title: Phase II trial of stereotactic body radiation therapy combined with erlotinib for patients with limited but progressive metastatic non-small-cell lung cancer.
abstract: OBJECTIVE
  Patients with stage IV non-small-cell lung cancer (NSCLC) who progress through first-line therapy have poor progression-free survival (PFS) and overall survival (OS), most commonly failing in original sites of gross disease. Cytoreduction with stereotactic body radiation therapy (SBRT) may help systemic agents delay relapse.
  
  
  METHODS
  Patients in our single arm phase II study had stage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemotherapy and were able to receive SBRT and concurrent erlotinib until disease progression. After erlotinib commencement, SBRT with equipotent fractionation was delivered to all sites of disease. PFS, OS, and other end points were evaluated.
  
  
  RESULTS
  Twenty-four patients (13 men and 11 women) with a median age of 67 years (range, 56-86 years) were enrolled with median follow-up of 11.6 months. All patients had progressed through platinum-based chemotherapy. A total of 52 sites were treated with 16 of 24 patients receiving SBRT to more than one site. Lung parenchyma was most often irradiated. Median PFS was 14.7 months, and median OS was 20.4 months. Most patients progressed in new distant sites with only three of 47 measurable lesions recurring within the SBRT field. Two grade 3 toxicities were radiation related. Zero of 13 patients tested were positive for an EGFR mutation.
  
  
  CONCLUSIONS
  Use of SBRT with erlotinib for unselected patients with stage IV NSCLC as a second- or subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted in high PFS and OS, substantially greater than historical values for patients who only received systemic agents.
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Puneeth
authors.initials: P
authors.lastname: Iyengar
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kavanagh
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Zabi
authors.initials: Z
authors.lastname: Wardak
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Irma
authors.initials: I
authors.lastname: Smith
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Chul
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: David E
authors.initials: DE
authors.lastname: Gerber
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Dowell
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Randall
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Abdulrahman
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: D Ross
authors.initials: DR
authors.lastname: Camidge
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Gaspar
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Doebele
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
authors.affiliation: Puneeth Iyengar, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, Hak Choy, Robert Timmerman, University of Texas Southwestern Medical Center, Dallas, TX; Brian D. Kavanagh, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, and Paul A. Bunn, University of Colorado School of Medicine, Aurora, CO. robert.timmerman@utsouthwestern.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Timmerman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003120:Colorado; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016634:Radiosurgery / Q000009:adverse effects / Q000401:mortality; D012307:Risk Factors; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors