title: Identification of metastatic nodal disease in a phase 1 dose-escalation trial of intraoperative sentinel lymph node mapping in non-small cell lung cancer using near-infrared imaging.
abstract: OBJECTIVE
  Early-stage non-small cell lung cancer (NSCLC) has a high recurrence rate and poor 5-year survival, particularly if lymph nodes are involved. Our objective was to perform a dose-escalation study to assess safety and feasibility of intraoperative near-infrared (NIR) fluorescence imaging to identify the first tumor-draining lymph nodes (ie, sentinel lymph nodes [SLNs] in patients with NSCLC).
  
  
  METHODS
  A-dose escalation phase 1 clinical trial assessing real-time NIR imaging after peritumoral injection of 3.8 to 2500 μg indocyanine green (ICG) was initiated in patients with suspected stage I/II NSCLC. Visualization of lymphatic migration, SLN identification, and adverse events were recorded.
  
  
  RESULTS
  Thirty-eight patients underwent ICG injection and NIR imaging via thoracotomy (n = 18) or thoracoscopic imaging (n = 20). SLN identification increased with ICG dose, with fewer than 25% SLNs detected in dose cohorts of 600 μg or less versus 89% success at 1000 μg or greater. Twenty-six NIR(+) SLNs were identified in 15 patients, with 7 NIR(+) SLNs (6 patients) harboring metastatic disease on histologic analysis. Metastatic nodal disease was never identified in patients with a histologically negative NIR(+) SLN. No adverse reactions were noted.
  
  
  CONCLUSIONS
  NIR-guided SLN identification with ICG was safe and feasible in this initial dose-escalation trial. ICG doses greater than 1000 μg yielded nearly 90% intrathoracic SLN visualization, with the presence or absence of metastatic disease in the SLN directly correlating with final nodal status of the lymphadenectomy specimen. Further studies are needed to optimize imaging parameters and confirm sensitivity and specificity of SLN mapping in NSCLC using this promising imaging technique.
authors.affiliation: Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Mass 02115, USA.
authors.forename: Denis M
authors.initials: DM
authors.lastname: Gilmore
authors.forename: Onkar V
authors.initials: OV
authors.lastname: Khullar
authors.forename: Michael T
authors.initials: MT
authors.lastname: Jaklitsch
authors.forename: Lucian R
authors.initials: LR
authors.lastname: Chirieac
authors.forename: John V
authors.initials: JV
authors.lastname: Frangioni
authors.forename: Yolonda L
authors.initials: YL
authors.lastname: Colson
mesh_terms: D000368:Aged; D001900:Boston; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary* / Q000601:surgery; D003952:Diagnostic Imaging / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes; D006801:Humans; D061705:Image-Guided Biopsy / Q000379:methods*; D007208:Indocyanine Green; D007430:Intraoperative Care; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D019265:Spectroscopy, Near-Infrared
chemical_list: D005456:Fluorescent Dyes; D007208:Indocyanine Green
keywords: 10.2; 10.4; CT; FFP; H&E; HSA; ICG; NIR; NSCLC; PET; SLN; computed tomography; fresh-frozen plasma; hematoxylin and eosin; human serum albumin; indocyanine green; near infrared; non–small cell lung cancer; positron emission tomographic; sentinel lymph node