Cognitive Testing + Brain Imaging for Childhood Brain Cancer

Overseen By Stephanie Perkins, M.D.

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Visual impairment, Cardiac pacemaker, Programmable shunt, Dental braces, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems the focus is on cognitive testing and brain imaging, so it's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of the treatment Neurocognitive testing, rsfcMRI, Resting-State Functional Connectivity Magnetic Resonance Imaging for childhood brain cancer?

Research shows that resting-state functional MRI (rsfMRI) can provide insights into brain organization and function, which may help predict cognitive outcomes in pediatric brain tumor patients. Studies have found altered brain network organization in these patients, suggesting that rsfMRI could be a useful tool in understanding and potentially improving cognitive deficits associated with childhood brain cancer. ^{1 2 3 4 5}

Is cognitive testing and brain imaging safe for children with brain cancer?

The studies suggest that resting-state functional MRI (a type of brain imaging) is generally safe for children, as it is used during routine clinical visits without reported safety issues. However, sedation with propofol during imaging may affect brain network organization. ^{1 2 4 6 7}

How does the treatment in the trial 'Cognitive Testing + Brain Imaging for Childhood Brain Cancer' differ from other treatments for this condition?

This treatment is unique because it combines cognitive testing with brain imaging to understand the impact of brain cancer and its treatment on cognitive functions and brain network organization, which is not typically a focus of standard treatments. It aims to provide insights into cognitive outcomes and potential predictors of long-term effects, which could inform future interventions. ^{1 2 3 5 6}

What is the purpose of this trial?

The investigators will focus on three cohorts of brain tumor patients aged, 4-18 years, to answer two critical questions: 1) Can the investigators acquire high quality data relevant to cognitive function during the peri-diagnostic period and, 2) can the investigators develop predictive models for cognitive outcomes using serial examination of functional imaging and cognitive function. Any patient with a newly diagnosed brain tumor aged 4-18 will be eligible for enrollment in cohort 1. Only patients with previously diagnosed tumors of the posterior fossa will be eligible for cohort 2. For cohort 3, eligible patients will include patients with a clinical diagnosis of posterior fossa syndrome with physical impairments that prohibit completion of the NIH Toolbox Cognitive Battery. The investigators have decided to expand the eligible tumor types to better capture the most significant deficit variability that can be caused by tumors outside the posterior fossa. Thus, this focus will provide a platform to analyze the impact that different tumor types and different standard treatments have on cognitive dysfunction. The rationale for inclusion of subjects on cohort 3 is that posterior fossa syndrome is one of the most cognitively devastating diagnoses following a posterior fossa surgery. The causes of posterior fossa syndrome and unknown and there are currently no interventions to improve symptoms. RsfcMRI would offer a novel and non-invasive assessment of posterior fossa syndrome patients by assessing connectivity within and outside of the cerebellum. Expanding the tumor eligibility will allow us to further explore the effect tumor location will have on cognitive testing and rsfcMRI. Here, repeated evaluations on and off therapy will provide the necessary data points to establish trajectories of cognitive development and recovery in this population.

Research Team

Stephanie Perkins, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for children aged 4-18 with new brain tumors, focusing on those with posterior fossa tumors or related syndromes. Participants need a life expectancy of at least one year and must consent along with their guardians.

Inclusion Criteria

I am 12-30 years old, was diagnosed with a brain tumor over 3 years ago, can undergo an MRI without sedation, and expect to live at least another year.

Exclusion Criteria

Cohort 1: Presence of visual impairment to an extent that the patient is unable to complete the computer testing, contraindication to MRI scan (i.e. due to cardiac pacemaker), programmable Shunt

Cohort 2: Presence of visual impairment to an extent that the patient is unable to complete the computer testing, contraindication to MRI scan (i.e. due to cardiac pacemaker)

I cannot have an MRI due to a pacemaker, dental braces, or needing sedation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Peri-diagnostic

Participants undergo neurocognitive testing and rsfcMRI during the peri-diagnostic period

Up to 2 weeks post-diagnosis or post-op

1 visit (in-person)

Longitudinal Assessment

Participants undergo repeated neurocognitive testing and rsfcMRI imaging every 6-9 months

6-9 months intervals for up to 27 months

3 visits (in-person)

Follow-up

Participants are monitored for cognitive recovery and outcomes

4 weeks

Treatment Details

Interventions

• Neurocognitive testing
• rsfcMRI

Trial Overview The study aims to collect data on cognitive function using neurocognitive tests and resting-state functional MRI (rsfcMRI) in kids during diagnosis and treatment to predict cognitive outcomes.

