Genu-Sparing Whole Brain Radiation for Brain Cancer

Recruiting at 2 trial locations

Overseen By Kristin Redmond, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Prior WBRT, MMSE<24, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 3-4 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with brain metastases.

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

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 Genu-Sparing Whole Brain Radiation Therapy for brain cancer?

Research shows that sparing the hippocampus during whole brain radiation therapy can help reduce cognitive decline (problems with thinking and memory) in patients with brain metastases. This approach, known as Hippocampal Avoidance Whole Brain Radiation Therapy, is considered effective in maintaining cognitive function while treating brain cancer. ^{1 2 3 4 5}

Is Genu-Sparing Whole Brain Radiation Therapy safe for humans?

Hippocampal-sparing whole brain radiation therapy, which is similar to genu-sparing, is generally considered safe and aims to reduce memory and cognitive side effects compared to traditional whole brain radiation. Studies have shown it may prevent treatment-related cognitive decline, and technological advances have improved its safety profile. ^{1 2 3 5 6}

What makes Genu-Sparing Whole Brain Radiation Therapy unique compared to other treatments for brain cancer?

Genu-Sparing Whole Brain Radiation Therapy is unique because it aims to protect the hippocampus (a part of the brain important for memory) during radiation treatment, potentially reducing memory decline, which is a common side effect of traditional whole brain radiation therapy. ^{1 2 3 4 7}

Research Team

Kristin Redmond, MD, PhD

Principal Investigator

The SKCCC at Johns Hopkins

Eligibility Criteria

This trial is for adults over 18 with brain metastases who can consent to treatment, have a performance status score of ≥70, and are expected to live at least 6 more months. They must be able to use contraception and have not had whole brain radiation before. Non-English speakers, those with serious illnesses preventing protocol adherence or MRI contraindications, are excluded.

Inclusion Criteria

My cancer diagnosis is confirmed by lab tests on tissue or fluid samples.

I am able to care for myself but may not be able to do active work.

Patients of childbearing potential (male or female) must practice adequate contraception due to possible harmful effects of radiation therapy on an unborn child

Exclusion Criteria

You cannot have an MRI due to a serious medical reason.

I have cancer that has spread to a specific part of my brain.

I have had whole brain radiation therapy before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive genu-sparing whole brain radiation therapy (GS-WBRT) with a standard dose of 3000 cGy in 10 fractions

3-4 weeks

10 visits (in-person)

Follow-up

Participants undergo cognitive testing at baseline and at 4, 6, and 12 months following completion of brain radiation to evaluate cognitive function and quality of life

12 months

3 visits (in-person)

Treatment Details

Interventions

• Genu-Sparing Whole Brain Radiation Therapy

Trial Overview The study tests genu-sparing whole brain radiation therapy (WBRT) aimed at preserving cognitive and neuropsychiatric functions in patients with brain metastases. It's designed for those who've possibly undergone prior stereotactic radiosurgery but haven't received WBRT.

Participant Groups

Group I: Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy Experimental Treatment 1 Intervention

Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction

Genu-Sparing Whole Brain Radiation Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Genu-Sparing Whole Brain Radiation Therapy for:

• Brain metastases

Approved in European Union as Hippocampal Avoidance Whole Brain Radiation Therapy for:

• Brain metastases
• Limited brain metastases

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Findings from Research

In a study of 260 patients with multiple brain metastases, it was found that only 1.1% of all metastases occurred within the hippocampus, indicating that hippocampal sparing during whole brain radiotherapy (WBRT) may be a viable strategy to reduce memory decline.

The research did not find a significant difference in the laterality of metastasis involvement in the left versus right hippocampus, suggesting that the proposed unilateral sparing approach may not provide a clear advantage in preventing recurrence in these regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Hippocampal Metastases: Laterality and Implications for Unilateral Hippocampal Avoiding Whole Brain Radiotherapy. Kazda, T., Misove, A., Burkon, P., et al.[2022]

TomoTherapy is the most effective method for Hippocampal Avoidance Whole Brain Radiotherapy (HA-WBRT), providing a significantly better dose distribution compared to IMRT and RapidArc, as indicated by a superior homogeneity index.

