Massachusetts General Hospital, Boston.
MD Anderson Cancer Center, Houston.
NEJM Evid. 2023 Jul;2(7):EVIDoa2200333. doi: 10.1056/EVIDoa2200333. Epub 2023 Apr 27.
Although lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery. METHODS: In this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity. RESULTS: Overall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine. CONCLUSIONS: The use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)
尽管保乳术和乳房切除术为乳腺癌患者提供了等效的生存机会，但保乳术后局部复发会增加乳腺癌的死亡率。阳性切缘，即意味着肿瘤切除不完全，是局部复发的最强预测指标，在手术后几天即可确定，需要进行第二次手术。方法：在这项前瞻性试验中，我们评估了 0 期至 3 期乳腺癌患者使用或不使用 pegulicianine 荧光引导手术（pFGS）的切缘状态。为了防止外科医生因预期 pFGS 辅助而进行小于标准的保乳术，患者以 10:1 的比例随机分配到 pFGS 组或对照组，因此随机分组不是为了为评估设备性能提供对照组。在接受 pFGS 的患者中，在 pegulicianine 信号部位切除额外的 pFGS 引导的腔缘。我们评估了三个主要终点：pFGS 引导的切缘含有癌症的患者百分比、敏感性和特异性。结果：总体而言，406 例患者接受了 1.0mg/kg 静脉注射 pegulicianine，随后进行保乳术。在随机分配的 392 例患者中，316 例患有浸润性癌，76 例患有原位癌。在 357 例接受 pFGS 的患者中，有 27 例 pFGS 引导的切缘切除了标准保乳术后遗留的肿瘤，其中 22 例来自标准切缘评估认为阴性的腔取向。pFGS 在 62 例阳性切缘患者中的 9 例中避免了第二次手术。在每切缘分析中，pFGS 的特异性为 85.2%，敏感性为 49.3%。由于不良事件，有 6 例患者停止了 pegulicianine 给药。有 2 例患者发生与 pegulicianine 相关的 3 级严重不良事件。结论：pFGS 在乳腺癌手术中的应用达到了清除残留肿瘤和特异性的预设阈值，但未达到预设的敏感性阈值。（由 Lumicell, Inc. 和美国国立卫生研究院资助；Clinicaltrials.gov 编号，NCT03686215。）
