Preoperative Radiosurgery for Brain Tumor

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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial finds out the possible benefits and/or side effects of radiosurgery before surgery (preoperative) in treating patients with high grade glioma. Radiosurgery uses special equipment to position the patient and precisely give a single large dose of radiation to the tumor. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pre-operative radiosurgery may improve the odds of brain tumor control and reduce treatment-related side effects.

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 data supports the effectiveness of the treatment Preoperative Radiosurgery for Brain Tumor?

Research shows that stereotactic radiosurgery (SRS), a key component of the treatment, is effective for brain metastases by focusing radiation precisely on the tumor, which helps preserve healthy brain tissue and improve outcomes. Additionally, intraoperative radiotherapy (IORT) has shown benefits in preventing tumor regrowth and allowing quicker progression to other treatments. ^{1 2 3 4 5}

Is preoperative radiosurgery for brain tumors generally safe in humans?

Research on advanced radiotherapy techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) shows that these methods are generally safe, with some risk of side effects such as gastrointestinal and genitourinary issues in prostate cancer treatment. These techniques are widely used and considered safe in clinical practice for various conditions. ^{6 7 8 9 10}

How is preoperative radiosurgery for brain tumors different from other treatments?

Preoperative radiosurgery for brain tumors is unique because it involves delivering a focused, high dose of radiation to the tumor before surgery, which can help shrink the tumor and make it easier to remove. This approach can also protect healthy brain tissue and allow for quicker recovery and transition to other treatments compared to traditional post-surgery radiation. ^{3 5 11 12 13}

Research Team

Daniel Trifiletti, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in the skull base. [2022]

2. United States 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. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. [2021]

4. Scotland pubmed.ncbi.nlm.nih.gov

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

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

Outcome assessment of intraoperative radiotherapy for brain metastases: results of a prospective observational study with comparative matched-pair analysis. [2023]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Results of IGRT in Prostate Cancer Treatment. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

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

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. [2023]

9. United States 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. [2022]

10. Japan 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. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Functional intercomparison of intraoperative radiotherapy equipment - Photon Radiosurgery System. [2023]

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

Intracranial intraoperative radiotherapy (IORT): evaluation of electrocorticography and peri-operative seizure risk. [2023]

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

Resection of supratentorial brain metastases with intraoperative radiotherapy. Is it safe? Analysis and experiences of a single center cohort. [2023]