Combination of chemotherapy and focused ultrasound for the treatment of unresectable pancreatic cancer: a proof-of-concept study.

OBJECTIVES: To investigate the safety and preliminary efficacy of the combined treatment of focused ultrasound (FUS) and chemotherapy (nab-paclitaxel plus gemcitabine, nPac/Gem) for patients with unresectable pancreatic cancer. METHODS: Patients pathologically diagnosed with unresectable pancreatic cancer were included. Low (Isppa = 1.5 kW/cm2), intermediate (2.0 kW/cm2), and high (2.5 kW/cm2) FUS intensity treatment groups were predefined. A 1% duty cycle and the 3+3 scheme were used. Six combined treatments were performed, and adverse events were assessed. Changes in tumor size and tumor response, CA 19-9 level, and patient-reported outcomes at the immediate follow-up (F/U) and/or at the 3-month F/U and survival were evaluated. RESULTS: Three participants were enrolled in each intensity group. No adverse device effect or dose-limiting toxicity occurred in any of the participants. Seven of the nine participants experienced a >15% tumor size decrease at the immediate F/U CT and at the 3-month F/U CT. The CA 19-9 level decreased in all of the participants at the immediate F/U. All participants in the intermediate-intensity treatment group showed a > 30% tumor size decrease, partial response, and a significant decrease in the CA 19-9 level at 3-month F/U and longer survival (p < 0.05). CONCLUSION: FUS with an intensity of 1.5 to 2.5 kW/cm2 was safe in the combined treatment of FUS and nPac/Gem. Considering the results of the change in tumor size, the change in CA 19-9 level, tumor response, and survival, these FUS parameters can be used for subsequent clinical trials. KEY POINTS: • No adverse device effect or dose-limiting toxicity occurred in any of the participants when focused ultrasound with an intensity of 1.5-2.5 kW/cm2 and a low duty cycle of 1% was combined with chemotherapy. • The intermediate-intensity group showed a >30% tumor size decrease, partial response, and a significant decrease in CA 19-9 in all of the participants at the 3-month follow-up and the longest survival. • Any focused ultrasound setting used in this study could be safe and optimal for subsequent clinical trials.

Optimization of structural variables of a flextensional transducer by the statistical multiple regression analysis method.

The performance of an acoustic transducer is determined by the effects of many structural variables, and in most cases the influences of these variables are not linearly independent of each other. To achieve optimal performance of an acoustic transducer, we must consider the cross-coupled effects of its structural variables. In this study, with the finite-element method, the variation of the operation frequency and sound pressure of a flextensional transducer in relation to its structural variables is analyzed. Through statistical multiple regression analysis of the results, functional forms of the operation frequency and sound pressure of the transducer in terms of the structural variables were derived, with which the optimal structure of the transducer was determined by means of a constrained optimization technique, the sequential quadratic programming method of Phenichny and Danilin. The proposed method can reflect all the cross-coupled effects of multiple structural variables, and can be extended to the design of general acoustic transducers.