Participant Groups

Group I: Cohort 4 Arm B Experimental Treatment 2 Interventions

* During standard of care MRI images, rsfcMRI imaging will be performed which will add 15 minutes of scan time. * Will complete cognitive testing using the NIH Toolbox Cognitive Battery * All patients will complete the Attention Deficit/Hyperactivity Disorder (ADHD) Rating Scale - 5 questionnaire. All patients will complete a self-reported assessment of neurological quality of life (QOL). Adult patients (age ≥ 18 years) will complete the adult version of the Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function measure. All pediatric patients will complete the pediatric version of the Neuro-QOL Cognitive Function measure. For patients \<18 years of age and for adult patients with parent present, parent/caregiver will complete the PROMIS® Parent Proxy for cognition. All adult patients will complete the Colorado Learning Difficulties Questionnaire (CLDQ). This questionnaire will be completed by parent/caregiver for patients \< 18 years of age.

Group II: Cohort 4 Arm A Experimental Treatment 2 Interventions

Undergo the following MRI images: RSFC MRI, T2/T1 MRI, and DTI. * Will complete cognitive testing using the NIH Toolbox Cognitive Battery * All patients will complete the Attention Deficit/Hyperactivity Disorder (ADHD) Rating Scale - 5 questionnaire. All patients will complete a self-reported assessment of neurological quality of life (QOL). Adult patients (age ≥ 18 years) will complete the adult version of the Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function measure. All pediatric patients will complete the pediatric version of the Neuro-QOL Cognitive Function measure. For patients \<18 years of age and for adult patients with parent present, parent/caregiver will complete the PROMIS® Parent Proxy for cognition. All adult patients will complete the Colorado Learning Difficulties Questionnaire (CLDQ). This questionnaire will be completed by parent/caregiver for patients \< 18 years of age.

Group III: Cohort 3 Experimental Treatment 1 Intervention

* During standard of care MRI images, rsfcMRI imaging will be performed which will add 15 minutes of scan time. * rsfcMRI will be obtained annually for total of 3 rsfcMRIs for each patient.

Group IV: Cohort 2 Experimental Treatment 2 Interventions

* Patients with diagnosis of a posterior tumor will undergo neurocognitive testing utilizing the NIH Toolbox. Testing will be every 6 months for children currently receiving therapy and annually for those that have completed all therapy for a total of 3 sessions. During standard of care MRI images, rsfcMRI imaging will be performed which will add 15 minutes of time. rsfcMRI will be obtained every 6 months for children currently receiving therapy and annually for those that have completed therapy for a total of 3 rsfcMRIs for each patient. * Patients in Cohort 1 will also be eligible to continue with the longitudinal assessment as just described. These participants will then undergo repeat neurocognitive testing using the NIH toolbox 6-9 months for an additional 3 testing sessions. rsfcMRI will be obtained during their follow-up imaging at 6-9 month intervals for a total of 3 additional rsfcMRIs (4 total scans).

Group V: Cohort 1 Experimental Treatment 2 Interventions

* Prior to surgery, subjects will have a complete standard of care history and physical exam by the neurosurgeon and then undergo peri-diagnostic neurocognitive testing utilizing the NIH Toolbox Cognitive Battery computer testing software for iPad (will take 45 minutes). The peri-diagnostic period will be defined as the period from first presentation to 2 weeks post-diagnosis or two weeks post-op, whichever is later. * Participants will also undergo a rsfcMRI during their standard of care MRI imaging which will add 15 minutes to their scan time

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Children's Discovery Institute

Collaborator

Trials

4

Recruited

430+

The Andrew McDonough B+ Foundation

Collaborator

Trials

3

Recruited

220+

Children's Discovery Institute

Collaborator

Trials

6

Recruited

540+

Neurosurgery Research & Education Foundation

Collaborator

Trials

1

Recruited

200+

The Andrew McDonough B+ (Be Positive) Foundation

Collaborator

Trials

1

Recruited

200+

Findings from Research

In a study of 49 pediatric brain tumor patients aged 7-18, significant alterations in functional brain network organization were observed, particularly in those who received propofol sedation, indicating that sedation may impact brain function during imaging.

