Fluorescence guided surgery is a technique that has widely been implemented and investigated over the last decade, and has repetitively revealed to be a vital tool during surgery. However, the... Show moreFluorescence guided surgery is a technique that has widely been implemented and investigated over the last decade, and has repetitively revealed to be a vital tool during surgery. However, the process of adopting this technique into standard of care along with developing and translating novel fluorescent agents into the clinic has proven to take time. Preclinical studies that have been validated several years ago have now slowly been making the transition into the surgical field to be appraised in patients.This thesis mainly focused on the clinical translation of ZW800-1 and cRGDZW800-1 which were developed for the intraoperative imaging of the ureters and colon cancer, respectively. Furthermore, this thesis focused on the further appraisal of a previously studied tumor-targeted fluorescent antibody (SGM-101) for the intraoperative imaging of primary, recurrent and metastasized colorectal cancer. Show less
Introduction The field of tumor-specific fluorescence-guided surgery has seen a significant increase in the development of novel tumor-targeted imaging agents. Studying patient benefit using... Show moreIntroduction The field of tumor-specific fluorescence-guided surgery has seen a significant increase in the development of novel tumor-targeted imaging agents. Studying patient benefit using intraoperative fluorescence-guided imaging for cancer surgery is the final step needed for implementation in standard treatment protocols. Translation into phase III clinical trials can be challenging and time consuming. Recent studies have helped to identify certain waypoints in this transition phase between studying imaging agent efficacy (phase I-II) and proving patient benefit (phase III). Trial initiation Performing these trials outside centers of expertise, thus involving motivated clinicians, training them, and providing feedback on data quality, increases the translatability of imaging agents and the surgical technique. Furthermore, timely formation of a trial team which oversees the translational process is vital. They are responsible for establishing an imaging framework (camera system, imaging protocol, surgical workflow) and clinical framework (disease stage, procedure type, clinical research question) in which the trial is executed. Providing participating clinicians with well-defined protocols with the aim to answer clinically relevant research questions within the context of care is the pinnacle in gathering reliable trial data. Outlook If all these aspects are taken into consideration, tumor-specific fluorescence-guided surgery is expected be of significant value when integrated into the diagnostic work-up, surgical procedure, and follow-up of cancer patients. It is only by involving and collaborating with all stakeholders involved in this process that successful clinical translation can occur. Aim Here, we discuss the challenges faced during this important translational phase and present potential solutions to enable final clinical translation and implementation of imaging agents for image-guided cancer surgery. Show less
For years, pancreatic cancer had a dismal prognosis with a long term survival of around 5%. Since the centralization of pancreatic cancer surgery and the introduction of systemic chemotherapy... Show moreFor years, pancreatic cancer had a dismal prognosis with a long term survival of around 5%. Since the centralization of pancreatic cancer surgery and the introduction of systemic chemotherapy with FOLFIRINOX, the median overall survival increased to around 20%. Radical tumor-margin free resection provides the patient with the best potential chance for cure. However, due to late onset of symptoms, the majority of patients present with inoperable disease. These patients can benefit from neoadjuvant therapy, or palliative chemotherapy. During clinical practice, this means that decision-making before and during surgery is critical to select the most optimal primary treatment modality. Currently, conventional imaging modalities lack sensitivity to detect small metastatic lesions, and are unable to visualize treatment response on neoadjuvant therapy. Tumor-specific molecular imaging in the form of fluorescence and photoacoustic imaging aids the surgeon to accurately recognize and resect malignant tissues in real-time during surgery. This thesis focuses on the challenges a surgeon faces during pancreatic cancer treatment, and the potential improvements that could be achieved by the use of tumor-specific imaging. In addition, the regulatory aspects of clinical translation of tumor-specific optical imaging agents are addressed. Show less
