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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how stereotactic radiosurgery, a precise form of radiation therapy, affects brain function in people with small cell lung cancer that has spread to the brain. Unlike the usual treatment targeting the entire brain, this method focuses only on cancer-affected areas, potentially reducing nervous system side effects. The trial seeks participants with small cell lung cancer and 10 or fewer brain metastases who have not received prior brain radiation. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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 prior data suggests that stereotactic radiosurgery is safe for treating brain metastasis?

Research has shown that stereotactic radiosurgery (SRS) is generally safe and well-tolerated for treating cancer that has spread to the brain. Studies have found that SRS effectively controls the disease in specific brain areas. For example, a review of 1,446 patients demonstrated that SRS worked well with fewer side effects.

Unlike whole brain radiation therapy, SRS targets only the cancer-affected areas. This focused approach reduces the risk of side effects on the nervous system. While all treatments can have some side effects, SRS is noninvasive, meaning it doesn't involve surgery and is less likely to cause significant harm.

Previous use of SRS for similar conditions suggests it is a promising and safe option for managing brain metastases. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Stereotactic Radiosurgery (SRS) is unique because it delivers highly focused radiation to brain metastases in a single or few sessions, minimizing exposure to surrounding healthy tissue. Unlike traditional whole-brain radiation therapy, which can affect the entire brain and potentially lead to cognitive side effects, SRS targets only the tumor, potentially reducing these risks. Researchers are excited about SRS because it offers a less invasive option that may provide effective tumor control with fewer side effects, improving the quality of life for patients with brain metastases.

What evidence suggests that stereotactic radiosurgery is effective for brain metastasis?

Research has shown that stereotactic radiosurgery (SRS), the treatment under study in this trial, effectively treats brain tumors from small cell lung cancer with fewer side effects on brain function than whole brain radiation therapy. Studies have found that SRS can lead to good survival rates while reducing the risk of cognitive problems. One study found that SRS has similar rates of cancer recurrence and survival as whole brain radiation but may help avoid some nervous system side effects. This targeted treatment focuses only on the affected brain areas, potentially protecting healthy brain tissue. ^{2 3 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 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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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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

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Radiation Therapy for Brain Metastases: An ASTRO ... A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung ...

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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.

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Stereotactic Radiosurgery (SRS) and Stereotactic Body ... - NCBI These noninvasive modalities offer effective management for a range of conditions, including brain metastases, benign brain tumors (such as ...

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

Safety and Feasibility of Stereotactic Radiosurgery for ... 1, 2, 3 Traditionally, patients with multiple brain metastases have a poor median survival of <6 months and often require whole brain radiation therapy (WBRT).

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Efficacy and Safety of Stereotactic Radiosurgery for ... This systematic review and meta-analysis of 32 studies comprising 1446 patients found associations with high local control (86%), high therapeutic ratio of ...