Lokale Tumorablation und Selektive Interne Radiotherapie für Patienten mit Metastasierten Neuroendokrinen Tumoren – Interventionelle Tumortherapieverfahren

Zusammenfassung

Die Eindämmung und Tumorkontrolle von Lebermetastasen ist von entscheidender Bedeutung für das Überleben von Patienten mit metastasierten Malignomen unterschiedlicher Entitäten, insbesondere auch bei neuroendokrinen Tumoren (NETs). Lokal ablative und lokoregionäre therapeutische Verfahren stellen sichere und effektive Therapieoptionen zur Behandlung von Lebermetastasen dar. In den aktuellen ENETS Konsensus-Leitlinien werden interventionelle Tumortherapien bei NET-Lebermetastasen in verschiedenen Situationen vorgeschlagen. Der Werkzeugkasten der lokalen (Thermoablation und lokale Radiotherapie) und der lokoregionären (selektive interne Radioembolisation (SIRT) und Chemoembolisation (TACE)) Verfahren bietet maßgeschneiderte Therapien für Patienten in unterschiedlichen Tumorstadien – von kurativen Therapieansätzen bis hin zur palliativen Symptomlinderung. Diese Übersichtsarbeit erläutert die vorhandenen Therapieoptionen, skizziert die Risiken der einzelnen Verfahren, stellt die aktuelle Evidenzlage vor und gibt eine Rationale an die Hand, welches therapeutische Verfahren in welcher klinischen Situation zu bevorzugen ist.

Abstract

The control of hepatic metastases has been shown to have a dominant influence on survival for patients suffering from a variety of tumor entities, including patients with neuroendocrine tumors (NETs). Local ablative and locoregional treatment methods have been shown to be effective and safe for the treatment of liver metastasis. Interventional therapy of NET liver metastases should be considered in different scenarios according to the actual ENETS consensus guidelines. A growing toolbox of local ablative (thermoablation and local, targeted radiotherapy) and locoregional (selective internal radioembolization (SIRT) and chemoembolization (TACE)) therapies enables a customized treatment strategy for patients in different stages of disease, ranging from curative therapy to palliative care. This article aims to give an overview about the different treatment options, the associated risks, the current evidence and provides a rationale for optimized treatment selection for patients with varying disease manifestations.

Schlüsselwörter

Neuroendokrine Tumoren - Interventionelle Therapie - Lokale Ablation - Lokoregionäre Therapie - Brachytherapie - Radiofrequenzablation (RFA) - Mikrowellenablation (MWA) - Selektive Interne Radiotherapie (SIRT) - Transarterielle Chemoembolisation (TACE)

Keywords

Neuroendocrine tumors - interventional therapy - local ablation therapy (LAT) - locoregional therapy (LRT) - brachytherapy - radiofrequency ablation (RFA) - microwave ablation (MWA) - radioembolisation (RE) - transarterial chemoembolisation (TACE)

