Efficacy of Endoscopic Ultrasound-Guided Ablation with the HybridTherm Probe in Locally Advanced or Borderline Resectable Pancreatic Cancer: A Phase II Randomized Controlled Trial

SIMPLE SUMMARY: Recently, tumour local thermal ablation has been investigated in pancreatic ductal adenocarcinoma (PDAC), hypothesizing that it may add local efficacy to the chemotherapy systemic activity inducing changes of tumour microenvironment and increased intra-tumour drug efficacy. In this phase II randomized controlled trial we investigated the efficacy of thermal ablation with the HybridTherm probe under endoscopic ultrasound-guidance (EUS) as complement to chemotherapy (HTP-CT arm) versus standard chemotherapy alone (CT arm), in locally advanced and borderline resectable PDAC. A sample size of 33 patients per arm was calculated to verify a 20% improved 6-months progression-free survival (6-PFS) rate with HTP-CT. We randomized 17 and 20 patients to HTP-CT and CT arms, respectively. Although not significantly, we found an improved 6-PFS rate in the HTP-CT arm. However, the overall survival was similar between the two arms. Thus, as the study is underpowered, further investigation of EUS-guided thermal ablation in selected patients is suggested. ABSTRACT: Endoscopic ultrasound-ablation with HybridTherm-Probe (EUS-HTP) significantly reduces tumour volume (TV) in locally-advanced pancreatic ductal adenocarcinoma (LA-PDAC). We aimed at investigating the clinical efficacy of EUS-HTP plus chemotherapy versus chemotherapy (HTP-CT and CT arms) in LA- and borderline-resectable (BR) PDAC, with 6-months progression-free survival (6-PFS) rate as primary endpoint. In a phase-II randomized-controlled-trial, 33 LA/BR-PDAC patients per-arm were planned to verify 20% improved 6-PFS rate. Radiological response (Choi criteria), TV and serum CA19.9 were assessed up to 6-months. Seventeen and 20 LA/BR-PDAC patients were randomized to HTP-CT or CT. Baseline and CT-related features were balanced. At 6-months, 6-PFS rate was 41.2% and 30% in HTP-CT and CT arms (p = 0.48), respectively. A decrease ≥50% of serum CA19.9 was achieved in 75% and 64.3% of HTP-CT and CT patients (p = 0.53), respectively. TV reduced up to 6-months in 64.3% and 47.1% of HTP-CT and CT patients (p = 0.35), respectively. Resection rate, PFS-time and overall survival (OS-time) were similar. HTP-CT achieves a non-significant 11.2%, 10.7% and 17.2% improved 6-PFS, CA19.9 decrease ≥50% and TV reduction rates over CT, without any impact on resection rate, PFS-time and OS-time. As the study was underpowered, these results suggest further investigation of EUS-local ablation in selected patients with localized disease after induction CT.