Concurrent FOLFIRINOX Plus High Intensity Focused Ultrasound for Pancreatic Cancer

Summary

In patients diagnosed with locally advanced pancreatic cancer (LAPC)/borderline resectable pancreatic cancer (BRPC) and planned chemotherapy using FOLFIRINOX, high intensity focused ultrasound (HIFU)/FOLFIRINOX combined treatment is performed on patients who agree to this study. The combined treatment group is treated in parallel with FOLFIRINOX and HIFU for the first four cycles and then CT is taken for reaction evaluation immediately, 2 months, and 4 months after the four-cycle treatment. For the response assessment, the response rate using RECIST ver. 1.1 and operable rate are evaluated and compared with the results of already established FOLFIRINOX single treatment in the investigators' institute. Time-to-progress and overall survival are calculated.

Timeline

Start

2021-08-09

Primary completion

2023-03

Completion

2024-12

Publications

• Background Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.
• Background Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Chone L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; Canadian Cancer Trials Group and the Unicancer-GI-PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. doi: 10.1056/NEJMoa1809775.
• Background Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernandez-Del Castillo C, Ferrone CR, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):963-969. doi: 10.1001/jamaoncol.2018.0329.
• Background Choi YH, Lee SH, You MS, Shin BS, Paik WH, Ryu JK, Kim YT, Kwon W, Jang JY, Kim SW. Prognostic Factors for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer Receiving Neoadjuvant FOLFIRINOX. Gut Liver. 2021 Mar 15;15(2):315-323. doi: 10.5009/gnl19182.
• Background Hackert T, Sachsenmaier M, Hinz U, Schneider L, Michalski CW, Springfeld C, Strobel O, Jager D, Ulrich A, Buchler MW. Locally Advanced Pancreatic Cancer: Neoadjuvant Therapy With Folfirinox Results in Resectability in 60% of the Patients. Ann Surg. 2016 Sep;264(3):457-63. doi: 10.1097/SLA.0000000000001850.
• Background Wu F, Wang ZB, Zhu H, Chen WZ, Zou JZ, Bai J, Li KQ, Jin CB, Xie FL, Su HB. Feasibility of US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer: initial experience. Radiology. 2005 Sep;236(3):1034-40. doi: 10.1148/radiol.2362041105. Epub 2005 Jul 29.
• Background Vidal-Jove J, Perich E, Del Castillo MA. Ultrasound Guided High Intensity Focused Ultrasound for malignant tumors: The Spanish experience of survival advantage in stage III and IV pancreatic cancer. Ultrason Sonochem. 2015 Nov;27:703-706. doi: 10.1016/j.ultsonch.2015.05.026. Epub 2015 May 27.
• Background Marinova M, Huxold HC, Henseler J, Mucke M, Conrad R, Rolke R, Ahmadzadehfar H, Rauch M, Fimmers R, Luechters G, Cuhls H, Radbruch L, Schild HH, Strunk H. Clinical Effectiveness and Potential Survival Benefit of US-Guided High-Intensity Focused Ultrasound Therapy in Patients with Advanced-Stage Pancreatic Cancer. Ultraschall Med. 2019 Oct;40(5):625-637. doi: 10.1055/a-0591-3386. Epub 2018 Apr 17.
• Background Li T, Wang YN, Khokhlova TD, D'Andrea S, Starr F, Chen H, McCune JS, Risler LJ, Mashadi-Hossein A, Hingorani SR, Chang A, Hwang JH. Pulsed High-Intensity Focused Ultrasound Enhances Delivery of Doxorubicin in a Preclinical Model of Pancreatic Cancer. Cancer Res. 2015 Sep 15;75(18):3738-46. doi: 10.1158/0008-5472.CAN-15-0296. Epub 2015 Jul 27.
