Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer

Abstract

Purpose: Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain.

Materials and Methods: 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU.

Results: Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients).

Conclusion: US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer.

Key points:

• US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.

• HIFU can be used for tumor volume reduction.

• Using HIFU, a significant reduction of cancer-related pain was achieved.

• HIFU provides clinical benefit in patients with pancreatic cancer.

Citation Format:

• Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 – 670

Zusammenfassung

Ziel: Evaluation des erstmalig im deutschsprachigen Raum eingesetzten Ultraschall(US)-gesteuerten hoch-intensiven fokussierten Ultraschalls (HIFU) bei Patienten mit inoperablem Pankreaskarzinom zur Reduktion von Tumorvolumen und tumorbedingter Schmerzsymptomatik.

Material und Methoden: 15 Patienten mit lokal fortgeschrittenem inoperablem Pankreaskarzinom und Tumorschmerz wurden mit HIFU behandelt (n = 6 Stadium III, n = 9 Stadium IV UICC). 13 Patienten erhielten gleichzeitig eine Standardchemotherapie. Die HIFU-Behandlung erfolgte mit dem JC HIFU System (Chongqing, China HAIFU Company) mit einer US-Vorrichtung zur Echtzeitbildgebung. Kontrolluntersuchungen (US, CT, MRT) und die klinische Evaluation durch validierte Fragebögen (NRS, BPI) wurden jeweils vor HIFU sowie in definierten Abständen bis zu 15 Monaten nach Therapie durchgeführt.

Ergebnisse: Trotz Gallengang- oder Duodenalstents (4/15) und der Ummauerung von Oberbauchgefäßen (15/15) war eine Behandlung bei allen Patienten möglich. Die mittlere Interventionsdauer lag bei 111 min, die therapeutische Schallzeit bei 1103 s, die Gesamtenergie bei 386 768 J. Die postinterventionelle Bildgebung zeigte eine Avaskularisation der behandelten Tumorregionen mit einer signifikanten Volumenreduktion von 63,8 % nach 3 Monaten. Eine signifikante Schmerzlinderung konnte bei 12 Patienten erreicht werden (komplett n = 6, partiell n = 6).

Schlussfolgerung: Der US-gesteuerte HIFU kann bei Patienten mit lokal fortgeschrittenem inoperablem Pankreaskarzinom, sofern ein geeignetes Schallfenster vorliegt, zur lokalen Tumorkontrolle und Linderung von tumorassoziierten Schmerzen eingesetzt werden.

Key words

pancreatic carcinoma - high-intensity focused ultrasound - tumor ablation - pain relief - cancer pain

^§ contributed equally.

