Proton Therapy for Pediatric Brain Cancer

Recruiting at 2 trial locations

Overseen By Bree Eaton, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Disqualifiers: Pacemakers, Cochlear implants, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how proton therapy, a special type of radiation treatment, works for children with brain cancer. The focus is on observing tumor changes over time using a detailed MRI scan. This scan allows doctors to compare the tumor's activity to healthy brain tissue without injections. Children with high-grade brain tumors who require radiation may be suitable candidates for this study. Participants will undergo several MRI scans throughout the treatment to monitor changes. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research in pediatric brain cancer treatment.

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.

What prior data suggests that proton therapy is safe for pediatric brain cancer?

Research has shown that proton therapy generally provides a safe way to treat brain tumors in children. It effectively controls tumors while better protecting healthy tissue compared to traditional radiation. This method uses precise proton beams, reducing damage to nearby healthy areas.

Some studies found changes visible on MRI scans after treatment, but most patients did not experience symptoms from these changes. This suggests that while proton therapy might cause some changes in the brain, it often does not lead to noticeable problems for the patient.

Overall, proton therapy is considered safer and more targeted than older radiation methods, making it a promising option for children with brain tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about proton therapy for pediatric brain cancer because it offers a targeted approach to radiation treatment. Unlike traditional radiation therapy, which can affect surrounding healthy tissues, proton therapy delivers precise doses of radiation directly to the tumor. This precision minimizes damage to healthy brain tissue, which is particularly important in children whose brains are still developing. By reducing harmful side effects, proton therapy has the potential to improve quality of life and long-term outcomes for young patients.

What evidence suggests that proton therapy might be an effective treatment for pediatric brain cancer?

Research has shown that proton therapy, under study in this trial, effectively treats brain tumors in children. Studies have found that it better protects cognitive abilities, such as reading skills, compared to traditional photon therapy. Proton therapy targets tumors more precisely, reducing radiation exposure to healthy brain areas. By safeguarding more of the brain, it aims to reduce long-term side effects and improve quality of life. Known for its accuracy and minimal side effects, proton therapy presents a promising option for young patients. ^{2 3 5 6 7}

Who Is on the Research Team?

Bree R. Eaton, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children with high-grade brain tumors (WHO grade 3-4) who are recommended to receive radiation therapy and can undergo MRI scans. It's open to all genders, races, and ethnic groups. The tumor must be in the upper part of the brain. Kids with significant illnesses that make MRI unsafe or have certain implants like pacemakers are not eligible.

Inclusion Criteria

My brain tumor is confirmed or suspected to be high-grade.

My brain tumor is located above the cerebellum.

Able to receive MRI scans

Exclusion Criteria

My brain tumor is non-cancerous and low-grade.

Patients with pacemakers, non-titanium aneurysm clips, neurostimulators, cochlear implants, non-titanium metal in ocular structures, or other incompatible implants which makes MRI safety an issue are excluded

Patients that have any significant medical illnesses that in the investigator's opinion cannot be adequately tolerate MRI scan are excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Imaging

Patients undergo spectroscopic MRI (sMRI) to obtain baseline data before receiving standard of care radiation therapy

1 week

1 visit (in-person)

Radiation Therapy

Patients receive standard of care radiation therapy guided by sMRI data

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with sMRI scans at 1, 4, and 7 months post-radiation therapy

7 months

3-4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Proton Therapy

Trial Overview

The study is testing how well a special type of MRI called spectroscopic imaging works alongside proton therapy to see changes in the metabolism of brain tumors in kids without using contrast agents. This non-invasive method could help distinguish between healthy tissue and tumor metabolism.

How Is the Trial Designed?

Group I: Diagnostic (sMRI) Experimental Treatment 2 Interventions

Patients undergo sMRI over less than 1 hour within 7 days prior to start of standard of care radiation therapy and at 10 weeks.

Group II: Group 2 Active Control 2 Interventions

Patients will undergo 3-4 sMRI scans at baseline prior to RT, 1 month, 4 months, and 7 months after RT, and/or at any time of suspected tumor recurrence.

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

Approved in United States as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in European Union as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in Canada as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in Japan as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Proton therapy (IMPT) provides better dose distribution and sparing of healthy tissues compared to photon therapy (IMRT) for pediatric patients with intracranial tumors, particularly benefiting younger patients with supratentorial tumors.

Infratentorial tumors showed significant sparing of the optic chiasm with IMPT, while brainstem sparing was less pronounced, indicating that IMPT can effectively reduce radiation exposure to critical structures in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Target Location, Size, and Patient Age on Normal Tissue Sparing- Proton and Photon Therapy in Paediatric Brain Tumour Patient-Specific Approach. Dell'Oro, M., Short, M., Wilson, P., et al.[2020]

Proton beam therapy (PBT) has been safely implemented for treating pediatric malignancies in a cohort of 47 patients under 25 years old, demonstrating its feasibility in a clinical setting on the Indian subcontinent.

The study found that while PBT is associated with some acute toxicities, such as dermatitis and hematologic toxicity, these effects were manageable, indicating that PBT can be a viable treatment option for young patients with specific tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India. Chilukuri, S., Burela, N., Uppuluri, R., et al.[2021]

In a study of 22 children with CNS germ cell tumors treated with proton therapy, there were no CNS recurrences and high survival rates were observed: 100% local control and overall survival, with 95% progression-free survival at a median follow-up of 28 months.

