Cognitive Changes of IDH-mutant and IDH-wildtype Glioma Patients After Chemoradiotherapy With Radiation Dose to the Resting State Networks

A Longitudinal Study to Correlate Cognitive Changes of IDH-mutant and IDH-wildtype Glioma Patients After Chemoradiotherapy With Radiation Dose to the Resting State Networks

Neurocognitive decline after radiation therapy is one of the most concerning complication for brain tumor patients and neuro-oncologists. There are increasing technological advances in evaluating the brain's neural connections responsible for the neurocognitive processes. For example, resting-state functional MRI (RS-fMRI) is an advanced imaging method that can identify the spatiotemporal distribution of the intrinsic functional networks within the brain (also referred to as resting state networks (RSNs) without requiring specific tasks by the imaged participants. Although there is evidence that shows that avoidance of specific neural networks during radiation therapy planning can lead to improved preservation of neurocognitive function afterward, it is important to first identify the most vulnerable and clinically relevant RSNs that correspond to cognitive decline. In this study, the investigators will prospectively perform RS-fMRI and neurocognitive evaluation using the NIH Toolbox Cognitive Battery (NIHTB-CB) on patients with gliomas before and after radiation therapy to generate preliminary data on what RSNs are most vulnerable to radiation injury leading to cognitive decline. A benign brain tumor cohort will also be followed to serve as control. The investigators will also evaluate the feasibility of incorporating RS-fMRI with radiation planning software for treatment optimization.

Inclusion Criteria:

• Cohort A: histological diagnosis of IDH-mutant astrocytoma or oligodendroglioma, WHO grade II-IV. IDH-mutation may be either by immunohistochemistry (IHC) or next-generation sequencing (NGS) as per routine clinical care.
• Cohort B: histological diagnosis of IDH-wildtype astrocytoma, WHO grade II-IV. IDH-wildtype status or absence of IDH-mutation may be either by IHC or NGS as per routine clinical care. The IDH-wildtype patients should have >80% probability to be alive in 6 months, and the online nomogram calculator below may be used to estimate the 6-month probability: http://cancer4.case.edu/rCalculator/rCalculator.html (Gittleman et al., 2016). The ideal patients are favorable IDH-wildtype astrocytoma patients who are expected to have prolonged survival, such as age ≤ 40 or grade 2-3 tumors.
• Cohort C: any non-infiltrative benign brain tumor histology, including but not limited to meningioma, pituitary tumor, schwannoma, craniopharngioma, hemangioblastoma, hemangiopericytoma, pineal tumor, pilocytic astrocytoma, and ganglioglioma.
• At least 18 years of age.
• Karnofsky performance status (KPS) of at least 70%
• Eligible for and planning to receive standard fractionated RT, which can be either photon-based or proton beam therapy.
• May be part of other clinical trials and can receive chemotherapy or experimental agents concurrently with or after RT as long as the other clinical trial does not exclude participation in this non-therapeutic study.
• Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).

Exclusion Criteria:

• Prior cranial RT or RT to the head and neck where potential field overlap may exist
• Gliomatosis, leptomeningeal, or metastatic involvement.
• Medical contraindication to MRI (e.g., unsafe foreign metallic implants, incompatible pacemaker, inability to lie still for long periods, severe to end-stage kidney disease or on hemodialysis).
• Require anesthesia to undergo MRI (e.g. severe claustrophobia), which would interfere with RS-fMRI acquisition and processing.
• Pregnant or breastfeeding.
• Non-English speaking, as the cognitive assessments will only be available in English.