Patients exhibited cognitive deficits in executive function domains over a median follow-up of 3.1 years, with a weak correlation found between decreased segregation in the default mode network and poorer vocabulary scores, suggesting potential predictors for long-term cognitive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive deficits and altered functional brain network organization in pediatric brain tumor patients. Seitzman, BA., Anandarajah, H., Dworetsky, A., et al.[2023]

Pediatric brain tumor patients treated with proton therapy showed significant cognitive deficits, particularly in attention and processing speed, with brain network organization being altered as indicated by resting-state functional MRI (rsfMRI).

Higher radiation doses to the right hippocampus were linked to worse cognitive performance in attention and inhibition, as well as decreased segregation in the dorsal attention network, highlighting the impact of radiation on brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognition and Brain System Segregation in Pediatric Brain Tumor Patients Treated with Proton Therapy. Dowling, AV., Seitzman, BA., Mitchell, TJ., et al.[2023]

A study of 16 adult survivors of childhood cerebellar tumors, averaging 14.9 years post-diagnosis, revealed significant differences in brain functional connectivity compared to matched controls, particularly in networks related to executive functions.

Survivors showed hyperconnectivity in the executive control network, default mode network, and salience network, suggesting that their brain connectivity patterns may reflect adaptations similar to those seen in other neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased frontal functional networks in adult survivors of childhood brain tumors. Chen, H., Wang, L., King, TZ., et al.[2019]

Resting state functional MRI (fMRI) can predict cognitive impairment in breast cancer patients with up to 100% accuracy at long-term follow-up, based on a study of 31 patients evaluated before treatment, after chemotherapy, and one year later.

The study found that specific brain regions, or hubs, were key indicators of cognitive outcomes, suggesting that brain injury may spread over time, highlighting the potential of fMRI in identifying patients at risk for long-term cognitive issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Long-Term Cognitive Outcome Following Breast Cancer with Pre-Treatment Resting State fMRI and Random Forest Machine Learning. Kesler, SR., Rao, A., Blayney, DW., et al.[2020]

In a study of 43 childhood cancer survivors (aged 7-16) who had completed treatment at least a year prior, it was found that while their overall cognitive performance was normal, they exhibited lower executive functions compared to healthy controls.

The study revealed significant differences in brain connectivity patterns, with survivors showing stronger connectivity in some areas and weaker in others, which correlated with poorer memory performance, indicating lasting effects of non-CNS cancer treatments on brain development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition. Spitzhüttl, JS., Kronbichler, M., Kronbichler, L., et al.[2023]

Pediatric brain tumor survivors showed poorer neurocognitive performance compared to healthy children, particularly in processing speed, divided attention, and working memory, despite similar parent ratings of day-to-day executive function.

The study found distinct patterns of brain connectivity in survivors, with lower connectivity in the salience network and higher in the default mode network, suggesting an adaptive hyperconnectivity that may relate to their cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Associations Among Functional Connectivity and Neurocognition in Survivors of Pediatric Brain Tumor and Healthy Peers. Seck, S., Kim, YJG., Cunningham, WA., et al.[2022]

A study involving 76 newly diagnosed breast cancer patients and 50 healthy controls found that baseline resting state fMRI can predict cognitive impairments, such as executive dysfunction and memory issues, after chemotherapy treatment.

Patients undergoing chemotherapy experienced a significant increase in executive dysfunction and a decrease in memory function over time, highlighting the potential for early neuroimaging assessments to identify those at risk for cognitive decline and improve patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer. Henneghan, AM., Gibbons, C., Harrison, RA., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cognitive deficits and altered functional brain network organization in pediatric brain tumor patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cognition and Brain System Segregation in Pediatric Brain Tumor Patients Treated with Proton Therapy. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Increased frontal functional networks in adult survivors of childhood brain tumors. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Predicting Long-Term Cognitive Outcome Following Breast Cancer with Pre-Treatment Resting State fMRI and Random Forest Machine Learning. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Pilot Study of Associations Among Functional Connectivity and Neurocognition in Survivors of Pediatric Brain Tumor and Healthy Peers. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer. [2021]