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Abstract/Video opens by clicking at the talk title.
Intra-operative imaging study group: discussing the road towards final clinical translation (#718)
Stephan Rogalla1, Friso Achterberg2
1 Stanford University, Department of Medicine, Stanford, United States of America
We are proud to announce that on this year's virtual study group, we are able to present two perspective talks about the road to final clinial translation of an optical imaging agent!
AcknowledgmentThe study group chairs would like to thank all presenters for their contribution.
Keywords: Clinical translation, optical imaging, surgical imaging, intraoperative imaging, fluorescence imaging
Clinical Translation of SGM-101, a Fluorescent Antibody Targeting Carcinoembryonic Antigen used in Fluorescence Guided Surgery for Colorectal Cancer: Lessons Learnt on the Journey from the Bench to the Bedside. (#691)
Bérénice Framery1, Marian Gutowski2, Karen Dumas1, Nathalie Muller3, Vincent Dubois3, Jérôme Quinonero3, François Scherninski4, Ruben Meijer5, Alexander Vahrmeijer5, André Pèlegrin6, Françoise Cailler1
1 SurgiMab, Montpellier, France
Surgery is the cornerstone of cancer treatment, the surgeon’s goal being to remove both gross and microscopic tumors to render the patient disease free. Although modern surgical advancements have improved surgical oncology, adequate tumor visualization remains a limitation preventing total removal of cancerous tissue. Indeed surgeons mostly rely on visual appearance and palpation to discriminate between tumor and normal tissue. However white light reflectance limits the differentiation between healthy tissue and tumor and can lead to residual cancer cells inadvertently left behind at the resection border. Moreover, the current development of minimally invasive surgery limits palpation.
Defined as positive surgical margins (PSMs), remaining cancerous cells post surgery generally have poor prognostic implications across different tumor types and typically require adjuvant treatments that confer significant increased costs and burden to the patient and healthcare system (Tringale et al., 2017).
Tumor-targeted fluorescence imaging has the potential to advance current practice of oncological surgery by selectively highlighting malignant tissue during surgery, thus offering pseudo-color distinction between tumor and adjacent normal tissue to improve accuracy of resection and potentially PSMs. Fluorescence imaging also has the potential to distinguish different anatomic structures to reduce inadvertent injury to healthy tissue (differentiation between fibrotic/scar tissue and tumor tissue).
Specialized intraoperative imaging systems using near-infrared (NIR) light and specific fluorescent contrast agents (probes) have been developed over the past several years with applications in open surgery, laparoscopy, thoracoscopy and robot-assisted surgery (Kaushal et al., 2008; Vahrmeijer et al., 2013). The properties of NIR optical imaging are perfectly suited for real-time fluorescence imaging during surgery. NIR light is invisible to the human eye and therefore does not alter the appearance of the surgical field. Background signal is minimal, as tissue exhibits virtually no auto fluorescence in this spectrum. Moreover, no ionizing radiation is required, adding to the safety of the technique.
However there are still not many fluorescent probes in the clinic with a clear specificity for tumors. Some teams have tried using therapeutic antibodies as carriers for a fluorochrome but they often lack specificity. In contrast, SurgiMab has developed the first fluorescent probe specific for digestive tumors that has proven both safe and effective in the clinic.
Indeed SurgiMab develops antibody-fluorochrome conjugates as in vivo diagnostic agents in oncology. SGM-101, SurgiMab’s most advanced product, is based on a tumor-specific, anti-carcinoembryonic antigen (CEA) monoclonal antibody and a NIR emitting fluorochrome. CEA is overexpressed in a wide range of human carcinomas, including colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. With SGM-101 the goal is to provide oncology surgeons with an intraoperative imaging tool that will allow them to visualize all tumors overexpressing CEA, whether during or surgery or during endoscopic diagnosis procedures.
SGM-101 safety and efficacy have both been demonstrated in two clinical trials, in patients going to surgery either for a peritoneal carcinomatosis of digestive origin, or for a pancreatic or colorectal cancer. Its efficacy is currently tested in a pivotal phase III trial in 10 clinical centers, in 4 countries.
Our talk will describe the main steps of the clinical translation of SGM-101, from an exciting concept first published in 1991 (Pèlegrin et al., 1991; Folli et al., 1992) to an industrially produced GMP molecule used by clinicians. We will concentrate on the lessons learnt while combining science and business and on what we identified as the keys to success towards clinical application of an injectable molecular imaging tool.
1 - Tringale Kathryn R., Pang John and Nguyen Quyen T. (2018) ‘Image‐guided surgery in cancer: A strategy to reduce incidence of positive surgical margins’, Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 0(0), p. e1412. doi: 10.1002/wsbm.1412.
2 - Kaushal, S. et al. (2008) ‘Fluorophore-conjugated anti-CEA Antibody for the Intraoperative Imaging of Pancreatic and Colorectal Cancer’, Journal of Gastrointestinal Surgery, 12, pp. 1938–1950. doi: 10.1007/s11605-008-0581-0.
2 - Vahrmeijer, A. L. et al. (2013) ‘Image-guided cancer surgery using near-infrared fluorescence’, Nature Reviews Clinical Oncology, 10(9), pp. 507–518. doi: 10.1038/nrclinonc.2013.123.
4 - Pèlegrin, A. et al. (1991) ‘Antibody-fluorescein conjugates for photoimmunodiagnosis of human colon carcinoma in nude mice’, Cancer, 67(10), pp. 2529–2537.
5 - Folli, S. et al. (1992) ‘Immunophotodiagnosis of colon carcinomas in patients injected with fluoresceinated chimeric antibodies against carcinoembryonic antigen’, Proceedings of the National Academy of Sciences of the United States of America, 89(17), pp. 7973–7977.
Keywords: Fluorescence-Guided-Surgery, cancer, SGM-101, clinical trial
The Clinical Translation of a Near-Infrared Fluorophore for Fluorescence-Guided Surgery (#705)
Ruben Meijer1, 2, Bérénice Framery3, Friso Achterberg1, Marion Deken1, Kim de Valk1, 2, Françoise Cailler3, Koos Burggraaf2, Alexander Vahrmeijer1
1 Leiden University Medical Center, General Surgery, Leiden, Netherlands
Near-infrared (NIR) fluorescence imaging is a promising intraoperative technique for real-time visualization of tumor tissue during surgery. The process of clinical translation of novel fluorescent agents is an essential part in the evolution of NIR fluorescence guided surgery. Poor visualization of tumors during surgery is one of the major challenges surgeons often face in oncologic patients, mainly due to the improved neo-adjuvant treatment patients receive. In these cases, NIR fluorescence imaging with the use of tumor-targeted fluorescent agents can play an essential role and help provide better oncologic results or patient outcomes. However, before this technique can be implemented in standard of care, optimal tumor-targeted fluorescent agents need to be developed and novel fluorescent agents need to undergo a successful process of clinical translation.
Keywords: Fluorescence-Guided Surgery, Oncology, Phase III, Surgical Inovation