Neoplasms

All Conditions

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Glioma

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Nerve Sheath Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

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Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Neurofibromatosis

Neurofibromatosis Type 1

Optic Pathway Glioma

Neuroepithelioma

Catherine Cassiman, MD

The goal of this project is to get more insight into the (neuro)ophthalmological characteristics of children with neurofibromatosis type 1. This way investigators would like to update the current guidelines for follow up and treatment of optic pathway gliomas. Clinical findings will be compared with the results of Optical coherence tomography (OCT) and MRI (magnetic resonance imaging).

Ophthalmological Screening and Follow-up of Optic Pathway Gliomas in Children With Neurofibromatosis Type 1.

Universitaire Ziekenhuizen KU Leuven

Astrocytoma

Ganglioglioma

Diffuse Astrocytoma

Pilocytic Astrocytoma

Pleomorphic Xanthoastrocytoma

Hippocampal-avoidance proton therapy

Thomas Merchant, MD

Thomas Merchant

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.

All patients will receive HA proton therapy to 52.2 CGE or 54 CGE in 29 or 30 fractions, depending on tumor location. Patients will receive weekly magnetic resonance imaging (MRI) scans during the course of proton therapy to monitor changes in solid tumor or cystic volume. Such changes may prompt adaptive therapy to improve coverage or minimize the RT dose to healthy structures. Neurocognitive outcomes, sensitive to measures of memory and learning, will be collected at baseline and continue to 5 years post therapy. Disease evaluation will be monitored with brain MRI.

Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma

A Phase II Study of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma

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. First RT dose constraints for bilateral hippocampi: volume receiving 40 CGE (V40CGE) ≤ 25%, dose to 100% of hippocampus (D100%) ≤ 5CGE. Second RT dose constraints for bilateral hippocampi: V40CGE ≤ 35%, D100% ≤ 10 CGE.

EFS will be calculated from the date of RT starts until disease progression, second malignancy, death of any cause or last follow up date.

CVLT-SD scores change of patients with HA feasible from baseline evaluation date to 3 years after treatment

CVLT-SD scores change from baseline evaluation date to 5 years after treatment

Cogstate neurocognitive scores in patients with proton therapy plans

CVLT-SD neurocognitive scores in patients with proton therapy plans

St. Jude Children's Research Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ophthalmological Screening and Follow-up of Optic Pathway Gliomas in Children With Neurofibromatosis Type 1.	NCT02078401	Neurofibromatos...		- 18 Years	Universitaire Ziekenhuizen KU Leuven
Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma	NCT04065776	Glioma Pilocytic Astro... Pilomyxoid Astr... Pleomorphic Xan... Ganglioglioma Optic Pathway G... Diffuse Astrocy...	Hippocampal-avo...	6 Years - 21 Years	St. Jude Children's Research Hospital
Ophthalmological Screening and Follow-up of Optic Pathway Gliomas in Children With Neurofibromatosis Type 1.	NCT02078401	Neurofibromatos...		- 18 Years	Universitaire Ziekenhuizen KU Leuven

Spots Global Cancer Trial Database for optic pathway glioma