Determination of tumor margins with surgical specimen mapping using near-infrared fluorescence

Rebecca W. Gao, Nutte T. Teraphongphom, Nynke S. van den Berg, Brock A. Martin, Nicholas J. Oberhelman, Vasu Divi, Michael J. Kaplan, Steven S. Hong, Guolan Lu, Robert Ertsey, Willemieke S.F.J. Tummers, Adam J. Gomez, F. Christopher Holsinger, Christina S. Kong, Alexander D. Colevas, Jason M. Warram, Eben L. Rosenthal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. Twenty-one adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 (n ¼ 3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A (n ¼ 5) received 0.5 mg/kg, cohort 2B (n ¼ 7) received 1 mg/kg, and cohort 3 (n ¼ 6) received 50 mg. Patients were followed 30 days postinfusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. In situ imaging demonstrated tumor-to-background ratio (TBR) of 2 to 3, compared with ex vivo specimen imaging TBR of 5 to 6. We obtained clear differentiation between tumor and normal tissue, with a 3-fold signal difference between positive and negative specimens (P < 0.05). We achieved high correlation of fluorescence intensity with tumor location with sensitivities and specificities >89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy, which are otherwise less amenable to image guidance.

Original languageEnglish
Pages (from-to)5144-5154
Number of pages11
JournalCancer Research
Issue number17
StatePublished - 1 Sep 2018
Externally publishedYes


Dive into the research topics of 'Determination of tumor margins with surgical specimen mapping using near-infrared fluorescence'. Together they form a unique fingerprint.

Cite this