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

63 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Proton radiation for brain tumors?

Proton radiation is effective for brain tumors because it targets tumors more precisely than traditional X-ray radiation, reducing damage to surrounding healthy tissue. This precision helps minimize side effects like neurocognitive decline and the risk of developing new cancers, making it a promising option for treating brain tumors, especially in children. ^{1 2 3 4 5}

Is proton radiation generally safe for treating brain tumors?

Proton radiation for brain tumors is generally considered safe, with studies showing limited severe side effects. Some patients may experience temporary symptoms, but these often improve over time. Safety data from various studies suggest that while there are risks, they are manageable and often related to preexisting conditions rather than the treatment itself. ^{6 7 8 9 10}

How is proton radiation treatment different from other treatments for brain tumors?

Proton radiation treatment is unique because it precisely targets brain tumors, reducing damage to surrounding healthy tissue and minimizing side effects like neurocognitive decline. This makes it especially beneficial for treating brain tumors in sensitive areas, such as in children, where traditional radiation might cause more harm. ^{1 2 4 11 12}

What is the purpose of this trial?

In this research study the investigators are looking at a type of radiation called proton radiation. Proton radiation has been shown to deliver virtually no radiation beyond the area of the tumor, sparing surrounding normal tissue from exposure. This may reduce side effects that patients would normally experience with conventional radiation therapy. In this research study the investigators are looking to determine if proton radiation with a reduced field size will be as effective in controlling tumor growth as photon therapy, while reducing the treatment-related side effects observed in patients with brain tumors.

Research Team

Helen A Shih, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

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

Proton Radiotherapy for Skull-Base Malignancies: Imaging Considerations of Radiotherapy and Complications. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Proton therapy for brain tumours in the area of evidence-based medicine. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Is proton beam therapy the future of radiotherapy? Part I: clinical aspects]. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Incidence and dosimetric parameters of pediatric brainstem toxicity following proton therapy. [2022]

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

Individual patient information to select patients for different radiation techniques. [2017]

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

Acute toxicity profile of patients with low-grade gliomas and meningiomas receiving proton therapy. [2014]

7. United States 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. [2020]

8. Ireland pubmed.ncbi.nlm.nih.gov

High-precision image-guided proton irradiation of mouse brain sub-volumes. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

A Prospective Study on Health-Related Quality of Life and Patient-Reported Outcomes in Adult Brain Tumor Patients Treated with Pencil Beam Scanning Proton Therapy. [2021]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas. [2023]

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

New technologies in radiation therapy for pediatric brain tumors: the rationale for proton radiation therapy. [2009]