Defining Symptom Trajectories to Inform Risk-Stratified Approaches to Symptom Management in Children with Advanced Cancer

/ABSTRACT The use of conventional and novel therapeutics to treat children with advanced cancer leads to burdensome physical and psychological symptoms. Advanced cancer is metastatic upon initial diagnosis, relapsed, progressed, or refractory to treatment, resulting in an uncertain and prolonged disease course. Symptom burden and associated suffering are amplified for these children due to disease burden, intense therapy, and often lengthy treatment. Symptom patterns (trajectories) have been identified in children diagnosed with early-stage cancer, but research characterizing symptom patterns over time in the understudied patient population of children with advanced cancer is sparse. Associations with the biopsychosocial context, including demographic, social, and physiologic risk factors, and their contribution to the variability in symptom burden among children with advanced cancer is also limited, hindering clinicians’ abilities to anticipate and intervene. Consequences of high symptom burden include diminished quality of life, worse physical function, and increased psychological stress. Further, there is a risk that children with advanced cancer will normalize their symptom suffering. This perception of symptom suffering as unavoidable threatens the efficacy of future symptom management interventions. Thus, there is a critical need to understand the symptom experiences of children living with advanced cancer to shift the clinical symptom management paradigm to proactive, risk-based approaches that anticipate symptom burden and improve clinical outcomes. The aims of this application are to (1) define symptom trajectories over time among children aged 8-18 with advanced cancer, (2) identify biopsychosocial characteristics that distinguish patient subgroups, and (3) examine the association between patient subgroups and health outcomes. To achieve these aims, we will prospectively enroll 228 children aged 8 to18 living with advanced cancer across five pediatric cancer centers. We will collect reports of symptoms, quality of life, psychological stress, and physical mobility reports every two weeks for 4 months. We will also collect measures of the biopsychosocial context, including demographic, social, and physiologic (disease and treatment) characteristics. The expected outcome of this research is the discovery of distinct symptom trajectories, with children who belong to a high symptom burden trajectory experiencing poorer health outcomes than children in lower symptom burden trajectories. The proposed research will also identify biopsychosocial characteristics that distinguish children who experience different symptom trajectories. Together, these outcomes hold promise for the development of risk-stratified approaches to symptom management in children with advanced cancer, providing researchers and clinicians with biopsychosocial targets for monitoring and intervention. These novel approaches are required to advance symptom management research and improve health outcomes for children with advanced cancer. Project Number: 1R01CA307143-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Kathleen Montgomery | Institution: UNIVERSITY OF WISCONSIN-MADISON, MADISON, WI | Award Amount: $689,340 | Activity Code: R01 | Study Section: Interdisciplinary Clinical Care in Specialty Care Settings Study Section[ICSC] View on NIH RePORTER: https://reporter.nih.gov/project-details/11272464