title: Pattern of Failure Analysis in Metastatic EGFR-Mutant Lung Cancer Treated with Tyrosine Kinase Inhibitors to Identify Candidates for Consolidation Stereotactic Body Radiation Therapy.
abstract: BACKGROUND
  The role of stereotactic body radiation therapy (SBRT) in patients with metastatic lung cancer harboring epidermal growth factor receptor (EGFR) mutations is not defined. We evaluated the pattern of failure in patients receiving tyrosine kinase inhibitor (TKI) therapy to identify candidates for consolidation SBRT.
  
  
  METHODS
  Computed tomography scans were reviewed in a cohort of EGFR-mutant patients enrolled on prospective TKI trials. Initial progression in sites of original disease (primary/metastatic) or new sites was classified as original site failure (OF) or distant site failure (DF), respectively. Simultaneous OF/DF was labeled ODF. Disease characteristics were analyzed for associations with patterns of failure using actuarial competing risks methodology.
  
  
  RESULTS
  Complete serial imaging was available in 49 patients with measurable disease. Median time to any progression was 8.3 months. The majority failed initially in original disease sites with OF, ODF, and DF frequencies being 47.0%, 32.6%, and 20.4%, respectively. Primary tumor size was the most significant predictor of OF in univariate and multivariate analysis (p = 0.004). Median time to progression was 3 months shorter in patients with OF compared with DF. Ten patients (20%) were retroactively classified as consolidation SBRT candidates based on the extent of disease at time of best response to TKI therapy, and in seven of these, initial progression occurred in original tumor sites.
  
  
  CONCLUSIONS
  Initial progression of TKI-treated cancers occurred predominantly in original disease sites. Consolidation SBRT was judged feasible in a subset of patients following maximum TKI response and may have prevented oligoprogression in most of these. In addition, we hypothesize that consolidation SBRT for residual disease could delay subsequent metastatic reseeding.
authors: *Department of Radiation Oncology, †Department of Radiology, and ‡Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors: Hani
authors: H
authors: Al-Halabi
authors: Karl
authors: K
authors: Sayegh
authors: Subba R
authors: SR
authors: Digamurthy
authors: Andrzej
authors: A
authors: Niemierko
authors: Zofia
authors: Z
authors: Piotrowska
authors: Henning
authors: H
authors: Willers
authors: Lecia V
authors: LV
authors: Sequist
mesh_terms: D015331:Cohort Studies; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016634:Radiosurgery / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors