Proton Radiation for Brain Tumors

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Antiretrovirals

Disqualifiers: Prior cranial radiation, Chemotherapy, Pregnancy, Brain metastases, Neurocognitive disorders, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores proton radiation therapy for brain tumors to determine if it controls tumor growth as effectively as traditional radiation, but with fewer side effects. Proton radiation precisely targets the tumor area, reducing harm to surrounding healthy tissues. This trial suits individuals diagnosed with certain brain tumors who need radiation therapy and can participate in ongoing cognitive tests. As an unphased trial, it offers a unique opportunity to contribute to pioneering research that could enhance future treatment options.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have had chemotherapy within 4 weeks before starting the study.

What prior data suggests that proton radiation is safe for treating brain tumors?

In a previous study, researchers found that proton radiation therapy posed a low risk of damaging the brainstem, a sensitive part of the brain. Very few patients experienced harm to this area. Another study showed that proton therapy is safe for treating brain and spine tumors, especially in patients without cancer in other parts of their bodies. Proton therapy also improves outcomes and reduces long-term side effects, particularly in children with cancer. Additionally, research indicates that proton therapy effectively controls tumors while reducing harmful side effects compared to traditional radiation. Overall, these studies suggest that proton radiation is well-tolerated and safe for treating brain tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Proton radiation therapy is unique because it uses protons instead of traditional X-rays to treat brain tumors. Unlike conventional radiation therapy, which can affect surrounding healthy tissue, proton therapy allows for more precise targeting of the tumor. This precision reduces damage to nearby healthy cells and potentially lessens side effects. Researchers are excited about this treatment because it could offer a safer and more effective option for patients, especially for tumors located near critical structures in the brain.

What evidence suggests that proton radiation is effective for brain tumors?

Research has shown that proton radiation, the treatment under study in this trial, effectively treats brain tumors. It targets tumors precisely, minimizing damage to surrounding healthy tissues. Consequently, patients experience fewer side effects than with traditional x-ray treatments. For instance, one study found that only 24% of patients receiving proton therapy felt fatigued, compared to 58% of those undergoing conventional x-ray therapy. Additionally, proton therapy has been linked to better control of cancer in the brain and spine and helps maintain patients' quality of life by reducing cognitive decline. ^{6 7 8 9 10}

Who Is on the Research Team?

Helen A Shih, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for people with specific brain tumors called low-grade gliomas or Grade III anaplastic glioma, which have certain genetic features. Participants must need radiation therapy, be expected to live more than 5 years, speak English, and be able to undergo MRI scans and cognitive tests.

Inclusion Criteria

I need to undergo radiation therapy.

Life expectancy greater than 5 years

Willing to participate in rigorous neurocognitive evaluations at baseline and serially following treatment

Exclusion Criteria

Baseline neurocognitive or emotional disorders

Pregnant or breastfeeding

I have been cancer-free from a different cancer for over 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Proton radiation therapy is delivered daily for approximately 6 weeks

6 weeks

6 weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years

Visits at 3, 6, 12, 24, 36, 48, 60, 72, and 84 months

What Are the Treatments Tested in This Trial?

Interventions

• Proton radiation

Trial Overview

The study is testing proton radiation therapy to see if it can control tumor growth as effectively as photon therapy while reducing side effects. Proton radiation aims to spare healthy tissue from exposure unlike conventional therapies.

How Is the Trial Designed?

Group I: Proton radiation therapy Experimental Treatment 1 Intervention

Single arm study delivering fractionated proton therapy over 6 week (54-59.4 Gy(RBE))

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a retrospective analysis of three patients who experienced treatment-related toxicities after intracranial proton therapy, it was found that the relative biological effectiveness (RBE) in the areas of toxicity was significantly higher than expected, leading to increased radiation doses and normal tissue complication probabilities (NTCP).

Multi-field optimized (MFO) treatment plans were developed that successfully reduced the dose-averaged linear energy transfer (LETd), RBE-weighted dose (DRBE), and NTCP in critical organs at risk, suggesting that these strategies could minimize toxicity without compromising the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spatial correlation of linear energy transfer and relative biological effectiveness with suspected treatment-related toxicities following proton therapy for intracranial tumors. Ödén, J., Toma-Dasu, I., Witt Nyström, P., et al.[2020]

Proton therapy (PT) is an effective radiotherapy option for treating both benign and malignant brain conditions, showing promise in reducing neurocognitive decline and the risk of second cancers.

PT has low rates of central nervous system necrosis, making it a safer alternative compared to traditional radiotherapy methods, with potential for further improvements through biological optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Radiotherapy for Skull-Base Malignancies: Imaging Considerations of Radiotherapy and Complications. Holtzman, AL., Dagan, R., Mendenhall, WM.[2023]

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 is recognized for its superior dose-distribution capabilities, particularly beneficial for treating deep-seated tumors near critical structures, making it the 'gold standard' for specific adult cancers like ocular melanoma and chordoma.

With over 60,000 patients treated globally, proton beam therapy is also being explored for pediatric cancers and other malignancies, showing promise in reducing side effects compared to conventional radiation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is proton beam therapy the future of radiotherapy? Part I: clinical aspects]. Bouyon-Monteau, A., Habrand, JL., Datchary, J., et al.[2018]

The study successfully established a method for image-guided proton irradiation in mouse brains, allowing for precise targeting and assessment of radiation effects, which is crucial for understanding potential adverse effects in normal tissues.

Using advanced imaging and Monte Carlo simulations, the research demonstrated a clear correlation between the proton dose distribution and DNA damage in the brain, highlighting the method's potential for translational studies in proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-precision image-guided proton irradiation of mouse brain sub-volumes. Suckert, T., Müller, J., Beyreuther, E., et al.[2021]

Proton therapy may offer significant advantages over traditional photon therapy for certain head and neck cancer patients, as it delivers similar doses to tumors while reducing exposure to surrounding healthy tissues.

A simulation model developed from data of 1013 patients can help identify which individuals are likely to benefit most from proton therapy, particularly those with a good prognosis and high risk of damage to adjacent organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual patient information to select patients for different radiation techniques. Quik, EH., Feenstra, TL., Postmus, D., et al.[2017]

Proton minibeam radiation therapy (pMBRT) demonstrated significant tumor control and eradication in 22% of glioma-bearing rats, indicating its potential effectiveness against high-grade gliomas.

pMBRT showed a remarkable reduction in neurotoxicity compared to standard proton therapy, allowing for the irradiation of large brain areas without substantial damage, thus widening the therapeutic window for treating infiltrative gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas. Prezado, Y., Jouvion, G., Patriarca, A., et al.[2023]

Proton radiation therapy provides similar tumor control as traditional photon radiation therapy for pediatric brain tumors, but with potentially fewer long-term side effects.

The superior physical properties of proton beams make them less likely to cause late effects, offering a safer treatment option for children undergoing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New technologies in radiation therapy for pediatric brain tumors: the rationale for proton radiation therapy. Kirsch, DG., Tarbell, NJ.[2009]

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Proton radiation allows experts to treat tumors in the brain and the spine more safely in a select group of patients who do not have cancer in other areas of ...

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