title: Clinical Implications of Isolated Bone Failure Without Systemic Disease Progression During EGFR-TKI Treatment.
abstract: We investigated the characteristics of patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) who had experienced isolated progression of bone metastases without aggravation of extraskeletal organs during EGFR-tyrosine kinase inhibitor (TKI) treatment.
  
  
  
  We retrospectively reviewed the data from 870 patients with EGFR-mutant NSCLC treated with EGFR-TKI from 2004 to 2014. Of these patients, 71 (8.2%), who had undergone radiation therapy to bone metastases because of skeletal-related events, impending skeletal-related events, or medically uncontrolled bone pain, were selected and defined as having bone failure (BF). BFs were classified into 2 categories according to the presence of accompanying disease progression in extraskeletal organs: isolated BF (IBF) and non-IBF.
  
  
  
  Of the 71 BF patients, 33 (46.5%) experienced IBF without aggravation of disease in extraskeletal organs. IBF was more frequent in the clinical benefit group (responders and stable for ≥ 6 months) than in nonclinical benefit group (54.4% vs. 14.3%; P = .007). IBF was also more frequent in those with good performance status (82.5% vs. 42.9%; P = .005) and 19 deletion (68.4% vs. 35.7%; P = .024). Female sex, good performance status, and clinical benefit from TKI were more frequent in patients with IBF than in those with non-IBF (female sex, 69.7% vs. 44.7%; P = .034; Eastern Cooperative Oncology Group 0 or 1, 87.9% vs. 63.2%; P = .017; clinical benefit from TKI, 93.9% vs. 68.4%; P = .007). Clinical benefit from EGFR-TKI was an independent predictor of IBF (adjusted odds ratio, 6.647; 95% confidence interval, 1.328-33.262; P = .021). Patients with IBF tended to exhibit longer survival times from the initiation of the TKI (20.7 vs. 11.1 months; P = .2) and from the onset of BF (8.6 vs. 3.4 months; P = .186).
  
  
  
  IBF without systemic disease progression frequently occurs in patients with clinical benefits from EGFR-TKI and is associated with better survival. This finding requires future studies to explore the differential activity of EGFR-TKI in the bones over time or in preference to other organs.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ji An
authors.initials: JA
authors.lastname: Hwang
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Joon Seon
authors.initials: JS
authors.lastname: Song
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Rho
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Choi
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: jclee@amc.seoul.kr.
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001847:Bone Diseases / Q000139:chemically induced / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Bone metastasis; Epidermal growth factor receptor; Non–small-cell lung cancer; Skeletal-related event; Tyrosine kinase inhibitor