Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer

Clin Cancer Res. 2017 Aug 15;23(16):4744-4752. doi: 10.1158/1078-0432.CCR-16-2968. Epub 2017 Apr 26.

Abstract

Purpose: Comprehensive cervical lymphadenectomy can be associated with significant morbidity and poor quality of life. This study evaluated the sensitivity and specificity of cetuximab-IRDye800CW to identify metastatic disease in patients with head and neck cancer.Experimental Design: Consenting patients scheduled for curative resection were enrolled in a clinical trial to evaluate the safety and specificity of cetuximab-IRDye800CW. Patients (n = 12) received escalating doses of the study drug. Where indicated, cervical lymphadenectomy accompanied primary tumor resection, which occurred 3 to 7 days following intravenous infusion of cetuximab-IRDye800CW. All 471 dissected lymph nodes were imaged with a closed-field, near-infrared imaging device during gross processing of the fresh specimens. Intraoperative imaging of exposed neck levels was performed with an open-field fluorescence imaging device. Blinded assessments of the fluorescence data were compared to histopathology to calculate sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).Results: Of the 35 nodes diagnosed pathologically positive, 34 were correctly identified with fluorescence imaging, yielding a sensitivity of 97.2%. Of the 435 pathologically negative nodes, 401 were correctly assessed using fluorescence imaging, yielding a specificity of 92.7%. The NPV was determined to be 99.7%, and the PPV was 50.7%. When 37 fluorescently false-positive nodes were sectioned deeper (1 mm) into their respective blocks, metastatic cancer was found in 8.1% of the recut nodal specimens, which altered staging in two of those cases.Conclusions: Fluorescence imaging of lymph nodes after systemic cetuximab-IRDye800CW administration demonstrated high sensitivity and was capable of identifying additional positive nodes on deep sectioning. Clin Cancer Res; 23(16); 4744-52. ©2017 AACR.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / chemistry
  • Benzenesulfonates / administration & dosage
  • Benzenesulfonates / chemistry
  • Cetuximab / administration & dosage*
  • Cetuximab / chemistry
  • Combined Modality Therapy
  • Diagnostic Imaging / methods
  • Female
  • Fluorescence
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / surgery*
  • Humans
  • Indoles / administration & dosage
  • Indoles / chemistry
  • Lymph Node Excision
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Sensitivity and Specificity

Substances

  • Antineoplastic Agents, Immunological
  • Benzenesulfonates
  • IRDye 800CW
  • Indoles
  • Cetuximab