Fortgeschrittenes Pankreaskarzinom: Hoch-intensiver fokussierter Ultraschall (HIFU) und andere lokal ablative Verfahren

Widmung

Diese Übersichtsarbeit widmen wir Herrn Univ.-Prof. Dr. med. Hans H. Schild, bei dem wir uns ganz herzlich für die langjährige und stete Unterstützung in allen klinischen und wissenschaftlichen Belangen bedanken möchten.

Zusammenfassung

Hintergrund Das lokal fortgeschrittene Pankreaskarzinom ist ein lebenslimitierender Tumor mit einer Vielzahl von Symptomen, u. a. Tumorschmerz. Lokal ablative Verfahren, die thermische oder auch nichtthermische Techniken anwenden, können als moderne Therapieoptionen zur Tumorkontrolle und symptomatischen Verbesserung eingesetzt werden. Dieser Artikel gibt einen Überblick über die derzeit verfügbaren Behandlungsverfahren und -ergebnisse, einschließlich unserer eigenen Erfahrungen mit dem hoch-intensiven fokussierten Ultraschall (HIFU).

Methode Unsere Erfahrungen mit der HIFU-Therapie beim Pankreaskarzinom basieren auf 89 Patienten (UICC III-IV). Neben den HIFU-Ergebnissen wurden Ergebnisse zur lokalen Tumorkontrolle, Sicherheit sowie Mortalität und behandlungsabhängigen Veränderung von Symptomen aus publizierten Studien zur Radiofrequenz-, Mikrowellen- und Kryoablation, irreversiblen Elektroporation und stereotaktischen Strahlentherapie einbezogen.

Ergebnisse Obwohl die unterschiedlichen Modalitäten überwiegend sicher durchführbar sind, bietet der HIFU mit seiner Nicht-Invasivität einen entscheidenden methodischen Vorteil. Mit HIFU konnte bei 85 % der Patienten eine effektive und langanhaltende Schmerzlinderung erreicht werden; bei 50 % war nach 6 Wochen keinerlei analgetische Medikation erforderlich. Leider sind Schmerzlinderung und Lebensqualität bei den anderen lokalen Behandlungsmethoden nur selten untersucht. Eine Tumormassenreduktion konnte mit allen ablativen Therapien erreicht werden, wobei diese 6 Monate nach HIFU im Mittel bei 60 % lag. Unterschiede in der behandlungsassoziierten Morbidität wurden berichtet, sind jedoch aufgrund der unausgewogenen Studienpopulationen nur eingeschränkt vergleichbar.

Schlussfolgerung Eine Vielzahl an lokal ablativen Behandlungsmodalitäten sind zur Tumormassenreduktion beim fortgeschrittenen Pankreaskarzinom verfügbar, bieten aber unterschiedlichen symptomatischen Nutzen. Eine effektive und langanhaltende Reduktion von Tumorschmerzen ohne Einführen von Nadeln oder Elektroden in den Tumorbereich bietet ausschließlich das HIFU-Verfahren. Randomisierte, kontrollierte klinische Studien zum direkten Vergleich der hier vorgestellten Modalitäten sind in der näheren Zukunft zu befürworten.

Kernaussagen: 

• Zur lokalen Behandlung des nicht operablen Pankreaskarzinoms stehen unterschiedliche ablative Therapien zur Verfügung.

• Die Tumormassenreduktion und Symptomlinderung stellen Hauptziele der lokalen Tumortherapie dar.

• HIFU unterscheidet sich durch seinen nichtinvasiven Zugang und die geringe Nebenwirkungsrate.

• Mit HIFU ist eine effektive, anhaltende Schmerzlinderung in > 80 % der Patienten möglich.

• Die HIFU-assoziierte Schmerzreduktion ist unabhängig vom Tumorstadium und Metastasierungsstatus.

Zitierweise

• Marinova M, Wilhelm-Buchstab T, Strunk H. Advanced Pancreatic Cancer: High-Intensity Focused Ultrasound (HIFU) and Other Local Ablative Therapies. Fortschr Röntgenstr 2019; 191: 216 – 227

Key words

abdomen - pancreas - ablation procedures - interventional procedures - ultrasound - adenocarcinoma

^* contributed equally.

