Hepatisch metastasiertes kolorektales Karzinom

ZUSAMMENFASSUNG

Für die multimodale Therapie des hepatisch metastasierten kolorektalen Karzinoms stehen neben der System- und der chirurgischen Therapie unterschiedliche lokalablative Verfahren zur Verfügung, die das therapeutische Spektrum maßgeblich erweitern. Die Verfügbarkeit dieser Verfahren erfordert eine hohe Kompetenz der beteiligten Partner. Eine enge interdisziplinäre Abstimmung in entsprechenden Tumorboards im Therapieverlauf ist notwendig, um eine onkologisch optimale Therapiestrategie zu entwickeln und diese auch immer wieder zu adaptieren.

ABSTRACT

About half of all patients with colorectal carcinoma (CRC) develop metastases mainly in the liver during the course of their disease. Metastatic disease is associated with a low 5-year overall survival rate of only 5–7%, particularly when there is no possibility of local treatment. However, if there is an opportunity to resect the metastases, especially isolated liver metastases, the chance of long-term survival is approximately 15–27% after both primary resection or secondary resection after neoadjuvant pretreatment. Overall, long-term survival of patients with metastatic CRC has improved significantly in recent years due to a combination of modern systemic therapies, advanced liver surgery and local ablative procedures.

Of note, for the vast majority of patients, metastatic resection does not mean cure, but a significant prolongation of overall survival with a good quality of life. Chemotherapy-free intervals after metastasis resection maintain quality of life and can help to reduce toxicity.

In this review, we would like to present the “toolbox” for the multidisciplinary treatment of metastatic CRC and give recommendations how the individual modalities should be optimally used, considering tumor-specific characteristics and patient preferences.

