiveness of the treatment Stereotactic Radiosurgery for Brain Cancer?

Research shows that stereotactic radiosurgery (SRS) is effective for treating brain metastases, improving outcomes and reducing side effects compared to whole-brain radiation therapy. Studies have demonstrated its success in managing multiple brain tumors, including those from melanoma, and in treating large brain metastases with technologies like CyberKnife and LINAC. ^{1 2 3 4 5}

Is stereotactic radiosurgery generally safe for humans?

Stereotactic radiosurgery (SRS) and related treatments like CyberKnife and Gamma Knife are generally considered safe, with most incidents leading to little or no harm to patients. Safety studies show that errors are often related to human performance and administrative issues, rather than the treatment itself, and efforts are ongoing to improve safety practices. ^{6 7 8 9 10}

How is stereotactic radiosurgery different from other treatments for brain cancer?

Stereotactic radiosurgery (SRS) is unique because it delivers a high dose of focused radiation to a specific area in the brain in a single session, unlike traditional radiation therapy which often involves multiple sessions. This precision allows it to target deep-seated brain tumors that are difficult to reach with surgery, and it can be used alone or in combination with other treatments for certain types of brain tumors and metastases. ^{1 11 12 13 14}

Research Team

Debra NAna Yeboa

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients over 3 years old with brain metastases who've had surgery to remove at least one tumor. They must have a good performance status, be able to undergo an MRI, and can't have had previous brain radiation or certain cancers like small-cell lung cancer. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

Patients must be able to undergo an MRI scan

I am a candidate for focused radiation therapy within 30 days after surgery.

I can care for myself but may not be able to do active work or play.

Exclusion Criteria

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

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

There is radiographic evidence of leptomeningeal disease prior to study entry

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo stereotactic radiosurgery to the surgical cavity within 30 days of the craniotomy or clinical observation after craniotomy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

Follow-up at 5-8 weeks, every 6-9 weeks for 1 year, every 3-4 months for 1 year, and then every 6 months thereafter

Treatment Details

Interventions

• Stereotactic Radiosurgery

Trial Overview The study compares stereotactic radiosurgery (SRS)—a precise form of radiation therapy—with just watching the patient after they've had surgery for brain tumors. The goal is to see if SRS offers better outcomes than not treating further.

Participant Groups

Group I: Arm I (SRS) Experimental Treatment 1 Intervention

Patients undergo stereotactic radiosurgery to the surgical cavity within 30 days of the craniotomy.

Group II: Arm II (observation) Active Control 1 Intervention

Patients undergo clinical observation after craniotomy.

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) 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 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]

Both stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) achieved similar local control rates for vestibular schwannomas, with SRS showing 100% and fSRS showing 94.2%.

However, fSRS was associated with a significantly higher risk of toxicities (42.3% vs. 8.3% for SRS), indicating that while both treatments are effective, fSRS may pose greater safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery and fractionated stereotactic radiosurgery for vestibular schwannomas: A comparison of clinical outcomes from the RSSearch patient registry. Singh, R., Ansinelli, H., Jenkins, J., et al.[2022]

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) 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]

Out of 221 reported incidents related to CyberKnife™ SRS and SBRT from 2012 to 2019, the majority (205 incidents) had little to no clinical impact, indicating a high level of safety in the treatment process.

Human performance issues were the most common contributing factor (79% of incidents), with many errors occurring during pre-treatment phases, highlighting the need for improved training and protocols to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Error Pathways in CyberKnife™ Radiation Therapy. Mullins, BT., Mazur, L., Dance, M., et al.[2020]

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]

Both gamma knife (GK) and linear accelerator (LINAC) systems provide comparable tumor control rates for vestibular schwannoma, with rates of 93% for GK and 94% for LINAC based on a meta-analysis of 39 studies involving 6516 patients.

GK may better preserve trigeminal nerve function, while LINAC is associated with a lower incidence of tinnitus, suggesting that each method has unique benefits regarding side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the long-term safety and efficacy of gamma knife and linear accelerator radiosurgery for vestibular schwannoma: A systematic review and meta-analysis. Guadix, SW., Tao, AJ., An, A., et al.[2022]

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 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) is an effective non-invasive technique for targeting deep brain lesions with high doses of radiation, but it does not provide benefits for newly diagnosed malignant gliomas.

For patients with brain metastases, SRS can improve median survival when combined with whole-brain radiation therapy (WBRT), and in some cases, SRS alone may be a viable treatment option without compromising survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of radiosurgery in the management of malignant brain tumors. Stieber, VW., Ellis, TL.[2019]

Stereotactic radiosurgery is an innovative technique that delivers a high dose of radiation to specific areas in the brain in just one session, allowing for effective treatment of various intracranial lesions.

In a study involving 24 patients treated since June 1992, the procedure has been well tolerated, indicating a favorable safety profile for this method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of intracranial lesions with stereotactic radiosurgery. Sinha, PP., Bloomfield, S., Smith, GK.[2004]

Stereotactic radiosurgery, particularly using high-energy X-rays and the gamma-knife technique, has become a promising treatment for conditions like arteriovenous malformations and certain slow-growing brain tumors, thanks to advancements in neuro-imaging and radiation delivery methods.

This treatment can be used alone or in combination with other therapies, such as surgery and embolization, and is effective for well-defined, deep-seated tumors, making it a valuable option for carefully selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactically guided radiosurgery using the linear accelerator. Blond, S., Coche-Dequeant, B., Castelain, B.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Stereotactic radiosurgery and fractionated stereotactic radiosurgery for vestibular schwannomas: A comparison of clinical outcomes from the RSSearch patient registry. [2022]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Guidelines for Multiple Brain Metastases Radiosurgery. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Common Error Pathways in CyberKnife™ Radiation Therapy. [2020]

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. England pubmed.ncbi.nlm.nih.gov

Assessing the long-term safety and efficacy of gamma knife and linear accelerator radiosurgery for vestibular schwannoma: A systematic review and meta-analysis. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [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. United States pubmed.ncbi.nlm.nih.gov

The role of radiosurgery in the management of malignant brain tumors. [2019]

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

The treatment of intracranial lesions with stereotactic radiosurgery. [2004]

14. Austria pubmed.ncbi.nlm.nih.gov

Stereotactically guided radiosurgery using the linear accelerator. [2020]