• Background Lee ES, Lee JY, Kim H, Choi Y, Park J, Han JK, Choi BI. Pulsed high-intensity focused ultrasound enhances apoptosis of pancreatic cancer xenograft with gemcitabine. Ultrasound Med Biol. 2013 Nov;39(11):1991-2000. doi: 10.1016/j.ultrasmedbio.2013.06.004. Epub 2013 Aug 22.
• Background Lee JY, Choi BI, Ryu JK, Kim YT, Hwang JH, Kim SH, Han JK. Concurrent chemotherapy and pulsed high-intensity focused ultrasound therapy for the treatment of unresectable pancreatic cancer: initial experiences. Korean J Radiol. 2011 Mar-Apr;12(2):176-86. doi: 10.3348/kjr.2011.12.2.176. Epub 2011 Mar 3.
• Background Rapoport N, Payne A, Dillon C, Shea J, Scaife C, Gupta R. Focused ultrasound-mediated drug delivery to pancreatic cancer in a mouse model. J Ther Ultrasound. 2013 Jul 1;1:11. doi: 10.1186/2050-5736-1-11. eCollection 2013.
• Background Park EJ, Ahn YD, Lee JY. In vivo study of enhanced chemotherapy combined with ultrasound image-guided focused ultrasound (USgFUS) treatment for pancreatic cancer in a xenograft mouse model. Eur Radiol. 2018 Sep;28(9):3710-3718. doi: 10.1007/s00330-018-5355-9. Epub 2018 Mar 29.
• Background Yu MH, Lee JY, Kim HR, Kim BR, Park EJ, Kim HS, Han JK, Choi BI. Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasound and Chemotherapy in a Pancreatic Cancer Xenograft Model. Korean J Radiol. 2016 Sep-Oct;17(5):779-88. doi: 10.3348/kjr.2016.17.5.779. Epub 2016 Aug 23.
• Background Kim JH, Kim H, Kim YJ, Lee JY, Han JK, Choi BI. Dynamic contrast-enhanced ultrasonographic (DCE-US) assessment of the early response after combined gemcitabine and HIFU with low-power treatment for the mouse xenograft model of human pancreatic cancer. Eur Radiol. 2014 Sep;24(9):2059-68. doi: 10.1007/s00330-014-3260-4. Epub 2014 Jun 25.
• Background Yoo C, Lee SS, Song KB, Jeong JH, Hyung J, Park DH, Song TJ, Seo DW, Lee SK, Kim MH, Lee SS, Kim JH, Jin HS, Park JH, Hwang DW, Lee JH, Lee W, Chang HM, Kim KP, Ryoo BY, Kim SC. Neoadjuvant modified FOLFIRINOX followed by postoperative gemcitabine in borderline resectable pancreatic adenocarcinoma: a Phase 2 study for clinical and biomarker analysis. Br J Cancer. 2020 Aug;123(3):362-368. doi: 10.1038/s41416-020-0867-x. Epub 2020 May 20.
• Background Janssen QP, Buettner S, Suker M, Beumer BR, Addeo P, Bachellier P, Bahary N, Bekaii-Saab T, Bali MA, Besselink MG, Boone BA, Chau I, Clarke S, Dillhoff M, El-Rayes BF, Frakes JM, Grose D, Hosein PJ, Jamieson NB, Javed AA, Khan K, Kim KP, Kim SC, Kim SS, Ko AH, Lacy J, Margonis GA, McCarter MD, McKay CJ, Mellon EA, Moorcraft SY, Okada KI, Paniccia A, Parikh PJ, Peters NA, Rabl H, Samra J, Tinchon C, van Tienhoven G, van Veldhuisen E, Wang-Gillam A, Weiss MJ, Wilmink JW, Yamaue H, Homs MYV, van Eijck CHJ, Katz MHG, Groot Koerkamp B. Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. J Natl Cancer Inst. 2019 Aug 1;111(8):782-794. doi: 10.1093/jnci/djz073.
• Background Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016 Jun;17(6):801-810. doi: 10.1016/S1470-2045(16)00172-8. Epub 2016 May 6.
• Background Rombouts SJ, Walma MS, Vogel JA, van Rijssen LB, Wilmink JW, Mohammad NH, van Santvoort HC, Molenaar IQ, Besselink MG. Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer. Ann Surg Oncol. 2016 Dec;23(13):4352-4360. doi: 10.1245/s10434-016-5373-2. Epub 2016 Jul 1.
• Lee DH, Lee JY, Kang SY, Lee SH, Paik WH, Cho IR, Kwon W, Jang JY. Non-thermal focused ultrasound with FOLFIRINOX for borderline resectable or locally advanced pancreatic cancer: An explorative phase II trial. Eur J Cancer. 2026 Jun 20;244:116903. doi: 10.1016/j.ejca.2026.116903. Online ahead of print.

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