Download PDF
Ultraschall Med 2019; 40(05): 625-637
DOI: 10.1055/a-0591-3386
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Clinical Effectiveness and Potential Survival Benefit of US-Guided High-Intensity Focused Ultrasound Therapy in Patients with Advanced-Stage Pancreatic Cancer

Klinische Wirksamkeit und potenzielle Überlebensvorteile der Therapie mit US-gesteuertem hoch-intensivem fokussiertem Ultraschall bei Patienten mit fortgeschrittenem Pankreaskarzinom
Milka Marinova   *
1   Department of Radiology, Medical School and University Clinics Bonn, Germany
,
Hannah C. Huxold   *
1   Department of Radiology, Medical School and University Clinics Bonn, Germany
,
Jana Henseler
1   Department of Radiology, Medical School and University Clinics Bonn, Germany
,
Martin Mücke
2   Department of Palliative Medicine, Department of General Practice and Family Medicine, Medical School and University Clinics Bonn, Germany
,
Rupert Conrad
3   Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy, Medical School and University Clinics Bonn, Germany
,
Roman Rolke
4   Department of Palliative Medicine, Medical School and University Clinics Aachen, Germany
,
Hojjat Ahmadzadehfar
5   Department of Nuclear Medicine, Medical School and University Clinics Bonn, Germany
,
Maximilian Rauch
1   Department of Radiology, Medical School and University Clinics Bonn, Germany
,
Rolf Fimmers
6   Institute of Medical biometry, Informatics and Epidemiology, Medical School and University Clinics Bonn, Germany
,
Guido Luechters
7   Center of Development Research, University of Bonn, Germany
,
Henning Cuhls
8   Department of Palliative Medicine, Medical School and University Clinics Bonn, Germany
,
Lukas Radbruch
8   Department of Palliative Medicine, Medical School and University Clinics Bonn, Germany
,
Hans H. Schild
1   Department of Radiology, Medical School and University Clinics Bonn, Germany
,
Holger Strunk
1   Department of Radiology, Medical School and University Clinics Bonn, Germany
› Author Affiliations
Further Information

Publication History

11 September 2017

23 February 2018

Publication Date:
17 April 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Purpose Pancreatic cancer (PaC) is a life-limiting tumor with a wide range of incapacitating symptoms such as cancer pain in more than 80 % of patients. This prospective interventional study addresses the clinical effectiveness of ultrasound-guided high-intensity focused ultrasound (HIFU) treatment for patients with advanced-stage PaC, including pain perception, tumor size and survival benefit.

Materials and Methods 50 patients with late-stage PaC underwent HIFU. Clinical assessment included evaluation of tumor volume by imaging and pain burden (pain severity, pain sensation, interference with daily activities) using the Brief Pain Inventory at baseline and follow-up. Median overall survival, progression-free survival and time to local progression were estimated using Kaplan-Meier analysis.

Results In 84 % of patients, significant early relief of cancer-induced abdominal pain was achieved by HIFU independent of metastatic status; it persisted during follow-up. Tumor volume reduction was 37.8 ± 18.1 % after 6 weeks and 57.9 ± 25.9 % after 6 months. 21 % of HIFU-treated patients had local tumor progression with a median time of 14.4 months from intervention. The median overall survival and progression-free survival were 16.2 and 16.9 months from diagnosis and 8.3 and 6.8 months from intervention.

Conclusion In patients with advanced pancreatic cancer and otherwise limited treatment options, HIFU resulted in significant early and long-lasting pain relief and tumor size reduction over time independent of metastatic status. Clinical data suggest an additional potential survival benefit.

Zusammenfassung

Ziel Das Pankreaskarzinom ist ein lebenslimitierender Tumor mit einer Vielzahl von tumorbedingen Beschwerden wie Tumorschmerzen bei mehr als 80 % der Patienten. Ziel dieser prospektiven Studie ist, die klinische Wirksamkeit des Ultraschall-gesteuerten hoch-intensiven fokussierten Ultraschalls (HIFU) in Bezug auf die Schmerintensität und -empfindung, die Tumorgröße und das Überleben zu evaluieren.

Material und Methode Fünfzig Patienten mit fortgeschrittenem Pankreaskarzinom wurden mit HIFU behandelt. Die klinische Evaluation umfasste die Beurteilung des Tumorvolumens durch bildgebende Verfahren sowie der Schmerzbelastung (Schmerzintensität, Schmerzempfindung, Beeinträchtigung der täglichen Aktivitäten) anhand des Brief-pain-inventory-Fragebogens initial und im Verlauf. Das mediane Gesamtüberleben, das progressionsfreie Überleben und die Zeit bis zum lokalen Progress wurden mit der Kaplan-Meier-Analyse evaluiert.

