Proton Therapy for Brain Tumor
Trial Summary
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop all current medications. However, you cannot receive concurrent chemotherapy or targeted therapy, including BRAF-inhibitors and MEK-inhibitors. If you have seizures, you can participate if they are well controlled on anticonvulsants.
What data supports the idea that Proton Therapy for Brain Tumor is an effective treatment?
The available research shows that Proton Therapy, specifically when used to spare the hippocampus, can be effective in protecting important brain areas during treatment. One study highlights its advantage in sparing neural stem cells compared to other methods like IMRT (Intensity-Modulated Radiation Therapy). Another study suggests that avoiding the hippocampus during whole-brain radiotherapy can help preserve neurocognitive function, which is important for memory and thinking skills. This suggests that Proton Therapy might be a better option for patients who need to protect their brain function while treating tumors.12345
What safety data exists for proton therapy for brain tumors?
The safety data for proton therapy, including hippocampal-avoidance techniques, is still being evaluated. Feasibility studies show that it is technically possible to spare the hippocampus during brain irradiation, which may help preserve neurocognitive function. Phase II trials have shown promise in preventing cognitive decline by avoiding the hippocampus. However, ongoing phase II and III studies are needed to confirm these benefits. Various radiotherapy techniques, such as intensity-modulated radiotherapy and volumetric modulated arc therapy, have been used to achieve hippocampal sparing, and these methods are being compared for their effectiveness and safety.14678
Is hippocampal-avoidance proton therapy a promising treatment for brain tumors?
What is the purpose of this trial?
Low-grade gliomas (LGGs) are the most common brain tumors in children, and a subset of these tumors are treated definitively with focal radiation therapy (RT). These patients often survive for many years after receiving RT and experience late deficits in memory. Verbal recall is an important measure of memory and is associated with other important functional outcomes, such as problem-solving, independence of every-day functioning, and quality of life. Decline in memory, as measured by verbal recall, is associated with RT dose to the hippocampi. Therefore, this phase II study investigates the feasibility of reducing RT doses to the hippocampi (i.e., hippocampal avoidance \[HA\]) by using proton therapy for midline or suprasellar LGGs.Primary Objective:* To determine the feasibility of HA with proton therapy in suprasellar or midline LGGs. Feasibility will be established if 70% of plans meet the first or second dose constraints shown below. 1. First priority RT dose constraints for bilateral hippocampi: volume receiving 40 CGE (V40CGE) ≤ 25%, dose to 100% of Hippocampus (D100%) ≤ 5CGE. 2. Second priority RT dose constraints for bilateral hippocampi: V40CGE ≤ 35%, D100% ≤ 10 CGE. Secondary Objectives:* To estimate the 3-year event-free-survival (EFS) for LGGs treated with HA.* To estimate the change in California Verbal Learning Test short-term delay (CVLT-SD) from baseline to 3 years and from baseline to 5 years* To compare CVLT-SD and Cogstate neurocognitive scores in patients with proton therapy plans that: (1) meet first priority RT dose constraints, (2) meet second priority RT dose constraints but not first priority RT dose constraints, and (3) that did not meet either first or second RT priority dose constraintsExploratory Objectives:* To describe the change in overall cognitive performance from baseline to 3 years and from baseline to 5 years with an age appropriate battery, including gold standard measures shown in the published studies to be sensitive to attention, memory processing speed and executive function that will afford comparison to historical controls.* To characterize longitudinal changes in connection strength within brain networks in the first 3 years after proton therapy and to investigate associations between these changes and neurocognitive performance with focus on the hippocampi.* To correlate the distribution and change in L-methyl-11C-methionine positron emission tomography (MET-PET) uptake to tumor progression and from baseline to 3 years and to investigate whether cases of pseudoprogression exhibit a differential pattern of uptake and distribution compared to cases of true progression after controlling for histology.* To investigate the effect of BRAF alteration, tumor histology and tumor location on PFS and OS in a prospective cohort of patients treated in a homogenous manner.* To investigate whether the methylation profiles of LGGs differ by tumor location (thalamic/midbrain vs. hypothalamic/optic pathway vs. others) and histologies (pilocytic astrocytoma vs. diffuse astrocytoma vs. others), which, in conjunction with specific genetic alterations, may stratify patients into different subgroups and highlight different therapeutic targets.* To record longitudinal measures of circulating tumor DNA (ctDNA) in plasma and correlate these measures with radiographic evidence of disease progression.* To bank formalin-fixed, paraffin-embedded (FFPE)/frozen tumors and whole blood from subjects for subsequent biology studies not currently defined in this protocol.* To quantify and characterize tumor infiltrating lymphocytes (TILs) and to characterize the epigenetics of T cells and the T cell receptor repertoire within the tumor microenvironment.* To estimate the cumulative incidence of endocrine deficiencies, vision loss, hearing loss and vasculopathy after proton therapy and compare these data to those after photon therapy.
Research Team
Thomas Merchant
Principal Investigator
St. Jude Children's Research Hospital
Eligibility Criteria
This trial is for children and young adults aged 6 to less than 22 with certain low-grade brain tumors, including pilocytic astrocytoma and diffuse astrocytoma. Participants must have measurable disease, be able to undergo MRI scans, and not have had previous CNS radiation or tumor invasion into the hippocampus. They should also have adequate organ function and controlled seizures if present.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive hippocampal-avoidance proton therapy to 52.2 CGE or 54 CGE in 29 or 30 fractions, with weekly MRI scans to monitor changes in tumor volume.
Follow-up
Participants are monitored for neurocognitive outcomes and disease progression with brain MRI, continuing up to 5 years post therapy.
Treatment Details
Interventions
- Hippocampal-avoidance proton therapy
Hippocampal-avoidance proton therapy is already approved in United States, European Union for the following indications:
- Low-grade gliomas (LGGs)
- Suprasellar or midline LGGs
- Low-grade gliomas (LGGs)
- Primary brain tumors
Find a Clinic Near You
Who Is Running the Clinical Trial?
St. Jude Children's Research Hospital
Lead Sponsor