title: The impact of local and regional disease extent on overall survival in patients with advanced stage IIIB/IV non-small cell lung carcinoma.
abstract: OBJECTIVE
  Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit.
  
  
  METHODS
  We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease.
  
  
  RESULTS
  On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1.54; P=.022) remained significant.
  
  
  CONCLUSIONS
  Patients with bulky central disease, bronchial/vascular compression, and/or pulmonary symptoms exhibited worse overall survival after first-line, platinum-based chemotherapy. A subset of these patients may be studied to determine whether early, planned palliative thoracic radiation could also be of benefit.
authors.affiliation: Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina 27599-7512, USA. daniel.higginson@gmail.com
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Higginson
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Chen
authors.forename: Gregg
authors.initials: G
authors.lastname: Tracton
authors.forename: David E
authors.initials: DE
authors.lastname: Morris
authors.forename: Jan
authors.initials: J
authors.lastname: Halle
authors.forename: Julian G
authors.initials: JG
authors.lastname: Rosenman
authors.forename: Mihaela
authors.initials: M
authors.lastname: Stefanescu
authors.forename: Erica
authors.initials: E
authors.lastname: Pham
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Marks
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011799:Quinazolines / Q000627:therapeutic use; D011859:Radiography; D047368:Tumor Burden
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D000068258:Bevacizumab; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride