Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection

Abstract

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting.

A clinical trial of intraoperative near‐infrared imaging to assess tumor extent and identify residual disease during anterior mediastinal tumor resection

“…17 All subjects presented with anterior mediastinal neoplasms identified by preoperative high-resolution computed tomography scanning. The sample size and the study design were based on consensus guidelines provided by the World Molecular Imaging Society.…”

Enhanced Visualization: From Intraoperative Tissue Differentiation to Augmented Reality

“…Surgeons, accordingly, are asked to announce their need for enhanced visualization techniques as these are key to further reducing the interventional trauma and improving our performance. As suggested by Tummers et al [20], Rosenthal et al [28], and de Boer et al [47], we believe it to be permissible to approve new surgical markers based on criteria different to those applied for diagnostic markers as they are used in only a small number of well-indicated instances and will allow for new forms of therapy that will possibly improve the chances of curing cancer. Accordingly, we must always balance the resultant advantage versus the potential risks when examining new approaches.…”

“…ICG is a fluorophore that emits light in the range of the so-called near-infrared window (700-930 nm), a range of the light spectrum in which the absorption by blood, water, and oxygen is the lowest and the fluoroscopic signal is the strongest. To derive a signal, excitation of ICG with light of a wavelength similar to the adsorption range and registration of the emitted signal by dedicated camera systems are required [20]. ICG can be injected intravenously and is suitable for visualization of tissue perfusion, e.g.…”

“…However, the pending approval for clinical application as well as some remaining skepticism concerning biocompatibility (toxic components, gene alteration, etc.) currently hamper their further development [20].…”

“…A list of ongoing studies is given in a consensus report published by Rosenthal et al [47] in 2016. This article (same as [20]) also gives insight into the problem of approval of these new dyes and discusses potential solutions and recommendations.…”