Preoperative Radiosurgery for Brain Tumor

Recruiting at 1 trial location

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Systemic anti-cancer therapy

Disqualifiers: Pregnancy, Nursing, Cranial radiotherapy, others

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

Compensation: Varies

Number of Visits: 4

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether administering a high dose of radiation to a brain tumor before surgery can help control the tumor and reduce side effects in individuals with high-grade glioma, a type of brain cancer. The study employs a precise form of radiation, called radiosurgery, to target the tumor directly. This approach may reduce the number of treatments needed and spare healthy brain tissue. Patients diagnosed with high-grade glioma, who have had a previous biopsy and are planning surgery, might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that you cannot have used systemic anti-cancer therapy in the previous 3 months.

What prior data suggests that this method is safe for treating brain tumors?

Research has shown that radiosurgery is generally well-tolerated. In studies, patients with brain tumors have undergone radiosurgery and experienced good results in controlling tumor growth. For example, one study found that 70% of patients had their tumors controlled after radiosurgery. This treatment targets tumors precisely, helping to protect healthy brain tissue.

While radiosurgery carries some risks, serious side effects are uncommon. Most patients experience mild side effects like headaches or tiredness, which usually improve over time. Radiosurgery has been used effectively for treating brain tumors, and past patients have tolerated it well.

Overall, radiosurgery offers a promising way to treat brain tumors with a focus on precision and fewer side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this approach to treating brain tumors because it combines multiple advanced techniques to potentially improve outcomes. Unlike traditional methods, which often involve surgery followed by weeks of radiation, this protocol uses radiosurgery as a preoperative step, providing a precise, high-dose radiation treatment in just one session before surgery. This innovative sequence aims to shrink the tumor more effectively and quickly before surgical removal. Additionally, the integration of MRI-guided stereotactic biopsies and the option of adding tumor treating fields (TTF) during standard radiation therapy could lead to better-targeted treatments and potentially fewer side effects, offering new hope for patients with brain tumors.

What evidence suggests that preoperative radiosurgery might be an effective treatment for high grade glioma?

Research has shown that radiosurgery, one of the treatments in this trial, can effectively treat brain tumors. One study found an 83% chance of controlling tumors 12 months after treatment. Radiosurgery uses a single large dose of radiation to target tumors, helping to shrink them over time. It aims to destroy tumor cells while minimizing damage to healthy tissue. This method has shown promise in managing both non-cancerous and cancerous brain tumors. ^{2 6 7 8 9}

Who Is on the Research Team?

Daniel Trifiletti, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults with high grade glioma (brain tumor) who are planning surgery and radiotherapy, have good blood counts, no prior cranial radiotherapy, can perform daily activities with minimal help (ECOG PS ≤2), not pregnant or nursing, agree to use contraception if of childbearing potential, and can provide consent. Excludes those with non-MRI compatible devices, recent cancer therapy within 3 months, medical issues preventing surgery or known low-grade gliomas.

Inclusion Criteria

Provide written informed consent

Ability to complete questionnaire(s) by themselves or with assistance

Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only

Exclusion Criteria

I am willing to participate in the study.

Investigator discretion that enrollment on the study would pose undo harm or risk to the patient

I am currently breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Preoperative Radiosurgery

Patients undergo MRI-guided stereotactic biopsy and preoperative radiosurgery in 1 fraction

2 weeks

1 visit (in-person)

Surgery

Patients undergo surgery within 14 days after radiosurgery

2 weeks

1 visit (in-person)

Postoperative Radiation and Chemotherapy

Patients receive standard of care radiation therapy over 30 fractions and temozolomide daily with or without tumor treating fields

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 2-3 months for 12 months, then every 3 months up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy
• Radiosurgery

Trial Overview The NeoGlioma Study is testing the effectiveness of radiosurgery before conventional brain tumor surgery. The goal is to see if this approach improves tumor control while reducing side effects compared to traditional methods that involve multiple radiation doses over a longer period.

How Is the Trial Designed?

Group I: Treatment (stereotactic biopsy, radiosurgery, surgery) Experimental Treatment 9 Interventions

Patients undergo MRI-guided stereotactic biopsy. Within 14 days of registration, patients undergo either standard of care surgery or radiosurgery in 1 fraction. Within 14 days, patients who underwent radiosurgery then undergo surgery. Within 4-6 weeks, all patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without TTF at the discretion of the treating neuro-oncologist. Additionally, patients undergo MRI and blood sample collection and optional biopsy throughout the study.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

In a study of 379 patients with non-metastatic Stage III-IV head and neck squamous cell cancer, IMRT with simultaneous integrated boost (IMRT+SIB) showed similar effectiveness in local control and survival rates compared to traditional 3D conformal radiotherapy (3D-CRT) and sequential IMRT (IMRTseq).

