Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging

  • Willemieke S. Tummers
  • Sarah E. Miller
  • Nutte T. Teraphongphom
  • Adam Gomez
  • Idan Steinberg
  • David M. Huland
  • Steve Hong
  • Sri-Rajasekhar Kothapalli
  • Alifia Hasan
  • Robert Ertsey
  • Bert A. Bonsing
  • Alexander L. Vahrmeijer
  • Rutger-Jan Swijnenburg
  • Teri A. Longacre
  • George A. Fisher
  • Sanjiv S. Gambhir
  • George A. Poultsides
  • Eben L. Rosenthal
Pancreatic Tumors

Abstract

Background

Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor.

Methods

A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo.

Results

Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue.

Conclusions

The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.

Notes

Acknowledgment

The authors acknowledge support from Stanford Cancer Institute Translational Research Grant, and Intuitive Surgical Clinical Robotics Research Grant. Tummers WS contribution to this work was supported in part by Michaël-van Vloten Fonds, Lisa Waller Hayes Foundation, Jo Kolk Studiefonds, McKinsey Grant, and Ketel1 Studiefonds. Huland DM contribution to this work was supported in part by NCI training grant: T32 CA118681.

Author Contributions

ELR, GAP, SSG, BAB, ALV, RJS and WST designed the research; WST, SEM, NT, AG, IS, DMH, SH, SRK, AH, RE, TAL, GAF, and GAP performed the research; and WST, SEM, and ELR analyzed data and wrote the paper.

Disclosure

The authors declare no potential conflicts of interest.

Supplementary material

10434_2018_6453_MOESM1_ESM.docx (9.3 mb)
Supplementary material 1 (DOCX 9495 kb)

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Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Willemieke S. Tummers
    • 1
    • 2
  • Sarah E. Miller
    • 3
  • Nutte T. Teraphongphom
    • 3
  • Adam Gomez
    • 4
  • Idan Steinberg
    • 1
  • David M. Huland
    • 1
  • Steve Hong
    • 3
  • Sri-Rajasekhar Kothapalli
    • 1
  • Alifia Hasan
    • 3
  • Robert Ertsey
    • 3
  • Bert A. Bonsing
    • 2
  • Alexander L. Vahrmeijer
    • 2
  • Rutger-Jan Swijnenburg
    • 2
  • Teri A. Longacre
    • 4
  • George A. Fisher
    • 5
  • Sanjiv S. Gambhir
    • 6
  • George A. Poultsides
    • 7
  • Eben L. Rosenthal
    • 3
    • 8
  1. 1.Department of Radiology, Molecular Imaging Program at Stanford (MIPS)Stanford UniversityStanfordUSA
  2. 2.Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
  3. 3.Department of OtolaryngologyStanford UniversityStanfordUSA
  4. 4.Department of PathologyStanford UniversityStanfordUSA
  5. 5.Department of Medical OncologyStanford UniversityStanfordUSA
  6. 6.Departments of Radiology, Bioengineering, and Materials Science & Engineering, Molecular Imaging Program at Stanford; Canary Center at Stanford for Early Cancer DetectionStanford UniversityStanfordUSA
  7. 7.Department of SurgeryStanford UniversityStanfordUSA
  8. 8.Stanford Cancer CenterStanford UniversityStanfordUSA

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