title: Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: implications for radiation target volume design.
abstract: OBJECTIVE
  Overall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (-) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design.
  
  
  METHODS
  Eighty R1-resected (37 ECE+ and 43 ECE-) patients received PORT (60Gy, 2Gy daily) between 2002 and 2011. Patients with N2 disease received limited elective nodal irradiation (ENI); for pN0-1 disease the use of ENI was optional. Among ECE- (extranodal-R1) patients there were 35 pN0-1 and eight pN2 cases; in pN0-1 patients, patterns of failure and outcomes were analyzed with respect to the use of ENI. Loco-regional failure (LRF) was defined as in-field relapse; isolated nodal failure (INF) was defined as out-of-field regional nodal recurrence occurring without LRF, irrespective of distant metastases.
  
  
  RESULTS
  The actuarial 3-year OS rate was 36.3% (median: 30 months). Three-year OS rates in the ECE- and ECE+ group were 40.4% and 31.4%, with median OS of 31 and 24 months, respectively (p=0.43). In multivariate analysis, the presence of ECE was correlated with OS (HR=3.02; 95% CI: 1.00-9.16; p=0.05). Three-year cumulative incidence of LRF (CILRF) was 14.5% and 15.5% in the ECE- and ECE+ groups, respectively (p=0.98). Three-year cumulative incidence of INF (CIINF) was 14.1% in the ECE- group and 11.1% in the ECE+ group (p=0.76). For pN0-1 patients treated with and without ENI (13 and 22 patients) 3-year CILRF rates were 7.7% and 20.8%, respectively (p=0.20); 3-year CIINF rates were 9.1% and 16.3%, respectively (p=0.65).
  
  
  CONCLUSIONS
  PORT resulted in a relatively good survival of R1-resected NSCLC patients. Relatively high incidence of INF was found in both ECE+ and ECE- patients. For ECE+ patients, treated with limited ENI, distant failure remains a major concern, so the design of ENI fields seems of lesser importance. Omission of ENI in pN0-1 (extranodal-R1) patients resulted in an unacceptably high incidence of INF. We postulate the use of some form of ENI in this setting.
authors: Department of Radiation Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, ul. Roentgena 5, Warsaw, Poland.
authors: Marta
authors: M
authors: Olszyna-Serementa
authors: Joanna
authors: J
authors: Socha
authors: Marek
authors: M
authors: Wierzchowski
authors: Lucyna
authors: L
authors: Kępka
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011184:Postoperative Period; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome