Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence.
Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence.
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DOI：
10.1158/0008-5472.can-18-0878
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发表时间：
2018-09-01
期刊：
影响因子：
11.2
通讯作者：
Rosenthal EL
中科院分区：
文献类型：
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作者：
Gao RW;Teraphongphom NT;van den Berg NS;Martin BA;Oberhelman NJ;Divi V;Kaplan MJ;Hong SS;Lu G;Ertsey R;Tummers WSFJ;Gomez AJ;Holsinger FC;Kong CS;Colevas AD;Warram JM;Rosenthal EL
对于许多实体瘤，手术切除仍然是金标准，肿瘤累及边缘与不良临床结局相关。近红外（NIR）荧光成像，使用分子剂已显示出在原位成像切除过程中的承诺。然而，对于成像条件困难的癌症，手术价值可能在于手术标本的肿瘤映射。因此，我们评估了一种新的方法，实时，术中肿瘤边缘评估。入组了21例计划接受标准治疗手术的经活检证实的头颈部鳞状细胞癌（HNSCC）成人患者。队列1（n=3）接受0.06 mg/kg静脉微剂量帕尼单抗-IRDye 800 CW，队列2A（n=5）接受0.5 mg/kg，队列2B（n=7）接受1 mg/kg，队列3（n=6）接受50 mg。在输注后30天对患者进行随访，并记录不良事件。使用几种闭合和宽视野设备进行成像。荧光与组织学相关，以确定灵敏度和特异性。原位成像显示肿瘤与背景比（TBR）为2-3，而离体标本成像TBR为5-6。我们获得了肿瘤和正常组织之间的明确区分，阳性和阴性标本之间的三倍信号差异（p<0.05）。我们实现了荧光强度与肿瘤位置的高度相关性，灵敏度和特异性>89%;荧光预测了肿瘤组织到标本切割表面的距离。这种使用癌症特异性试剂检测手术标本中涉及肿瘤的边缘的新方法在具有复杂解剖结构的切除中提供了高度灵敏和特异性的实时术中手术导航，否则这些解剖结构不太适合图像引导。
For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor-mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. 21 adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 (n=3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A (n=5) received 0.5mg/kg, cohort 2B (n=7) received 1mg/kg, and cohort 3 (n=6) received 50 mg. Patients were followed 30 days post-infusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. In situ imaging demonstrated tumor-to-background ratio (TBR) of 2-3, compared to ex vivo specimen imaging TBR of 5-6. We obtained clear differentiation between tumor and normal tissue, with a three-fold signal difference between positive and negative specimens (p<0.05). We achieved high correlation of fluorescence intensity with tumor location with sensitivities and specificities >89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy which are otherwise less amenable to image guidance.