Publication History

Article published online:
29 November 2021

• Literatur

• 1 Van Cutsem E, Cervantes A, Adam R. et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 2016; 27: 1386-1422
• 2 Bale R, Putzer D, Schullian P. Local Treatment of Breast Cancer Liver Metastasis. Cancers 2019; 11: 1341
• 3 de Baere T, Deschamps F, Tselikas L. et al. GEP-NETS UPDATE: Interventional radiology: role in the treatment of liver metastases from GEP-NETs. Eur J Endocrinol 2015; 172: R151-R166
• 4 de Baere T, Tselikas L, Gravel G. et al. Interventional radiology: Role in the treatment of sarcomas. Eur J Cancer 2018; 94: 148-155
• 5 Perrodin S, Lachenmayer A, Maurer M. et al. Percutaneous stereotactic image-guided microwave ablation for malignant liver lesions. Sci Rep 2019; 9: 13836
• 6 Perrodin SF, Renzulli MM, Maurer MH. et al. Can Microwave Ablation be an Alternative to Resection for the Treatment of Neuroendocrine Liver Metastases?. Endocr Pract 2020; 26: 378-387
• 7 Tang K, Zhang B, Dong L. et al. Radiofrequency ablation versus traditional liver resection and chemotherapy for liver metastases from gastric cancer. J Int Med Res 2020; 48: 030006052094050
• 8 Pavel M, O’’Toole D, Costa F. et al. ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site. Neuroendocrinology 2016; 103: 172-185
• 9 Berber E, Siperstein A. Local Recurrence After Laparoscopic Radiofrequency Ablation of Liver Tumors: An Analysis of 1032 Tumors. Ann Surg Oncol 2008; 15: 2757-2764
• 10 Ohnishi T, Yasuda I, Nishigaki Y. et al. Intraductal chilled saline perfusion to prevent bile duct injury during percutaneous radiofrequency ablation for hepatocellular carcinoma. J Gastroenterol Hepatol 2008; 23: e410-e415
• 11 Kim Y, Rhim H, Cho OK. et al. Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors. Eur J Radiol 2006; 59: 432-441
• 12 Livraghi T, Solbiati L, Meloni MF. et al. Treatment of Focal Liver Tumors with Percutaneous Radio-frequency Ablation: Complications Encountered in a Multicenter Study. Radiology 2003; 226: 441-451
• 13 Vietti Violi N, Duran R, Guiu B. et al. Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. Lancet Gastroenterol Hepatol 2018; 3: 317-325
• 14 Ruers T, Van Coevorden F, Punt CJA. et al. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. JNCI J Natl Cancer Inst 2017; 109
• 15 Nordlinger B, Sorbye H, Glimelius B. et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 2013; 14: 1208-1215
• 16 Tanis E, Nordlinger B, Mauer M. et al. Local recurrence rates after radiofrequency ablation or resection of colorectal liver metastases. Analysis of the European Organisation for Research and Treatment of Cancer #40004 and #40983. Eur J Cancer 2014; 50: 912-919
• 17 Mazzaglia PJ, Berber E, Milas M. et al. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Surgery 2007; 142: 10-19
• 18 Schippers AC, Collettini F, Steffen IG. et al. Initial Experience with CT–Guided High-Dose-Rate Brachytherapy in the Multimodality Treatment of Neuroendocrine Tumor Liver Metastases. J Vasc Interv Radiol 2017; 28: 672-682
• 19 Hass P, Steffen IG, Powerski M. et al. First report on extended distance between tumor lesion and adjacent organs at risk using interventionally applied balloon catheters: a simple procedure to optimize clinical target volume covering effective isodose in interstitial high-dose-rate brachytherapy of liver malignomas. J Contemp Brachytherapy 2019; 11: 152-161
• 20 Tateishi R, Shiina S, Teratani T. et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma: An analysis of 1000 cases. Cancer 2005; 103: 1201-1209
• 21 Choi D, Lim HK, Kim MJ. et al. Liver Abscess After Percutaneous Radiofrequency Ablation for Hepatocellular Carcinomas: Frequency and Risk Factors. Am J Roentgenol 2005; 184: 1860-1867
• 22 Böning G, Büttner L, Jonczyk M. et al. Complications of Computed Tomography-Guided High-Dose-Rate Brachytherapy (CT-HDRBT) and Risk Factors: Results from More than 10 Years of Experience. Cardiovasc Intervent Radiol 2020; 43: 284-294
