A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound

Abstract

BackgroundPancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60–90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma.MethodsAn electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ 2, and Cochran’s Q test for heterogeneity among studies. The I2 was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias.ResultsThe meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ 2 (variance among studies) was 0.195, and I2 (percentage of variation among studies) was 40% (95% CI: 1–64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76–86).ConclusionsHIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

Effects of high‑intensity focused ultrasound treatment on peripancreatic arterial and venous blood vessels in pancreatic cancer

“…It was first reported in 2000 that HIFU successfully ablates and treats pancreatic cancer (29). Several studies have confirmed the safety and efficacy of HIFU in the treatment of pancreatic cancer (10,(14)(15)(16)(19)(20)(21)(22)(23)(24)(25)(29)(30)(31)(32)(33)(34). The most common complications observed following HIFU treatment of pancreatic cancer include skin burns (10,15,17,(21)(22)(23)(30)(31)(32), pancreatitis (10,18,23,31,32), duodenal fistula (23,31) and obstructive jaundice (19,34).…”

“…widely used in the treatment of uterine fibroids and hepatocellular carcinoma, with good therapeutic results (12). Previous studies have confirmed that HIFU therapy effectively alleviates cancer-associated abdominal pain, reduces tumor volume and may confer an additional survival benefit (11,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). However, vascular complications caused by this treatment have been reported, including secondary occlusion of the superior mesenteric artery (24) and portal vein thrombosis (25).…”

<p>High-intensity focused ultrasound enhances the effect of bufalin by inducing apoptosis in pancreatic cancer cells</p>

“…[21][22][23][24][25] Results from a meta-analysis showed that approximately 80% of patients with advanced PC who received HIFU therapy experienced pain reduction. 26 Ji et al 27 also reported that HIFU treatment was effective and the adverse events (AEs) associated with the treatment were rare and tolerable, especially for old patients and those with poor performance status. 28 Our previous study was also consistent with these results.…”

Focused ultrasound for immuno-adjuvant treatment of pancreatic cancer: An emerging clinical paradigm in the era of personalized oncotherapy

“…Typical study endpoints have included safety and feasibility confirmation, tumor volume reduction, and pain relief [104–110]. A comprehensive review of all clinical treatment series employing palliative FUS therapy for pancreatic cancer treatment is beyond the scope of this paper; but we direct the reader to an excellent recent meta-analysis by Dababou et a l that examined 23 studies on this topic and showed an overall pain reduction in 81% of treated patients (95% CI: 76–86) [111]. A recent, moderately powered (n=689) retrospective analysis from China revealed an independent median overall survival benefit from ablative FUS treatment for patients with unresectable PDA who also received a variety of multi-modal treatment regimens, without severe adverse events (7.1 versus 5 months; p=0.005) [112].…”