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 studies how well spectroscopic magnetic resonance imaging (MRI) guided proton therapy works in assessing metabolic change in pediatric patients with brain tumors. The non-invasive imaging, such as spectroscopic MRI may help to map the differences in tumor metabolism compared to healthy tissue without injection of any contrast agent.

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.

Is proton therapy safe for children with brain cancer?

Proton therapy is generally considered safe for children with brain cancer, as it can reduce side effects by targeting tumors more precisely than traditional radiation. However, there is limited information on acute side effects, and ongoing studies aim to better understand these risks. ^{1 2 3 4 5}

How is proton therapy different from other treatments for pediatric brain cancer?

Proton therapy is unique because it uses protons instead of traditional X-rays to target brain tumors, allowing for more precise delivery of radiation that spares healthy brain tissue. This can reduce side effects and is especially beneficial for children, whose brains are still developing. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment Proton Therapy for Pediatric Brain Cancer?

Research shows that proton therapy, including intensity-modulated proton therapy (IMPT), provides better dose distribution and reduces side effects compared to traditional photon therapy for pediatric brain tumors. This means it can target the tumor more precisely while sparing healthy brain tissue, which is especially important for children. ^{1 2 6 8 10}

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

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 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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

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

Proton radiotherapy for pediatric central nervous system germ cell tumors: early clinical outcomes. [2022]

2. Switzerland 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. [2020]

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

Radiation Therapy for Pediatric Brain Tumors using Robotic Radiation Delivery System and Intensity Modulated Proton Therapy. [2020]

4. England 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

A comparative study of dose distribution of PBT, 3D-CRT and IMRT for pediatric brain tumors. [2018]

6. United States 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. [2022]

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

Proton radiation therapy for head and neck cancer. [2018]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study. [2021]

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

Preliminary Experience of Treating Children and Young Adults With Image-Guided Proton Beam Therapy in India. [2021]