Proton Therapy for Brain Tumor
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: St. Jude Children's Research Hospital
Must not be taking: Chemotherapy, BRAF-inhibitors, MEK-inhibitors
Disqualifiers: Prior CNS radiation, Metastatic disease, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
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 constraints
Exploratory 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.
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.
12345What 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.
14678Is hippocampal-avoidance proton therapy a promising treatment for brain tumors?
Yes, hippocampal-avoidance proton therapy is promising because it can protect important brain areas like the hippocampus, which helps with memory and learning, while still treating brain tumors effectively. This approach aims to reduce the risk of cognitive decline after treatment.
145910Eligibility 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
I am between 6 and 21 years old.
My tumor is in the central part of my brain or near it.
I have been diagnosed with a specific type of low-grade brain tumor.
+11 more
Exclusion Criteria
I have never had radiation therapy to my brain.
My cancer has not spread to other parts of my body.
My cancer is located in my spine or near the base of my skull.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
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.
6 weeks
Weekly visits for MRI scans
Follow-up
Participants are monitored for neurocognitive outcomes and disease progression with brain MRI, continuing up to 5 years post therapy.
5 years
Regular visits for neurocognitive assessments and MRI scans
Participant Groups
The study tests whether proton therapy that avoids the hippocampi can help treat brain tumors without harming memory. It aims to see if this approach is feasible by meeting specific radiation dose constraints on the hippocampi while estimating survival rates and changes in verbal recall over time.
1Treatment groups
Experimental Treatment
Group I: Hippocampal-avoidance proton therapyExperimental Treatment1 Intervention
Hippocampal-avoidance proton therapy
Hippocampal-avoidance proton therapy is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Hippocampal-avoidance proton therapy for:
- Low-grade gliomas (LGGs)
- Suprasellar or midline LGGs
🇪🇺 Approved in European Union as Hippocampal-sparing proton therapy for:
- Low-grade gliomas (LGGs)
- Primary brain tumors
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
St. Jude Children's Research HospitalMemphis, TN
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Who Is Running the Clinical Trial?
St. Jude Children's Research HospitalLead Sponsor
References
Volumetric modulated arc therapy for hippocampal-sparing radiotherapy in transformed low-grade glioma: A treatment planning case report. [2022]Timing of radiotherapy for low-grade gliomas is still controversial due to concerns of possible adverse late effects. Prevention of possible late cognitive sequelae by hippocampal avoidance has shown promise in phase II trials. A patient with progressive low-grade glioma with gradual dedifferentiation into anaplastic astrocytoma is presented along with description of radiotherapy planning process attempting to spare the hippocampus. To our knowledge, this is the first described case using volumetric modulated arc technique to spare hippocampus during transformed low-grade glioma radiotherapy. Using modern intensity-modulated radiotherapy systems it is possible to selectively spare hippocampus together with other standard organs at risk. For selected patients, an attempt to spare hippocampus can be considered as long as other dose characteristics are not significantly compromised compared to standard treatment plan created without any effort to avoid hippocampus.
Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial. [2021]Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function.
Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. [2023]Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases (BM). This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.
In silico trial of simulation-free hippocampal-avoidance whole brain adaptive radiotherapy. [2023]Label="Background and Purpose" NlmCategory="UNASSIGNED">Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) can be a time-consuming process compared to conventional whole brain techniques, thus potentially limiting widespread utilization. Therefore, we evaluated the in silico clinical feasibility, via dose-volume metrics and timing, by leveraging a computed tomography (CT)-based commercial adaptive radiotherapy (ART) platform and workflow in order to create and deliver patient-specific, simulation-free HA-WBRT.
SU-E-T-568: Hippocampus and Neural Stemcell Sparing Using Proton Therapy in Whole Brain Irradiation. [2019]To investigate feasibility of using proton therapy (PT) in neural stemcell sparing and to compare its dosimetric advantage to IMRT. To investigate the robustness of the proton plan in hippocampus sparing by introducing translation and rotation errors in treatment plan.
Leukoencephalopathy after prophylactic whole-brain irradiation with or without hippocampal sparing: a longitudinal magnetic resonance imaging analysis. [2020]Neurocognitive changes are well described after prophylactic or therapeutic whole-brain radiotherapy (WBRT) and have been reported as early as 3 months after radiotherapy (RT). Therefore, WBRT with protection of the hippocampal region (hippocampal avoidance, HA) has been proposed to preserve neurocognition. Our aim was to compare the risk of leukoencephalopathy after prophylactic cranial irradiation (PCI) with or without HA.
Dosimetric evaluation of intensity-modulated radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for hippocampal-avoidance whole brain radiotherapy. [2022]Whole brain radiotherapy (WBRT) is a vital tool in radiation oncology and beyond, but it can result in adverse health effects such as neurocognitive decline. Hippocampal Avoidance WBRT (HA-WBRT) is a strategy that aims to mitigate the neuro-cognitive side effects of whole brain radiotherapy treatment by sparing the hippocampi while delivering the prescribed dose to the rest of the brain. Several competing modalities capable of delivering HA-WBRT, include: Philips Pinnacle step-and-shoot intensity modulated radiotherapy (IMRT), Varian RapidArc volumetric modulated arc therapy (RapidArc), and helical TomoTherapy (TomoTherapy).
Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy. [2022]The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques.
Hippocampal sparing radiation therapy for brain metastases: treatment techniques and clinical implementation. [2023]High doses of radiation to the hippocampus have been correlated with increased cognitive decline following radiation therapy for brain metastases. To mitigate these effects, a variety of hippocampal sparing techniques have been implemented for both whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS). The goal of this review article is to provide a practical resource for the clinical implementation of hippocampal-sparing radiation therapy, starting with a brief background on the function and delineation of the hippocampal structure, as well as radiation effects on the hippocampus and the most widely recommended dose constraints. Considerations for treatment simulation are discussed, including options for cranial immobilization and optional head tilt. Hippocampal sparing has been demonstrated for WBRT using helical TomoTherapy, static intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) with a variety of patient setup positions, beam arrangements, and planning parameters. Tomotherapy has been shown to achieve slightly greater hippocampal sparing in some studies, while VMAT enables the most efficient treatment delivery. Hippocampal sparing has also been evaluated in a wide range of studies for both GammaKnife and linear accelerator (LINAC)-based SRS, with the proximity of metastases to the hippocampus being the most significant predictor of hippocampal dose. The methods and resulting hippocampal doses from these studies on both WBRT and SRS are discussed, as well as the role of automation in hippocampal sparing radiation therapy.
Hippocampal-sparing whole-brain radiotherapy: a "how-to" technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. [2022]Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases.