Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages.

Florian Janke,Manuel Feisst,Farastuk Bozorgmehr,Andreas Günther,Michael Meister,Carlos F Silva,Thomas Muley,Steffen Dietz,Heiko Golpon,Sabina Janciauskiene,Gudula Heussel,Stephan Rheinheimer,Holger Sültmann,Michael Thomas,Marc A Schneider,Claus P Heussel,Sabine Wrenger

doi:10.3390/cancers12040954

Abstract

Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from 50 patients were taken at baseline and at three early time points after therapy initiation. DNA mutations, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved cytokeratin 18 (M30 antigen), and soluble cytokeratin 18 (M65 antigen) were measured in serum and plasma samples. Baseline and first follow-up CT scans were evaluated and correlated with biomarker data. The detection rate of the individual biomarkers was between 56% and 100%. While only keratin 18 correlated with the tumor load at baseline, we found several individual markers correlating with the tumor response to treatment for each of the three time points of blood draws. A combination of the five best markers at each time point resulted in highly significant marker panels indicating therapeutic response (R2 = 0.78, R2 = 0.71, and R2 = 0.71). Our study demonstrates that an early measurement of biomarkers immediately after therapy start can assess tumor response to treatment and might support an adaptation of treatment to improve patients’ outcome.

Highlights

Lung cancer is the most common cause of cancer-related death worldwide with non-small cell lung cancer (NSCLC) being the predominant entity with approximately 85% of cases [1]
Group A (n = 25) received conventional chemotherapy since no targetable molecular alteration was detected during routine diagnostics
First blood sample was collected within 24 h prior to therapy start

Summary

Introduction

Lung cancer is the most common cause of cancer-related death worldwide with non-small cell lung cancer (NSCLC) being the predominant entity with approximately 85% of cases [1]. Regardless of the type of therapy, the gold standard for clinical monitoring of therapy efficacy in lung cancer patients is change in tumor size according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST-1.1) criteria These changes are often evident in CT and MRI imaging with a delay of several weeks after initiation of systemic treatment and, unsuitable for frequent therapy monitoring and early assessment of response. The analysis of circulating biomarkers such as circulating tumor DNA (ctDNA), circulating microRNAs (miRNAs), and disease-associated protein markers offers a minimal-invasive tool to overcome this limitation, permitting frequent sample collection and timely assessment of the patient’s disease status This would allow for early detection of non-responders and avoid side effects and costs of ineffective treatment

Objectives

Methods

Results

Discussion

Conclusion