IMRT+SIB significantly reduced acute toxicity, with lower rates of severe mucositis, dermatitis, and the need for feeding tubes during treatment, suggesting it is a safer option for patients undergoing chemoradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 3D confromal radiotherapy and intensity modulated radiotherapy with or without simultaneous integrated boost during concurrent chemoradiation for locally advanced head and neck cancers. Spiotto, MT., Weichselbaum, RR.[2021]

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]

In a study of 70 patients undergoing surgery for brain metastases (BMs) with intraoperative radiotherapy (ioRT), the treatment was found to be safe, with only 13% experiencing adverse events, including a 3% rate of postoperative death.

Functional outcomes showed that while 30% of patients improved post-surgery, there was no significant overall deterioration in functional status, suggesting that ioRT combined with surgery may be a feasible option for treating supratentorial BMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resection of supratentorial brain metastases with intraoperative radiotherapy. Is it safe? Analysis and experiences of a single center cohort. Krauss, P., Steininger, K., Motov, S., et al.[2023]

Intraoperative radiation therapy (IORT) following brain metastasis resection demonstrated a low radiation necrosis rate of 2.9% and a high local control rate of 97.1% over one year, indicating its safety and efficacy.

The median overall survival for patients receiving IORT was 17.5 months, which is comparable to outcomes from traditional external beam radiation therapy (EBRT), suggesting that IORT is a viable alternative for immediate post-surgical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome assessment of intraoperative radiotherapy for brain metastases: results of a prospective observational study with comparative matched-pair analysis. Layer, JP., Hamed, M., Potthoff, AL., et al.[2023]

In a study of 260 men with localized prostate cancer treated with high-dose IGRT and IMRT, the combination resulted in a low rate of late toxicity, with only 4.4% experiencing grade 2 gastrointestinal issues and 7.1% with grade 2 genitourinary issues after 7 years.

The treatment showed high efficacy, with a 7-year prostate-specific antigen relapse-free survival rate of 97.1% for low-risk patients, indicating that this approach is both safe and effective for managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. Doležel, M., Odrážka, K., Vaňásek, J., et al.[2021]

Intraoperative Radiotherapy (IORT) using Photon Radiosurgery Systems (PRS) shows stable performance over time, with average output levels maintained at 99.12% during testing, indicating reliability for clinical use.

The dosimetric characteristics of the x-ray sources were consistent, with measurements falling within manufacturer tolerances, suggesting that all four systems can effectively deliver radiation therapy with similar performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional intercomparison of intraoperative radiotherapy equipment - Photon Radiosurgery System. Armoogum, KS., Parry, JM., Souliman, SK., et al.[2023]

Intensity-modulated radiation therapy (IMRT) resulted in significantly lower rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity compared to (125)I seed implants, with 3-year rates of 3.5% GU and 2.4% GI toxicity for IMRT versus 19.2% GU and 7.7% GI for (125)I.

Both treatments showed similar biochemical failure rates, with IMRT having a 4-year freedom from failure rate of 99.5% compared to 93.5% for (125)I, indicating that while both are effective, IMRT may be safer with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Eade, TN., Horwitz, EM., Ruth, K., et al.[2022]

Intensity-modulated stereotactic radiotherapy (IMSRT) provides better conformity and coverage for planning target volumes (PTV) compared to stereotactic conformal radiotherapy (SCRT), especially for irregular and multifocal lesions, based on a study of 10 patients.

IMSRT also offers improved sparing of organs at risk (OAR), resulting in lower doses to these critical areas, although it may increase the volume of normal tissue receiving a low dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in the skull base. Baumert, BG., Norton, IA., Davis, JB.[2022]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

Intra-operative radiotherapy (IORT) for brain tumors can be safely administered during surgical resection without increasing the risk of seizures, as shown in a study of 24 patients, where only 3 experienced seizures post-IORT.

Electrocorticography (ECoG) monitoring during IORT showed no significant electrophysiological changes or seizure activity, indicating that the procedure does not adversely affect brain function during or after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial intraoperative radiotherapy (IORT): evaluation of electrocorticography and peri-operative seizure risk. Cifarelli, CP., Vargo, JA., Sener, U., et al.[2023]

The combination of stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) improves local tumor control and neurological function in patients with brain metastases, particularly benefiting those with a single metastasis, as it is associated with better survival compared to WBRT alone.

Current studies on SRS compared to other treatments like WBRT or neurosurgery show limited quality and inconclusive evidence, highlighting the need for more rigorous research to assess the effectiveness and safety of these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. Müller-Riemenschneider, F., Schwarzbach, C., Bockelbrink, A., et al.[2021]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

Citations

1. 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 ...

2. 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.

3. 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 ...

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. 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 and ...

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

Outcomes of Gamma Knife Radiosurgery for Brain ... Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) ...

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. nature.com nature.com/articles/s41598-022-13853-3

Clinical outcomes of patients with multiple courses ... Actuarial post-GKRS survival rates at 1, 2, 3, 4, and 5 years following initial GKRS were 88.1%, 79.5%, 65.3%, 51.4%, and 37.3%, respectively.

9. advancesradonc.org advancesradonc.org/article/S2452-1094(23)00230-0/fulltext

Stereotactic Radiosurgery in the Management of Brain ... Stereotactic radiosurgery in the management of brain metastases: a case-based radiosurgery society practice guideline.