title: Osteoblastic progression during EGFR tyrosine kinase inhibitor therapy in mutated non-small cell lung cancer: a potential blunder.
abstract: OBJECTIVE
  Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, including the onset of new osteoblastic lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course. We aim to describe this clinical phenomenon in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene-activating mutations treated with tyrosine kinase inhibitor (TKI).
  
  
  METHODS
  We retrospectively reviewed the computed tomography scans of 43 EGFR-mutated patients with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantity and/or density of lesions, and assessing objective tumor response to treatment.
  
  
  RESULTS
  Osteoblastic reaction was detected in 10 cases (23%), showing different patterns: dimensional or density increase of known osteosclerotic metastases (pattern A, n = 4); response of previously lytic lesions (pattern B, n = 2); onset of new osteosclerotic lesions (pattern C, n = 4). Seven patients had partial response to TKI treatment, with response rate of 70%, vs 50% of patients with bone metastases without this reaction. No difference in terms of median overall survival or progression-free survival emerged between patients with or without osteoblastic reaction.
  
  
  CONCLUSIONS
  The correct clinico-radiologic interpretation of osteoblastic reaction is crucial to avoid waste of therapeutic lines when TKI treatment has not yet exhausted its potential effectiveness. Clinical implications of ambiguous radiologic findings as described in this study deserve further discussion.
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bersanelli
authors.affiliation: Radiology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bini
authors.affiliation: Radiology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Rabaiotti
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facchinetti
authors.affiliation: Radiology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: De Filippo
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bortesi
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma - Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology*; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors