title: Standardized Uptake Decrease on [18F]-Fluorodeoxyglucose Positron Emission Tomography After Neoadjuvant Chemotherapy Is a Prognostic Classifier for Long-Term Outcome After Multimodality Treatment: Secondary Analysis of a Randomized Trial for Resectable Stage IIIA/B Non-Small-Cell Lung Cancer.
abstract: A confirmatory analysis was performed to determine the prognostic value of metabolic response during induction chemotherapy followed by bimodality/trimodality treatment of patients with operable locally advanced non-small-cell lung cancer.
  
  
  
  Patients with potentially operable stage IIIA(N2) or selected stage IIIB non-small-cell lung cancer received three cycles of cisplatin/paclitaxel (induction chemotherapy) followed by neoadjuvant radiochemotherapy (RCT) to 45 Gy (1.5 Gy twice per day concurrent cisplatin/vinorelbine) within the ESPATUE (Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA[N2] and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy) trial. Positron emission tomography scans were recommended before (t0) and after (t2) induction chemotherapy. Patients who were eligible for surgery after neoadjuvant RCT were randomly assigned to definitive RCT or surgery. The prognostic value of percentage of maximum standardized uptake value (%SUVmax) remaining in the primary tumor after induction chemotherapy-%SUVremaining = SUVmax(t2)/SUVmax(t0)-was assessed by proportional hazard analysis and receiver operating characteristic analysis.
  
  
  
  Overall, 161 patients were randomly assigned (155 from the Essen and Tübingen centers), and 124 of these received positron emission tomography scans at t0 and t2. %SUVremaining as a continuous variable was prognostic for the three end points of overall survival, progression-free survival, and freedom from extracerebral progression in univariable and multivariable analysis (P < .016). The respective hazard ratios per 50% increase in %SUVremaining from multivariable analysis were 2.3 (95% CI, 1.5 to 3.4; P < .001), 1.8 (95% CI, 1.3 to 2.5; P < .001), and 1.8 (95% CI, 1.2 to 2.7; P = .006) for the three end points. %SUVremaining dichotomized at a cut point of maximum sum of sensitivity and specificity from receiver operating characteristic analysis at 36 months was also prognostic. Exploratory analysis revealed that %SUVremaining was likewise prognostic for overall survival in both treatment arms and was more closely associated with extracerebral distant metastases (P = .016) than with isolated locoregional relapses (P = .97).
  
  
  
  %SUVremaining is a predictor for survival and other end points after multimodality treatment and can serve as a parameter for treatment stratification after induction chemotherapy or for evaluation of adjuvant new systemic treatment options for high-risk patients.
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Pöttgen
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gauler
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bellendorf
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Guberina
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bockisch
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Schwenzer
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Heinzelmann
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Cordes
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Schuler
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Welter
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Stamatis
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Godehard
authors.initials: G
authors.lastname: Friedel
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Kaid
authors.initials: K
authors.lastname: Darwiche
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Eberhardt
authors.affiliation: Christoph Pöttgen, Thomas Gauler, Alexander Bellendorf, Maja Guberina, Andreas Bockisch, Sebastian Cordes, Martin H. Schuler, Karl-Heinz Jöckel, Wilfried Eberhardt, and Martin Stuschke, University Hospital Essen; University of Duisburg-Essen; Stefan Welter, Georgios Stamatis, and Kaid Darwiche, Ruhrlandklinik, Essen; Nina Schwenzer and Frank Heinzelmann, University Hospital Tübingen; University of Tübingen, Tübingen; and Godehard Friedel, Robert-Bosch-Krankenhaus; Klinikum Schillerhöhe, Gerlingen, Germany. martin.stuschke@uk-essen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Stuschke
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011379:Prognosis
chemical_list: D019788:Fluorodeoxyglucose F18