• References

• 1 Goldberg SN, Gazelle GS, Mueller PR. Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance. American journal of roentgenology 2000; 174: 323-331
• 2 Kovach SJ, Hendrickson RJ, Cappadona CR. et al. Cryoablation of unresectable pancreatic cancer. Surgery 2002; 131: 463-464
• 3 Sato M, Watanabe Y, Kashu Y. et al. Sequential percutaneous microwave coagulation therapy for liver tumor. American journal of surgery 1998; 175: 322-324
• 4 Varshney S, Sewkani A, Sharma S. et al. Radiofrequency ablation of unresectable pancreatic carcinoma: feasibility, efficacy and safety. JOP: Journal of the pancreas 2006; 7: 74-78
• 5 Dale PS, Souza JW, Brewer DA. Cryosurgical ablation of unresectable hepatic metastases. Journal of surgical oncology 1998; 68: 242-245
• 6 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
• 7 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. Eur Radiol 2016; DOI: 101007/s00330-016-4239-0.
• 8 Strunk HM, Henseler J, Rauch M. et al. Klinischer Einsatz des hoch-intensiven fokussierten Ultraschalls (HIFU) zur Tumor- und Schmerzreduktion bei fortgeschrittenem Pankreaskarzinom. Clinical use of high-intensity focused ultrasound (HIFU) for tumor and pain reduction in advanced pancreatic cancer. Fortschr Röntgenstr 2016; 188: 1-9 ahead of print DOI http://dxdoiorg/101055/s-0042-105517 2016
• 9 Marinova M, Huxold HC, Henseler J. et al. Clinical effectiveness and potential survival benefit of US-guided high-intensity focused ultrasound in patients with advanced pancreatic cancer. Ultraschall in Med, ahead of print 2018
• 10 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; 26: 4047-4056
• 11 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.
• 12 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
• 13 Marinova M, Strunk HM, Rauch M. et al. Hoch-intensiver fokussierter Ultraschall (HIFU) zur Linderung tumorbedingter Schmerzen bei inoperablem Pankreaskarzinom: Evaluation anhand der Schmerzempfindungsskala (SES). [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.
• 14 Strunk HM, Lützow C, Henseler J. et al. Mesenteric vessel patency following HIFU-therapy in patients with locally invasive pancreatic cancer. Ultraschall in Medzin/European Journal of Ultrasound, accepted/in print 2017
• 15 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
• 16 Anzidei M, Marincola BC, Bezzi M. et al. Magnetic resonance-guided high-intensity focused ultrasound treatment of locally advanced pancreatic adenocarcinoma: preliminary experience for pain palliation and local tumor control. Investigative radiology 2014; 49: 759-765
• 17 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
• 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 Lee JY, Choi BI, Ryu JK. et al. Concurrent chemotherapy and pulsed high-intensity focused ultrasound therapy for the treatment of unresectable pancreatic cancer: initial experiences. Korean journal of radiology: official journal of the Korean Radiological Society 2011; 12: 176-186
• 20 Li JJ, Xu GL, Gu MF. et al. Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors. World journal of gastroenterology: WJG 2007; 13: 2747-2751
• 21 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
• 22 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
• 23 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
• 24 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
• 25 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
• 26 Yu T, Luo J. Adverse events of extracorporeal ultrasound-guided high intensity focused ultrasound therapy. PloS one 2011; 6: e26110
• 27 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: W245-252
• 28 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
• 29 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
• 30 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
• 31 Zhao J, Zhao F, Shi Y. et al. The efficacy of a new high intensity focused ultrasound therapy for locally advanced pancreatic cancer. J Cancer Res Clin Oncol 2017; 143: 2105-2111
• 32 D'Onofrio M, Ciaravino V, De Robertis R. et al. Percutaneous ablation of pancreatic cancer. World journal of gastroenterology: WJG 2016; 22: 9661-9673