• 23 Mohnike K, Wolf S, Damm R. et al. Radioablation of liver malignancies with interstitial high-dose-rate brachytherapy: Complications and risk factors. Strahlenther Onkol 2016; 192: 288-296
• 24 Powerski M, Penzlin S, Hass P. et al. Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors: A systematic analysis of 102 cases. Strahlenther Onkol 2019; 195: 265-273
• 25 Cheung TT, Ng KK, Poon RT. et al. Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2009; 16: 655-660
• 26 Takaki H, Yamakado K, Nakatsuka A. et al. Frequency of and Risk Factors for Complications After Liver Radiofrequency Ablation Under CT Fluoroscopic Guidance in 1500 Sessions: Single-Center Experience. Am J Roentgenol 2013; 200: 658-664
• 27 Mohnike K, Sauerland H, Seidensticker M. et al. Haemorrhagic Complications and Symptomatic Venous Thromboembolism in Interventional Tumour Ablations: The Impact of Peri-interventional Thrombosis Prophylaxis. Cardiovasc Intervent Radiol 2016; 39: 1716-1721
• 28 Ricke J, Mohnike K, Pech M. et al. Local Response and Impact on Survival After Local Ablation of Liver Metastases From Colorectal Carcinoma by Computed Tomography–Guided High-Dose-Rate Brachytherapy. Int J Radiat Oncol 2010; 78: 479-485
• 29 Ricke J, Seidensticker M, Lüdemann L. et al. In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation. Int J Radiat Oncol 2005; 62: 776-784
• 30 Seidensticker M, Seidensticker R, Mohnike K. et al. Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes. Radiat Oncol 2011; 6: 40
• 31 Seidensticker M, Seidensticker R, Damm R. et al. Prospective Randomized Trial of Enoxaparin, Pentoxifylline and Ursodeoxycholic Acid for Prevention of Radiation-Induced Liver Toxicity. PLoS ONE 2014; 9: e112731
• 32 Lammer J, Malagari K, Vogl T. et al. On Behalf of the PRECISION V Investigators Prospective Randomized Study of Doxorubicin-Eluting-Bead Embolization in the Treatment of Hepatocellular Carcinoma: Results of the PRECISION V Study. Cardiovasc Intervent Radiol 2010; 33: 41-52
• 33 Vogl TJ, Lammer J, Lencioni R. et al. Liver, Gastrointestinal, and Cardiac Toxicity in Intermediate Hepatocellular Carcinoma Treated With PRECISION TACE With Drug-Eluting Beads: Results From the PRECISION V Randomized Trial. Am J Roentgenol 2011; 197: W562-W570
• 34 Ruszniewski P, O’Toole D. Ablative Therapies for Liver Metastases of Gastroenteropancreatic Endocrine Tumors. Neuroendocrinology 2004; 80: 74-78
• 35 Jia Z, Tu J, Cao C. et al. Liver abscess following transarterial chemoembolization for the treatment of hepatocellular carcinoma: A retrospective analysis of 23 cases. J Cancer Res Ther 2018; 14: 628
• 36 Lv W-F, Lu D, He Y-S. et al. Liver Abscess Formation Following Transarterial Chemoembolization: Clinical Features, Risk Factors, Bacteria Spectrum, and Percutaneous Catheter Drainage. Medicine (Baltimore) 2016; 95: e3503
• 37 Woo S, Chung JW, Hur S. et al. Liver Abscess After Transarterial Chemoembolization in Patients With Bilioenteric Anastomosis: Frequency and Risk Factors. Am J Roentgenol 2013; 200: 1370-1377
• 38 Guiu B, Deschamps F, Aho S. et al. Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: Lipiodol vs. drug-eluting beads. J Hepatol 2012; 56: 609-617
• 39 Deipolyi AR, Oklu R, Al-Ansari S. et al. Safety and Efficacy of 70–150 μm and 100–300 μm Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma. J Vasc Interv Radiol 2015; 26: 516-522
• 40 Bouvier A, Ozenne V, Aubé C. et al. Transarterial chemoembolisation: effect of selectivity on tolerance, tumour response and survival. Eur Radiol 2011; 21: 1719-1726
• 41 Saxena A, Chua TC, Bester L. et al. Factors Predicting Response and Survival After Yttrium-90 Radioembolization of Unresectable Neuroendocrine Tumor Liver Metastases: A Critical Appraisal of 48 Cases. Ann Surg 2010; 251: 910-916
• 42 Braat AJAT, Kappadath SC, Ahmadzadehfar H. et al. Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases: International Multicenter Study on Efficacy and Toxicity. Cardiovasc Intervent Radiol 2019; 42: 413-425
• 43 Braat AJAT, Ahmadzadehfar H, Kappadath SC. et al. Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy. Cardiovasc Intervent Radiol 2020; 43: 246-253
