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

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to find out if there are differences in the resting state brain networks of children and young adults (ages 6-25) after treatment with proton beam radiation therapy (PBRT). The researchers will use resting state functional connectivity magnetic resonance imagining (rs-fcMRI) scanning to detect these differences. The researchers will also check for differences in participants' thinking and quality of life through a cognitive assessment and a questionnaire. Both people undergoing PBRT for a brain tumor and healthy people will take part in this study so that the researchers can compare the brain networks (connections in the brain that are involved in certain function, such as memory or attention), thinking patterns, and quality of life of these two groups of participants. The study researchers think that rs-fcMRI scans may be an effective way to look at the brain networks after treatment with PBRT and see if this treatment causes differences in those networks, including damage to the brain (neurotoxicity). rs-fcMRI scans take images when a patient is in a resting state, which means the patient is not performing a task or thinking about anything in particular. This study will provide valuable information about how PBRT affects brain networks, thinking (cognitive) abilities, and quality of life in children and young adults. The study results may have an impact on future treatment approaches for brain cancer and the use of PBRT in children and young adults.

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 data supports the idea that Proton Beam Radiotherapy for Brain Tumor is an effective treatment?

The available research shows that Proton Beam Radiotherapy (PBRT) is effective for treating brain tumors, especially in children. One study found that PBRT can lead to better outcomes in terms of maintaining intelligence levels compared to traditional photon radiation. This is because PBRT targets the tumor more precisely, reducing damage to healthy brain tissue. Another study highlights that PBRT can improve the quality of life for patients with brain tumors during and after treatment. While more research is needed, especially in comparing PBRT to other treatments, current data suggests that PBRT is beneficial for brain tumors, particularly in pediatric cases. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Proton Beam Radiotherapy for brain tumors?

Proton Beam Radiotherapy (PBRT) is shown to reduce radiation exposure to normal tissues compared to traditional photon radiation, which may lead to better cognitive outcomes in children with brain tumors. Additionally, PBRT has been associated with improved quality of life and outcomes in head and neck cancers, and it appears to be more beneficial than photon approaches for certain pediatric brain tumors. ^{1 2 3 4 5}

What safety data exists for proton beam therapy for brain tumors?

The safety data for proton beam therapy (PBT) for brain tumors includes studies on health-related quality of life (HRQoL) and neurocognitive outcomes. One study focused on HRQoL in patients with primary brain tumors treated with PBT, assessing acute symptoms and quality of life changes. Another study compared the change in intelligence quotient (IQ) in pediatric brain tumor patients treated with PBT versus photon radiation, suggesting that PBT may lead to better neurocognitive outcomes due to reduced dose to normal tissues. ^{1 3 6 7 8}

Is proton beam therapy safe for treating brain tumors?

Proton beam therapy (PBT) is generally considered safe for treating brain tumors, as it is designed to target tumors precisely, potentially reducing damage to surrounding healthy tissue. Studies have shown that PBT can maintain health-related quality of life during and after treatment, and it may lead to better outcomes compared to traditional radiation in some cases. ^{1 3 6 7 8}

Is Proton Beam Radiotherapy a promising treatment for brain tumors?

Yes, Proton Beam Radiotherapy (PBRT) is a promising treatment for brain tumors. It has unique properties that allow it to target tumors more precisely, reducing damage to surrounding healthy tissue. This can improve the quality of life for patients during and after treatment. PBRT has shown benefits in treating certain types of tumors, such as those in the brain, and is considered an important new technology in cancer treatment. ^{2 4 8 9 10}

How is Proton Beam Radiotherapy different from other treatments for brain tumors?

Proton Beam Radiotherapy (PBRT) is unique because it uses protons to precisely target tumors, minimizing damage to surrounding healthy tissue. This precision is due to a physical property called the Bragg Peak, which allows the radiation to deposit most of its energy directly at the tumor site, potentially improving outcomes and reducing side effects compared to traditional radiation therapies. ^{2 4 8 9 10}

Research Team

Andrei Holodny, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

References

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

Comparing Intelligence Quotient Change After Treatment With Proton Versus Photon Radiation Therapy for Pediatric Brain Tumors. [2022]

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

Proton beam radiation therapy for head and neck malignancies. [2021]

3. England 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. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

An evidence based review of proton beam therapy: the report of ASTRO's emerging technology committee. [2018]

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

Proton beam therapy in pediatric oncology. [2022]

6. United States 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. [2022]

7. United States 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. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Patterns of Proton Beam Therapy Use in Clinical Practice between 2007 and 2019 in Korea. [2022]

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

Proton minibeam radiation therapy for treating metastases: A treatment plan study. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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