Stereotactic Radiosurgery for Brain Cancer

(NASRS Trial)

Recruiting at 1 trial location

Overseen By David Shultz, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Pregnancy, Prior cranial radiotherapy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).

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 have had cytotoxic chemotherapy within 7 days before the treatment. Other medications, like targeted therapies, may be allowed at the discretion of your doctor.

Is stereotactic radiosurgery generally safe for treating brain conditions?

Stereotactic radiosurgery (SRS) is generally considered safe for treating brain conditions, though there is a low risk of adverse radiation effects (AREs), which can sometimes be confused with tumor progression. Long-term safety concerns include a potential risk of developing secondary brain tumors, but this risk is not well-defined. SRS combined with other treatments like chemotherapy appears to be safe without significant additional side effects. ^{1 2 3 4 5}

How is neoadjuvant stereotactic radiosurgery different from other treatments for brain cancer?

Neoadjuvant stereotactic radiosurgery is unique because it is given before surgery, which helps avoid issues like irregular targeting and tumor spread during surgery, and offers more convenience for patients compared to the traditional approach of surgery followed by radiation. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Neoadjuvant Stereotactic Radiosurgery for brain cancer?

Research shows that stereotactic radiosurgery, when used after surgery for brain metastases (cancer spread to the brain), can reduce the risk of cancer coming back and improve quality of life compared to whole-brain radiotherapy. This suggests that stereotactic radiosurgery can be an effective treatment option for brain cancer. ^{11 12 13 14 15}

Who Is on the Research Team?

David Shultz, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for patients with 1-6 brain metastases, where at least one tumor is large enough to consider surgery but hasn't been operated on yet. Participants must be able to undergo stereotactic radiosurgery (SRS), have a good performance status (ECOG ≤2), and not be pregnant or have certain conditions like widespread cancer in the spinal fluid or previous treatments that would exclude them.

Inclusion Criteria

My brain scan shows lesions smaller than 3.0 cm, and I have no immediate surgery planned.

I can take care of myself and am up and about more than half of my waking hours.

My MRI shows 1-6 cancer spots, with the largest no bigger than 3.0 cm.

Exclusion Criteria

My cancer is a type of metastatic germ cell tumor, small cell carcinoma, lymphoma, or brain tumor.

Inability to complete MRI with contrast of the head or known allergy to gadolinium

I have had brain radiation for my current cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant stereotactic radiosurgery (NASRS) for brain metastases

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Regular visits as per study protocol

Long-term follow-up

Participants are monitored for survival and long-term outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Neoadjuvant Stereotactic Radiosurgery

Trial Overview The study tests neoadjuvant stereotactic radiosurgery (NASRS) on patients with large brain tumors before any surgical intervention. It's a phase II trial focusing on those who haven't had their tumors removed yet and can tolerate this precise form of radiation therapy aimed at shrinking the tumors.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 1 Intervention

Neoadjuvant SRS

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

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]

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]

Stereotactic radiosurgery after the surgical removal of brain metastases significantly reduces the risk of local recurrence of cancer, based on findings from two clinical trials presented in 2016.

This treatment approach also improves the quality of life for patients compared to traditional whole-brain radiotherapy, suggesting it should be adopted as a new standard of care for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery Keeps Brain Metastases at Bay. [2018]

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]

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]

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 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]

A review of 77 studies involving 6384 patients found that stereotactic radiosurgery (SRS) combined with systemic therapies (like chemotherapy and immunotherapy) is safe, showing no significant increase in skin toxicities, bleeding, or radiation necrosis.

The median SRS dose was 20 Gy, and the findings support the continuation of systemic treatments alongside SRS for patients with brain metastases, indicating that this combination does not adversely affect patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. Borius, PY., Régis, J., Carpentier, A., et al.[2021]

Stereotactic radiosurgery (SRS) is an effective treatment for brain metastases, but it carries a low risk of adverse radiation effects (AREs), similar to conventional radiation therapy.

Differentiating between AREs and tumor recurrence is crucial for determining the appropriate treatment, and the review proposes a management algorithm to help clinicians navigate this challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adverse radiation effects after radiosurgery. Monaco, EA., Niranjan, A., Kano, H., et al.[2012]

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) is increasingly being used for patients with multiple brain metastases, showing similar survival rates for those with more than 4 lesions compared to those with 4 or fewer, while maintaining neurocognitive function and quality of life.

While whole-brain radiation therapy (WBRT) has been the traditional treatment for multiple brain metastases, it is associated with significant cognitive decline and does not significantly improve overall survival, making SRS a more favorable option for selected patients, especially those with a better prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery for Multiple Brain Metastases. Kraft, J., Zindler, J., Minniti, G., et al.[2020]

Neoadjuvant stereotactic radiosurgery (SRS) before resection of brain metastases showed high local control rates of 100% at 6 months and 87.6% at 12 months in a study of 24 patients, suggesting it is an effective treatment strategy.

This approach may reduce the risks associated with postoperative SRS, such as irregular target delineation and tumor seeding, and preliminary literature indicates that neoadjuvant SRS could lead to better outcomes compared to traditional postoperative SRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm. Li, YD., Coxon, AT., Huang, J., et al.[2023]

Stereotactic radiosurgery effectively targets small, well-defined brain metastases while protecting surrounding healthy brain tissue, making it a suitable treatment option for these types of tumors.

Recent advancements in radiosurgical planning, including improved blocking patterns and beam shaping, have enhanced the precision of radiation delivery, reducing the risk of radiation toxicity to the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiobiology of brain metastasis: applications in stereotactic radiosurgery. Jagannathan, J., Sherman, JH., Mehta, GU., et al.[2019]

In a study of 103 patients with metastatic brain tumors treated with gamma knife surgery (GKS), those with lung cancer had a significantly lower rate of local treatment failure compared to patients with breast or renal cancer, indicating that the primary tumor site influences treatment outcomes.

Higher Paddick's conformity index (CI) was associated with an increased rate of local treatment failure, suggesting that this parameter may not effectively prevent recurrence, while early tumor enlargement post-treatment does not necessarily indicate a poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors related to the local treatment failure of γ knife surgery for metastatic brain tumors. Woo, HJ., Hwang, SK., Park, SH., et al.[2010]

Citations

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

Stereotactic radiosurgery as an adjunct to surgery and external beam radiotherapy in the treatment of patients with malignant gliomas. [2022]

2. United States 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. [2022]

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

Predicting the outcome of radiotherapy in brain metastasis by integrating the clinical and MRI-based deep learning features. [2023]

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

Stereotactic Radiosurgery Keeps Brain Metastases at Bay. [2018]

5. Scotland pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Risk of radiation-associated intracranial malignancy after stereotactic radiosurgery: a retrospective, multicentre, cohort study. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

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

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

Predictors of response to Gamma Knife radiosurgery for intracranial meningiomas. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Management of adverse radiation effects after radiosurgery. [2012]

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

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

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

Stereotactic Radiosurgery for Multiple Brain Metastases. [2020]

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

Neoadjuvant stereotactic radiosurgery for brain metastases: a new paradigm. [2023]

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

Radiobiology of brain metastasis: applications in stereotactic radiosurgery. [2019]

15. Austria pubmed.ncbi.nlm.nih.gov

Factors related to the local treatment failure of γ knife surgery for metastatic brain tumors. [2010]