Clinical Exposome of Patient-Reported Outcomes for Patients With Metastatic Breast Cancer

OBJECTIVES: The exposome refers to all exposures to which an individual is subjected throughout lifetime. The most immediate sphere for patients with severe conditions such as metastatic breast cancer is likely to be the clinical than the environmental exposome. Recently, clinical research data and Electronic Health Records (EHRs) have become a potential source for tracing the clinical exposome. Since Patient-Reported Outcomes (PROs) are sensitive to the exposome, this conceptual paper examines the methodological implication of conducting clinical exposome research on PROs.

METHODS: We performed a scoping review along with an analysis of real-world clinical data. We adapted exposome methods to clinical information by focusing on hypothesis-driven processes within high-dimensional data and on generating new insights into how specific clinical exposures are mapped to specific PRO dimensions.

RESULTS: Unstructured information in electronic Clinical Research Forms (eCRFs) and EHRs including heterogeneous entries (e.g. misspellings, synonyms, commercial and generic names, deviations in expressions) will be refined into specific structured variables (e.g. co-medications, family history or occasional symptoms) using a large language models (LLMs). Structured data in eCRFs, such as disease characteristics, treatments, comorbidities, critical clinical events, psychometric measures, and medical procedures in EHRs, will be used directly and in combination to describe the clinical patterns of the disease and treatment pathway. A minimum of 200 longitudinal clinical variables times the number of repeated measures will be used. The exposome-wide association study (ExWAS) will then screen each clinical exposure with individual PRO questions and dimensions. We will use cross-validated Lasso regression models to assess how a set of clinical variables affect PROs.

CONCLUSIONS: The clinical exposome approach will serve both the research and the routine use of PROs, as it helps map and isolate the effects of clinical exposures with respect to specific PRO dimensions.