Department of Gastroenterology, Indiana University Health Medical Center, Indianapolis, Indiana, USA.
Department of Radiology, Indiana University Health Medical Center, Indianapolis, Indiana, USA.
Gastrointest Endosc. 2019 Feb;89(2):390-398. doi: 10.1016/j.gie.2018.09.007. Epub 2018 Sep 14.
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.
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/ m intravenously) and gemcitabine (1000 mg /m intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity.
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 cm (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.
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.).
局部晚期胰腺癌（LAPC）预后不良。目前有关人类胰腺癌光动力疗法（PDT）应用的数据有限。我们假设 EUS 引导 PDT 治疗 LAPC 是安全的，技术上可行的，并产生剂量和时间依赖性的肿瘤坏死程度增加。
在一项单中心、前瞻性、剂量递增的 1 期研究中，治疗初治的 LAPC 患者接受静脉注射血卟啉单甲醚（Concordia Laboratories Inc，巴巴多斯圣迈克尔），2 天后接受 EUS-PDT。EUS-PDT 通过 19 号穿刺针穿刺和插入 1.0 厘米的光扩散器（Pioneer Optics，康涅狄格州布鲁姆菲尔德），并用 630nm 光（Diomed Inc，马萨诸塞州安多弗）照射进行。PDT 后 18 天进行 CT 扫描以评估胰腺坏死的变化。Nab-紫杉醇（125mg/m 静脉内）和吉西他滨（1000mg/m 静脉内）在 CT 后 7 天开始，并在 4 周内每周给予 3 次（1 个周期），直至疾病进展或不可接受的毒性。
12 例（平均年龄 67±6 岁；8 例男性）患者的肿瘤位于头部和/或颈部（8 例）或体部和/或尾部（4 例），接受了 EUS-PDT。与基线影像学相比，EUS-PDT 后 6 例（50%）患者的肿瘤体积和坏死百分比增加。总体坏死体积和百分比的平均增加分别为 10±26cm（P=0.20）和 18%±22%（P=0.016）。中位随访 10.5 个月（范围 1.0-37.4 个月）后，中位无进展生存期（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）。2 例患者尝试手术切除，病理显示完全缓解（n=1）和残留 2mm 肿瘤（n=1）。发生 8 例严重不良事件，均与 EUS 或 EUS-PDT 无关。
EUS-PDT 治疗 LAPC 似乎是安全的，并可产生可测量的影像学定义的肿瘤坏死。需要进行 2 期研究。（临床试验注册号：NCT01770132.）。
