Paolo Giorgio Arcidiacono MD FASGE

Transcription

1 LOCAL ABLATIVE TREATMENT OF PANCREATIC SOLID LESIONS. WHERE ARE WE NOW? Paolo Giorgio Arcidiacono MD FASGE Pancreato-Biliary Endoscopy & Endosonography Division Pancreas Translational & Clinical Research Center San Raffaele Scientific Institute IRCCS Vita Salute San Raffaele University Milan, Italy

2 Background Pancreatic ductal adenocarcinoma (PDAC) cancer still carries a poor prognosis SEER Stat Fact Sheets: Pancreas Cancer.

3 Rationale for local treatment Locally advanced cancer Increase resection rate Reduce metastatic tumour spreading Treat recurrence after surgery Increase survival

4 Ablative therapies Surgical open or laparoscopic access EUS guided access

5 J Surg Oncol Oct 1;94(5): High operative risk of cool-tip radiofrequency ablation for unresectable pancreatic head cancer. Wu Y, Tang Z, Fang H, Gao S, 12 pts open surgery without guidance Cool-tip RFA Monopolar Complications 18.8% pancreatic fistula 25% mortality haemorrhage High temperature (> 100 ) and long application time (> 10 min) Standard use of cool-tip RFA was dangerous for pancreatic head cancer close to portal vein, in which a 5-mm minimum safe distance between RFA site and major peripancreatic vessels might not be enough to avoid injury to the vessels.

6 24% abdominal complications 3% deaths

7

8

9

10 EUS Thermal Ablation The potential advantage of the application of an ablation device under EUS control is its real-time imaging guidance into a deeply located target like the pancreas which is extremely difficult to reach by a percutaneous approach the mini-invasive approach when compared to the RF treatment during laparoscopic or open surgery Subsequent treatments

11 EUS Guided Radiofrequency Ablation in the Pancreas: Results in a Porcine Model Goldberg, et al. GIE 1999; Vol. 50, No.3, pp. 392 Pathology: discrete, 8-12 mm foci of coagulation necrosis.

12

13 Type of study Patients number Setting Results Previous ex-vivo Animal study 6 bovine liver samples W 6 minutes 50 W showed the most effective depth and size of ablation zone (> respect to 30 and 80 W) 80 W produced higher tip temperatures, tissue charring (not coagulative necrosis) In vivo Animal study 10 Adult pigs RFA EUS-guided (body-tail) 18 G needle (1 cm active electrode) 50 W 5 minutes Technically feasible. Well-demarcated discrete ablation zone with a peripheral wall of fibrosis. Diam of ablate zone: 14.5 ± 1.5 mm (EUS) 23 ± 1.5 mm (hysto) No significant complications except for intestinal wall adhesions and retroperitoneal fibrosis located at the adjacent organs. Kim HJ et al. Gastrointest Endosc 2012;76(5):

14 Type of study Patients number Setting Results In vivo human case series 3 tertiary care centres 3 patients with a symptomatic pancreatic insulinoma, not eligible for surgery To avoid any thermal injury to adjacent normal pancreatic tissue, lesions larger than 1 cm were preferred RFA EUS-guided 19 G needle (1-cm length of exposed needle electrode) 50 W sec If needed the electrode is repositioned under EUS visualization to ablate another proximal area along the same trajectory. Additional passes can be used to further ablate the same lesion Rapid symptom relief with biochemical improvement in all the patients (EUS necrosis after seconds of treatment: mm x 5 mm) No procedure-related adverse events Patients symptom-free at 11 to 12 months of follow-up) Follow-up: blood tests, CT-scan and EUS Lakhtakia S et al. Gastrointest Endosc 2016;83(1):234-9

