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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1880-1888
Number of pages9
JournalAnnals of Surgical Oncology
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2018

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Molecular Imaging
Pancreatic Neoplasms
Optical Imaging
Neoplasms
Adenocarcinoma
Multimodal Imaging
Safety
Fluorescent Dyes
Epidermal Growth Factor Receptor
Pancreatitis
Fluorescence
Cetuximab
Neoplasm Metastasis
Sensitivity and Specificity
IRDye800

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Tummers, W. S., Miller, S. E., Teraphongphom, N. T., Gomez, A., Steinberg, I., Huland, D. M., ... Rosenthal, E. L. (2018). Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Annals of Surgical Oncology, 25(7), 1880-1888. https://doi.org/10.1245/s10434-018-6453-2
Tummers, Willemieke S. ; Miller, Sarah E. ; Teraphongphom, Nutte T. ; Gomez, Adam ; Steinberg, Idan ; Huland, David M. ; Hong, Steve ; Kothapalli, Sri-Rajasekhar ; Hasan, Alifia ; Ertsey, Robert ; Bonsing, Bert A. ; Vahrmeijer, Alexander L. ; Swijnenburg, Rutger Jan ; Longacre, Teri A. ; Fisher, George A. ; Gambhir, Sanjiv S. ; Poultsides, George A. ; Rosenthal, Eben L. / Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. In: Annals of Surgical Oncology. 2018 ; Vol. 25, No. 7. pp. 1880-1888.
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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.",
author = "Tummers, {Willemieke S.} and Miller, {Sarah E.} and Teraphongphom, {Nutte T.} and Adam Gomez and Idan Steinberg and Huland, {David M.} and Steve Hong and Sri-Rajasekhar Kothapalli and Alifia Hasan and Robert Ertsey and Bonsing, {Bert A.} and Vahrmeijer, {Alexander L.} and Swijnenburg, {Rutger Jan} and Longacre, {Teri A.} and Fisher, {George A.} and Gambhir, {Sanjiv S.} and Poultsides, {George A.} and Rosenthal, {Eben L.}",
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Tummers, WS, Miller, SE, Teraphongphom, NT, Gomez, A, Steinberg, I, Huland, DM, Hong, S, Kothapalli, S-R, Hasan, A, Ertsey, R, Bonsing, BA, Vahrmeijer, AL, Swijnenburg, RJ, Longacre, TA, Fisher, GA, Gambhir, SS, Poultsides, GA & Rosenthal, EL 2018, 'Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging', Annals of Surgical Oncology, vol. 25, no. 7, pp. 1880-1888. https://doi.org/10.1245/s10434-018-6453-2

Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. / Tummers, Willemieke S.; Miller, Sarah E.; Teraphongphom, Nutte T.; Gomez, Adam; Steinberg, Idan; Huland, David M.; Hong, Steve; Kothapalli, Sri-Rajasekhar; Hasan, Alifia; Ertsey, Robert; Bonsing, Bert A.; Vahrmeijer, Alexander L.; Swijnenburg, Rutger Jan; Longacre, Teri A.; Fisher, George A.; Gambhir, Sanjiv S.; Poultsides, George A.; Rosenthal, Eben L.

In: Annals of Surgical Oncology, Vol. 25, No. 7, 01.07.2018, p. 1880-1888.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging

AU - Tummers, Willemieke S.

AU - Miller, Sarah E.

AU - Teraphongphom, Nutte T.

AU - Gomez, Adam

AU - Steinberg, Idan

AU - Huland, David M.

AU - Hong, Steve

AU - Kothapalli, Sri-Rajasekhar

AU - Hasan, Alifia

AU - Ertsey, Robert

AU - Bonsing, Bert A.

AU - Vahrmeijer, Alexander L.

AU - Swijnenburg, Rutger Jan

AU - Longacre, Teri A.

AU - Fisher, George A.

AU - Gambhir, Sanjiv S.

AU - Poultsides, George A.

AU - Rosenthal, Eben L.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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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Tummers WS, Miller SE, Teraphongphom NT, Gomez A, Steinberg I, Huland DM et al. Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging. Annals of Surgical Oncology. 2018 Jul 1;25(7):1880-1888. https://doi.org/10.1245/s10434-018-6453-2