Biography: Zhihong Zhang earned her PhD in Nursing and Health Science from the University of Rochester School of Nursing. Her PhD dissertation focused on understanding symptom responses to cancer treatment in older adults with advanced cancer to inform treatment decision-making. Zhihong Zhang is currently a postdoctoral researcher at Columbia University. She plans to expand her dissertation work by integrating data science approaches to better understand and support the treatment experiences of older adults with advanced cancer.
PhD Dissertation Abstract
Background and Significance: Older adults with advanced cancer are at a high risk of developing new or worsening symptoms during cancer treatment, leading to adverse outcomes. Notably, substantial variations are observed in symptom trajectories during cancer treatment, reflecting varied abilities in patients' symptom response to cancer treatment. The NIH resilience conceptual model specifies resilience as a system's adaptive response to stressors, reflecting the ability to resist, recover, and grow from stressors. This theoretical lens of resilience may help in understanding the varied symptom response during cancer treatment, offering insights for symptom management and treatment tolerability in older adults with advanced cancer.
Purpose/Objective(s) and/or Specific Aims: The specific aims are: 1) to identify resilience in symptom response by examining the trajectories of a summary severity score of multiple symptoms; 2) to identify baseline factors associated with resilience in symptom response; 3) to examine the association between resilience in symptom response and functional status over six months; 4) to explore concordance among resilience indicated by the summary severity score of multiple symptoms and individual symptom responses.
Methods: A secondary data analysis utilized data from older adults aged 70 and above with incurable advanced cancer who were initiating new systemic treatment and enrolled in a national multisite clinical trial (GAP 70+ study, ClinicalTrials.gov, NCT02054741).
Symptoms were assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the Geriatric Depression Scale. Functional status was assessed with the Instrumental Activities of Daily Living. Data on symptoms and functional status were collected prior to the new treatment and 4-6 weeks, 3 months, and 6 months later. Symptom trajectories were estimated using growth mixture models. Resilience in symptom response to cancer treatment was indicated by a "resist" trajectory (consistently no/mild symptoms), "recover" trajectory (initially increased severity but recovering to no/mild severity), or "grow" trajectory (symptoms improving to no/mild severity) during cancer treatment.
In contrast, non-resilience was indicated by the persistence of moderate or severe symptoms without remission to no/mild severity or death during follow-ups. Resilience in both the summary severity score and individual symptom responses were identified. Baseline factors associated with resilience in the summary severity score, including demographics, aging-related conditions, and clinical factors, were examined using a generalized linear mixture model. A longitudinal linear mixture model was used to evaluate the association between resilience in the summary severity score and functional status over six months. Concordance between resilience in the summary severity score and 12 core individual symptoms was also explored using percentages of agreement and Fleiss' kappa test.
Results/Findings: Participants providing PRO-CTCAE data at least once during the six months were included (N=710). Only 17.8% of older adults with advanced cancer exhibited resilience in symptom response to cancer treatment during the six months. Receiving single/multi-agent chemotherapy, experiencing impairments with comorbidities, and having poor social support reduced the likelihood of exhibiting resilience in symptom response to cancer treatment. Older adults with resilience in symptom response maintained higher functional status over time, while those without resilience experienced continued functional decline without recovery at six months post-initiation of a new systemic treatment. Moderate concordance (Kappa=0.467) was observed between resilience indicated by the summary severity score and individual symptom responses. Patients exhibiting resilience in individual symptom responses only demonstrated resilience in the summary severity score in about half of the cases. Conversely, patients with resilience in the summary severity score exhibited resilience in most individual symptom responses.
Conclusion(s): Resilience in symptom response proves to be a valuable theoretical framework for understanding individuals' varied abilities in their symptom response to cancer treatment. This study also supports the use of a summary severity score to better represents individuals' overall ability in responding to cancer treatment symptoms compared to individual symptom responses. However, only one in five older adults with advanced cancer exhibited resilience in their symptom response to treatment, indicating poor treatment tolerability.
Implications for Science: This study represents a pioneering effort in exploring variable symptom responses through the lens of resilience theory, offering an innovative approach to understanding individual heterogeneity in response to cancer treatment and advancing symptom science. Furthermore, it provides compelling evidence for the validity of utilizing a summary symptom severity score to indicate resilience, rather than focusing solely on individual symptoms commonly used in literature, thus contributing to the advancement of resilience measures for research.
Implications for Profession: The low resilience rate in symptom response highlights poor treatment tolerability and emphasizes the importance of ongoing symptom monitoring and management. Additionally, identified risk factors for resilience in symptom response could inform treatment decision-making in this population. Older adults with these risk factors may have a lower likelihood of resisting, recovering, or growing from cancer treatment and may benefit from treatment modification and additional supportive care.