RapidArc, while not as effective in dose distribution as TomoTherapy, offers the fastest treatment delivery time, making it a suitable alternative when time efficiency is a priority.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric evaluation of intensity-modulated radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for hippocampal-avoidance whole brain radiotherapy. Rong, Y., Evans, J., Xu-Welliver, M., et al.[2022]

In a study of 518 patients with brain metastases, those who survived 4 months or longer showed a significant reduction in neurocognitive function failure (NCFF) when treated with hippocampal avoidant whole brain radiotherapy (HA-WBRT) compared to standard WBRT.

Patients with lower baseline cognitive impairment (as measured by the MD Anderson Symptom Inventory-Brain Tumor scores) and those with primary lung tumors experienced greater neuroprotective benefits from HA-WBRT, highlighting the importance of individual patient characteristics in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. Cherng, HR., Sun, K., Bentzen, S., et al.[2023]

In a preliminary study of five patients with brain metastases, modern intensity-modulated radiotherapy (IMRT) techniques successfully spared the hippocampus during whole-brain radiotherapy, significantly reducing the radiation dose to this critical area.

The helical tomotherapy and LINAC-based IMRT methods achieved an average dose reduction to the hippocampus by 87% and 81%, respectively, while maintaining acceptable target coverage, suggesting potential neurocognitive benefits that warrant further investigation in a Phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. Gondi, V., Tolakanahalli, R., Mehta, MP., et al.[2022]

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) combined with a simultaneous integrated boost (SIB) showed a local tumor control rate of 73% and a median intracranial progression-free survival of 40 weeks in a study of 20 patients.

The treatment was found to be safe, with no significant acute or late toxicities observed, suggesting it may help prevent cognitive decline associated with standard whole brain radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: Local tumour control and survival. Oehlke, O., Wucherpfennig, D., Fels, F., et al.[2022]

Whole-brain radiotherapy (WBRT) is a common treatment for lung cancer patients with brain metastases, but it can lead to cognitive decline due to radiation damage to the hippocampus.

Hippocampal-sparing WBRT is a promising technique that aims to reduce cognitive side effects while still effectively treating brain metastases, supported by both preclinical and clinical evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer. Zhao, R., Kong, W., Shang, J., et al.[2022]

The study demonstrated the feasibility and safety of using hippocampal sparing whole brain radiotherapy (HSWBRT) combined with simultaneous integrated boost (SIB) for patients with 1-5 brain metastases, effectively minimizing radiation exposure to the hippocampus, which is crucial for memory preservation.

The dosimetric results showed that the mean dose to the hippocampus was kept low (8.06 Gy for HSWBRT), while still delivering effective treatment to the metastatic lesions, indicating a potential for improved quality of life for patients by reducing long-term radiation toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal Sparing Whole Brain Radiotherapy and Integrated Simultaneous Boost vs Stereotactic Radiosurgery Boost: A Comparative Dosimetric Planning Study. Cheah, SK., Matthews, T., Teh, BS.[2017]

References

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

Incidence of Hippocampal Metastases: Laterality and Implications for Unilateral Hippocampal Avoiding Whole Brain Radiotherapy. [2022]

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

Dosimetric evaluation of intensity-modulated radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for hippocampal-avoidance whole brain radiotherapy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. [2023]

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

Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: Local tumour control and survival. [2022]

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

Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer. [2022]

7. Thailand pubmed.ncbi.nlm.nih.gov

Hippocampal Sparing Whole Brain Radiotherapy and Integrated Simultaneous Boost vs Stereotactic Radiosurgery Boost: A Comparative Dosimetric Planning Study. [2017]