15 Type of study Patients number Setting Results In vivo Human Feasibility Safety 6 unresectable pancreatic cancers (3,8 cm mean size of lesions) RFA EUS-guided 18 G needle (1 cm length of the exposed tip of the RFA electrode) 20 to 50 W ablation power 10 seconds time of ablation Depending on tumor size the procedure was REPEATED to sufficiently cover the tumor (until the hyperechoic zone around the electrode tip sufficiently covered the tumor) (+ punctures, 2 treatments in 2 patients) Feasibility study: technical success and safety. No major adverse events (2 abdominal pain)-no procedure-related mortality. (control post-rfa with contrastenhanced EUS) Large tumors required multiple needle punctures and RFA applications suboptimal treatment (but systemic antitumor immune response?). Limited follow-up duration (max 6 month) Song TJ et al. Gastrointest Endosc 2016;83(2):440-3

16 Habib RFA EUS Probe

17

18 Hybrid-Therm hybrid cryotherm probe (Hybrid-Therm ERBE, Germany) combines bipolar RF-ablation with cryotechnology (CT). is basically a bipolar RF ablation probe that is internally cooled with carbon dioxide, which allows efficient cooling A bipolar system is assumed to create ablations with less collateral thermal damage than monopolar systems but with the trade-off to loose over all efficiency. the more effective cooling by cryogenic gas increases the RFinduced interstitial devitalization, having additional devitalizing effects same effect with less power

19 22/40 HybridTherm: bipolar gas-cooled RFA probe ERBECRYO 2 HybridTherm Probe VIO 300D Ø Probe = 2.2 mm ( 14 G) Ø Sheath= 3.1 mm ( 11 G) Electrodes Lengh = 1400 mm (55 inch) US mark

20 HybridTherm: bipolar gas-cooled RFA probe Electrodes CO 2 CO 2 Necrotic cooling Zone 23

21 Endoscopy 2008 Feasibility, efficacy, safety Histological changes complications 14 pigs Application time range s

22 Petrone MC et al. Gastrointest Endosc 2010 Effective in destroying neoplastic pancreatic tissue The extent of necrotic area related to application time

23 Arcidiacono PG et al. Primary Endpoints - Feasibility - Safety Results CTP successfully applied in 73% (16/22) Safe procedure

24 Results 35 patients with unresectable stage III PDAC (after CT and/or RT) EUS-HTP was feasible in 26/35 pts (74.3%); EUS-HTP was not possible in 9/35 pts (25.7%) due to tumor stiffness, vessel interposition or post-surgical altered anatomy; the ablation time was significantly dependent on the tumor size, with a mean duration of seconds (range ).

25 Results CT scans were able to determine the lesion volumes in 24/26 pts (92.3%) and of the necrotic area in 16/26 pts (61.5%);

26 Results No significant changes in the absolute tumor volumes (ATV) were observed during the first and second post treatment evaluation, compared to the pre-treatment CT evaluation Mean ATV ± SD (mm 3 ) at CT-scan evaluation Mean (range) time after EUS-HTP (days) P = P = CT scan pre- HTP 29.9 ± I CT scan post-htp 35.6 ± (2 56) II CT scan post-htp ± (13 100)

27 1. significant positive correlation between the ablation time and the necrotic tissue volume 2. significant positive correlation between the ablation volume and absolute volume. The longer the ablation duration was and the larger the absolute lesion volume, the larger was the ablation volume. 1. Correlation Ablation Time - Necrotic Volume after the first CT (R = 0.66, p = 0.013) 2. Correlation Absolute Volume and Ablated Volume (R = 0.92, p < )

28 Survival An analysis of the median survival time for patients treated only once and for those treated two or more times revealed an increase of the survival time from 5 to 9 month (p=0.066). The overall median post-htp survival time (one or more HTP treatments) was 6 month (range 1-22 month), with 2 patients still alive (3 and 9 month after HTP). Kaplan-Meier survival curve

29

30 Conclusions Local ablative treatment are a promising tool to be included in the multimodality treatment of locally advanced pancreatic cancer Further data and prospective studies are needed to define its efficacy in different clinical settings

31

32 Multicenter Phase II-III Randomized controlled study of CT vs CT+HTP in the treatment of borderline resectable and locally advanced pancreatic cancer PG Arcidiacono Milan, Italy Iglesias Garcia Santiago, Spain Zhou Shanghai, China Neuhaus Dusseldorf, Germany Reddy Hyderabad, India Deprez, Bruxelles, Belgium

33