Pre-Surgery Radiosurgery for Brain Tumor

Overseen By Cynthia Martin

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Methotrexate, Adriamycin, Epirubicine, Navelbin

Disqualifiers: Whole brain radiation, >4 metastases, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether targeted radiation (radiosurgery) to a brain tumor before surgery, known as Neoadjuvant Stereotactic Radiosurgery, can preserve brain tissue and potentially reduce the need for additional radiation. The trial also seeks to determine the optimal radiation dose and monitor side effects. Ideal participants have a known cancer diagnosis (excluding certain types like small cell lung cancer) and a brain tumor that can be surgically removed. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial requires that you stop taking methotrexate, adriamycin, epirubicine, or navelbin for one week before or during the study. Other medications will be reviewed individually to see if they are suitable for the study.

What prior data suggests that neoadjuvant stereotactic radiosurgery is safe for brain tumor patients?

Research shows that neoadjuvant stereotactic radiosurgery, a type of targeted radiation therapy, is generally well-tolerated by patients. It effectively controls brain tumors with few side effects. Earlier studies found that complications, such as cancer spreading to the brain lining, occurred in 10% to 30% of cases. Doctors consider these rates manageable.

Although researchers continue to study this treatment, it appears to have a safety profile similar to other post-surgery radiation techniques. While this trial is in its early stages, focusing on finding the best radiation dose should help reduce side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for brain tumors, which typically involves neurosurgical resection followed by radiation therapy, this treatment uses neoadjuvant stereotactic radiosurgery to deliver targeted radiation before surgery. Researchers are excited about this approach because it allows for precise targeting of the tumor with high-dose radiation, potentially reducing its size and making surgical removal easier and more effective. This method could minimize damage to surrounding healthy tissue and improve patient outcomes by addressing the tumor more aggressively from the outset.

What evidence suggests that neoadjuvant stereotactic radiosurgery might be an effective treatment for brain tumors?

Research has shown that targeted radiation treatment before surgery, known as neoadjuvant stereotactic radiosurgery, may help treat brain tumors. In this trial, participants will receive neoadjuvant stereotactic radiosurgery before neurosurgical resection. Studies suggest this method can shrink tumors, making them easier to remove during surgery. It might also protect healthy brain tissue and reduce the need for additional radiation after surgery. Early findings indicate that patients experience fewer complications and recover better. Overall, initial results suggest this approach could effectively manage brain tumors. ^{1 6 7 8 9}

Who Is on the Research Team?

Stephen Shiao, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with a life expectancy of at least 3 months who have certain types of cancer, excluding small cell lung cancer, lymphoma, and germ cell cancers. They must have one brain tumor suitable for surgery and radiosurgery, be able to follow study requirements, not be pregnant if applicable, and have a performance status indicating they are mostly independent.

Inclusion Criteria

Life expectancy ≥ 3 months

I have a brain lesion smaller than 40 mm that can be removed or treated with SRS.

Written informed consent obtained from subject, or a legally designated power of attorney and ability for subject to comply with the requirements of the study

Exclusion Criteria

I am taking specific cancer drugs and will discuss my treatment with the study leader.

I have had whole brain radiation in the last three months.

I have more than 4 brain metastases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive neoadjuvant stereotactic radiosurgery prior to neurosurgical resection

1-2 weeks

Neurosurgery

Participants undergo neurosurgical resection of the indexed brain metastasis

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of maximum tolerated dose and adverse events

1 month

Long-term follow-up

Participants are monitored for long-term outcomes, including rates of salvage treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Neoadjuvant Stereotactic Radiosurgery
• Neurosurgical Resection

Trial Overview

The trial tests whether giving stereotactic radiosurgery (a type of focused radiation therapy) before surgically removing brain tumors can improve outcomes and reduce the need for additional treatments. It also aims to determine the best dose of radiation by monitoring effectiveness and side effects.

How Is the Trial Designed?

Group I: Neoadjuvant stereotactic radiosurgery Experimental Treatment 2 Interventions

Stereotactic radiosurgery will be performed prior to neurosurgical resection of the indexed brain metastasis. The dose of radiation to be administered to the indexed lesion will be established as a function of tumor size.

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Published Research Related to This Trial

In a study of 75 patients with WHO Grade I meningiomas treated with stereotactic radiosurgery (SRS), 52% showed no volumetric tumor growth, while 92% had stable diametric measurements, indicating that SRS is effective in controlling tumor growth in most cases.

