Digital health intervention for comorbid insomnia and neurocognitive impairment in adult survivors of childhood cancer: Results from a randomized clinical trial.

10003 Background: Survivors of childhood cancer are at risk of developing both insomnia and cognitive impairment, which may persist decades following treatment. Cognitive behavioral therapy for insomnia (CBT-I) is the gold-standard treatment for insomnia, yet the impact of improved sleep on comorbid cognitive dysfunction has not been evaluated in survivors. Methods: Survivors enrolled in the Childhood Cancer Survivor Study (CCSS; median age 44 [range 23-66] years; 73% female; 37% leukemia, 23% lymphoma, 18% sarcoma, 14% Wilms, 8% neuroblastoma) with comorbid insomnia and neurocognitive impairment were randomized 1:1 to 9-week digital CBT-I vs. online sleep education (SE). Insomnia severity index (ISI), neurocognitive problems (CCSS-Neurocognitive Questionnaire [NCQ]), emotional health (Patient Health Questionnaire/Generalized Anxiety Disorder), and quality of life (PROMIS) were measured at baseline and 9-week and 6-month follow-ups. Intent-to-treat models estimated treatment effects for ISI (mean difference [MD] between CBT-I and SE of change from baseline to follow-ups) adjusted for age, sex, and cranial radiation. Cohen’s d estimated effect size. Additional models estimated treatment effects on secondary outcomes and mediation by improved ISI. Results: 439 of 541 randomized survivors completed baseline assessments and started the intervention (82% CBT-I; 81% SE); 353 of those completed 9-week (76% CBT-I; 85% SE) and 305 completed 6-month (61% CBT-I; 78% SE) post-intervention assessments. Survivors randomized to CBT-I reported improved ISI scores at 9 weeks (MD=-2.4[95%CI -3.4, -1.4]; Cohen’s d =0.50) and 6 months post-intervention (MD=- 3.5[-4.6, -2.4]; d =0.72) vs. SE (both p’s<0.001). Survivors randomized to CBT-I reported greater improvement in memory (9wks: MD=-0.3SD [-0.5, -0.1], p=0.003; 6mos: MD=-0.5SD [-0.7, -0.3], p<0.001) and task efficiency (9wks: MD=-0.3SD [-0.5, -0.1], p=0.003; 6mos: MD=-0.5SD [-0.7, -0.3], p<0.001) vs. SE. Effects of CBT-I on cognitive function were mediated by improved ISI scores (42-65% mediated, all p’s <0.001). Insomnia responders (those who reported a change in ISI from >8 [mild to severe insomnia] to <8 [no insomnia]) also reported improved quality of life (9wks: mental beta=1.7[95%CI 0.4, 3.0], physical=2.1 [1.0, 3.1]; 6mos: mental=3.5 [2.0, 5.0], physical=3.3 [2.1, 4.5]), and emotional health (9wks: anxiety beta=-1.3 [-2.1,-0.5], depression=-1.8[-2.6, -1.0]; 6mos: anxiety=-1.8 [-2.7, -0.8], depression=-2.4 [-3.4, -1.4]). Conclusions: Use of a fully automated digital health treatment of insomnia confers immediate and long-term benefits to comorbid cognitive impairment and quality of life in survivors of childhood cancer. Given its efficacy and availability, digital CBT-I should be considered for the behavioral treatment of insomnia and comorbid symptoms in survivors. Clinical trial information: NCT04317742 .