Proton therapy, particularly intensity-modulated proton therapy (IMPT), showed significant advantages over traditional intensity-modulated photon radiotherapy (IMRT) by providing better tumor coverage while sparing normal brain tissue, suggesting a safer treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiotherapy for pediatric central nervous system germ cell tumors: early clinical outcomes. MacDonald, SM., Trofimov, A., Safai, S., et al.[2022]

Proton beam therapy (PBT) significantly reduces the average dose of radiation to normal brain tissue compared to both intensity-modulated photon radiotherapy (IMRT) and 3D conventional radiotherapy (3D-CRT) in pediatric brain tumor treatments, based on a study of 12 patients.

The reduction in normal brain dose is particularly pronounced for larger tumors and those located at the periphery of the brain, indicating that PBT may be a safer option for these specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of dose distribution of PBT, 3D-CRT and IMRT for pediatric brain tumors. Takizawa, D., Mizumoto, M., Yamamoto, T., et al.[2018]

Proton beam therapy (PBT) is feasible for treating infants with central nervous system tumors, showing promising short-term outcomes with a 3-year overall survival rate of 76.5% among 51 infants studied.

However, the treatment is associated with significant logistical challenges and potential for higher-grade toxicities, including late effects like endocrinopathy and hearing loss, highlighting the need for careful monitoring and longer follow-up to assess long-term impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. Jazmati, D., Steinmeier, T., Ahamd Khalil, D., et al.[2021]

In a study involving 18 pediatric patients, intensity-modulated proton therapy (IMPT) significantly reduced the maximum dose to critical organs like the cochlea and eye, as well as the mean dose to normal brain tissue, compared to robotic radiation delivery system photon therapy.

Robotic radiation delivery system plans showed a sharper dose fall-off around the tumor, while IMPT provided a smaller volume of low-dose exposure, indicating that both techniques have unique advantages in minimizing radiation exposure to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy for Pediatric Brain Tumors using Robotic Radiation Delivery System and Intensity Modulated Proton Therapy. Lin, MH., Yang, M., Dougherty, J., et al.[2020]

Proton radiation therapy, particularly intensity-modulated proton therapy (IMPT), offers better dose localization compared to conventional photon radiation therapy, potentially reducing damage to surrounding healthy tissues in patients with head and neck and skull base tumors.

Initial clinical experiences suggest that IMPT may lead to fewer acute and long-term toxicities, and ongoing multi-institutional trials aim to further establish its effectiveness in treating these complex tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation therapy for head and neck cancer. Chan, AW., Liebsch, NJ.[2018]

In a study of 422 pediatric patients receiving proton therapy, those treated with passively scattered proton therapy had a significantly higher risk of hematologic toxicity compared to those receiving pencil beam scanning proton therapy, indicating that the choice of treatment technique can impact safety outcomes.

Uninsured patients and those receiving concurrent chemotherapy were found to have an increased risk of gastrointestinal and hematologic toxicities, suggesting that socioeconomic factors and additional treatments may influence the overall safety profile of proton therapy in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated With Acute Toxicity in Pediatric Patients Treated With Proton Radiation Therapy: A Report From the Pediatric Proton Consortium Registry. Breen, WG., Paulino, AC., Hartsell, WF., et al.[2022]

This systematic review aims to evaluate the effectiveness of proton beam therapy (PBT) for treating children with CNS tumors, comparing it to traditional photon radiotherapy, although the evidence base is expected to be limited and of low quality, primarily consisting of case series studies.

The review will assess various outcomes, including survival rates and adverse events, but highlights concerns about potential biases and the need for higher-quality research to better understand the efficacy of PBT compared to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness and safety of proton beam radiation therapy in children with malignant central nervous system (CNS) tumours: protocol for a systematic review. Main, C., Dandapani, M., Pritchard, M., et al.[2023]

In a study of 15 patients with radiation-associated brain image change (RAIC) after intensity modulated proton therapy (IMPT), a significant correlation was found between the dose of radiation and the linear energy transfer (LETd), indicating that higher LETd may increase the risk of RAIC.

The analysis showed that for patients receiving higher doses (60 to 70 Gy), the probability of developing RAIC increased with LETd, suggesting that assessing LETd in treatment plans could be clinically important to minimize potential brain damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mixed Effect Modeling of Dose and Linear Energy Transfer Correlations With Brain Image Changes After Intensity Modulated Proton Therapy for Skull Base Head and Neck Cancer. Engeseth, GM., He, R., Mirkovic, D., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5566707/

Proton Beam Therapy for Pediatric Brain Tumor - PMC

Merchant et al. have shown that PBT may preserve reading ability compared to photon radiotherapy. Three retrospective studies have reported treatment results ...

2.

advancesradonc.org

advancesradonc.org/article/S2452-1094(23)00102-1/fulltext

The Pediatric Proton and Photon Therapy Comparison ...

Modeling studies indicate that proton beam scanning results in the lowest out-of-field dose while data for photon treatments and passive ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9737072/

Proton Beam Therapy for Pediatric Tumors of the Central ...

By sparing a large volume of the brain from radiation doses, proton beam therapy aims at reducing long-term side effects and preserving ...

4.

ejcped.com

ejcped.com/article/S2772-610X(25)00030-3/fulltext

Proton beam therapy in paediatric radiation oncology

Proton Beam Therapy (PBT) is an increasingly utilised modality for treating tumours by utilising the physical properties of accelerated proton beams.

5.

frontiersin.org

frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1554765/full

Non-cancer effects after proton beam therapy for pediatric ...

Proton radiotherapy is considered an effective and precise cancer treatment method causing minimal side effects. We conducted a narrative review ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12554329/

Therapeutic Outcomes and Toxicity Mitigation of Proton Beam ...

Across the 10 studies that met inclusion criteria, proton therapy consistently demonstrated effectiveness in tumor control while significantly ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0093775420300026

The role of proton therapy in pediatric malignancies

Proton radiotherapy has promised an advantage in safely treating pediatric malignancies with an increased capability to spare normal tissues.