Background and Aims

Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible, and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis.

Methods

In a single-center, prospective, dose-escalation phase 1 study, patients with treatment-naïve LAPC received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael, Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics, Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover, Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic necrosis. Nab-paclitaxel (125 mg/ m² intravenously) and gemcitabine (1000 mg /m² intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity.

Results

Twelve patients (mean age, 67 ± 6 years; 8 male) with tumors (mean diameter, 45.2 ± 12.9 mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT. Compared with baseline imaging, increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50%) after EUS-PDT. The mean overall increases in volume and percentage necrosis were 10 ± 26 cm³ (P = .20) and 18% ± 22% (P = .016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4 months), median progression-free (PFS) and overall survival (OS) were 2.6 months (95% confidence interval, 0.7, not estimable) and 11.5 months (95% confidence interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2 patients, and pathology showed a complete response (n = 1) and residual 2-mm tumor (n = 1). There were 8 serious adverse events and none related to EUS or EUS-PDT.

Conclusion

EUS-PDT for LAPC appears to be safe and produces measurable imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial registration number: NCT01770132.)

中文翻译：

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EUS指导的光动力疗法治疗局部晚期胰腺癌的1期研究

背景和目标

局部晚期胰腺癌（LAPC）的预后较差。有限的数据描述了光动力疗法（PDT）在人类胰腺癌中的应用。我们假设，针对LAPC的EUS指导的PDT是安全的，技术上可行的，并且会产生剂量和时间依赖性的图像定义的肿瘤坏死程度增加。

方法

在一项单中心，前瞻性，剂量递增的1期研究中，未接受过LAPC治疗的患者接受了静脉注射porfimer钠（Concordia Laboratories Inc，圣迈克尔，巴巴多斯），随后2天后进行了EUS-PDT。EUS-PDT通过使用19号针头进行穿刺并插入1.0-cm的光扩散器（Pioneer Optics，Bloomfield，Conn）并用630-nm的光（Diomed Inc，Andover，Mass）进行照明来进行。PDT后18天进行CT扫描以评估胰腺坏死的变化。CT后7天开始使用Nab-紫杉醇（静脉注射125 mg / m ²）和吉西他滨（静脉注射1000 mg / m ²），每周一次，共4周中的3周（1个周期），直到疾病进展或出现不可接受的毒性。

结果

对12例头部和/或颈部（8）或身体和/或尾部（4）肿瘤（平均直径45.2±12.9毫米）的患者（平均年龄67±6岁；男性8位）进行了EUS-PDT。与基线显像相比，EUS-PDT后12例患者中有6例（50％）观察到肿瘤坏死的体积和百分比增加。体积和坏死百分比的平均总体增加为10±26 cm ³（P  = .20）和18％±22％（P = .016）。在中位随访10.5个月（范围1.0-37.4个月）后，中位无进展期（PFS）和总生存期（OS）分别为2.6个月（95％置信区间，0.7，不可估计）和11.5个月（95） ％置信区间1.1、16.9）。尝试手术切除的2例患者，病理显示完全缓解（n = 1）和残留的2毫米肿瘤（n = 1）。有8例严重不良事件，与EUS或EUS-PDT无关。

结论

用于LAPC的EUS-PDT似乎是安全的，并会产生可测量的影像明确的肿瘤坏死。必须进行2期研究。（临床试验注册号：NCT01770132。）