Ultrasound-Guided Quantitative Fluorescence Molecular Endoscopy for Monitoring Response in Patients with Esophageal Cancer Following Neoadjuvant Chemoradiotherapy

Abstract

Abstract Purpose: The ability to identify residual tumor tissues in patients with locally advanced esophageal cancer following neoadjuvant chemoradiotherapy (nCRT) is essential for monitoring the treatment response. Using the fluorescent tracer bevacizumab-800CW, we evaluated whether ultrasound-guided quantitative fluorescent molecular endoscopy (US-qFME), which combines quantitative fluorescence molecular endoscopy (qFME) with ultrasound-guided needle biopsy/single-fiber fluorescence (USNB/SFF), can be used to identify residual tumor tissues in patients following nCRT. Experimental Design: Twenty patients received an additional endoscopy procedure the day before surgery. qFME was performed at the primary tumor site (PTS) and in healthy tissue to first establish the optimal tracer dose. USNB/SFF was then used to measure intrinsic fluorescence in the deeper PTS layers and lymph nodes (LN) suspected for metastasis. Finally, the intrinsic fluorescence and the tissue optical properties—specifically, the absorption and reduced scattering coefficients—were combined into a new parameter called omega. Results: First, a 25-mg bevacizumab-800CW dose allowed for clear differentiation between the PTS and healthy tissue, with a target-to-background ratio (TBR) of 2.98 (IQR, 1.86–3.03). Moreover, we found a clear difference between the deeper esophageal PTS layers and suspected LN compared to healthy tissues, with TBR values of 2.18 and 2.17, respectively. Finally, our new parameter, omega, further improved the ability to differentiate between the PTS and healthy tissue. Conclusions: Combining bevacizumab-800CW with US-qFME may serve as a viable strategy for monitoring the response to nCRT in esophageal cancer and may help stratify patients regarding active surveillance versus surgery.