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Importance: The associations of spiritual and religious factors with patient-reported outcomes among adolescents with cancer are unknown. Objective: To model the association of spiritual and religious constructs with patient-reported outcomes of anxiety, depressive symptoms, fatigue, and pain interference. Design, Setting, and Participants: This cross-sectional study used baseline data, collected from 2016 to 2019, from an ongoing 5-year randomized clinical trial being conducted at 4 tertiary-referral pediatric medical centers in the US. A total of 366 adolescents were eligible for the clinical trial, and 126 were randomized; participants had to be aged 14 to 21 years at enrollment and be diagnosed with any form of cancer. Exclusion criteria included developmental delay, scoring greater than 26 on the Beck Depression Inventory II, non-English speaking, or unaware of cancer diagnosis. Exposures: Spiritual experiences, values, and beliefs; religious practices; and overall self-ranking of spirituality's importance. Main Outcomes and Measures: Variables were taken from the Brief Multidimensional Measurement of Religiousness/Spirituality (ie, feeling God's presence, daily prayer, religious service attendance, being very religious, and being very spiritual) and the spiritual well-being subscales of the Functional Assessment of Chronic Illness Therapy (meaning/peace and faith). Predefined outcome variables were anxiety, depressive symptoms, fatigue, and pain interference from Patient-Reported Outcomes Measurement Information System pediatric measures. Results: A total of 126 individuals participated (72 [57.1%] female participants; 100 [79.4%] white participants; mean [SD] age, 16.9 [1.9] years). Structural equation modeling showed that meaning and peace were inversely associated with anxiety (β = -7.94; 95% CI, -12.88 to -4.12), depressive symptoms (β = -10.49; 95% CI, -15.92 to -6.50), and fatigue (β = -8.90; 95% CI, -15.34 to -3.61). Feeling God's presence daily was indirectly associated with anxiety (β = -3.37; 95% CI, -6.82 to -0.95), depressive symptoms (β = -4.50; 95% CI, -8.51 to -1.40), and fatigue (β = -3.73; 95% CI, -8.03 to -0.90) through meaning and peace. Considering oneself very religious was indirectly associated with anxiety (β = -2.81; 95% CI, -6.06 to -0.45), depressive symptoms (β = -3.787; 95% CI, -7.68 to -0.61), and fatigue (β = -3.11, 95% CI, -7.31 to -0.40) through meaning and peace. Considering oneself very spiritual was indirectly associated with anxiety (β = 2.11; 95% CI, 0.05 to 4.95) and depression (β = 2.8, 95% CI, 0.07 to 6.29) through meaning and peace. No associations were found between spiritual scales and pain interference. Conclusions and Relevance: In this study, multiple facets of spirituality and religiousness were associated with anxiety, depression, and fatigue, all of which were indirectly associated with the participant's sense of meaning and peace, which is a modifiable process. Although these results do not establish a causal direction, they do suggest palliative interventions addressing meaning-making, possibly including a spiritual or religious dimension, as a novel focus for intervention development.
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