title: Areas of high 18F-FDG uptake on preradiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for non-small cell lung cancer.
abstract: The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. Areas of high (18)F-FDG uptake on preradiotherapy (18)F-FDG PET/CT have been reported to identify intratumor subvolumes at high risk of relapse after radiotherapy. We wanted to confirm these observations on a cohort of patients included in 3 sequential prospective studies. Our aim was to assess an appropriate threshold (percentage of maximum standardized uptake value [SUVmax]) to delineate subvolumes on staging (18)F-FDG PET/CT scans assuming that a smaller target volume would facilitate isotoxic radiotherapy dose escalation.
  
  
  METHODS
  Thirty-nine patients with inoperable stage II or III NSCLC, treated with chemoradiation or with radiotherapy alone, were extracted from 3 prospective studies (ClinicalTrials.gov identifiers NCT01261585, NCT01261598, and RECF0645). All patients underwent (18)F-FDG PET/CT at initial staging, before radiotherapy, during radiotherapy, and during systematic follow-up in a single institution. All (18)F-FDG PET/CT acquisitions were coregistered on the initial scan. Various subvolumes in the initial acquisition (30%, 40%, 50%, 60%, 70%, 80%, and 90% SUVmax thresholds) and in the 3 subsequent acquisitions (40% and 90% SUVmax thresholds) were pasted on the initial scan and compared.
  
  
  RESULTS
  Seventeen patients had a local relapse. The SUVmax measured during radiotherapy was significantly higher in locally relapsed tumors than in locally controlled tumors (mean, 6.8 vs. 4.6; P = 0.02). The subvolumes delineated on initial PET/CT scans with 70%-90% SUVmax thresholds were in good agreement with the recurrent volume at a 40% SUVmax threshold (common volume/baseline volume, 0.60-0.80). The subvolumes delineated on initial PET/CT scans with 30%-60% SUVmax thresholds were in good to excellent agreement with the core volume of the relapse (90% SUVmax threshold) (common volume/recurrent volume and overlap fraction indices, 0.60-0.93). The agreement was moderate (>0.51) when a 70% SUVmax threshold was used to delineate on initial PET/CT scans.
  
  
  CONCLUSIONS
  High (18)F-FDG uptake areas on pretreatment PET/CT scans identify tumor subvolumes at greater risk of relapse in patients with NSCLC treated by concomitant chemoradiation. We propose a 70% SUVmax threshold to delineate areas of high (18)F-FDG uptake on initial PET/CT scans as the target volumes for potential radiotherapy dose escalation.
authors.affiliation: Nuclear Medicine Department, Henri Becquerel Cancer Center and Rouen University Hospital, Rouen, France QuantIF-LITIS (EA [Equipe d'Accueil] 4108-FR CNRS [Fédération de Recherche-Centre National pour la Recherche Scientifique] 3638), Faculty of Medicine, University of Rouen, Rouen, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Calais
authors.affiliation: Nuclear Medicine Department, Henri Becquerel Cancer Center and Rouen University Hospital, Rouen, France QuantIF-LITIS (EA [Equipe d'Accueil] 4108-FR CNRS [Fédération de Recherche-Centre National pour la Recherche Scientifique] 3638), Faculty of Medicine, University of Rouen, Rouen, France Department of Radiotherapy and Medical Physics, Henri Becquerel Cancer Centre and Rouen University Hospital, Rouen, France; and.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Thureau
authors.affiliation: QuantIF-LITIS (EA [Equipe d'Accueil] 4108-FR CNRS [Fédération de Recherche-Centre National pour la Recherche Scientifique] 3638), Faculty of Medicine, University of Rouen, Rouen, France Department of Radiotherapy and Medical Physics, Henri Becquerel Cancer Centre and Rouen University Hospital, Rouen, France; and.
authors.forename: Bernard
authors.initials: B
authors.lastname: Dubray
authors.affiliation: Nuclear Medicine Department, Henri Becquerel Cancer Center and Rouen University Hospital, Rouen, France QuantIF-LITIS (EA [Equipe d'Accueil] 4108-FR CNRS [Fédération de Recherche-Centre National pour la Recherche Scientifique] 3638), Faculty of Medicine, University of Rouen, Rouen, France Department of Radiotherapy and Medical Physics, Henri Becquerel Cancer Centre and Rouen University Hospital, Rouen, France; and.
authors.forename: Romain
authors.initials: R
authors.lastname: Modzelewski
authors.affiliation: QuantIF-LITIS (EA [Equipe d'Accueil] 4108-FR CNRS [Fédération de Recherche-Centre National pour la Recherche Scientifique] 3638), Faculty of Medicine, University of Rouen, Rouen, France Department of Pneumology, Rouen University Hospital, Rouen, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Thiberville
authors.affiliation: Nuclear Medicine Department, Henri Becquerel Cancer Center and Rouen University Hospital, Rouen, France QuantIF-LITIS (EA [Equipe d'Accueil] 4108-FR CNRS [Fédération de Recherche-Centre National pour la Recherche Scientifique] 3638), Faculty of Medicine, University of Rouen, Rouen, France Department of Radiotherapy and Medical Physics, Henri Becquerel Cancer Centre and Rouen University Hospital, Rouen, France; and.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gardin
authors.affiliation: Nuclear Medicine Department, Henri Becquerel Cancer Center and Rouen University Hospital, Rouen, France QuantIF-LITIS (EA [Equipe d'Accueil] 4108-FR CNRS [Fédération de Recherche-Centre National pour la Recherche Scientifique] 3638), Faculty of Medicine, University of Rouen, Rouen, France pierre.vera@chb.unicancer.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vera
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D002986:Clinical Trials as Topic; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG PET/CT; 18F-FDG uptake; local relapse; lung cancer; radiotherapy; target volume