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

• Published in: European radiology 2023-04, Vol.33 (4), p.2620-2628
• Main Authors: Lee, Jae Young, Oh, Do-Youn, Lee, Kyung-Hun, Lee, Sang Hyub, Lee, Dong Ho, Kang, Kookjin, Kang, Soo Yeon, Park, Dong Hyuk
• Format: Article
• Language: English
• Subjects: Albumins - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Cancer therapies; Chemotherapy; Clinical trials; Combined treatment; Constraining; Deoxycytidine - therapeutic use; Diagnostic Radiology; Gemcitabine; Humans; Imaging; Internal Medicine; Interventional; Interventional Radiology; Medicine; Medicine & Public Health; Neuroradiology; Paclitaxel; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - drug therapy; Patients; Radiology; Survival; Toxicity; Treatment Outcome; Tumors; Ultrasonic imaging; Ultrasound
• ISSN: 1432-1084; 0938-7994; 1432-1084
• DOI: 10.1007/s00330-022-09271-8

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/cm 2 ), intermediate (2.0 kW/cm 2 ), and high (2.5 kW/cm 2 ) 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/cm 2 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/cm 2 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 .