Tumor-Specific Fluorescence-Guided Surgery for Pancreatic Cancer Using Panitumumab-IRDye800CW: A Phase I Dose-Escalation study

Background— Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma (PDAC) with positive margins in 30%−70% of patients. The present study AUTHORS’ CONTRIBUTIONS GL designed the study, collected, analyzed, and interpreted the data, and wrote the manuscript. NSvdB collected and interpreted the data, and revised the manuscript. BAM conducted the histopathological processing and diagnosis, interpreted the data, and revised the manuscript. NN, ZPH, and SvK with data analysis and interpretation. SF and QZ assisted with data collection. SUC, RCR and GY recruited and consented participants for the study and obtained regulatory and ethics approval. GAF signed on participant enrollment, the study drug infusion, and assisted with review of adverse events. ELR holds the IND for panitumumab- IRDye800CW, designed the shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumor-specific intraoperative imaging may have added value for treatment of patients with PDACs through improved patient selection and enhanced visualization of surgical margins, metastatic lymph nodes, and distant metastasis.

[1]  N. S. van den Berg,et al.  Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer , 2019, Molecular Imaging and Biology.

[2]  N. S. van den Berg,et al.  Predicting Therapeutic Antibody Delivery into Human Head and Neck Cancers , 2020, Clinical Cancer Research.

[3]  N. S. van den Berg,et al.  Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer , 2019, Nature Communications.

[4]  Andrew D. Newton,et al.  Intraoperative Near-infrared Imaging Can Identify Neoplasms and Aid in Real-time Margin Assessment During Pancreatic Resection. , 2019, Annals of surgery.

[5]  B. Martin,et al.  The Sentinel Margin: Intraoperative Ex Vivo Specimen Mapping Using Relative Fluorescence Intensity , 2019, Clinical Cancer Research.

[6]  B. G. Sibinga Mulder,et al.  Impact of resection margin status on recurrence and survival in pancreatic cancer surgery , 2019, The British journal of surgery.

[7]  N. S. van den Berg,et al.  Rapid, non-invasive fluorescence margin assessment: Optical specimen mapping in oral squamous cell carcinoma. , 2019, Oral oncology.

[8]  N. S. van den Berg,et al.  Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer. , 2018, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[9]  Alexander L. Vahrmeijer,et al.  Image-Guided Surgery in Patients with Pancreatic Cancer: First Results of a Clinical Trial Using SGM-101, a Novel Carcinoembryonic Antigen-Targeting, Near-Infrared Fluorescent Agent , 2018, Annals of Surgical Oncology.

[10]  Guolan Lu,et al.  Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence. , 2018, Cancer research.

[11]  Thinzar M. Lwin,et al.  The development of fluorescence guided surgery for pancreatic cancer: from bench to clinic , 2018, Expert review of anticancer therapy.

[12]  Eben L. Rosenthal,et al.  Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging , 2018, Annals of Surgical Oncology.

[13]  Soyeon Ahn,et al.  Management of recurrent pancreatic cancer after surgical resection: a protocol for systematic review, evidence mapping and meta-analysis , 2018, BMJ Open.

[14]  N. S. van den Berg,et al.  Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers , 2018, Theranostics.

[15]  J. Kleeff,et al.  The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma , 2017, Annals of surgery.

[16]  P. Kuppen,et al.  Selection of optimal molecular targets for tumor-specific imaging in pancreatic ductal adenocarcinoma , 2017, Oncotarget.

[17]  E. Rosenthal,et al.  Sensitivity and Specificity of Cetuximab-IRDye800CW to Identify Regional Metastatic Disease in Head and Neck Cancer , 2017, Clinical Cancer Research.

[18]  Vasilis Ntziachristos,et al.  Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study , 2016, Clinical Cancer Research.

[19]  Alexander L. Vahrmeijer,et al.  Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery , 2016, Molecular Imaging and Biology.

[20]  Dong Shik Lee,et al.  EGFR expression in pancreatic intraepithelial neoplasia and ductal adenocarcinoma. , 2015, International journal of clinical and experimental pathology.

[21]  Joshua S Richman,et al.  Safety and Tumor Specificity of Cetuximab-IRDye800 for Surgical Navigation in Head and Neck Cancer , 2015, Clinical Cancer Research.

[22]  Benjamin D. Smith,et al.  Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. , 2014, Cancer research.

[23]  Cornelis J H van de Velde,et al.  Near‐infrared fluorescence‐guided resection of colorectal liver metastases , 2013, Cancer.

[24]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[25]  M. Büchler,et al.  Pancreatic Cancer Surgery in the New Millennium: Better Prediction of Outcome , 2011, Annals of surgery.

[26]  N. Dreyer,et al.  Registries for Evaluating Patient Outcomes: A User’s Guide , 2010 .

[27]  M. Gagner,et al.  Laparoscopic Whipple procedure: review of the literature. , 2009, Journal of hepato-biliary-pancreatic surgery.

[28]  Takeaki Ishizawa,et al.  Real‐time identification of liver cancers by using indocyanine green fluorescent imaging , 2009, Cancer.

[29]  M. Gönen,et al.  Preoperative CA 19-9 and the Yield of Staging Laparoscopy in Patients with Radiographically Resectable Pancreatic Adenocarcinoma , 2008, Annals of Surgical Oncology.

[30]  J. Donohue,et al.  Long-Term Survival After Pancreatoduodenectomy for Pancreatic Adenocarcinoma: Is Cure Possible? , 2008, Annals of surgery.

[31]  A. Bhardwaj,et al.  Epidermal Growth Factor Receptor Expression in Pancreatic Carcinoma Using Tissue Microarray Technique , 2006, Digestive Surgery.

[32]  Y. Ogata,et al.  Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings , 2006, Journal of Gastrointestinal Surgery.

[33]  R. Wolff,et al.  Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  I. Cameron,et al.  Indications for staging laparoscopy in pancreatic cancer. , 2016, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[35]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.