• 44 Zuckerman DA, Kennard RF, Roy A. et al. Outcomes and toxicity following Yttrium-90 radioembolization for hepatic metastases from neuroendocrine tumors—a single-institution experience. J Gastrointest Oncol 2018; 10: 118-127
• 45 Memon K, Lewandowski RJ, Mulcahy MF. et al. Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes. Int J Radiat Oncol 2012; 83: 887-894
• 46 Strosberg J, El-Haddad G, Wolin E. et al. Phase 3 Trial of ¹⁷⁷ Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med 2017; 376: 125-135
• 47 Egger ME, Armstrong E, Martin RCG. et al. Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis. J Am Coll Surg 2020; 230: 363-370
• 48 Frilling A, Clift AK, Braat AJAT. et al. Radioembolisation with 90Y microspheres for neuroendocrine liver metastases: an institutional case series, systematic review and meta-analysis. HPB 2019; 21: 773-783
• 49 Benson AB, Geschwind J-F, Mulcahy MF. et al. Radioembolisation for liver metastases: Results from a prospective 151 patient multi-institutional phase II study. Eur J Cancer 2013; 49: 3122-3130
• 50 Paprottka PM, Hoffmann R-T, Haug A. et al. Radioembolization of Symptomatic, Unresectable Neuroendocrine Hepatic Metastases Using Yttrium-90 Microspheres. Cardiovasc Intervent Radiol 2012; 35: 334-342
• 51 Vilgrain V, Esvan M, Ronot M. et al. A meta-analysis of diffusion-weighted and gadoxetic acid-enhanced MR imaging for the detection of liver metastases. Eur Radiol 2016; 26: 4595-4615
• 52 Chow PKH, Gandhi M, Tan S-B. et al. SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. J Clin Oncol 2018; 36: 1913-1921
• 53 Ricke J, Klümpen HJ, Amthauer H. et al. Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma. J Hepatol 2019; 71: 1164-1174
• 54 Mascarenhas N, Ryu R, Salem R. Hepatic Radioembolization Complicated by Abscess. Semin Interv Radiol 2011; 28: 222-225
• 55 Cholapranee A, van Houten D, Deitrick G. et al. Risk of Liver Abscess Formation in Patients with Prior Biliary Intervention Following Yttrium-90 Radioembolization. Cardiovasc Intervent Radiol 2015; 38: 397-400
• 56 Geisel D, Powerski M-J, Schnapauff D. et al. No Infectious Hepatic Complications Following Radioembolization with 90Y Microspheres in Patients with Biliodigestive Anastomosis. Anticancer Research 2014; 34: 4315-4321
• 57 Devulapalli KK, Fidelman N, Soulen MC. et al. ⁹⁰ Y Radioembolization for Hepatic Malignancy in Patients with Previous Biliary Intervention: Multicenter Analysis of Hepatobiliary Infections. Radiology 2018; 288: 774-781
• 58 Sag AA, Savin MA, Lal NR. et al. Yttrium-90 Radioembolization of Malignant Tumors of the Liver: Gallbladder Effects. Am J Roentgenol 2014; 202: 1130-1135
• 59 Powerski M, Busse A, Seidensticker M. et al. Prophylactic Embolization of the Cystic Artery Prior to Radioembolization of Liver Malignancies—An Evaluation of Necessity. Cardiovasc Intervent Radiol 2015; 38: 678-684
• 60 Sangro B, Gil-Alzugaray B, Rodriguez J. et al. Liver disease induced by radioembolization of liver tumors: Description and possible risk factors. Cancer 2008; 112: 1538-1546
• 61 Gil-Alzugaray B, Chopitea A, Iñarrairaegui M. et al. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology 2013; 57: 1078-1087
• 62 Levillain H, Bagni O, Deroose CM. et al. International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres. Eur J Nucl Med Mol Imaging 2021; 48: 1570-1584
• 63 Tomozawa Y, Jahangiri Y, Pathak P. et al. Long-Term Toxicity after Transarterial Radioembolization with Yttrium-90 Using Resin Microspheres for Neuroendocrine Tumor Liver Metastases. J Vasc Interv Radiol 2018; 29: 858-865
• 64 Su Y-K, Mackey RV, Riaz A. et al. Long-Term Hepatotoxicity of Yttrium-90 Radioembolization as Treatment of Metastatic Neuroendocrine Tumor to the Liver. J Vasc Interv Radiol 2017; 28: 1520-1526
• 65 Wasan HS, Gibbs P, Sharma NK. et al. First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials. Lancet Oncol 2017; 18: 1159-1171
• 66 van Hazel GA, Heinemann V, Sharma NK. et al. SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer. J Clin Oncol 2016; 34: 1723-1731