C-SMART – Cognitive Strategies, Mindfulness, and Rehabilitation Therapy: Development and Phase I Trial of a Neuropsychological Intervention in Neuro-Oncology

Background Adult patients with primary brain tumors experience significant cognitive sequelae yet remain underrepresented in behavioral intervention research. We present the development and preliminary evaluation of C-SMART (Cognitive Strategies, Mindfulness, and Rehabilitation Therapy), an integrated cognitive rehabilitation and mindfulness-based intervention designed for patients with primary brain tumor and mild cognitive decline. Stakeholder input was systematically incorporated prior to launching a single-arm pilot trial assessing feasibility and acceptability. Methods Following the NIH ORBIT Model, Phase Ia convened two advisory boards: one comprised of brain tumor patients and caregivers (n=4) and another of neuro-oncology professionals (n=5) to inform C-SMART intervention development. Next, feasibility and acceptability were investigated in a single-arm Phase Ib design (n = 18 patients; n = 14 caregivers), with an exploratory aim of assessing preliminary signal change on neurocognitive performance and patient-reported outcomes. Results Phase Ia results supported an individually tailored neuropsychological intervention integrating mindfulness training and caregiver involvement to address patient-centered goals. Phase Ib results met all primary aims of feasibility and acceptability, with rates of enrollment, retention, and satisfaction exceeding established benchmarks. Caregiver involvement was robust, with reported benefit. Qualitative data from exit interviews supported the benefits of C-SMART on self-efficacy and interpersonal functioning with recommendations to increase caregiver involvement. Exploratory outcomes demonstrated signal change, supporting progression to a Phase II trial. Conclusions C-SMART is the first consensus-supported, individualized, mindfulness-based, neuropsychological intervention in neuro-oncology. Evidence provides strong support for feasibility and acceptability of the tailored intervention with key recommendations for optimization, including increased structure for caregiver involvement and self-efficacy outcome measurement.