Background

Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma, with positive margins in 30–70% of patients. In this study, we aimed to evaluate the use of intraoperative tumour-specific imaging to enhance a surgeon's ability to detect visually occult cancer in real time.

Methods

In this single-centre, open-label, single-arm study, done in the USA, we enrolled patients who had clinically suspicious or biopsy-confirmed pancreatic ductal adenocarcinomas and were scheduled for curative surgery. Eligible patients were 19 years of age or older with a life expectancy of more than 12 weeks and a Karnofsky performance status of at least 70% or an Eastern Cooperative Oncology Group or Zubrod level of one or lower, who were scheduled to undergo curative surgery. Patients were sequentially enrolled into each dosing group and 2–5 days before surgery, patients were intravenously infused with 100 mg of unlabelled panitumumab followed by 25 mg, 50 mg, or 75 mg of the near-infrared fluorescently labelled antibody (panitumumab-IRDye800CW). The primary endpoint was to determine the optimal dose of panitumumab-IRDye800CW in identifying pancreatic ductal adenocarcinomas as measured by tumour-to-background ratio in all patients. The tumour-to-background ratio was defined as the fluorescence signal of the tumour divided by the fluorescence signal of the surrounding healthy tissue. The dose-finding part of this study has been completed. This study is registered with ClinicalTrials.gov, NCT03384238.

Findings

Between April, 2018, and July, 2019, 16 patients were screened for enrolment onto the study. Of the 16 screened patients, two (12%) patients withdrew from the study and three (19%) were not eligible; 11 (69%) patients completed the trial, all of whom were clinically diagnosed with pancreatic ductal adenocarcinoma. The mean tumour-to-background ratio of primary tumours was 3·0 (SD 0·5) in the 25 mg group, 4·0 (SD 0·6) in the 50 mg group, and 3·7 (SD 0·4) in the 75 mg group; the optimal dose was identified as 50 mg. Intraoperatively, near-infrared fluorescence imaging provided enhanced visualisation of the primary tumours, metastatic lymph nodes, and small (<2 mm) peritoneal metastasis. Intravenous administration of panitumumab-IRDye800CW at the doses of 25 mg, 50 mg, and 75 mg did not result in any grade 3 or higher adverse events. There were no serious adverse events attributed to panitumumab-IRDye800CW, although four possibly related adverse events (grade 1 and 2) were reported in four patients.

Interpretation

To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumour-specific intraoperative imaging might have added value for treatment of patients with pancreatic ductal adenocarcinomas through improved patient selection and enhanced visualisation of surgical margins, metastatic lymph nodes, and distant metastasis.

Funding

National Institutes of Health and the Netherlands Organization for Scientific Research.

中文翻译：

---

使用帕尼单抗-IRDye800CW 治疗胰腺癌的肿瘤特异性荧光引导手术：1 期单中心、开放标签、单臂、剂量递增研究。

背景

完全手术切除仍然是胰腺导管腺癌的主要治疗选择，30-70% 的患者切缘阳性。在这项研究中，我们旨在评估术中肿瘤特异性成像的使用，以提高外科医生实时检测视觉隐匿性癌症的能力。

方法

在这项在美国进行的单中心、开放标签、单臂研究中，我们招募了临床可疑或活检证实为胰腺导管腺癌并计划接受治愈性手术的患者。符合条件的患者为 19 岁或以上、预期寿命超过 12 周且 Karnofsky 体能状态至少为 70% 或东部肿瘤合作组或 Zubrod 水平为 1 或更低，并计划接受治愈性手术的患者。患者被依次纳入每个给药组，并在手术前 2-5 天，向患者静脉输注 100 mg 未标记的帕尼单抗，然后是 25 mg、50 mg 或 75 mg 的近红外荧光标记抗体（帕尼单抗-IRDye800CW） . 主要终点是确定帕尼单抗-IRDye800CW 在识别胰腺导管腺癌中的最佳剂量，通过所有患者的肿瘤与背景比来衡量。肿瘤与背景比定义为肿瘤的荧光信号除以周围健康组织的荧光信号。该研究的剂量发现部分已经完成。本研究已在 ClinicalTrials.gov 注册，NCT03384238。

发现

在 2018 年 4 月至 2019 年 7 月期间，对 16 名患者进行了筛选以参加研究。在 16 名接受筛查的患者中，两名 (12%) 患者退出研究，三名 (19%) 患者不符合条件；11 名（69%）患者完成了试验，所有患者均被临床诊断为胰腺导管腺癌。原发肿瘤的平均肿瘤与背景比在 25 mg 组中为 3·0 (SD 0·5)，在 50 mg 组中为 4·0 (SD 0·6) 和 3·7 (SD 0·5) 4) 在 75 mg 组中；最佳剂量被确定为 50 毫克。术中，近红外荧光成像增强了对原发肿瘤、转移性淋巴结和小 (<2 mm) 腹膜转移的可视化。以 25 mg、50 mg 和 75 mg 的剂量静脉注射帕尼单抗-IRDye800CW 未导致任何 3 级或更高级别的不良事件。

解释

据我们所知，这项研究首次展示了帕尼单抗-IRDye800CW 用于检测胰腺导管腺癌的临床应用，并表明帕尼单抗-IRDye800CW 在胰腺癌手术中是安全可行的。通过改进患者选择和增强手术切缘、转移淋巴结和远处转移的可视化，肿瘤特异性术中成像可能为胰腺导管腺癌患者的治疗增加价值。

资金

美国国立卫生研究院和荷兰科学研究组织。