Proton Therapy for Brain Tumor

Overseen By Thomas Merchant

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Chemotherapy, BRAF-inhibitors, MEK-inhibitors

Disqualifiers: Prior CNS radiation, Metastatic disease, 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: Unknown

Duration: 6 weeks

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat certain brain tumors in children using proton therapy, a type of radiation treatment designed to protect memory. It targets tumors in specific brain areas, such as the center or near the optic nerves, and aims to minimize radiation exposure to memory-related regions. Suitable participants have a diagnosed brain tumor in these areas and have not received prior radiation. The goal is to determine if this approach, known as hippocampal-avoidance proton therapy, can maintain memory and quality of life while effectively treating the tumor. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research that could enhance future treatment options for children with brain tumors.

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

The trial protocol does not specify if you need to stop all current medications. However, you cannot receive concurrent chemotherapy or targeted therapy, including BRAF-inhibitors and MEK-inhibitors. If you have seizures, you can participate if they are well controlled on anticonvulsants.

What prior data suggests that this proton therapy technique is safe for treating brain tumors?

Research has shown that hippocampal-avoidance proton therapy is a promising treatment for brain tumors like low-grade gliomas. This therapy aims to protect the hippocampus, a crucial part of the brain involved in memory and learning. Studies have found that this type of proton therapy can reduce the risk of cognitive problems, such as difficulties with planning and organizing.

One study found that this therapy could lower the amount of radiation reaching the hippocampus, helping to preserve memory function. Specifically, the average radiation dose to the hippocampus was reduced from 13.7 to 5.4, demonstrating its effectiveness in protecting this important area. This reduction is important because it helps maintain memory and learning abilities.

Overall, these findings suggest that hippocampal-avoidance proton therapy is well-tolerated and may have fewer side effects compared to other radiation treatments. It offers a safer option for protecting memory in children with brain tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about hippocampal-avoidance proton therapy for brain tumors because it offers a unique approach to radiation treatment. Traditional radiation therapies often affect the hippocampus, a crucial area for memory and cognitive function. This new therapy specifically avoids the hippocampal region, potentially reducing cognitive side effects while still targeting the tumor effectively. By preserving more of the brain's healthy tissue, this method could improve patients' quality of life during and after treatment.

What evidence suggests that hippocampal-avoidance proton therapy is effective for low-grade gliomas?

Research shows that hippocampal-avoidance proton therapy, which participants in this trial will receive, can reduce radiation exposure to the hippocampus in people with brain tumors. Studies have found that proton therapy delivers less radiation to the hippocampus than traditional photon therapy. Lowering radiation to the hippocampus is important because it may help protect memory and thinking skills. In related research, patients who received whole-brain radiation therapy that avoided the hippocampus had better memory and quality of life. These findings suggest that using proton therapy to avoid the hippocampus might protect brain functions while treating tumors. ^{1 2 4 6 7}

Who Is on the Research Team?

Thomas Merchant

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 6 to less than 22 with certain low-grade brain tumors, including pilocytic astrocytoma and diffuse astrocytoma. Participants must have measurable disease, be able to undergo MRI scans, and not have had previous CNS radiation or tumor invasion into the hippocampus. They should also have adequate organ function and controlled seizures if present.

Inclusion Criteria

I am between 6 and 21 years old.

My tumor is in the central part of my brain or near it.

I have been diagnosed with a specific type of low-grade brain tumor.

Exclusion Criteria

I have never had radiation therapy to my brain.

My cancer has not spread to other parts of my body.

My cancer is located in my spine or near the base of my skull.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hippocampal-avoidance proton therapy to 52.2 CGE or 54 CGE in 29 or 30 fractions, with weekly MRI scans to monitor changes in tumor volume.

6 weeks

Weekly visits for MRI scans

Follow-up

Participants are monitored for neurocognitive outcomes and disease progression with brain MRI, continuing up to 5 years post therapy.

5 years

Regular visits for neurocognitive assessments and MRI scans

What Are the Treatments Tested in This Trial?

Interventions

• Hippocampal-avoidance proton therapy

Trial Overview The study tests whether proton therapy that avoids the hippocampi can help treat brain tumors without harming memory. It aims to see if this approach is feasible by meeting specific radiation dose constraints on the hippocampi while estimating survival rates and changes in verbal recall over time.

How Is the Trial Designed?

Group I: Hippocampal-avoidance proton therapy Experimental Treatment 1 Intervention

Hippocampal-avoidance proton therapy

Hippocampal-avoidance proton therapy is already approved in United States, European Union for the following indications:

Approved in United States as Hippocampal-avoidance proton therapy for:

• Low-grade gliomas (LGGs)
• Suprasellar or midline LGGs

Approved in European Union as Hippocampal-sparing proton therapy for:

• Low-grade gliomas (LGGs)
• Primary brain tumors

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

Proton therapy (PT) showed a significant dosimetric advantage over intensity-modulated radiation therapy (IMRT) in sparing neural stem cells and the hippocampus during whole brain irradiation, with much lower mean doses to these critical areas.