• 33 D'Onofrio M, Crosara S, De Robertis R. et al. Percutaneous Radiofrequency Ablation of Unresectable Locally Advanced Pancreatic Cancer: Preliminary Results. Technology in cancer research & treatment 2017; 16: 285-294
• 34 Lerardi AM, Lucchina N, Bacuzzi A. et al. Percutaneous ablation therapies of inoperable pancreatic cancer: a systematic review. Ann Gastroenterol 2015; 28: 431-439
• 35 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
• 36 Zhang Y, Shi J, Zeng J. et al. Percutaneous Irreversible Electroporation for Ablation of Locally Advanced Pancreatic Cancer: Experience From a Chinese Institution. Pancreas 2017; 46: e12-e14
• 37 Dromi SA, Walsh MP, Herby S. et al. Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology 2009; 251: 58-66
• 38 Cantore M, Girelli R, Mambrini A. et al. Combined modality treatment for patients with locally advanced pancreatic adenocarcinoma. The British journal of surgery 2012; 99: 1083-1088
• 39 Frigerio I, Girelli R, Giardino A. et al. Short term chemotherapy followed by radiofrequency ablation in stage III pancreatic cancer: Results from a single center. J Hepatobiliary Pancreat Sci 2013; 20: 574-577
• 40 Girelli R, Frigerio I, Salvia R. et al. Feasibility and safety of radiofrequency ablation for locally advanced pancreatic cancer. The British journal of surgery 2010; 97: 220-225
• 41 Girelli R, Frigerio I, Giardino A. et al. Results of 100 pancreatic radiofrequency ablations in the context of a multimodal strategy for stage III ductal adenocarcinoma. Langenbecks Arch Surg 2013; 398: 63-69
• 42 Matsui Y, Nakagawa A, Kamiyama Y. et al. Selective thermocoagulation of unresectable pancreatic cancers by using radiofrequency capacitive heating. Pancreas 2000; 20: 14-20
• 43 Spiliotis JD, Datsis AC, Michalopoulos NV. et al. Radiofrequency ablation combined with palliative surgery may prolong survival of patients with advanced cancer of the pancreas. Langenbecks Arch Surg 2007; 392: 55-60
• 44 Wu Y, Tang Z, Fang H. et al. High operative risk of cool-tip radiofrequency ablation for unresectable pancreatic head cancer. Journal of surgical oncology 2006; 94: 392-395
• 45 Hamamoto S, Okuma T, Yamamoto A. et al. Radiofrequency ablation and immunostimulant OK-432: combination therapy enhances systemic antitumor immunity for treatment of VX2 lung tumors in rabbits. Radiology 2013; 267: 405-413
• 46 Carrafiello G, Ierardi AM, Fontana F. et al. Microwave ablation of pancreatic head cancer: safety and efficacy. Journal of vascular and interventional radiology: JVIR 2013; 24: 1513-1520
• 47 Lygidakis NJ, Sharma SK, Papastratis P. et al. Microwave ablation in locally advanced pancreatic carcinoma--a new look. Hepato-gastroenterology 2007; 54: 1305-1310
• 48 Hinshaw JL, Lubner MG, Ziemlewicz TJ. et al. Percutaneous tumor ablation tools: microwave, radiofrequency, or cryoablation--what should you use and why?. Radiographics: a review publication of the Radiological Society of North America, Inc 2014; 34: 1344-1362
• 49 Li J, Chen X, Yang H. et al. Tumour cryoablation combined with palliative bypass surgery in the treatment of unresectable pancreatic cancer: a retrospective study of 142 patients. Postgraduate medical journal 2011; 87: 89-95
• 50 Song ZG, Hao JH, Gao S. et al. The outcome of cryoablation in treating advanced pancreatic cancer: a comparison with palliative bypass surgery alone. J Dig Dis 2014; 15: 561-569
• 51 Narayanan G, Hosein PJ, Beulaygue IC. et al. Percutaneous Image-Guided Irreversible Electroporation for the Treatment of Unresectable, Locally Advanced Pancreatic Adenocarcinoma. Journal of vascular and interventional radiology: JVIR 2017; 28: 342-348
• 52 Belfiore G, Belfiore MP, Reginelli A. et al. Concurrent chemotherapy alone versus irreversible electroporation followed by chemotherapy on survival in patients with locally advanced pancreatic cancer. Med Oncol 2017; 34: 38
• 53 Dunki-Jacobs EM, Philips P, Martin 2nd RC. Evaluation of resistance as a measure of successful tumor ablation during irreversible electroporation of the pancreas. Journal of the American College of Surgeons 2014; 218: 179-187
