保乳术中实时检测残留乳腺癌的新方法

　　获得无肿瘤切缘，对于预防乳腺癌保乳术后复发至关重要。不过，现有手术方法残留阳性切缘造成20%～40%的患者进行第二次手术，故亟需保乳术中实时检测残留乳腺癌的新方法。

　　2020年1月2日，美国乳腺外科医师学会和美国肿瘤外科学会《肿瘤外科学报》在线发表哈佛大学麻省总医院、细胞发光技术公司的研究报告，探讨了新型蛋白酶激活荧光成像系统（LUM）保乳术中实时检测残留乳腺癌的可行性。

　　该研究入组拟行乳腺癌手术女性45例，术前按每公斤体重静脉注射1毫克可被肿瘤细胞周围蛋白酶激活的LUM015荧光剂，术中手持无菌探头，通过LUM成像系统，对乳腺肿瘤切除腔壁和切除标本可能残留肿瘤部位的荧光进行定量分析，并将实时预测结果显示于监视器，随后与组织病理学检查结果进行关联，包括乳腺导管浸润癌、乳腺小叶浸润癌、乳腺导管原位癌。

　　结果，40例患者共计570个乳腺肿瘤切除腔壁切缘表面被用于残留乳腺癌算法制定，影像分析并显示每2.6厘米直径圆形切缘表面大约需要1秒。所有乳腺癌亚型都可以与邻近正常组织进行区分。

　　对于所有成像的乳腺肿瘤切除腔壁表面，肿瘤检测的真阳性率为84%。真阴性率为73%，某些良性组织显示荧光信号增加。

　　对于8例标准术后切缘阳性患者，残留肿瘤检测的真阳性率为100%；其中2例由于LUM015荧光剂信号位于已被切除的额外组织，故避免了进行第二次手术。

　　因此，该研究结果表明，LUM015荧光剂和LUM成像系统可以快速发现乳腺癌患者乳腺肿瘤切除腔内残留的肿瘤，并可减少切缘阳性率。

Ann Surg Oncol. 2020 Jan 2. [Epub ahead of print]

Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery.

Barbara L. Smith, Conor R. Lanahan, Michelle C. Specht, Bridget N. Kelly, Carson Brown, David B. Strasfeld, Jorge M. Ferrer, Upahvan Rai BS, Rong Tang, Travis Rice-Stitt, Anna Biernacka, Elena F. Brachtel, Michele A. Gadd.

Massachusetts General Hospital, Boston, MA, USA; Lumicell, Inc, Newton, MA, USA.

BACKGROUND: Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20-40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor.

METHODS: Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with real-time predictive results displayed on a monitor intraoperatively, and later correlated with histopathology.

RESULTS: In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter circular margin surface. All breast cancer subtypes could be distinguished from adjacent normal tissue. For all imaged cavity surfaces, sensitivity for tumor detection was 84%. Among 8 patients with positive margins after standard surgery, sensitivity for residual tumor detection was 100%; 2 of 8 were spared second surgeries because additional tissue was excised at sites of LUM015 signal. Specificity was 73%, with some benign tissues showing elevated fluorescent signal.

CONCLUSIONS: The LUM015 agent and LUM Imaging System allow rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.

DOI: 10.1245/s10434-019-08158-1