Proton Beam Radiotherapy for Brain Tumor

Overseen By Andrei Holodny, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Benzodiazepines, Antihistamines

Disqualifiers: Intellectual disability, Psychiatric disorder, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Varies based on individual treatment plans

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how proton beam radiotherapy (PBRT) affects brain networks, thinking abilities, and quality of life in children and young adults with brain tumors. Researchers will use special brain scans and tests to compare those undergoing PBRT with healthy participants. The goal is to determine if PBRT changes brain connections or causes any damage. This study could help improve future brain cancer treatments. Individuals with a primary or metastatic brain tumor recommended for PBRT, who can tolerate an MRI scan, may be eligible to participate. As an unphased trial, participants have the opportunity to contribute to groundbreaking research that could enhance future treatment options.

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

The trial protocol does not specify that you need to stop your current medications. However, if you are taking medications that affect the central nervous system, like benzodiazepines or antihistamines, you should avoid them on the day of imaging and neurocognitive assessment, unless they are part of your prescribed regimen.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. However, if you are taking medications that affect the central nervous system, like benzodiazepines or antihistamines, you should avoid them on the day of imaging and cognitive tests, unless they are part of your prescribed regimen.

What prior data suggests that proton beam radiotherapy is safe for brain tumor patients?

Research has shown that proton beam radiotherapy (PBRT) is generally safe for treating brain tumors. Studies have found that it controls tumors as effectively as traditional radiation therapies but with fewer harmful side effects. This precision allows it to target the tumor more accurately, potentially causing less harm to surrounding healthy brain tissue.

Some studies have reported promising results regarding the long-term safety of PBRT, although the number of patients studied remains small. In one comparison, patients who received proton therapy had similar cancer-free survival rates to those who underwent traditional radiation, but the proton therapy group experienced fewer side effects.

Overall, these findings suggest that PBRT is well-tolerated and could be a safer option for treating brain tumors, particularly concerning its long-term effects on healthy brain tissue. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Proton Beam Radiotherapy (PBRT) is unique because it uses protons instead of traditional X-rays to target brain tumors, offering a more precise form of radiation therapy. This precision means that PBRT can deliver higher doses of radiation directly to the tumor while minimizing damage to the surrounding healthy brain tissue. Researchers are excited because this could potentially reduce side effects and improve quality of life for patients compared to conventional radiotherapy options. Additionally, the integration of neurocognitive and quality-of-life assessments alongside advanced MRI techniques in this approach could provide deeper insights into patient outcomes, setting a new standard for personalized care in brain tumor treatment.

What evidence suggests that Proton Beam Radiotherapy might be an effective treatment for brain tumors?

Research has shown that Proton Beam Radiotherapy (PBRT) effectively treats brain tumors while protecting nearby healthy tissue. Studies have found that PBRT targets tumors with great precision, reducing side effects compared to traditional radiation. This precision is crucial for children and young adults, as it may lower the risk of developing new cancers later in life. Additionally, research highlights PBRT's success in controlling tumors and its ability to improve quality of life by causing fewer long-term effects on the brain. Overall, PBRT offers a promising option for treating brain tumors with fewer complications. Participants in this trial will receive PBRT, and researchers will compare their outcomes to healthy matched controls to assess neurocognitive and quality-of-life impacts. ^{2 3 5 6 7}

Who Is on the Research Team?

Andrei Holodny, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 6-25 with brain tumors who are undergoing or recommended to receive proton beam radiation therapy (PBRT), can have an MRI without sedation, and take medications as directed. Healthy individuals in the same age range with no major illnesses can also participate as controls.

Inclusion Criteria

I am advised to undergo proton beam radiation therapy for my brain tumor.

I am between 6 and 25 years old.

I have been diagnosed with a brain tumor.

Exclusion Criteria

I have completed some neuropsychological tests in the past year.

As per medical record or self or parent report, there is an existing diagnosis of intellectual disability and/or prior IQ testing that documents Full Scale IQ standard score <70 at baseline.

I have a psychiatric disorder, mood disturbance, had a stroke or brain bleed, or have a neurodegenerative disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo proton beam radiation therapy (PBRT) for brain tumors

Varies based on individual treatment plans

Follow-up

Participants undergo rs-fcMRI scanning and neurocognitive assessments 3-5 months post-PBRT

3-5 months

1 visit (in-person)

Long-term Follow-up

Participants are monitored for differences in brain networks, cognitive abilities, and quality of life

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Proton Beam Radiotherapy (PBRT)

Trial Overview

The study examines how PBRT affects brain function and quality of life by comparing resting state brain networks, cognitive abilities, and well-being between patients treated with PBRT and healthy participants using rs-fcMRI scans and neurocognitive assessments.

How Is the Trial Designed?

Group I: patients Experimental Treatment 2 Interventions

A full neurocognitive battery with quality-of-life assessment will be conducted and an rs-fcMRI sequence will be added to the brain MRI performed as standard of care follow-up between 3-5 months post-PBRT.

Group II: healthy matched controls Experimental Treatment 2 Interventions

Healthy participants will be asked to complete the MRI scan and undergo neurocognitive assessment.

