Evaluating Biomarkers of Cognitive Dysfunction in Patients With Cancer

PRIMARY OBJECTIVES:

1. Assess plasma biomarkers for Aβ, GFAP, phospho Tau, and NfL pre- and post-radiotherapy.
2. Determine APOE genotype.
3. Evaluate neuropsychiatric testing aligned with standard of care brain MRIs and serum markers.
4. Measure brain morphometrics pre- and post-radiotherapy with standard of care brain MRIs.

SECONDARY OBJECTIVES:

1\. Measure patient-reported quality of life changes pre- and post-radiotherapy using a standard University of California, San Francisco (UCSF) -approved questionnaire.

OUTLINE:

This is a single-arm, non-randomized, open-label pilot study. Participants will be study duration spans 12 months post-brain radiotherapy.

• Blood sample (Procedure): Blood sample will be collected
• Brain magnetic resonance imaging (MRI) (Procedure): Brain MRI will be performed during the course of data collection
• Brain Health Assessment (Procedure): Brain Health Assessment will be performed during the course of data collection
• Quality of Life (QoL) Questionnaire (Radiation): QoL questionnaire will be given to participants during the course of data collection

Primary outcomes

• Mean change in serum Amyloid-beta peptide (Aβ) [Up to 12 months]: Mean change in biomarker for Aβ over time will be reported
• Mean change in serum Amyloid-beta peptide (Aβ) by APOE genotype [Up to 12 months]: Mean change in biomarker for Aβ by APOE genotype over time will be reported
• Mean change of score on the European Organization for Research and Treatment of Cancer quality of life questionnaire - Brain Module (EORTC-QLQ-BN20) [Up to 18 months from date of first radiation dose]: The EORTC QLQ-BN20 consists of 20 questions; seven single item symptom scales (headaches, seizures, drowsiness, hair loss, itchy skin, leg weakness and bladder control), along with four multi-item scales (future uncertainty, visual disorder, motor dysfunction and communication deficit). Raw scores for the QLQ-BN20 items are computed by calculating the mean of the items in each subscale, or the item for each individual and linearly transform the scores to a 0-100 scale. A higher score represents worse QOL for all QLQ-BN20 scales and single items.
• Mean change in serum Glial Fibrillary Acidic Protein (GFAP) [Up to 12 months]: Mean change in biomarker for GFAP over time will be reported
• Mean change in serum Glial Fibrillary Acidic Protein (GFAP) by APOE genotype [Up to 12 months]: Mean change in biomarker for GFAP by APOE genotype over time will be reported
• Mean change in serum Phosphorylated TAU (p-TAU) [Up to 12 months]: Mean change in biomarker for p-TAU over time will be reported
• Mean change in serum Phosphorylated TAU (p-TAU) by APOE genotype [Up to 12 months]: Mean change in biomarker for p-TAU by APOE genotype over time will be reported
• Mean change in serum Neurofilament Light Chain (NfL) [Up to 12 months]: Mean change in biomarker for NfL over time will be reported
• Mean change in serum Neurofilament Light Chain (NfL) by APOE genotype [Up to 12 months]: Mean change in biomarker for NfL by APOE genotype over time will be reported
• Mean change in Brain Health Assessment by APOE genotype [Up to 12 months]: Mean change in of Brain Health Assessment by APOE genotype over time will be reported
• Mean change in Hippocampal Volume [Up to 12 months]: Mean change in Hippocampal Volume as measured by MRI over time will be reported
• Mean change in Hippocampal Volume by APOE genotype [Up to 12 months]: Mean change in Hippocampal Volume as measured by MRI by APOE genotype over time will be reported

Secondary outcomes

• Change in scores on the European Organization for Research and Treatment of Cancer quality of life questionnaire 30 (EORTC-QLQ-C30) over time [Up to 18 months from date of first radiation dose]: The functional domains measure the quality of life in Physical functioning, Role functioning, Emotional functioning, Cognitive functioning, Social functioning. Scores consists of responses to items with responses ranging from 1="Not at all" to 4="Very Much". The raw score is calculated by estimating the mean of the items that make up each domains with a resulting total range of 1 - 4. These scores are then transformed to standardized scale score, so that scores range from 0 to 100. A high score for the functional domains represents a high level of functioning.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. >= 18 years old
2. Diagnosis of a primary brain tumor OR #3. Not both #2 and #3.
3. Diagnosis of primary solid tumor and secondary involvement of the brain
4. If the patient has brain metastases: fewer than 5 brain metastases (post-operative and definitive allowed), none > 1 cm in max diameter.
5. Candidate for standard of care / usual care (SOC) focused brain radiotherapy.
6. No prior brain radiotherapy, including whole brain radiotherapy.
7. Eastern Cooperative Oncology Group (ECOG) functional score 0 or 1.
8. Estimated life expectancy post-treatment of > 2 years.

Exclusion Criteria:

1. Diagnosis of neurodegenerative disease (Alzheimer's disease, Parkinson's disease).
2. Diagnosis of memory disorder pre-treatment.
3. Leptomeningeal disease or disease involving either hippocampus.

• Jean Nakamura, MD, Principal investigator, University of California, San Francisco