Abstract
Objective
Preclinical trials have demonstrated promising results for increased tumor uptake and therapeutic effect of drugs combined with focused ultrasound (FUS) and microbubbles (MBs). The aim of this clinical trial was to investigate whether FUS and MB could improve the effect of chemotherapy in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) and to investigate safety and feasibility.
Methods
Twenty patients with inoperable PDAC were included and randomized for either chemotherapy combined with FUS and MBs or only chemotherapy, but one patient in the FUS and MB group had later to be excluded. A new dual-frequency transducer for imaging (4.5 MHz) and treatment (0.35 MHz) was used. After chemotherapy (FOLFIRINOX or nab-paclitaxel-gemcitabine), the treatment group was exposed to FUS (frequency 0.35 MHz, mechanical index 0.5, pulse length 2.9 ms (1000 cycles), pressure amplitude 0.3 MPa and MBs (SonoVue) for 35 min). Nine boluses of MBs were injected intravenously (i.v) with a 3.5 min interval. Patients were scheduled for two months of treatment. Changes in the size of tumors were determined from Computed Tomography (CT) -images.
Results
Treatment with FUS and MB is safe with the used settings. No additional effects of FUS and MBs regarding tumor volume or resectability were observed. Overall survival increased, from 9.8 months to 11.7 months for the patients receiving FUS + MB, although not statistically significant.
Conclusion
FUS combined with MBs is a safe, feasible, and available strategy for potentially improving the effect of chemotherapy in pancreatic cancer patients. Therapeutic effect was not demonstrated in this trial. Reducing the time between chemotherapy and injection of MB and FUS and optimization of ultrasound parameters may improve the treatment effect. Multicenter trials with standardized protocols should be performed.