• 54 Kluger MD, Epelboym I, Schrope BA. et al. Single-Institution Experience with Irreversible Electroporation for T4 Pancreatic Cancer: First 50 Patients. Annals of surgical oncology 2016; 23: 1736-1743
• 55 Mansson C, Brahmstaedt R, Nilsson A. et al. Percutaneous irreversible electroporation for treatment of locally advanced pancreatic cancer following chemotherapy or radiochemotherapy. European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2016; 42: 1401-1406
• 56 Martin 2nd RC, Kwon D, Chalikonda S. et al. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Annals of surgery 2015; 262: 486-494 ; discussion 92–94
• 57 Yan L, Chen YL, Su M. et al. A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma. Chinese medical journal 2016; 129: 2920-2925
• 58 Alagappan M, Pollom EL, von Eyben R. et al. Albumin and Neutrophil-Lymphocyte Ratio (NLR) Predict Survival in Patients With Pancreatic Adenocarcinoma Treated With SBRT. Am J Clin Oncol 2018; 41: 242-247
• 59 Chuong MD, Springett GM, Freilich JM. et al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated. International journal of radiation oncology, biology, physics 2013; 86: 516-522
• 60 Comito T, Cozzi L, Clerici E. et al. Can Stereotactic Body Radiation Therapy Be a Viable and Efficient Therapeutic Option for Unresectable Locally Advanced Pancreatic Adenocarcinoma? Results of a Phase 2 Study. Technology in cancer research & treatment 2017; 16: 295-301
• 61 Dholakia AS, Chaudhry M, Leal JP. et al. Baseline metabolic tumor volume and total lesion glycolysis are associated with survival outcomes in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy. International journal of radiation oncology, biology, physics 2014; 89: 539-546
• 62 Gurka MK, Collins SP, Slack R. et al. Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety. Radiat Oncol 2013; 8: 44
• 63 Herman JM, Chang DT, Goodman KA. et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer 2015; 121: 1128-1137
• 64 Hoyer M, Roed H, Sengelov L. et al. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology 2005; 76: 48-53
• 65 Koong AC, Le QT, Ho A. et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. International journal of radiation oncology, biology, physics 2004; 58: 1017-1021
• 66 Mahadevan A, Jain S, Goldstein M. et al. Stereotactic body radiotherapy and gemcitabine for locally advanced pancreatic cancer. International journal of radiation oncology, biology, physics 2010; 78: 735-742
• 67 Mahadevan A, Miksad R, Goldstein M. et al. Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer. International journal of radiation oncology, biology, physics 2011; 81: e615-e622
• 68 Rwigema JC, Parikh SD, Heron DE. et al. Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas. Am J Clin Oncol 2011; 34: 63-69
• 69 Schellenberg D, Goodman KA, Lee F. et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. International journal of radiation oncology, biology, physics 2008; 72: 678-686
• 70 Schellenberg D, Kim J, Christman-Skieller C. et al. Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer. International journal of radiation oncology, biology, physics 2011; 81: 181-188
• 71 Song Y, Yuan Z, Li F. et al. Analysis of clinical efficacy of CyberKnife((R)) treatment for locally advanced pancreatic cancer. Onco Targets Ther 2015; 8: 1427-1431
• 72 Tozzi A, Comito T, Alongi F. et al. SBRT in unresectable advanced pancreatic cancer: preliminary results of a mono-institutional experience. Radiat Oncol 2013; 8: 148
• 73 Zhu X, Li F, Ju X. et al. Prognostic role of stereotactic body radiation therapy for elderly patients with advanced and medically inoperable pancreatic cancer. Cancer Med 2017; 6: 2263-2270
• 74 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
• 75 Salgado S, Sharaiha R, Gaidhane M. et al. Ablation therapies for pancreatic cancer: an updated review. Minerva Gastroenterol Dietol 2014; 60: 215-225
• 76 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
• 77 Hynynen K, Lulu BA. Hyperthermia in cancer treatment. Investigative radiology 1990; 25: 824-834
• 78 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
• 79 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