Stereotactic Radiosurgery for Brain Metastasis

Overseen By Jing Li

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Metastatic cancer, Leptomeningeal disease, Pregnant, others

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

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: 1

Duration: Up to 36 months

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial investigates how stereotactic radiosurgery affects brain functions while treating patients with small cell lung cancer that has spread to the brain (brain metastasis). Standard of care treatment consists of whole brain radiation therapy, which targets the entire brain, and may result in side effects affecting the nervous system. Stereotactic radiosurgery only targets areas of the brain that are suspected to be affected by the disease. The purpose of this trial is to learn if and how patients' brain functions are affected by the use of stereotactic radiosurgery rather than whole brain radiation therapy in managing brain metastasis caused by small cell lung cancer. Stereotactic radiosurgery may help patients avoid nervous system side effects caused by whole brain radiation therapy.

Will I have to stop taking my current medications?

The trial information 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 Radiosurgery for Brain Metastasis?

Research shows that Stereotactic Radiosurgery (SRS) can prolong survival in patients with a single brain metastasis and maintain functional independence in those with up to three brain metastases. Additionally, SRS, including CyberKnife Radiosurgery, is effective in managing brain metastases based on total tumor volume, offering a precise and localized treatment option. ^{1 2 3 4 5}

Is stereotactic radiosurgery safe for humans?

Research shows that stereotactic radiosurgery (SRS), including methods like CyberKnife and Gamma Knife, is generally safe for treating brain metastases and other conditions, with a focus on reducing side effects compared to traditional whole brain radiation therapy. ^{1 6 7 8 9}

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

Stereotactic radiosurgery (SRS) is unique because it delivers a single, highly focused dose of radiation directly to the brain metastasis, minimizing damage to surrounding healthy tissue. Unlike whole brain radiation therapy, which affects the entire brain, SRS targets only the tumor, making it a precise and less invasive option. ^{4 10 11 12 13}

Research Team

Jing Li

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for English-speaking patients with small cell lung cancer that has spread to the brain, who have not had prior brain radiation therapy. They must be physically able to participate (ECOG <=3), have 10 or fewer brain metastases, and no history of psychiatric/neurologic illness affecting cognition. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

My doctor has assessed my ability to perform daily activities.

My diagnosis of small cell lung cancer is confirmed through tissue samples.

Patient's primary language is English

Exclusion Criteria

I do not have a history of metastatic cancer other than small cell, or any uncontrolled non-metastatic cancer.

I do not have a psychiatric or neurological illness affecting my thinking, except if it's due to brain metastasis.

You cannot participate if tests find cancer cells in your spinal fluid.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo stereotactic radiosurgery (SRS) in the absence of disease progression or unacceptable toxicity

Up to 36 months

Multiple visits as per MRI surveillance schedule

Follow-up

Participants are monitored for safety, cognitive decline, and tumor control post-treatment

36 months

Follow-up at 1, 3, 6, 9, 12, 16, 20, 24, 30, and 36 months after SRS

Treatment Details

Interventions

• Stereotactic Radiosurgery

Trial Overview The trial studies stereotactic radiosurgery's effect on brain function in treating brain metastasis from small cell lung cancer. It compares this targeted approach to standard whole-brain radiation therapy, aiming to reduce nervous system side effects.

Participant Groups

Group I: Treatment (SRS) Experimental Treatment 2 Interventions

Patients undergo SRS in the absence of disease progression or unacceptable toxicity. Patients whose disease progresses may be treated with additional courses of SRS per physician discretion.

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

In a study of 4,327 patients with brain metastases from non-small cell lung cancer, it was found that treatment at non-academic facilities significantly increased the likelihood of receiving LINAC SRS over Gamma Knife SRS, especially in the Midwestern, Northeastern, and Southern US regions.

Patients receiving higher doses of radiation (18-24 Gy) were also more likely to receive LINAC SRS, and those living within 20 miles of a treatment facility had a 27% higher chance of receiving LINAC, suggesting that geographic accessibility plays a role in treatment modality choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of linear accelerator versus Gamma Knife stereotactic radiosurgery use for brain metastases in the United States. McClelland Iii, S., Degnin, C., Chen, Y., et al.[2022]

Stereotactic radiosurgery (SRS) is an effective treatment for patients with brain metastases, particularly prolonging survival for those with a single metastasis and maintaining functional independence for patients with up to three metastases.

As SRS technology becomes more widely used, careful patient selection and treatment planning are essential to maximize its benefits and integrate it safely with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in intracranial stereotactic radiotherapy for metastases. Pinkham, MB., Whitfield, GA., Brada, M.[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]

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]

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]

Moderately dosed stereotactic radiosurgery (SRS) for one to four brain metastases showed a median overall survival of 7.5 months, with high local brain control rates of 87% at 6 months and 79% at 12 months, indicating its efficacy in treating limited brain metastases.

The study suggests that initial SRS alone can be a safe treatment option, as only 22% of patients required additional whole-brain radiotherapy, and significant predictors of survival included the time between the primary diagnosis and brain metastases, as well as the volume of the treated metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. Meisner, J., Meyer, A., Polivka, B., et al.[2021]

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]

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

Radiosurgery (SRS) using a mono-isocentric, non-coplanar technique effectively treated 172 patients with multiple brain metastases, achieving a 2-year local progression-free survival (LPFS) rate of 71.6%.

The study indicates that higher biological effective doses (BED) correlate with better local control, and the technique allows for safe treatment of patients with many metastases while delaying the need for whole-brain radiation therapy (WBRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique. Alongi, F., Nicosia, L., Figlia, V., et al.[2021]

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]

In a study of 51 patients treated with stereotactic radiosurgery (SRS) for brain metastases, the median survival time was 15 months, indicating that SRS is an effective treatment option.

Patients without active extracranial disease had significantly longer survival compared to those with active disease, highlighting the importance of managing systemic disease for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for the treatment of brain metastases; results from a single institution experience. Burke, D., Mascott, C., Rock, L., et al.[2021]

Stereotactic radiosurgery is a valuable treatment option for both intracranial and extracranial lesions, often used alongside surgery, conventional radiation, and chemotherapy.

The review highlights the evolution and variety of stereotactic radiosurgery machines, including the Gamma Knife, indicating a growing range of technologies available for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of stereotactic radiosurgery: a cross-platform comparison. Nguyen, T., Hsu, W., Lim, M., et al.[2011]

References

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

Predictors of linear accelerator versus Gamma Knife stereotactic radiosurgery use for brain metastases in the United States. [2022]

2. England pubmed.ncbi.nlm.nih.gov

New developments in intracranial stereotactic radiotherapy for metastases. [2022]

3. Scotland pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

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

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

7. Germany pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

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

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. [2017]

10. Italy pubmed.ncbi.nlm.nih.gov

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

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

12. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for the treatment of brain metastases; results from a single institution experience. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Delivery of stereotactic radiosurgery: a cross-platform comparison. [2011]