Proton Beam Radiotherapy (PBRT) is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Proton Beam Radiotherapy for:

• Brain tumors
• Pediatric brain tumors
• Low-grade gliomas
• Ependymomas
• Chordomas
• Chondrosarcomas

Approved in United States as Proton Beam Radiotherapy for:

• Brain tumors
• Pediatric brain tumors
• Low-grade gliomas
• Ependymomas
• Chordomas
• Chondrosarcomas
• Medulloblastoma
• Pineal tumors
• Germ cell tumors

Approved in United Kingdom as Proton Beam Radiotherapy for:

• Pediatric brain tumors
• Low-grade astrocytoma
• Ependymomas
• Chordomas
• Chondrosarcomas

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Proton beam radiation therapy (PBRT) effectively targets tumors in the head and neck while minimizing damage to surrounding healthy tissues, which can significantly enhance patients' quality of life during and after treatment.

Recent advancements in PBRT technology have improved treatment outcomes for various head and neck cancers, including sinonasal tumors and chondrosarcomas, and ongoing developments in intensity-modulated proton therapy promise even more comprehensive treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam radiation therapy for head and neck malignancies. Frank, SJ., Selek, U.[2021]

Proton minibeam radiation therapy (pMBRT) shows promise for treating brain, lung, and liver metastases, providing similar or better tumor coverage compared to stereotactic radiotherapy (SRT) while using fewer treatment fields.

pMBRT significantly reduces the dose to organs-at-risk and keeps normal tissue exposure below tolerance limits, suggesting a safer treatment option compared to conventional proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton minibeam radiation therapy for treating metastases: A treatment plan study. Ortiz, R., Belshi, R., De Marzi, L., et al.[2023]

In a study of 150 pediatric patients with brain tumors, those treated with proton beam radiation therapy (PBRT) showed no decline in IQ over time, while those treated with photon radiation (XRT) experienced an average decline of 1.1 points per year.

Although PBRT did not lead to IQ impairment, the study found that the overall IQ slopes did not significantly differ between PBRT and XRT groups, suggesting that while PBRT may be safer, its cognitive benefits compared to modern XRT protocols need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors. Kahalley, LS., Ris, MD., Grosshans, DR., et al.[2022]

In a study of 151 patients with organ-confined prostate cancer, proton beam therapy (PBT) demonstrated a low incidence of late Grade 2 or greater rectal toxicities, reported at only 2.0% after 2 years of follow-up.

The study indicates that PBT is a safe treatment option for localized prostate cancer, with minimal acute and late toxicities, suggesting it can effectively control side effects while delivering targeted radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional Phase II study of proton beam therapy for organ-confined prostate cancer focusing on the incidence of late rectal toxicities. Nihei, K., Ogino, T., Onozawa, M., 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]

In a study of 266 adult patients with primary brain tumors treated with proton beam therapy (PBT), significant declines in health-related quality of life (HRQoL) were observed, particularly in physical and cognitive functioning, three months post-treatment.

Fatigue and depression were the most common symptoms reported, highlighting the need for effective symptom management strategies and evidence-based guidelines to improve HRQoL for patients undergoing PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients with primary brain tumors during and three months after treatment with proton beam therapy. Langegård, U., Fransson, P., Bjork-Eriksson, T., et al.[2022]

In a study of 64 patients with unresectable stage III non-small cell lung cancer (NSCLC), concurrent chemotherapy and proton beam radiotherapy (PBT) resulted in a median overall survival of 26.5 months and a 5-year overall survival rate of 29%, indicating promising efficacy for this treatment approach.

The treatment was associated with relatively low rates of severe toxic effects, with no grade 5 toxicities reported, suggesting that PBT may reduce the harmful side effects compared to traditional photon therapy, although further optimization of the technique is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Radiotherapy and Concurrent Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer: Final Results of a Phase 2 Study. Chang, JY., Verma, V., Li, M., et al.[2022]

Proton beam therapy (PBT) has seen a significant increase in usage in Korea, with 5,398 out of 54,035 patients receiving it between 2007 and 2019, indicating its growing acceptance in clinical practice.

Liver cancer has become the most common type of cancer treated with PBT, rising from 20% of cases in 2008-2009 to 32% in 2018-2019, while its use for prostate cancer has declined significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of Proton Beam Therapy Use in Clinical Practice between 2007 and 2019 in Korea. Lee, SU., Yang, K., Moon, SH., et al.[2022]

Proton beam therapy (PBT) shows potential benefits for treating certain cancers, such as pediatric CNS tumors and large ocular melanomas, but current evidence does not support its superiority over traditional photon-based therapies for most other cancer types.

The American Society of Radiation Oncology (ASTRO) recommends further robust clinical trials to better define the appropriate use of PBT, as existing data is insufficient to endorse its routine application in many malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence based review of proton beam therapy: the report of ASTRO's emerging technology committee. Allen, AM., Pawlicki, T., Dong, L., et al.[2018]

Proton beam therapy (PBT) shows potential advantages over traditional photon therapy in treating pediatric brain and solid tumors, particularly in reducing early and late side effects of radiation, although data on outcomes is still limited due to the small number of treated children.

As more treatment centers adopt PBT, there is a need to optimize overall cancer care and follow-up to ensure effective disease control and improve the quality of life for survivors, while also considering the long-term costs associated with radiation side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy in pediatric oncology. Merchant, TE.[2022]

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