The proton therapy plan was found to be robust against setup errors, such as translation and rotation, ensuring effective treatment delivery while minimizing damage to surrounding healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SU-E-T-568: Hippocampus and Neural Stemcell Sparing Using Proton Therapy in Whole Brain Irradiation. Su, Z., Wu, J., Kirby, N., et al.[2019]

The study demonstrated that simulation-free hippocampal-avoidance whole brain radiotherapy (HA-WBRT) is clinically feasible for patients with central nervous system cancers, successfully creating treatment plans that met all necessary constraints for safety and efficacy.

Using an adaptive radiotherapy platform, the median dose to the hippocampus was slightly lower in the adaptive plans compared to standard plans, and the average time for creating these adaptive plans was about 45 minutes, indicating a practical workflow for implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In silico trial of simulation-free hippocampal-avoidance whole brain adaptive radiotherapy. Price, AT., Kang, KH., Reynoso, FJ., 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]

High doses of radiation to the hippocampus can lead to cognitive decline, prompting the development of hippocampal-sparing techniques in radiation therapy for brain metastases.

Techniques such as helical TomoTherapy, intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) have been shown to effectively spare the hippocampus during treatment, with Tomotherapy providing slightly better sparing in some cases, while VMAT offers efficient treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal sparing radiation therapy for brain metastases: treatment techniques and clinical implementation. Woods, K., Shen, ZL., Xu, Z., et al.[2023]

Patients with small-cell lung cancer who received hippocampal avoidance prophylactic cranial irradiation (HA-PCI) showed a significantly higher risk of leukoencephalopathy, indicated by increased Fazekas scores, compared to those who received non-HA-PCI.

Despite the intention to protect neurocognition with HA-PCI, the findings suggest that this approach may lead to more prominent radiological changes, warranting further long-term studies to assess its impact on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leukoencephalopathy after prophylactic whole-brain irradiation with or without hippocampal sparing: a longitudinal magnetic resonance imaging analysis. Mayinger, M., Kraft, J., Lohaus, N., et al.[2020]

This case study presents the first use of volumetric modulated arc therapy to spare the hippocampus during radiotherapy for a patient with a low-grade glioma that transformed into anaplastic astrocytoma, highlighting a novel approach in treatment planning.

The technique allows for selective protection of the hippocampus while still effectively targeting the tumor, suggesting that for certain patients, this method can be beneficial without compromising the overall treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Volumetric modulated arc therapy for hippocampal-sparing radiotherapy in transformed low-grade glioma: A treatment planning case report. Kazda, T., Pospisil, P., Vrzal, 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]

Hippocampal sparing techniques during brain irradiation are being explored to minimize cognitive side effects, as the hippocampus is crucial for memory and is negatively impacted by radiation, leading to potential declines in neurocognitive function.

Current studies indicate that it is technically feasible to implement hippocampal sparing in radiotherapy, and while ongoing phase II and III trials are needed to confirm its cognitive benefits, preliminary evidence supports its use to protect memory function in patients undergoing brain tumor treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. Kazda, T., Jancalek, R., Pospisil, P., et al.[2022]

In a study involving 65 patients with brain metastases, hippocampal avoidance whole-brain radiotherapy (HA-WBRT) demonstrated better preservation of memory function at 6 months compared to conformal WBRT (C-WBRT), particularly in recognition and memory scores.

Despite the cognitive benefits observed with HA-WBRT, there were no significant differences in overall survival or brain progression-free survival between the two treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial. Yang, WC., Chen, YF., Yang, CC., et al.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10847568/

Hippocampal sparing in whole-brain radiotherapy for brain ... WBRT increases the median survival time to 3-6 months and completely relieves headache and intracranial hypertension in more than 50% of patients, making it the ...

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14039-6

Intensity-modulated proton therapy for hippocampal-sparing ... Compared with photon plans, proton plans significantly reduce the dose to the hippocampus, lenses, eyeballs and parotids in hippocampal-sparing PCI.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405631618300575

Advantages of intensity modulated proton therapy during ... IMPT offered significant benefits relative to VMAT for hippocampal sparing. Hippocampal mean dose was reduced from 13.7 ± 0.8 Gy with VMAT to 5.4 ± 0.3 GyE ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04065776

NCT04065776 | Evaluation of Hippocampal-Avoidance ... Neurocognitive outcomes, sensitive to measures of memory and learning, will be collected at baseline and continue to 5 years post therapy. Disease evaluation ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.19.03359

Benefit of Treatment With Hippocampal Avoidance Whole ... This hippocampal avoidant WBRT (HA-WBRT) was tested in a phase II trial, with results supporting preservation of memory and quality of life (QOL) ...

6. withpower.com withpower.com/trial/proton-therapy-for-brain-tumor-9d7f1

Proton Therapy for Brain Tumor Yes, hippocampal-avoidance proton therapy is promising because it can protect important brain areas like the hippocampus, which helps with memory and learning, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8768900/

The Advantage of Proton Therapy in Hypothalamic-Pituitary ... The study reported significantly lower risk of cognitive failure, mainly attributable to less deterioration in executive function at 4 months (23.3% versus 40.4 ...