TY - JOUR T1 - Early response detection in systemic lung cancer treatment using cell-free methylated SHOX2 (mSHOX2) plasma DNA JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2015.PA524 VL - 46 IS - suppl 59 SP - PA524 AU - Bernd Schmidt AU - Julia Beyer AU - Dimo Dietrich AU - Nina Lambrecht AU - Michael Fleischhacker Y1 - 2015/09/01 UR - http://erj.ersjournals.com/content/46/suppl_59/PA524.abstract N2 - Introduction: Response detection in systemic lung cancer treatment is based on CT imaging after 2 to 3 therapy cycles (i.e. 2-3 months). Unfortunately there is no convincing biomarker to indicate early after therapy start whether the patients respond to therapy. Previous studies have shown interesting performance of the DNA-methylation marker mSHOX2 in a diagnostic setting. The aim of this pilot study was therefore to find out whether a longitudinal quantification of cell-free mSHOX2 plasma DNA might be also useful for response detection.Material and Methods: We enrolled 36 patients receiving chemotherapy for advanced stage lung cancer (30 NSCLC, 6 SCLC). DNA was isolated from cell-free EDTA plasma taken before and during therapy (every 7 to 10 days) for approx. 3 months (re-staging) followed by bisulfite treatment. The simultaneous quantification of mSHOX2 and actin (reference gene) was performed by real-time PCR.Results: According to CT-based re-staging, 22 patients were classified as non-responders and 14 as responders. We observed a tight correlation between radiological data and the change of plasma mSHOX2 level. A ROC analysis showed a high discriminatory power for both patient groups already one week after therapy start (AUC 0.844). Also, Kaplan-Meier and Cox Proportional Hazards analyses revealed a strong relationship between survival and plasma mSHOX2 value p≤0.001 (hazard ratio 11.08) providing some evidence for mSHOX2 also being a prognostic marker.Conclusion: Cell-free methylated SHOX2 DNA (mSHOX2) allowed early response detection and proved beneficial as prognostic biomarker. A confirmatory multicenter study is on the way. ER -