In this prospective single-arm observational imaging study, patients undergoing intra-cranial (non-brain parenchyma) or head and neck radiation therapy will be identified in the Department of Radiation Oncology (N=50). After patients provide written informed consent, serial multiparametric MRI, assessments of cognitive function and blood samples will be collected at baseline, during radiation treatment, and 1, 3, 6, 12, and 24 months post-treatment.
Initial Institutional Review Board (IRB) approval of the study was given on 2/14/2019 by MD Anderson. After completing addition administrative set up, including the activation meeting, the study was activated on 8/22/2019. The enrollment of patients in the trial was delayed following the study start due to several reasons including the following:
1. Contracts and acquisition of hardware for the cognitive assessments required time to complete. We have purchased hardware (i.e., a laptop and an iPad) to collect digital neurocognitive assessments from patients. We established a formal consulting agreement with Dr. Mathias Basner, an expert in NASA Cognition in astronauts and astronauts surrogate populations. The laptop was formally calibrated by Pulsar Informatics, Inc., for use with the NASA Cognition battery. We licensed Cogstate C3 and purchased equipment for this test. All digital testing platforms were installed and piloted on the devices. Dr. Wefel’s research team has been trained on all neurocognitive tests, devices, and measures used in this project, and has developed a laboratory protocol manual for the project.
2. One of the lead scientists involved moved to a different institution. This required another adjustment and re-approval of the study plan. A new collaborator, Dr. Simona Shaitelman, is conducting the biofluid collection an analysis.
3. While we were able to secure additional funding for the incorporation of novel and promising MRI technique (i.e., rs-fMRI) for the evaluation of neurocognitive deterioration as part of the imaging biomarker assessment, this required re-approval of the amended study protocol by MD Anderson.
4. Enrollment of patients in the study was halted during COVID-19 pandemic (March-July of 2020). We resumed pre-screening activities in August 2020. Of note, while the pre-screening and trial enrollment is reactivated, the COVID-19 pandemic continues to impact study accrual as many patients are still preferring to have their clinical appointments carried out remotely through virtual visits, which prohibits eligible enrollment on this trial protocol. We have spent this additional time required for the listed items above to develop a workflow and establish a multi-departmental research clinical team to run this study. This required presentations at research meetings for the CNS and Head and Neck Radiation Oncology groups, the institutional IT team, the Radiation Oncology Biomarker working group, Diagnostic Radiology and Imaging Physics research meetings, and Neuropsychology research team. Additionally, we have developed databases for this trial protocol and a centralized imaging workflow, including the necessary software pipelines for image analysis.
We also completed work around image analysis, including preclinical development work for the rs-fMRI portion of the project for which we received additional, complementary, independent funding. We established a network of connections of the brain using brain images of several patients and developed a network analysis of the connections. Radiotherapy dose maps were registered to the network and correlated with changes in the network metrics between different periods of time. This will be applied to future patient’s brain images in this project.
As of January 5th, 2021, we have pre-screened 20 patients and recruited and enrolled one patient in the study. We obtained baseline comprehensive neurocognitive testing, NASA Cognition testing, CogState C3 testing, and patient reported outcomes. We have likewise obtained all tests and PRO (patient-reported outcomes) during the on-treatment weekly visits with no deviations from the planned study calendar. We worked with Dr. Basner to review the initial NASA Cognition test results and data visualization to confirm this new technology was functioning as intended. We have reviewed, scored, and entered all data into our study specific database.
In the past two years we have established the foundation to run this unique study at MD Anderson. We are now actively screening brain, and head and neck cancer patients to be enrolled in the IRB protocol associated with this project. Despite the delays caused by COVID-19 restrictions at MD Anderson, we anticipate successful enrollment of patients in year 3 of this project and complete enrollment by Spring 2022.
Abstracts for Journals and Proceedings
Mitchell D, Liu H, Shaitelman S, Phan J, Farhat M, Johnson J, Slack Tidwell R, Wefel J, Chung C. "Quantitative imaging and biofluid biomarkers predictive of neurocognitive toxicity from brain irradiation. " 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.
Abstracts. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021