Pre-Surgical Radiosurgery for Brain Metastases

Overseen By Zachary Buchwald, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Emory University

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: HIV, Uncontrolled illness, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This early phase I trial identifies the side effects of stereotactic radiosurgery before surgery in treating patients with cancer that has spread to the brain (brain metastases). Radiation may stimulate an anti-tumor immune response. Giving stereotactic radiosurgery before surgery may reduce the risk of the cancer coming back after surgery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on immunosuppressive medications other than dexamethasone or if you are receiving other investigational agents.

What data supports the effectiveness of the treatment Pre-Surgical Radiosurgery for Brain Metastases?

Research shows that stereotactic radiosurgery (SRS), like CyberKnife, can effectively manage brain metastases by targeting specific areas with high doses of radiation, potentially improving survival without the need for whole-brain radiation therapy (WBRT). This approach may help maintain cognitive function and quality of life compared to traditional methods. ^{1 2 3 4 5}

Is pre-surgical radiosurgery for brain metastases safe for humans?

Research shows that stereotactic radiosurgery (SRS), including methods like Gamma Knife and CyberKnife, is generally safe for treating brain metastases, with safety guidelines and checklists in place to minimize risks. Studies have evaluated the safety of SRS for both small and large brain metastases, indicating it is a viable option with manageable toxicity. ^{3 6 7 8 9}

How is pre-surgical radiosurgery for brain metastases different from other treatments?

Pre-surgical radiosurgery (SRS) for brain metastases is unique because it is performed before surgical removal of the tumor, which helps to better define the treatment area and reduce radiation exposure to healthy brain tissue. This approach can potentially improve precision and safety compared to post-operative SRS or whole brain radiation therapy (WBRT). ^{3 10 11 12 13}

Research Team

Zachary Buchwald, MD, PhD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with cancer that has spread to the brain, visible on MRI. They must have a life expectancy of more than 12 weeks, be able to undergo surgery, and follow study procedures. Pregnant or nursing women, those on immunosuppressants (except dexamethasone), or with certain serious illnesses can't participate.

Inclusion Criteria

Life expectancy > 12 weeks as determined by the investigator

I am willing and able to follow the study's schedule and procedures.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I am taking immunosuppressive medication, but not dexamethasone.

Pregnant or nursing women are excluded

Human immunodeficiency virus (HIV)-positive

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo stereotactic radiosurgery (SRS) to the brain metastasis for 1-3 fractions over 1-5 days and receive dexamethasone until the day of surgical resection

1-3 weeks

Surgery

Patients undergo surgical resection of the brain metastasis

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

120 days, then every 12 weeks

Treatment Details

Interventions

• Dexamethasone
• Resection
• Stereotactic Radiosurgery

Trial Overview The trial tests if stereotactic radiosurgery before surgery can prevent cancer from returning in patients with brain metastases. It's an early phase I trial focused on understanding side effects and how well this pre-surgery radiation works as a treatment.

Participant Groups

Group I: Arm B (SRS, high dose dexamethasone, surgery) Experimental Treatment 2 Interventions

Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive high dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

Group II: Arm A (SRS, low dose dexamethasone, surgery) Experimental Treatment 3 Interventions

Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive low dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

Resection is already approved in United States, European Union for the following indications:

Approved in United States as Surgical Resection for:

• Colorectal Cancer
• Liver Metastases
• Lung Metastases

Approved in European Union as Surgical Excision for:

• Colorectal Cancer
• Liver Metastases
• Lung Metastases

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 for brain metastases from breast cancer showed a high tumor control rate of 93% and a median survival of 13 months post-treatment, indicating its efficacy as a treatment option.

The absence of multiple brain metastases was the only significant factor associated with longer survival, while the treatment had a low complication rate, with only a few cases of radiation-induced edema that did not require further surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for brain metastases from breast cancer. Firlik, KS., Kondziolka, D., Flickinger, JC., et al.[2019]

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) 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]

In a study comparing two treatment methods for patients with one or two brain metastases, whole-brain radiotherapy plus stereotactic radiosurgery (WBRT+SRS) showed similar survival and control rates to surgery plus whole-brain radiotherapy with a boost (OP+WBRT+boost), with 1-year survival rates of 65% and 63%, respectively.

WBRT+SRS is less invasive than OP+WBRT+boost, making it a potentially preferable option for patients, although further confirmation through randomized trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A matched-pair analysis comparing whole-brain radiotherapy plus stereotactic radiosurgery versus surgery plus whole-brain radiotherapy and a boost to the metastatic site for one or two brain metastases. Rades, D., Kueter, JD., Pluemer, A., et al.[2009]

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]

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]

The implementation of a safety checklist for Gamma Knife stereotactic radiosurgery (SRS) over 1500 procedures in 8 years has resulted in no reported human errors, highlighting its effectiveness in enhancing safety.

The checklist addresses specific indications for irradiating tissue volumes and functional disorders, promoting a zero-tolerance approach to errors and fostering multidisciplinary cooperation in neurosurgical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lausanne checklist for safe stereotactic radiosurgery. Tuleasca, C., Zeverino, M., Patin, D., et al.[2020]

Hypofractionated Gamma Knife radiosurgery is effective for treating large metastatic brain tumors (average volume of 18.3 cm³), achieving a local control rate of 90% and a median survival time of 16.2 months.

The treatment demonstrated low toxicity, with only 8.3% of patients experiencing grade 1 side effects and a single case of radiation necrosis, indicating it is a safe option for patients who cannot undergo surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated Stereotactic Gamma Knife Radiosurgery for Large Brain Metastases: A Retrospective, Single Center Study. Kim, JW., Park, HR., Lee, JM., et al.[2022]

Patients with newly diagnosed brain metastases showed significantly better survival outcomes when treated with stereotactic radiosurgery (SRS) alone compared to whole brain radiation therapy (WBRT) alone, indicating SRS may be a more effective treatment option (p<0.001).

The study highlights the importance of considering patient factors such as age, performance status (ECOG-PS), and primary tumor type when determining treatment plans, as these factors significantly influenced survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodality treatment of brain metastases: an institutional survival analysis of 275 patients. Elaimy, AL., Mackay, AR., Lamoreaux, WT., et al.[2022]

Stereotactic radiosurgery (SRS) significantly improved overall survival (OS) for patients with multiple brain metastases, with a median OS of 15.7 months compared to 8.0 months for those receiving whole-brain radiotherapy (WBRT).

SRS also demonstrated a high local control rate of 91.7% for individual brain metastases, indicating it is an effective treatment option for managing multiple brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases. El Shafie, RA., Celik, A., Weber, D., et al.[2021]

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]

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]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

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

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

Stereotactic radiosurgery for brain metastases from breast cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

A matched-pair analysis comparing whole-brain radiotherapy plus stereotactic radiosurgery versus surgery plus whole-brain radiotherapy and a boost to the metastatic site for one or two brain metastases. [2009]

6. Germany pubmed.ncbi.nlm.nih.gov

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

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

Fractionated stereotactic radiosurgery for large brain metastases. [2018]

8. Austria pubmed.ncbi.nlm.nih.gov

Lausanne checklist for safe stereotactic radiosurgery. [2020]

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

Fractionated Stereotactic Gamma Knife Radiosurgery for Large Brain Metastases: A Retrospective, Single Center Study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Multimodality treatment of brain metastases: an institutional survival analysis of 275 patients. [2022]

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

A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases. [2021]

12. 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]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases-Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept. [2020]