• References

• 1 Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. The New England journal of medicine 2014; 371: 1039-1049
• 2 Seufferlein T, Porzner M, Heinemann V et al. Ductal pancreatic adenocarcinoma. Deutsches Arzteblatt international 2014; 111: 396-402
• 3 Aaronson NK, Ahmedzai S, Bergman B et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85: 365-376
• 4 Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. The New England journal of medicine 2011; 364: 1817-1825
• 5 Ghosn M, Farhat F, Kattan J et al. FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer. Am J Clin Oncol 2007; 30: 15-20
• 6 Trouilloud I, Dupont-Gossard AC, Malka D et al. Fixed-dose rate gemcitabine alone or alternating with FOLFIRI.3 (irinotecan, leucovorin and fluorouracil) in the first-line treatment of patients with metastatic pancreatic adenocarcinoma: an AGEO randomised phase II study (FIRGEM). European journal of cancer 2014; 50: 3116-3124
• 7 Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. The New England journal of medicine 2013; 369: 1691-1703
• 8 Sultana A, Smith CT, Cunningham D et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2007; 25: 2607-2615
• 9 Reddy SK, Elsayem A, Talukdar R. Supportive Care: Symptom Management. Pancreatic Cancer 2005; 479-498
• 10 Yan BM, Myers RP. Neurolytic celiac plexus block for pain control in unresectable pancreatic cancer. The American journal of gastroenterology 2007; 102: 430-438
• 11 Wu F, Wang ZB, Chen WZ et al. Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. Ultrasonics sonochemistry 2004; 11: 149-154
• 12 Marinova M, Rauch M, Mücke M et al. High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity. Eur Radiol 2016; ahead of print; DOI: 10.1007/s00330-016-4239-0.
• 13 Marinova M, Strunk HM, Rauch M et al. Use of high-intensity focused ultrasound (HIFU) in inoperable pancreatic cancer for tumor pain relief: evaluation with pain sensation scale (SES). Der Schmerz 2016; ahead of print
• 14 Sacks D, McClenny TE, Cardella JF et al. Society of Interventional Radiology clinical practice guidelines. Journal of vascular and interventional radiology: JVIR 2003; 14: S199-S202
• 15 Radbruch L, Loick G, Kiencke P et al. Validation of the German version of the Brief Pain Inventory. Journal of pain and symptom management 1999; 18: 180-187
• 16 Li PZ, Zhu SH, He W et al. High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer. Hepatobiliary & pancreatic diseases international: HBPD INT 2012; 11: 655-660
• 17 Wang K, Chen Z, Meng Z et al. Analgesic effect of high intensity focused ultrasound therapy for unresectable pancreatic cancer. International journal of hyperthermia: the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 2011; 27: 101-107
• 18 Gao HF, Wang K, Meng ZQ et al. High intensity focused ultrasound treatment for patients with local advanced pancreatic cancer. Hepato-gastroenterology 2013; 60: 1906-1910
• 19 Keane MG, Bramis K, Pereira SP et al. Systematic review of novel ablative methods in locally advanced pancreatic cancer. World journal of gastroenterology: WJG 2014; 20: 2267-2278
• 20 Ierardi AM, Lucchina N, Petrillo M et al. Systematic review of minimally invasive ablation treatment for locally advanced pancreatic cancer. La Radiologia medica 2014; 119: 483-498
• 21 Salgado S, Sharaiha R, Gaidhane M et al. Ablation therapies for pancreatic cancer: an updated review. Minerva Gastroenterol Dietol 2014; 60: 215-225
• 22 Dimitrov D, Feradova H, Gincheva D et al. Ablative techniques in advanced pancreatic cancer: do they affect the quality of life?-Review. J Pancreas (online) 2015; 16: 425-431
• 23 Sofuni A, Moriyasu F, Sano T et al. The current potential of high-intensity focused ultrasound for pancreatic carcinoma. Journal of hepato-biliary-pancreatic sciences 2011; 18: 295-303
• 24 Hynynen K, Lulu BA. Hyperthermia in cancer treatment. Investigative radiology 1990; 25: 824-834
• 25 Hwang JH, Wang YN, Warren C et al. Preclinical in vivo evaluation of an extracorporeal HIFU device for ablation of pancreatic tumors. Ultrasound in medicine & biology 2009; 35: 967-975
• 26 Wu F, Zhou L, Chen WR. Host antitumour immune responses to HIFU ablation. International journal of hyperthermia: the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 2007; 23: 165-171
• 27 Hu Z, Yang XY, Liu Y et al. Investigation of HIFU-induced anti-tumor immunity in a murine tumor model. Journal of translational medicine 2007; 5: 34
• 28 Liu F, Hu Z, Qiu L et al. Boosting high-intensity focused ultrasound-induced anti-tumor immunity using a sparse-scan strategy that can more effectively promote dendritic cell maturation. Journal of translational medicine 2010; 8: 7
• 29 Orsi F, Zhang L, Arnone P et al. High-intensity focused ultrasound ablation: effective and safe therapy for solid tumors in difficult locations. American journal of roentgenology 2010; 195: W245-W252
• 30 Sung HY, Jung SE, Cho SH et al. Long-term outcome of high-intensity focused ultrasound in advanced pancreatic cancer. Pancreas 2011; 40: 1080-1086
• 31 Wang K, Zhu H, Meng Z et al. Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer. Onkologie 2013; 36: 88-92
• 32 Wu F, Wang ZB, Zhu H et al. Feasibility of US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer: initial experience. Radiology 2005; 236: 1034-1040
• 33 Xiong LL, Hwang JH, Huang XB et al. Early clinical experience using high intensity focused ultrasound for palliation of inoperable pancreatic cancer. JOP: Journal of the pancreas 2009; 10: 123-129
• 34 Zhao H, Yang G, Wang D et al. Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer. Anti-cancer drugs 2010; 21: 447-452
• 35 Zhou Y. High-intensity focused ultrasound treatment for advanced pancreatic cancer. Gastroenterology research and practice 2014; 2014: 205325
• 36 Polati E, Finco G, Gottin L et al. Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. The British journal of surgery 1998; 85: 199-201
• 37 Andre T, Balosso J, Louvet C et al. Combined radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) as palliative treatment for localized unresectable or adjuvant treatment for resected pancreatic adenocarcinoma: results of a feasibility study. International journal of radiation oncology, biology, physics 2000; 46: 903-911
• 38 Ceha HM, van Tienhoven G, Gouma DJ et al. Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma. Cancer 2000; 89: 2222-2229
• 39 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. Ultrasonics sonochemistry 2015; 27: 703-706
• 40 Yu T, Luo J. Adverse events of extracorporeal ultrasound-guided high intensity focused ultrasound therapy. PloS one 2011; 6: e26110 DOI: 10.1371/journal.pone.0026110.