Radiosurgery for Brain Tumor

Overseen By Erin Murphy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Case Comprehensive Cancer Center

Disqualifiers: Unfit for surgery, Prior whole brain radiotherapy, MRI contraindication, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase I/II trial studies the ability to stop brain metastases from coming back after treatment with radiosurgery followed by surgical resection. It will also evaluate the side effects of these combined treatments and help determine the best radiosurgery dose. Radiosurgery focuses the x-rays directly to the tumor and cause less damage to the normal tissue in the brain.

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 Radiosurgery for Brain Tumor?

Research shows that stereotactic radiosurgery (SRS), including Gamma Knife radiosurgery, is effective for treating brain metastases and can improve survival when used with or instead of whole-brain radiation therapy. It is also used for other brain conditions like meningiomas and pituitary adenomas, suggesting its effectiveness in targeting specific brain areas with high precision. ^{1 2 3 4 5}

Is radiosurgery generally safe for treating brain tumors?

Radiosurgery, including Stereotactic Radiosurgery (SRS) and Gamma Knife Radiosurgery, is generally considered safe for treating various brain conditions, though there are rare reports of it being associated with new malignancies. Safety checklists are used to minimize errors and complications, and it has been proven safe for many patients, although the risks for larger tumors are less understood. ^{6 7 8 9 10}

How is the treatment Radiosurgery unique for brain tumors?

Radiosurgery (SRS) is unique because it uses focused beams of radiation to target brain tumors precisely, allowing treatment of deep-seated areas without invasive surgery. It is often used for brain metastases and can be an alternative to whole-brain radiation therapy, offering a non-invasive option with potentially fewer side effects. ^{5 11 12 13 14}

Research Team

Erin Murphy, MD

Principal Investigator

Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for patients with certain types of cancer that have spread to the brain, specifically those with 1-4 brain metastases where at least one lesion is sizable but operable. Participants must be physically able to undergo surgery and radiosurgery, have a good performance status (Karnofsky score ≥ 70), and not have specific cancers like small cell lung cancer or lymphoma.

Inclusion Criteria

I am mostly able to care for myself and carry out normal activities.

I have had targeted radiation for other tumors, not the one planned for surgery.

My cancer is not small cell lung cancer, lymphoma, or germ cell cancer.

Exclusion Criteria

I cannot join in study activities because of my health or mental condition.

I cannot or do not want to come back for all required follow-up visits.

My treatment plan cannot limit radiation to 10 Gy or less to my optic nerve/chiasm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiosurgery

Participants undergo radiosurgery to focus x-rays directly on the tumor

1 day

1 visit (in-person)

Surgical Resection

Within 2 weeks of radiosurgery, participants undergo surgical resection of brain metastases

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes after treatment

Up to 3 years

Treatment Details

Interventions

• Radiosurgery
• Therapeutic Conventional Surgery

Trial Overview The study tests if using radiosurgery before surgical removal of brain tumors can prevent them from returning. It aims to find the safest dose of focused x-ray radiation (radiosurgery) that causes minimal damage to healthy brain tissue while being effective against tumors.

Participant Groups

Group I: Treatment (radiosurgery, surgery) Experimental Treatment 3 Interventions

Patients undergo radiosurgery on day 0. Within 2 weeks, patients undergo surgical resection.

Radiosurgery is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Stereotactic Radiosurgery for:

• Brain metastases
• Arteriovenous malformations (AVMs)
• Benign brain tumors
• Malignant brain tumors

Approved in European Union as Gamma Knife Radiosurgery for:

• Brain metastases
• Arteriovenous malformations (AVMs)
• Benign brain tumors
• Malignant brain tumors

Approved in Canada as Stereotactic Radiosurgery for:

• Brain metastases
• Arteriovenous malformations (AVMs)
• Benign brain tumors
• Malignant brain tumors

Approved in Japan as Gamma Knife Radiosurgery for:

• Brain metastases
• Arteriovenous malformations (AVMs)
• Benign brain tumors
• Malignant brain tumors

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Findings from Research

In a study of 58 patients who underwent resection of brain metastases after stereotactic radiosurgery (SRS), the median survival after resection was 7.7 months, with survival rates of 65%, 30%, and 16% at 6, 12, and 24 months, respectively.

Factors such as preoperative classification, performance status, systemic disease status, and the time interval between SRS and resection were found to significantly influence patient survival, with better outcomes observed in patients with delayed local progression after SRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The results of resection after stereotactic radiosurgery for brain metastases. Kano, H., Kondziolka, D., Zorro, O., et al.[2010]

In a study of 58 patients with malignant gliomas treated with stereotactic radiosurgery (SRS), 47.1% experienced local recurrence within the radiation field, indicating some localized effectiveness of SRS.

