Hwang E Shelley, Beitsch Peter, Blumencranz Peter, Carr David, Chagpar Anees, Clark Lynne, Dekhne Nayana, Dodge Daleela, Dyess Donna L, Gold Linsey, Grobmyer Stephen, Hunt Kelly, Karp Stephen, Lesnikoski Beth-Ann, Wapnir Irene, Smith Barbara L
Duke Cancer Institute and Duke University Health System, Durham, North Carolina.
Dallas Surgical Group, Dallas, Texas.
JAMA Surg. 2022 Jul 1;157(7):573-580. doi: 10.1001/jamasurg.2022.1075.
Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time.
To collect safety and initial efficacy data on the novel pegulicianine fluorescence-guided system (pFGS) when used to identify residual cancer in the tumor bed of female patients undergoing BCS.
DESIGN, SETTING, AND PARTICIPANTS: This prospective single-arm open-label study was conducted as a nonrandomized multicenter controlled trial at 16 academic or community breast centers across the US. Female patients 18 years and older with newly diagnosed primary invasive breast cancer or ductal carcinoma in situ DCIS undergoing BCS were included, excluding those with previous breast cancer surgery and a history of dye allergies. Of 283 consecutive eligible patients recruited, 234 received a pegulicianine injection and were included in the safety analysis; of these, 230 were included in the efficacy analysis. Patients were enrolled between February 6, 2018, and April 10, 2020, and monitored for a 30-day follow-up period. Data were analyzed from April 10, 2020, to August 5, 2021.
Participants received an injection of a novel imaging agent (pegulicianine) a mean (SD) of 3.2 (0.9) hours prior to surgery at a dose of 1 mg/kg. After completing standard of care (SOC) excision, pFGS was used to scan the lumpectomy cavity to guide the removal of additional shave margins.
Adverse events and sensitivity, specificity, and reexcision rate.
Of 234 female patients enrolled (median [IQR] age, 62.0 [55.0-69.0] years), 230 completed the trial and 1 patient with a history of allergy to contrast agents had an anaphylactic reaction and recovered without sequelae. Correlation of pFGS with final margin status on a per-margin analysis showed a marked improvement in sensitivity over standard pathology assessment of the main lumpectomy specimen (69.4% vs 38.2%, respectively). On a per-patient level, the false-negative rate of pFGS was 23.7% (9 of 38), and sensitivity was 76.3% (29 of 38). Among 32 patients who underwent excision of pFGS-guided shaves, pFGS averted the need for reexcision in 6 (19%).
In this pilot feasibility study, the safety profile of pegulicianine was consistent with other imaging agents used in BCS, and was associated with a reduced need for second surgery in patients who underwent intraoperative additional excision of pFGS-guided shaves. These findings support further development and clinical performance assessment of pFGS in a prospective randomized trial.
ClinicalTrials.gov Identifier: NCT03321929.
保乳手术（BCS）后切缘阳性在标准病理评估中常被发现。术中对乳房肿块切除腔进行评估有可能实时降低标准治疗BCS后的残留疾病或再次切除率。
收集新型派古利西宁荧光引导系统（pFGS）用于识别接受BCS的女性患者肿瘤床残留癌时的安全性和初步疗效数据。
设计、设置和参与者：这项前瞻性单臂开放标签研究作为一项非随机多中心对照试验，在美国16个学术或社区乳腺中心进行。纳入年龄在18岁及以上、新诊断为原发性浸润性乳腺癌或原位导管癌（DCIS）且接受BCS的女性患者，排除既往有乳腺癌手术史和染料过敏史的患者。在连续招募的283例符合条件的患者中，234例接受了派古利西宁注射并纳入安全性分析；其中，230例纳入疗效分析。患者于2018年2月6日至2020年4月10日入组，并进行了30天的随访监测。数据于2020年4月10日至2021年8月5日进行分析。
参与者在手术前平均（标准差）3.2（0.9）小时接受一剂新型成像剂（派古利西宁）注射，剂量为1mg/kg。在完成标准治疗（SOC）切除后，使用pFGS扫描乳房肿块切除腔，以指导切除额外的剃除边缘组织。
不良事件以及敏感性、特异性和再次切除率。
在纳入的234例女性患者中（中位[四分位间距]年龄，62.0[55.0 - 69.0]岁），230例完成试验，1例有造影剂过敏史的患者发生过敏反应，恢复后无后遗症。在逐边缘分析中，pFGS与最终切缘状态的相关性显示，其敏感性比主要乳房肿块切除标本的标准病理评估有显著提高（分别为69.4%和38.2%）。在患者层面上，pFGS的假阴性率为23.7%（38例中的9例），敏感性为76.3%（38例中的29例）。在32例接受pFGS引导下剃除组织切除的患者中，pFGS避免了6例（19%）患者的再次切除。
在这项初步可行性研究中，派古利西宁的安全性与BCS中使用的其他成像剂一致，并且与接受术中pFGS引导下额外切除剃除组织的患者二次手术需求减少相关。这些发现支持在一项前瞻性随机试验中对pFGS进行进一步开发和临床性能评估。
ClinicalTrials.gov标识符：NCT03321929。
