title: Quantification of cell-free mSHOX2 Plasma DNA for therapy monitoring in advanced stage non-small cell (NSCLC) and small-cell lung cancer (SCLC) patients.
abstract: OBJECTIVE
  Most patients suffering from advanced lung cancer die within a few months. To exploit new therapy regimens we need better methods for the assessment of a therapy response.
  
  
  METHODS
  In a pilot study we prospectively enrolled 36 patients with advanced NSCLC and SCLC (34 stage IV, 2 stage IIIB) of whom 34 received standard platinum-based chemo/radiotherapy and two were treated with a tyrosine kinase inhibitor. We measured the levels of extracellular methylated SHOX2 DNA (mSHOX2) in plasma before and during therapy until re-staging. The mSHOX2 analysis was blinded with respect to the clinical data making it an observational study.
  
  
  RESULTS
  According to the re-staging of 31 first-line patients, 19 patients were classified as non-responders while 12 patients were in the responder group. We observed a tight correlation between radiological data and the change of plasma mSHOX2 level as the equivalent for a therapy response. A ROC analysis showed a high discriminatory power for both patient groups already one week after therapy start (AUC 0.844). Additionally, a 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 predictive marker.
  
  
  CONCLUSIONS
  The longitudinal measurement of extracellular plasma mSHOX2 DNA yields information about the response to cytotoxic treatment and allows an early assessment of treatment response for lung cancer patients. If confirmed in a larger study this would be a valuable tool for selecting and guiding a cytotoxic treatment.
authors: Clinic for Internal Medicine I, Department of Pneumology, UKH, Halle/Saale, Germany.
authors: Bernd
authors: B
authors: Schmidt
authors: Clinic for Internal Medicine I, Department of Pneumology, UKH, Halle/Saale, Germany.
authors: Julia
authors: J
authors: Beyer
authors: University Hospital Bonn, Institute of Pathology, Bonn, Germany.
authors: Dimo
authors: D
authors: Dietrich
authors: Clinic for Internal Medicine I, Department of Pneumology, UKH, Halle/Saale, Germany.
authors: Ines
authors: I
authors: Bork
authors: Metanomics Health GmbH, Berlin, Germany.
authors: Volker
authors: V
authors: Liebenberg
authors: Clinic for Internal Medicine I, Department of Pneumology, UKH, Halle/Saale, Germany.
authors: Michael
authors: M
authors: Fleischhacker
mesh_terms: D003131:Combined Modality Therapy; D004247:DNA / Q000097:blood; D019175:DNA Methylation; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D011446:Prospective Studies; D012372:ROC Curve; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D018398:Homeodomain Proteins; C484664:SHOX2 protein, human; D004247:DNA; D066246:ErbB Receptors