Purpose: The ability to identify residual tumor tissues in patients with locally advanced esophageal cancer (EC) 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. Patients and Methods: Eighteen 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 in lymph nodes (LN) suspected for metastasis. Finally, the intrinsic fluorescence and the tissue optical properties, the absorption and the reduced scattering coefficient, were combined into a new parameter: omega. Results: First, a dose of 25 mg bevacizumab-800CW 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 both 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 EC and may help stratify patients with respect to active surveillance versus surgery.

中文翻译：

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超声引导定量荧光分子内镜监测食管癌新辅助放化疗后的反应


目的：识别新辅助放化疗（nCRT）后局部晚期食管癌（EC）患者残留肿瘤组织的能力对于监测治疗反应至关重要。使用荧光示踪剂贝伐珠单抗-800CW，我们评估了将定量荧光分子内窥镜（qFME）与超声引导针活检/单纤维荧光（USNB/SFF）相结合的超声引导定量荧光分子内窥镜（US-qFME）是否可用于识别 nCRT 后患者体内残留的肿瘤组织。患者和方法：18 名患者在手术前一天接受了额外的内窥镜检查。在原发肿瘤部位 (PTS) 和健康组织中进行 qFME，首先确定最佳示踪剂剂量。然后使用 USNB/SFF 测量更深的 PTS 层和疑似转移的淋巴结 (LN) 中的内在荧光。最后，本征荧光和组织光学特性、吸收和折减散射系数被组合成一个新参数：Ω。结果：首先，25 mg 贝伐珠单抗-800CW 的剂量可以清楚地区分 PTS 和健康组织，目标背景比 (TBR) 为 2.98（IQR：1.86-3.03）。此外，我们发现较深的食管 PTS 层和疑似 LN 与健康组织相比存在明显差异，TBR 值分别为 2.18 和 2.17。最后，我们的新参数 omega 进一步提高了区分 PTS 和健康组织的能力。结论：将 bevacizumab-800CW 与 US-qFME 相结合可能作为监测 EC 中 nCRT 反应的可行策略，并可能有助于对主动监测与手术进行患者分层。