Genu-Sparing Whole Brain Radiation for Brain Cancer

Recruiting at 3 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method of administering whole brain radiation therapy to individuals with brain cancer, aiming to protect brain regions responsible for thinking and mood. The researchers aim to determine if this approach can preserve cognitive and emotional functions while treating brain metastases (cancer that has spread to the brain). Suitable candidates have a solid tumor cancer diagnosis, are scheduled for whole brain radiation, and do not have cancer spread to a specific brain area called the genu. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance the quality of life for future patients.

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 prior data suggests that genu-sparing whole brain radiation therapy is safe?

Research has shown that treatments similar to genu-sparing whole brain radiation are generally safe. For instance, hippocampal-sparing whole brain radiation therapy aims to protect memory and thinking skills. In a study with brain cancer patients, these treatments helped reduce memory and thinking problems.

While genu-sparing radiation remains under study, similar techniques provide promising safety insights. These treatments aim to minimize effects on important brain areas, indicating good safety potential. However, like any treatment, side effects may occur, so discussing with a doctor is crucial to determine if this trial is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard whole brain radiation therapy, which can affect various parts of the brain, genu-sparing whole brain radiation therapy specifically avoids the genu of the corpus callosum. This precision aims to preserve cognitive function by sparing critical brain areas associated with memory and processing speed. Researchers are excited because this approach could potentially reduce cognitive side effects while still effectively treating brain cancer, offering a better quality of life for patients.

What evidence suggests that genu-sparing whole brain radiation therapy is effective for brain cancer?

Research has shown that protecting parts of the brain, such as the hippocampus, during whole brain radiation therapy can reduce problems with thinking and memory. One study found that patients who received memory-sparing whole brain radiation therapy maintained better thinking and memory skills, even with multiple brain tumors. In this trial, participants will receive Genu-Sparing Whole Brain Radiation Therapy, designed to protect important brain areas, potentially improving thinking and emotional health. This method aims to treat cancer while minimizing damage to critical brain regions involved in memory and thinking. ^{1 2 4 6 7}

Who Is on the Research Team?

Kristin Redmond, MD, PhD

Principal Investigator

The SKCCC at Johns Hopkins

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-brain-neoplasms-6-2017-11632

Genu-Sparing Whole Brain Radiation 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 ...

2. patlynk.com patlynk.com/trial/NCT03223922

Neurocognitive Functioning With Genu-Sparing Whole ... This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2452109423001653

Dosimetric Results From a Phase 2 Trial of Memory ... We report our preliminary experience using a “memory-avoidance” WBRT (MA-WBRT) approach that spares these substructures for patients with >15 brain metastases.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4239301/

Hippocampal-Avoidance Whole-Brain Radiation Therapy This study of 401 patients demonstrated that the vast majority of patients with brain metastases (90.5%) had some decline in NCF before initiation of treatment.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9279690/

The Cognitive Effects of Radiotherapy for Brain Metastases This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases.

6. redjournal.org redjournal.org/article/S0360-3016(21)00001-8/abstract

Reducing Radiation-Induced Cognitive Toxicity: Sparing ... Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: Phase III trial NRG Oncology CC001.

7. irochouston.mdanderson.org irochouston.mdanderson.org/rpc/credentialing/files/RTOG-0933-Master[1].pdf

radiation therapy oncology group rtog 0933 a phase ii trial ... HA-WBRT poses important challenges in conformally avoiding the centrally located hippocampus with its unique anatomic shape, while allowing for uniform dose ...