Ergebnisse Nach HIFU wurde bei 84 % der Patienten eine signifikante frühzeitige Reduktion von tumorinduzierten Bauchschmerzen unabhängig vom Metastasierungsstatus erreicht; dieser Effekt blieb im Verlauf erhalten. Die Tumorvolumenreduktion betrug 37,8 ± 18,1 % nach 6 Wochen und 57,9 ± 25,9 % nach 6 Monaten. 21 % der HIFU-behandelten Patienten hatten einen lokalen Tumorprogress mit einer medianen Zeit von 14,4 Monaten nach Intervention. Das mittlere Gesamtüberleben und das progressionsfreie Überleben waren jeweils 16,2 und 16,9 Monate ab Erstdiagnose und 8,3 und 6,8 Monate ab HIFU-Intervention.

Schlussfolgerung Bei Patienten mit fortgeschrittenem Pankreaskarzinom führte HIFU zu einer signifikanten und anhaltenden Schmerzlinderung und Tumorvolumenreduktion im zeitlichen Verlauf unabhängig vom Metastasierungsstatus. Die Auswertung der Überlebensdaten gibt zusätzlich Hinweise auf einen potenziellen Vorteil.

Key words

abdomen - pancreatic carcinoma - high-intensity focused ultrasound - therapeutic ultrasound - pain management

* contributed equally to this manuscript and share first co-authorship


Supplement

 

  • References

  • 1 Carrato A, Falcone A, Ducreux M. et al. A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality of Life and Costs. J Gastrointest Cancer 2015; 46: 201-211
    CrossrefPubMedGoogle Scholar
  • 2 Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. The New England journal of medicine 2014; 371: 1039-1049
    CrossrefPubMedGoogle Scholar
  • 3 Schmidt-Hansen M, Berendse S, Hamilton W. Symptoms of Pancreatic Cancer in Primary Care: A Systematic Review. Pancreas 2016; 45: 814-818
    CrossrefPubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 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
    CrossrefPubMedGoogle Scholar
  • 6 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
    PubMedGoogle Scholar
  • 7 Zhang L, Wang ZB. High-intensity focused ultrasound tumor ablation: review of ten years of clinical experience. Frontiers of medicine in China 2010; 4: 294-302
    CrossrefPubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 Seufferlein T, Porzner M, Heinemann V. et al. Ductal pancreatic adenocarcinoma. Deutsches Arzteblatt international 2014; 111: 396-402
    PubMedGoogle Scholar
  • 10 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
    CrossrefPubMedGoogle Scholar
  • 11 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
    CrossrefPubMedGoogle Scholar
  • 12 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
    PubMedGoogle Scholar
  • 13 Salgado S, Sharaiha R, Gaidhane M. et al. Ablation therapies for pancreatic cancer: an updated review. Minerva Gastroenterol Dietol 2014; 60: 215-225
    PubMedGoogle Scholar
  • 14 Sofuni A, Moriyasu F, Sano T. et al. Safety trial of high-intensity focused ultrasound therapy for pancreatic cancer. World journal of gastroenterology: WJG 2014; 20: 9570-9577
    CrossrefPubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 17 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
    CrossrefPubMedGoogle Scholar
  • 18 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
    CrossrefPubMedGoogle Scholar
  • 19 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
    PubMedGoogle Scholar
  • 20 Lillemoe KD, Cameron JL, Kaufman HS. et al. Chemical splanchnicectomy in patients with unresectable pancreatic cancer. A prospective randomized trial. Annals of surgery 1993; 217: 447-455 ; discussion 456–447
    CrossrefPubMedGoogle Scholar
  • 21 Marinova M, Rauch M, Mucke M. et al. High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity. European radiology 2016; DOI: 10.1007/s00330-016-4239-0.
    CrossrefPubMedGoogle Scholar
  • 22 Marinova M, Strunk HM, Rauch M. et al. High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer: Evaluation with the pain sensation scale (SES). Schmerz 2016; DOI: 10.1007/s00482-016-0140-7.
    CrossrefPubMedGoogle Scholar
  • 23 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. Rofo 2016; 188: 662-670
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Scheffer HJ, Vroomen LG, de Jong MC. et al. Ablation of Locally Advanced Pancreatic Cancer with Percutaneous Irreversible Electroporation: Results of the Phase I/II PANFIRE Study. Radiology 2017; 282: 585-597
    CrossrefPubMedGoogle Scholar
  • 25 Yu T, Luo J. Adverse events of extracorporeal ultrasound-guided high intensity focused ultrasound therapy. PloS one 2011; 6: e26110
    CrossrefPubMedGoogle Scholar
  • 26 Bjerregaard JK, Mortensen MB, Schonnemann KR. et al. Characteristics, therapy and outcome in an unselected and prospectively registered cohort of pancreatic cancer patients. European journal of cancer 2013; 49: 98-105
    CrossrefPubMedGoogle Scholar
  • 27 Moore MJ, Goldstein D, Hamm J. et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2007; 25: 1960-1966
    CrossrefPubMedGoogle Scholar
  • 28 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
    CrossrefPubMedGoogle Scholar
  • 29 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
    CrossrefPubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar