title: Mediastinal downstaging after induction treatment is not a significant prognostic factor to select patients who would benefit from surgery: the clinical value of the lymph node ratio.
abstract: OBJECTIVE
  Multimodal management of N2 non-small-cell lung cancer is still a matter of debate. In particular, the place of surgery for persistent N2 after induction treatment is controversial and surgery is usually reserved for patients experiencing a mediastinal downstaging (pN1 and pN0). We aimed to evaluate whether there might exist subgroups of pN2 according to the lymph node ratio (LNR).
  
  
  METHODS
  Between 1996 and 2012, we retrospectively reviewed the data from 152 potentially resectable cN2 patients who underwent an induction treatment before surgery.
  
  
  RESULTS
  The median follow-up time was 32 months (2-112). The average age at the time of diagnosis was 58.52 ± 10.47 years. In univariate analysis, overall survival (OS) was significantly influenced by extracapsular spread (32 ± 5.33 vs 24 ± 12.73 months, P = 0.01), pN after surgery (65 ± 2.45 months for pN0, 44 ± 2.14 months for pN1 and 19 ± 1.72 months for pN2, P <0.0001) and LNR ≥ 1/3 (30 ± 3.77 months vs 16 ± 1.39 months, P <0.0001). When pN0 and pN1 patients were staged according to the LNR, the OS was divided by two for pN1 patients with an LNR ≥ 1/3 (48 ± 2.64 months vs 26 ± 5.65 months, P <0.001), whereas it decreased from 26 ± 0.87 to 15 ± 1.85 months (P <0.0001) for pN2 patients. OS was significantly better with adjuvant radio-chemotherapy than with chemotherapy or radiation therapy alone (P <0.0001). In multivariate analysis, mediastinal downstaging {Hazard Ratio (HR): 0.184 (95% confidence interval (CI): 0.084-0.403), P <0.0001} and LNR [HR: 0.359 (95% CI: 0.194-0.665], P = 0.001) remained significantly independent prognostic factors.
  
  
  CONCLUSIONS
  The LNR may potentially identify subgroups of pN+ patients and allow enhancement of adjuvant treatments. Because pN2 with a low LNR had an equivalent survival to pN1 with a high LNR, mediastinal downstaging does not seem to be a sufficient prognostic factor to exclude patients after induction treatment from surgery.
authors.affiliation: Department of Thoracic Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France EA3430: Federation of Translational Medicine, University of Strasbourg, Strasbourg, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Renaud
authors.affiliation: Department of Thoracic Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France pierre-emmanuel.falcoz@wanadoo.fr.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Falcoz
authors.affiliation: Department of Thoracic Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Olland
authors.affiliation: Department of Thoracic Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Reeb
authors.affiliation: Department of Thoracic Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santelmo
authors.affiliation: Department of Thoracic Surgery, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Massard
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D059146:Metastasectomy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D009367:Neoplasm Staging; D018579:Patient Selection; D011013:Pneumonectomy / Q000009:adverse effects / Q000401:mortality; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
keywords: Induction treatment; Lymph node ratio; Lymph nodes; Mediastinal downstaging; Non-small-cell lung cancer; Persistent N2