A mediation analysis of neurocognitive deficits and patient-reported mood among patients with lung cancer with brain metastases.

12044 Background: Advances in lung cancer therapeutics have led to a growing population of patients with lung cancer who are facing the challenges of living with the sequela of brain metastases and the therapies used to treat them. Patients experience neurocognitive deficits, difficulties with functioning, and mood symptoms. However, the mechanisms by which neurocognitive deficits contribute to mood symptoms in this patient population remain to be fully elucidated. In this study, we aimed to evaluate patient-reported functioning as a mediator between neurocognitive deficits and mood symptoms. Methods: Using a prospectively collected single-site registry, we conducted an exploratory cross-sectional study among patients with lung cancer with brain metastases at the time of evaluation for stereotactic radiosurgery. The registry included data on patient demographic and clinical characteristics, neurocognitive deficits per clinician exam (visual impairment, cranial nerve deficit, sensory deficit, motor deficit, gait impairment/incoordination, decline in ability to concentrate, decline in memory), and patient-reported functioning (self-care, usual activities, mobility) and mood symptoms (anxiety/depression) from the European Quality of Life 5-Dimensions 3-Level Version. First, we selected functional domains significantly associated with mood symptoms in a logistic regression analysis to test as potential mediators. Then, we used a regression-based path analysis to test the selected functional domain as a mediator between neurocognitive deficits and mood symptoms. The mediation model adjusted for age, performance status, tobacco use, extracranial disease status, prior brain surgery, and prior brain radiation. Results: Of 463 patients, 33.9% demonstrated any neurocognitive deficit, 38.7% self-reported any functional difficulty (self-care, usual activities, or mobility), and 15.3% reported mood symptoms. Difficulty with usual activities was associated with increased mood symptoms (OR=1.65, 95% CI=1.36, 1.97), which we then tested as a mediator. Motor deficits (OR=1.66, 95% CI=1.30, 2.38) and gait impairment/incoordination (OR=1.50, 95% CI=1.19, 2.09) had positive indirect effects on mood symptoms (i.e. increased mood symptoms) through difficulties with usual activities. No other neurocognitive deficits showed significant effects on mood symptoms. Conclusions: Among patients with lung cancer with brain metastases, the associations of motor deficits and gait impairment/incoordination with worsened mood are mediated by difficulties with engaging in usual activities. These findings underscore the potential for tailored supportive care, utilizing strategies from cognitive rehabilitation, palliative care and psychology, to improve patients’ mood by helping them adapt to and cope with difficulties in engaging in their usual activities.