However, over half of the patients (52.9%) showed disease progression outside the SRS treatment area, suggesting that SRS alone does not significantly improve overall survival and highlighting the need for a multidisciplinary approach in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern of disease progression following stereotactic radiosurgery in malignant glioma patients. Choi, SW., Cho, KR., Choi, JW., et al.[2020]

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]

The Gamma Knife Center of St. Louis has successfully treated 5,696 patients with various neuro-oncologic disorders using stereotactic radiosurgery (SRS) since 1997, demonstrating its efficacy in managing conditions like brain metastases and meningiomas.

SRS can be tailored to individual patients and may be used alone or in combination with other treatments, such as surgery or new medical therapies, highlighting its versatility in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Role of Gamma Knife Stereotactic Radiosurgery in Neuro-Oncology. Desai, R., Rich, KM.[2020]

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]

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]

Stereotactic radiosurgery (SRS) is highly effective for treating large intracranial meningiomas, achieving a tumor control rate of 99% at 3 years and 92% at 7 years in a study of 116 patients with tumors larger than 10 cm³.

However, the complication rate is notably higher for supratentorial tumors (44%) compared to skull base tumors (18%), suggesting that while SRS is safe for skull base meningiomas, surgical resection may be a better option for larger supratentorial meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgery for large-volume (> 10 cm3) benign meningiomas. Bledsoe, JM., Link, MJ., Stafford, SL., et al.[2022]

This case report highlights the first documented instance of undifferentiated high-grade pleomorphic sarcoma developing after stereotactic radiosurgery (SRS) for a presumed benign vestibular schwannoma, indicating a potential risk of malignant transformation associated with SRS.

The patient experienced a good initial response to SRS over 7.5 years, but later developed rapid tumor growth and neurological decline, emphasizing the importance of monitoring and counseling patients about the rare but serious risk of malignancy following SRS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-induced sarcoma in a large vestibular schwannoma following stereotactic radiosurgery: case report. Schmitt, WR., Carlson, ML., Giannini, C., et al.[2011]

A case study of a 21-year-old female who underwent stereotactic radiosurgery (SRS) for a ruptured arteriovenous malformation (AVM) revealed the development of a glioblastoma (GBM) six years post-treatment, highlighting a rare but serious potential long-term risk associated with SRS.

While SRS is generally considered safe, this case underscores the importance of informing patients about the potential risk of radiation-induced malignancies, particularly glioblastomas, which can occur even years after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma after AVM radiosurgery. Case report and review of the literature. Xhumari, A., Rroji, A., Enesi, E., et al.[2018]

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]

In a study of 64 patients with glioblastoma multiforme (GBM), those who received a gamma knife stereotactic radiosurgery (GK-SRS) boost in addition to external beam radiotherapy (EBRT) had a median overall survival of 25 months, compared to 13 months for those who received EBRT alone.

The addition of GK-SRS significantly improved survival rates without causing severe acute toxicity, indicating it is a safe and effective adjuvant therapy for GBM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme. Nwokedi, EC., DiBiase, SJ., Jabbour, S., 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 30 patients receiving Gamma Knife stereotactic radiosurgery for 10 or more brain metastases, the mean dose to the whole brain was low at 1.8 Gy, indicating a potentially safe treatment approach.

The treatment allowed nearly half of the patients to avoid additional whole-brain radiotherapy, with only a 6.6% incidence of grade 2 radionecrosis, suggesting that Gamma Knife SRS can effectively manage multiple brain metastases with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases. Sita, TL., Gopalakrishnan, M., Rooney, MK., et al.[2022]

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]

References

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

The results of resection after stereotactic radiosurgery for brain metastases. [2010]

2. Scotland pubmed.ncbi.nlm.nih.gov

Pattern of disease progression following stereotactic radiosurgery in malignant glioma patients. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Guidelines for Multiple Brain Metastases Radiosurgery. [2019]

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

Therapeutic Role of Gamma Knife Stereotactic Radiosurgery in Neuro-Oncology. [2020]

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

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

6. Austria pubmed.ncbi.nlm.nih.gov

Lausanne checklist for safe stereotactic radiosurgery. [2020]

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

Radiosurgery for large-volume (> 10 cm3) benign meningiomas. [2022]

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

Radiation-induced sarcoma in a large vestibular schwannoma following stereotactic radiosurgery: case report. [2011]

9. Austria pubmed.ncbi.nlm.nih.gov

Glioblastoma after AVM radiosurgery. Case report and review of the literature. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

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

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

Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme. [2022]

12. 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]

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

Mean Brain Dose Remains Uninfluenced by the Lesion Number for Gamma Knife Stereotactic Radiosurgery for 10+ Metastases. [2022]

14. Ireland pubmed.ncbi.nlm.nih.gov

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