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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment for brain tumors that have spread from other parts of the body. It combines two methods: radiosurgery (also known as Stereotactic Radiosurgery or Gamma Knife Radiosurgery), which uses focused x-rays to target the tumor, and surgical removal of the tumor. The researchers aim to determine if this approach can prevent tumor recurrence and identify the optimal x-ray dose. Individuals with 1 to 4 brain tumors visible on an MRI, with at least one large enough to require this treatment, may qualify to participate. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that radiosurgery is generally well-tolerated for treating brain tumors. One study found that the treatment successfully controlled tumors in 97.8% of cases. However, about 25% of patients experienced brain swelling, known as perilesional edema. Other side effects from radiation were noted, but specific details were not provided.

Despite these side effects, radiosurgery directs x-rays precisely at the tumor, protecting healthy brain tissue more effectively than other treatments. Overall, while side effects can occur, the treatment has proven effective in controlling tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about radiosurgery for brain tumors because it offers a non-invasive alternative to traditional surgery. Unlike conventional treatments that may require open surgery, radiosurgery uses focused beams of radiation to target and shrink tumors precisely, minimizing damage to surrounding healthy tissue. Additionally, the combination of radiosurgery with surgical resection within two weeks could potentially improve outcomes by reducing the tumor size before surgery, making it easier to remove and possibly enhancing recovery times. This approach provides a promising option for patients who might not be candidates for more invasive procedures.

What evidence suggests that radiosurgery followed by surgical resection could be effective for brain tumors?

Studies have shown that radiosurgery can effectively control brain tumors. One study demonstrated a 70% success rate in controlling tumors. Another study found an 83% chance of keeping the tumor stable for 12 months with a specific type of radiosurgery. This trial will involve patients undergoing radiosurgery followed by surgical resection within two weeks. The treatment precisely targets the tumor, helping to protect the surrounding healthy brain tissue. While these results are promising, effectiveness can vary depending on the tumor's size and other factors. ^{4 6 7 8 9}

Who Is on the Research Team?

Erin Murphy, MD

Principal Investigator

Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9931898/

Outcomes of single brain metastasis treated with gamma ... The median percentage of tumor control after radiosurgery treatment was 70% (IQR: 65–78) and only 26.2% (n = 27) of patients had > 80% tumor control over the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6774481/

Long-term outcome data from 121 patients treated with ... A total of 29 (24%) of the 121 patients had PRTE at any point following GKSRS salvage treatment as reported by 2 neuroradiologists. Only 2 (1.7%) patients had ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025046316

Staged Gamma Knife radiosurgery for large brain metastases Staged Gamma Knife radiosurgery for large brain metastases resulted in an 83 % probability of local control at 12 months.

4. nature.com nature.com/articles/s41467-024-47998-8

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

5. thejns.org thejns.org/focus/view/journals/neurosurg-focus/55/2/article-pE5.pdf

a systematic review and meta-analysis of clinical outcomes A minimally invasive treatment op- tion for large metastatic brain tumors: long-term results of two-session Gamma Knife stereotactic radiosurgery. Radiat. Oncol ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37823677/

Outcomes of Gamma Knife Radiosurgery for Brain ... The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2667242123000064

Outcomes of single brain metastasis treated with gamma ... The median percentage of tumor control after radiosurgery treatment was 70% (IQR: 65–78) and only 26.2% (n = 27) of patients had > 80% tumor control and ...

8. mayoclinic.org mayoclinic.org/tests-procedures/brain-stereotactic-radiosurgery/about/pac-20384679

Brain stereotactic radiosurgery Brain tumor before and after Gamma Knife treatment · Benign tumors may shrink over a period of months to years. · Malignant tumors may shrink ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11909010/

Transforming Brain Tumor Care: The Global Impact of ... This study corroborates the clinical efficacy of SRS and reinforces its critical role in the multidisciplinary treatment of patients with brain tumors and ...