A lower conformity index was significantly linked to the development of edema post-SRS, suggesting that careful planning of radiation delivery can help minimize adverse effects like swelling in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas. Mansouri, A., Larjani, S., Klironomos, G., et al.[2022]

Stereotactic radiosurgery (SRS) was safely administered to 30 patients with malignant gliomas after standard radiotherapy, showing no significant acute or late toxicity, which suggests it is a feasible option for dose escalation in treatment.

The study reported a median survival of 13.9 months, with 1- and 2-year disease-specific survival rates of 57% and 25%, respectively, indicating that while SRS can be effective, further research is needed to fully understand its impact on long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery as an adjunct to surgery and external beam radiotherapy in the treatment of patients with malignant gliomas. Gannett, D., Stea, B., Lulu, B., et al.[2022]

In a study of 115 patients with malignant gliomas, the addition of stereotactic radiosurgery to conventional treatments significantly improved 2-year survival rates, particularly for patients in worse prognostic classes (classes 3-6).

The median survival for patients treated with radiosurgery was 96 weeks, compared to historical data showing lower survival rates, indicating that radiosurgery may enhance treatment outcomes, although further research through randomized trials is needed to confirm its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgery in the initial management of malignant gliomas: survival comparison with the RTOG recursive partitioning analysis. Radiation Therapy Oncology Group. Sarkaria, JN., Mehta, MP., Loeffler, JS., et al.[2022]

Stereotactic radiosurgery is an effective and noninvasive treatment for brain metastases, providing ablative doses of radiation for long-term control of macroscopic disease, especially in patients with a limited number of metastases.

While there is mature data supporting the use of stereotactic radiosurgery in combination with whole-brain radiation therapy, more prospective randomized studies are needed to clarify its effectiveness in patients with multiple metastases and in various treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery for Treatment of Brain Metastases. Badiyan, SN., Regine, WF., Mehta, M.[2018]

A novel deep learning model using MRI and clinical data was developed to predict local control or failure of brain metastases after stereotactic radiation therapy, showing improved accuracy over standard clinical variables.

The best-performing model achieved an area under the curve (AUC) of 0.86, indicating strong predictive capability, particularly highlighting the significance of tumor margins in determining treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting the outcome of radiotherapy in brain metastasis by integrating the clinical and MRI-based deep learning features. Jalalifar, SA., Soliman, H., Sahgal, A., et al.[2023]

In a study of 4905 patients who underwent Gamma Knife stereotactic radiosurgery, the long-term risk of developing secondary intracranial malignancies or malignant transformation of benign tumors was found to be very low, with an incidence of 6.8 per 100,000 patient-years, similar to the general population's risk.

The findings suggest that stereotactic radiosurgery is a safe treatment option for conditions like benign tumors and arteriovenous malformations, providing reassurance for patients and physicians regarding its long-term safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of radiation-associated intracranial malignancy after stereotactic radiosurgery: a retrospective, multicentre, cohort study. Wolf, A., Naylor, K., Tam, M., et al.[2020]

Pre-operative stereotactic radiosurgery (SRS) for brain metastases significantly reduces dose exposure to healthy brain tissue compared to post-operative SRS, with a median volume receiving 28 Gy being lower in the pre-operative setting (6.79 ccm) than in the extended field post-operative setting (10.79 ccm).

The study found that the morphology of the resection cavity post-surgery differs significantly from the original lesion, which could complicate treatment planning; thus, pre-operative SRS may provide better delineation and treatment planning advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases-Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept. El Shafie, RA., Tonndorf-Martini, E., Schmitt, D., et al.[2020]

In a study of 404 patients with brain metastases, preoperative stereotactic radiosurgery (SRS) showed low rates of cavity local recurrence (13.7%) and adverse radiation effects (7.4%), indicating it is a safe option before surgical resection.

The median overall survival for patients receiving preoperative SRS was 17.2 months, with factors like systemic disease status and extent of resection significantly influencing survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors for Progression and Toxic Effects After Preoperative Stereotactic Radiosurgery for Patients With Resected Brain Metastases. Prabhu, RS., Akinyelu, T., Vaslow, ZK., et al.[2023]

Citations

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Preoperative Stereotactic Radiosurgery for Brain Metastases

This study aimed to determine the safety of preoperative SRS via a phase 1 dose escalation trial and compare outcomes—including nLMD, classical LMD, local ...

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The INTERNEO individual patient data pooled analysis

Neoadjuvant stereotactic radiosurgery (NaSRS) is an emerging treatment option for brain metastases (BrM) planned for resection. The aim of this study was to ...

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sciencedirect.com

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