title: Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer.
abstract: BACKGROUND
  Many patients with oncogene-driven non-small-cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors experience limited sites of disease progression. This study investigated retrospectively the benefits of local ablative therapy (LAT) to central nervous system (CNS) and/or limited systemic disease progression and continuation of crizotinib or erlotinib in patients with metastatic ALK gene rearrangement (ALK+) or EGFR-mutant (EGFR-MT) NSCLC, respectively.
  
  
  METHODS
  Patients with metastatic ALK+ NSCLC treated with crizotinib (n = 38) and EGFR-MT NSCLC treated with erlotinib (n = 27) were identified at a single institution. Initial response to the respective kinase inhibitors, median progression-free survival (PFS1), and site of first progression were recorded. A subset of patients with either nonleptomeningeal CNS and/or four sites or fewer of extra-CNS progression (oligoprogressive disease) suitable for LAT received either radiation or surgery to these sites and continued on the same tyrosine kinase inhibitors. The subsequent median progression-free survival from the time of first progression (PFS2) and pattern of progression were recorded.
  
  
  RESULTS
  Median progression-free survival in ALK+ patients on crizotinib was 9.0 months, and 13.8 months for EGFR-MT patients on erlotinib. Twenty-five of 51 patients (49%) who progressed were deemed suitable for local therapy (15 ALK+, 10 EGFR-MT; 24 with radiotherapy, one with surgery) and continuation of the same targeted therapy. Post-LAT, 19 of 25 patients progressed again, with median PFS2 of 6.2 months.
  
  
  CONCLUSIONS
  Oncogene-addicted NSCLC with CNS and/or limited systemic disease progression (oligoprogressive disease) on relevant targeted therapies is often suitable for LAT and continuation of the targeted agent, and is associated with more than 6 months of additional disease control.
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Cancer Center, Colorado. Electronic address: andrew.weickhardt@ucdenver.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Weickhardt
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Cancer Center, Colorado.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Scheier
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Cancer Center, Colorado.
authors.forename: Joseph Malachy
authors.initials: JM
authors.lastname: Burke
authors.affiliation: Department of Radiation Oncology, University of Colorado Cancer Center, Colorado.
authors.forename: Gregory
authors.initials: G
authors.lastname: Gan
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health and University of Colorado, Colorado.
authors.forename: Xian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Cancer Center, Colorado.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.affiliation: Department of Pathology, University of Colorado Cancer Center, Colorado.
authors.forename: Dara L
authors.initials: DL
authors.lastname: Aisner
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health and University of Colorado, Colorado.
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Gaspar
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health and University of Colorado, Colorado.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kavanagh
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Cancer Center, Colorado.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Doebele
authors.affiliation: Department of Medicine, Division of Medical Oncology, University of Colorado Cancer Center, Colorado.
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D000077547:Crizotinib; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011799:Quinazolines; D000077547:Crizotinib; D000069347:Erlotinib Hydrochloride; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases