Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013.

中文翻译：

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使用氨基乙酰丙酸的术中荧光成像检测非常隐匿的乳腺癌：一项 II 期随机对照试验

由于保乳手术 (BCS) 后的正切缘而再次切除会对患者的预后和医疗保健成本产生负面影响。无法可视化边缘参与是 BCS 的一个重大挑战。5-氨基乙酰丙酸盐酸盐 (5-ALA HCl) 是一种非荧光口服前药，可导致癌细胞中荧光卟啉的细胞内积累。这项单中心 II 期随机对照试验评估了原型手持式荧光成像设备加 5-ALA 在 BCS 术中对浸润性乳腺癌进行可视化的安全性、可行性和诊断准确性。54 名患者被纳入并随机接受不接受 5-ALA 或口服 5-ALA HCl（15 或 30 mg/kg）。45 名患者（n = 15/组）被纳入分析。对切​​除的手术标本进行荧光成像，并从大体标本临床分界的肿瘤边界内外收集活组织检查，用于盲法组织病理学。在没有 5-ALA 的情况下，组织自发荧光成像缺乏肿瘤特异性荧光对比度。两种 5-ALA 剂量都引起亮红色的肿瘤荧光，与正常组织的自发荧光相比，肿瘤的可视化得到改善。在 15 mg/kg 5-ALA 组中，检测粗略划分的肿瘤边界内外乳腺癌的阳性预测值 (PPV) 分别为 100.0% 和 55.6%。在 30 mg/kg 5-ALA 组中，PPV 在划定的肿瘤边界内外分别为 100.0% 和 50.0%。没有观察到不良事件，并证实了这种成像设备-5-ALA组合方法的临床可行性。这是使用实时手持术中荧光成像设备在浸润性乳腺癌中可视化 5-ALA 诱导荧光​​的第一个已知临床报告。Clinicaltrials.gov 标识符 NCT01837225。2013 年 4 月 23 日注册。