Development and Validation of Models to Predict Poor Health-Related Quality of Life Among Adult Survivors of Childhood Cancer.

Importance: Risk prediction models are important to identify survivors of childhood cancer who are at risk of experiencing poor health-related quality of life (HRQOL) as they age. Objective: To develop and validate prediction models for a decline in HRQOL among adult survivors of childhood cancer. Designs, Setting, and Participants: This prognostic study included 4755 adults from the Childhood Cancer Survivor Study (CCSS) diagnosed between January 5, 1970, and December 31, 1986, who completed baseline (time 0 [November 3, 1992, to August 28, 2003]) and 2 follow-up (time 1 [February 12, 2002, to May 21, 2005] and time 2 [January 6, 2014, to November 30, 2016]) surveys. Data were analyzed from June 19, 2019, to February 2, 2022. Exposures: Sociodemographic, lifestyle, and emotional factors, and chronic health conditions (CHCs) were assessed at time 0 and time 1, and neurocognitive factors were assessed at time 1 to predict HRQOL at time 2 and a decline in HRQOL between time 1 and time 2. Impaired health states were defined as CHC grades 2 to 4 using the modified Common Terminology Criteria for Adverse Events, version 4.03, and mental and neurocognitive status as 1 SD or more below reference levels. Main Outcomes and Measures: Health-related quality of life was operationalized using the Medical Outcomes Study 36-Item Short Form Health Survey Physical (PCS) and Mental (MCS) Component Summary and classified by optimal (≥40) or suboptimal (<40) at each point (main outcome). A decline in HRQOL was defined as a change from optimal to suboptimal between time 1 and time 2. Multivariable logistic regression identified factors associated with HRQOL decline. The cohort was randomly split into training (80%) and test (20%) data sets for model development and validation; the area under the receiver operating characteristic curve was used to evaluate prediction performance. Results: A total of 4755 adults (mean [SD] age at time 0, 24.3 [7.6] years; 2623 [55.2%] women) were included in the analysis. Between time 1 and time 2, 285 of 3294 survivors (8.7%) had declining PCS and 278 of 3294 (8.4%) had declining MCS. Risk factors associated with PCS decline included female sex (odds ratio [OR], 1.67 [95% CI, 1.25-2.24]), family income less than $20 000 vs $80 000 or more (OR, 2.00 [95% CI, 1.21-3.30]), presence of CHCs (OR for neurological, 2.16 [95% CI, 1.51-3.10]; OR for endocrine, 2.25 [95% CI, 1.44-3.52]; OR for gastrointestinal tract, 1.89 [95% CI, 1.32-2.69]; OR for respiratory, 1.66 [95% CI, 1.06-2.59]; OR for cardiovascular, 1.53 [95% CI, 1.14-2.06]), and depression (OR, 1.79 [95% CI, 1.20-2.67]). Risk factors associated with MCS decline included unemployment vs full-time employment (OR, 1.68; [95% CI, 1.19-2.38]), current vs never cigarette smoking (OR, 2.03 [95% CI, 1.37-3.00]), depression (OR, 4.29 [95% CI, 2.44-7.55]), somatization (OR, 1.63 [95% CI, 1.05-2.53]), impaired task efficiency (OR, 1.90 [95% CI, 1.34-2.68]), and impaired organization (OR, 1.67 [95% CI, 1.12-2.48]). The areas under the receiver operating characteristic curve for the test models were 0.74 (95% CI, 0.67-0.81) for declining PCS and 0.68 (95% CI, 0.60-0.75) for declining MCS. Conclusions and Relevance: In this prognostic study of adult survivors of childhood cancer who experienced declining HRQOL, CHCs were associated with a decline in physical HRQOL, whereas current smoking and emotional and neurocognitive impairment were associated with a decline in mental HRQOL. These findings suggest that interventions targeting modifiable risk factors are needed to prevent poor HRQOL in this population.