Details

Autor(en) / Beteiligte

• Nassar, Yomna M
• Ojara, Francis Williams
• Pérez-Pitarch, Alejandro
• Geiger, Kimberly
• Huisinga, Wilhelm
• Hartung, Niklas
• Michelet, Robin
• Holdenrieder, Stefan
• Joerger, Markus
• Kloft, Charlotte

Titel

C-Reactive Protein as an Early Predictor of Efficacy in Advanced Non-Small-Cell Lung Cancer Patients: A Tumor Dynamics-Biomarker Modeling Framework

Ist Teil von

• Cancers, 2023-11, Vol.15 (22), p.5429

Ort / Verlag

Basel: MDPI AG

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• In oncology, longitudinal biomarkers reflecting the patient’s status and disease evolution can offer reliable predictions of the patient’s response to treatment and prognosis. By leveraging clinical data in patients with advanced non-small-cell lung cancer receiving first-line chemotherapy, we aimed to develop a framework combining anticancer drug exposure, tumor dynamics (RECIST criteria), and C-reactive protein (CRP) concentrations, using nonlinear mixed-effects models, to evaluate and quantify by means of parametric time-to-event models the significance of early longitudinal predictors of progression-free survival (PFS) and overall survival (OS). Tumor dynamics was characterized by a tumor size (TS) model accounting for anticancer drug exposure and development of drug resistance. CRP concentrations over time were characterized by a turnover model. An x-fold change in TS from baseline linearly affected CRP production. CRP concentration at treatment cycle 3 (day 42) and the difference between CRP concentration at treatment cycles 3 and 2 were the strongest predictors of PFS and OS. Measuring longitudinal CRP allows for the monitoring of inflammatory levels and, along with its reduction across treatment cycles, presents a promising prognostic marker. This framework could be applied to other treatment modalities such as immunotherapies or targeted therapies allowing the timely identification of patients at risk of early progression and/or short survival to spare them unnecessary toxicities and provide alternative treatment decisions.