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Publication in AAPSJ supported by DDMoRe

A Population Pharmacodynamic Model for Lactate Dehydrogenase and Neuron Specific Enolase to Predict Tumor Progression in Small Cell Lung Cancer Patients

Núria Buil-Bruna, José-María López-Picazo, Marta Moreno-Jiménez, Salvador Martín-Algarra, Benjamin Ribba, and Iñaki F. Trocóniz AAPSJ

Abstract

The development of individualized therapies poses a major challenge in oncology. Significant hurdles to overcome include better disease monitoring and early prediction of clinical outcome. Current clinical practice  consists of using Response Evaluation Criteria in Solid Tumors (RECIST) to categorize response to treatment. However, the utility of RECIST is restricted due to limitations on the frequency of measurement and its  categorical rather than continuous nature. We propose a population modeling framework that relates circulating biomarkers in plasma, easily obtained from patients, to tumor progression levels assessed by imaging  scans (i.e., RECIST categories). We successfully applied this framework to data regarding lactate dehydrogenase (LDH) and neuron specific enolase (NSE) concentrations in patients diagnosed with small cell lung cancer (SCLC). LDH and NSE have been proposed as independent prognostic factors for SCLC. However, their prognostic and predictive value has not been demonstrated in the context of standard clinical practice. Our model incorporates an underlying latent variable (“disease level”) representing (unobserved) tumor size dynamics, which is assumed to drive  biomarker production and to be influenced by exposure to treatment; these assumptions are in agreement with the known physiology of SCLC and these biomarkers. Our model predictions of unobserved disease level  are strongly correlated with disease progression measured by RECIST criteria. In conclusion, the proposed framework enables prediction of treatment outcome based on circulating biomarkers and therefore can be a  powerful tool to help clinicians monitor disease in SCLC.

Work package: 

Associated members

Academia
Iñaki Troconiz's picture
Iñaki Troconiz
University of Navarra
Núria Buil's picture
Núria Buil
University of Navarra