Skull Base and Low Grade Glioma Neurocognitive Magnetic Resonance Imaging (MRI) Study

NCT ID: NCT01212731

Last Updated: 2020-04-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2017-10-17

Brief Summary

The purpose of this study is to:

• estimate the degree of memory loss, if any following radiotherapy to the base of skull or brain as measured by standard neurocognitive battery testing.
• describe radiotherapy dose-related changes in vascular perfusion, in spectroscopic parameters of neuronal injury and changes in the degree and directionality of tissue water diffusivity (diffusion tensor imaging) as a measure of white axonal injury.
• to relate these imaging characteristics to the degree of memory loss.

Detailed Description

Data suggests that regions of the normal brain exposed to radiation doses that has otherwise been regarded as safe and not limited by current radiation treatment planning may contribute to the risk of late neurocognitive injury. Radiation dose-dependent subclinical vascular effects have been reported in irradiated normal brain tissue and have been hypothesized to be a potential mechanism of action. Direct neuronal injury is another potential mechanism of injury. 1)Estimate the degree of cognitive loss following RT. 2) Demonstrate evidence of radiation induced subclinical vascular and neuronal injury in adjacent brain regions receiving exit doses of radiation. Subjects will include patients with malignancies of the skull of the skull base or patients with low grade glioma who require radiotherapy. Baseline MRI imaging of the brain utilizing established techniques will be used to identify and characterize the regions of interest anatomically adjacent to the regions of intended high dose irradiation. The MRI data for the ROIs will be registered with the radiotherapy treatment planning CT in order to create a single volume of data where each voxel corresponds to a vector containing the multi-parametric information. Subsequent repeat MRI imaging will be at 1.5, 4.5, 12 and 24 months following completion of the radiotherapy for patients with low grade glioma and 1.5 and 12 months post radiotherapy for patients with malignancies involving the skull base. Both cohorts will repeat standard neurocognitive evaluation at 1.5, 4.5,12 and 24 months following completion of radiotherapy. Analysis: Neurocognitive domains will be evaluated at the designated time points.

Conditions

Malignancy; Glioma; Radiotherapy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cohort 1

Subjects with a histological diagnosis of malignancy of the base of skull necessitating irradiation to a minimum of 60 Gy, ECOG PS 0-1 with no evidence of metastatic disease and an estimate life expectancy of at least 1 year and who is able to provide informed consent. Subjects will undergo standard CT simulation and radiotherapy treatment planning.

Photon treatment plans

Intervention Type: RADIATION

10 of the 30 subjects on Cohort 1 will receive photon treatment plans.

Proton Treatment Plans

Intervention Type: RADIATION

20 subjects from Cohort 1 will receive proton treatment plans with malignancies involving the base of skull.

Neurocognitive evaluation

Intervention Type: BEHAVIORAL

Verbal and Visual memory; immediate attention, working memory, and processing speed; executive functions and affect and depression.

Advanced MRI imaging

Intervention Type: DEVICE

Anatomic Imaging, Blood volume measurements, Diffusion Tensor Imaging, DTI Image Processing

Cohort 2

Subjects with a histological diagnosis of low grade glioma requiring radiotherapy. ECOG PS 0-1 with no evidence of metastatic disease and an estimated life expectancy of at least 1 year and who is able to provide informed consent. Subjects will undergo standard CT simulation and radiotherapy treatment planning.

Neurocognitive evaluation

Intervention Type: BEHAVIORAL

Verbal and Visual memory; immediate attention, working memory, and processing speed; executive functions and affect and depression.

Advanced MRI imaging

Intervention Type: DEVICE

Anatomic Imaging, Blood volume measurements, Diffusion Tensor Imaging, DTI Image Processing

Interventions

Photon treatment plans

10 of the 30 subjects on Cohort 1 will receive photon treatment plans.

Intervention Type: RADIATION

Proton Treatment Plans

20 subjects from Cohort 1 will receive proton treatment plans with malignancies involving the base of skull.

Intervention Type: RADIATION

Neurocognitive evaluation

Verbal and Visual memory; immediate attention, working memory, and processing speed; executive functions and affect and depression.

Intervention Type: BEHAVIORAL

Advanced MRI imaging

Anatomic Imaging, Blood volume measurements, Diffusion Tensor Imaging, DTI Image Processing

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Study subjects capable of providing informed consent.
• Study subjects with an ECOG performance status of 0-1.
• Study subjects aged 18 or greater.
• Study subjects with a histological diagnosis of a malignancy of the paranasal sinuses or the nasopharynx requiring either definitive or post-operative radiation to a minimum prescribed dose of 60 Gy.
• Study subjects deemed capable of undergoing standard CT simulation and radiotherapy treatment planning and delivery including the capacity to comply with standard immobilization devices to the head and nexk for daily irradiation.
• Study subjects without any evidence of distant metastasis.
• Study subjects with an estimated life expectancy of at least 1 year.
• Study subjects who are able to receive a standard MRI study and deemed capable of complying with the immobilization needs.
• Female study subjects of reproductive potential with a negative pregnancy test prior to each scheduled MRI study.

• Histological confirmed diagnosis of low grade glioma of the CNS
• WHO grade II
• Patients must have a Karnofsky Performance Status of greater than or equal to 60.
• Age greater than or equal to 18.
• Patients must be able to provide informed consent.
• Adequate bone marrow function:WBC greater than or equal to 4000/mm3, platelets greater than or equal to 100,000 mm3.
• Women of child-bearing potential as long as she agrees to use a recognized method of birth control (e.g. oral contraceptive, IUD, condoms, or other barrier methods, etc.). Hysterectomy or meopause must be clinically documented.
• Study subjects deemed capable of undergoing standard CT simulation and radiotherapy treatment planning and delivery including the capacity to comply with standard immobilization devices to the brain for daily irradiation.

Exclusion Criteria

• Study subjects with questionable performance status and in whom the treating physician is suspicious that a life expectancy of at least 1 year is possible.
• Study subjects with anxiety that precludes the safe administration of a MRI for the imaging time required.
• Study subjects with major psychiatric diagnosis prior to neuro-oncologic diagnosis.
• For neuropsychological studies, study subjects with neurological or behavioral issues that would preclude compliance with study procedures. (Karnofsky Performance Scale score of less than 60, indicating that the patients needs considerable assistance for self care and frequent medical care).
• Study subjects with an inability to undergo MR Imaging for any reason.
• Study subjects with a history of renal transplant or known renal disorder with a calculated GFR > 45mL/1min [gadolinium restriction]
• For neuropsychological studies, study subjects with mixed language background with only one year of educationin an English-speaking school.
• Pregnant women, women planning to become pregnant and women who are nursing.

• Prior or simultaneous malignancies within the past two years (other than cutaneous squamos or basal cell carcinoma, melanoma in situ or well differentiated thyroid carcinoma).
• Patients with the following histologies are excluded: Gliomatosis cerebri, WHO III or IV gliomas.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michelle Alonso Basanta, MD

Role: PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at Penn Medicine

Locations

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

UPCC 08310

Identifier Type: -

Identifier Source: org_study_id