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Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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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.

Author information

Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, USA

    Willemieke S. Tummers MD, Idan Steinberg Ph.D, David M. Huland Ph.D & Sri-Rajasekhar Kothapalli Ph.D

  2. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

    Willemieke S. Tummers MD, Bert A. Bonsing MD, PhD, Alexander L. Vahrmeijer MD, PhD & Rutger-Jan Swijnenburg MD, PhD

  3. Department of Otolaryngology, Stanford University, Stanford, CA, USA

    Sarah E. Miller BS, Nutte T. Teraphongphom Ph.D, Steve Hong MD, Alifia Hasan MBA, Robert Ertsey M.Sc & Eben L. Rosenthal MD, FACS

  4. Department of Pathology, Stanford University, Stanford, CA, USA

    Adam Gomez MD & Teri A. Longacre MD

  5. Department of Medical Oncology, Stanford University, Stanford, CA, USA

    George A. Fisher MD

  6. Departments of Radiology, Bioengineering, and Materials Science & Engineering, Molecular Imaging Program at Stanford; Canary Center at Stanford for Early Cancer Detection, Stanford University, Stanford, CA, USA

    Sanjiv S. Gambhir MD, PhD

  7. Department of Surgery, Stanford University, Stanford, CA, USA

    George A. Poultsides MD

  8. Stanford Cancer Center, Stanford University, Stanford, CA, USA

    Eben L. Rosenthal MD, FACS

Authors
  1. Willemieke S. Tummers MD
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  2. Sarah E. Miller BS
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  3. Nutte T. Teraphongphom Ph.D
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  4. Adam Gomez MD
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  5. Idan Steinberg Ph.D
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  6. David M. Huland Ph.D
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  7. Steve Hong MD
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  8. Sri-Rajasekhar Kothapalli Ph.D
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  9. Alifia Hasan MBA
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  10. Robert Ertsey M.Sc
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  11. Bert A. Bonsing MD, PhD
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  12. Alexander L. Vahrmeijer MD, PhD
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  13. Rutger-Jan Swijnenburg MD, PhD
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  14. Teri A. Longacre MD
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  15. George A. Fisher MD
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  16. Sanjiv S. Gambhir MD, PhD
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  17. George A. Poultsides MD
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  18. Eben L. Rosenthal MD, FACS
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Corresponding author

Correspondence to Eben L. Rosenthal MD, FACS.

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Tummers, W.S., Miller, S.E., Teraphongphom, N.T. et al. Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Ann Surg Oncol 25, 1880–1888 (2018). https://doi.org/10.1245/s10434-018-6453-2

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  • DOI: https://doi.org/10.1245/s10434-018-6453-2

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