Schlüsselwörter

Darmkrebs - Lebermetastasen - multimodale Therapie

Keywords

Colorectal cancer - liver metastases - multimodal

Publikationsverlauf

Artikel online veröffentlicht:
20. Mai 2022

• Literatur

• 1 OʼConnell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 2004; 96: 1420-1425 DOI: 10.1093/jnci/djh275.
• 2 Adam R, Wicherts DA, de Haas RJ. et al Patients With Initially Unresectable Colorectal Liver Metastases: Is There a Possibility of Cure?. J Clin Oncol 2009; 27: 1829-1835 DOI: 10.1200/JCO.2008.19.9273.
• 3 Adam R, Haas RJd, Wicherts DA. et al Is Hepatic Resection Justified After Chemotherapy in Patients With Colorectal Liver Metastases and Lymph Node Involvement?. J Clin Oncol 2008; 26: 3672-3680 DOI: 10.1200/jco.2007.15.7297.
• 4 Kopetz S, Chang GJ, Overman MJ. et al Improved Survival in Metastatic Colorectal Cancer Is Associated With Adoption of Hepatic Resection and Improved Chemotherapy. J Clin Oncol 2009; 27: 3677-3683 DOI: 10.1200/JCO.2008.20.5278.
• 5 Boudjema K, Locher C, Sabbagh C. et al Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases: A Prospective, Open-label, Randomized, Controlled Trial. Ann Surg 2021; 273: 49-56 DOI: 10.1097/SLA.0000000000003848.
• 6 Douillard JY, Oliner KS, Siena S. et al Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369: 1023-1034 DOI: 10.1056/NEJMoa1305275.
• 7 Arnold D, Lueza B, Douillard JY. et al Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol 2017; 28: 1713-1729 DOI: 10.1093/annonc/mdx175.
• 8 Geissler M, Martens UM, Knorrenschield R. et al 475OmFOLFOXIRI + panitumumab versus FOLFOXIRI as first-line treatment in patients with RAS wild-type metastatic colorectal cancer m (CRC): A randomized phase II VOLFI trial of the AIO (AIO-KRK0109). Ann Oncol 2017; 28 (Suppl. 05) 159 DOI: 10.1093/annonc/mdx393.002.
• 9 André T, Shiu KK, Kim TW. et al Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med 2020; 383: 2207-2218 DOI: 10.1056/NEJMoa2017699.
• 10 Boeckx N, Koukakis R, Op de Beeck K. et al Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies. Ann Oncol 2017; 28: 1862-1868 DOI: 10.1093/annonc/mdx119.
• 11 Tejpar S, Stintzing S, Ciardiello F. et al Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol 2017; 03: 194-201 DOI: 10.1001/jamaoncol.2016.3797.
• 12 Rivera F, Karthaus M, Hecht JR. et al Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis 2017; 32: 1179-1190 DOI: 10.1007/s00384-017-2800-1.
• 13 Cremolini C, Loupakis F, Antoniotti C. et al FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the openlabel, phase 3 TRIBE study. Lancet Oncol 2015; 16: 1306-1315 DOI: 10.1016/s1470-2045(15)00122-9.
• 14 Falcone A, Ricci S, Brunetti I. et al Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 2007; 25: 1670-1676 DOI: 10.1200/jco.2006.09.0928.
• 15 Modest DP, Martens UM, Riera-Knorrenschild J. et al FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). J Clin Oncol 2019; 37: 3401-3411 DOI: 10.1200/jco.19.01340.
• 16 Mitry E, Fields AL, Bleiberg H. et al Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 2008; 26: 4906-4911 DOI: 10.1200/JCO.2008.17.3781.
• 17 Leitlinienprogramm Onkologie. S3-Leitlinie Kolorektales Karzinom. Langversion 2.1. AWMF-Registrierungsnummer: 021/007OL. 2019. https://www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/Kolorektales_Karzinom/Version_2/LL_KRK_Langversion_2.1.pdf Stand: 24.09.2021
• 18 Kanemitsu Y, Shitara K, Mizusawa J. et al Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial. J Clin Oncol 2021; 39: 1098-1107 DOI: 10.1200/JCO.20.02447.
• 19 House MG, Ito H, Gonen M. et al Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1,600 patients during two decades at a single institution. J Am Coll Surg 2010; 210 744–752 752-745 DOI: 10.1016/j.jamcollsurg.2009.12.040.
• 20 Fong Y, Fortner J, Sun RL. et al Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999; 230: 309-318 discussion 318–321
• 21 Hamady ZZ, Lodge JP, Welsh FK. et al One-millimeter cancerfree margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg 2014; 259: 543-548 DOI: 10.1097/SLA.0b013e3182902b6e.
• 22 Gotra A, Sivakumaran L, Chartrand G. et al Liver segmentation: indications, techniques and future directions. Insights Imaging 2017; 08: 377-392 DOI: 10.1007/s13244-017-0558-1.
• 23 Cieslak KP, Bennink RJ, de Graaf W. et al Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection. HPB (Oxford) 2016; 18: 773-780 DOI: 10.1016/j.hpb.2016.06.006.
• 24 Jaeck D, Oussoultzoglou E, Rosso E. et al A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg 2004; 240: 1037-1049 DOI: 10.1097/01.sla.0000145965.86383.89. discussion 1049–1051
• 25 Le Roy B, Gallon A, Cauchy F. et al Combined biembolization induces higher hypertrophy than portal vein embolization before major liver resection. HPB (Oxford) 2020; 22: 298-305 DOI: 10.1016/j.hpb.2019.08.005.
• 26 Schnitzbauer AA, Lang SA, Goessmann H. et al Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg 2012; 255: 405-414 DOI: 10.1097/SLA.0b013e31824856f5.
• 27 Schadde E, Ardiles V, Robles-Campos R. et al Early survival and safety of ALPPS: first report of the International ALPPS Registry. Ann Surg 2014; 260: 829-836 DOI: 10.1097/SLA.0000000000000947. discussion 836–828
• 28 Sandstrom P, Rosok BI, Sparrelid E. et al ALPPS Improves Resectability Compared With Conventional Two-stage Hepatectomy in Patients With Advanced Colorectal Liver Metastasis: Results From a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial). Ann Surg 2018; 267: 833-840 DOI: 10.1097/SLA.0000000000002511.
• 29 Günther RW, Thelen M, Albrecht T. et al Interventionelle Radiologie. In: Mahnken AH, Thomas C, Wilhelm K, Hrsg Stuttgart: Thieme. 2019: 662-685
• 30 Vogl TJ, Pereira PL, Helmberger T. et al Updated S3 guidelines – diagnosis and treatment of colorectal carcinoma: relevance for radiological diagnosis and intervention. Rofo 2019; 191: 298-310
• 31 Lahat E, Eshkenazy R, Zendel A. et al Complications after percutaneous ablation of liver tumors: a systematic review. Hepatobiliary Surg Nutr 2014; 03: 317
• 32 Nemcek AA. Complications of radiofrequency ablation of neoplasms. Semin Intervent Radiol 2006; 23: 177-187
• 33 Ruers T, Van Coevorden F, Punt CJ. et al Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. J Natl Cancer Instit 2017; 109: djx015 DOI: 10.1093/jnci/djx015.
• 34 Glassberg MB, Ghosh S, Clymer JW. et al Microwave ablation compared with radiofrequency ablation for treatment of hepatocellular carcinoma and liver metastases: a systematic review and meta-analysis. Onco Targets Ther 2019; 12: 6407
• 35 Imai K, Allard M, Castro Benitez C. et al Long-term outcomes of radiofrequency ablation combined with hepatectomy compared with hepatectomy alone for colorectal liver metastases. Br J Surg 2017; 104: 570-579
• 36 Vogl T, Zegelman A, Bechstein W. et al Therapie von Lebermetastasen des kolorektalen Karzinoms: Übersicht der hyperthermen Ablationsverfahren. Dtsch Med Wochenschr 2013; 138: 792-798
• 37 Fiorentini G, Aliberti C, Tilli M. et al Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: final results of a phase III study. Anticancer Res 2012; 32: 1387-1395
• 38 Martin RC, Scoggins CR, Schreeder M. et al Randomized controlled trial of irinotecan drug-eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver-limited metastasis. Cancer 2015; 121: 3649-3658
• 39 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 DOI: 10.1093/annonc/mdw235.
• 40 Robin TP, Raben D, Schefter TE. A Contemporary Update on the Role of Stereotactic Body Radiation Therapy (SBRT) for Liver Metastases in the Evolving Landscape of Oligometastatic Disease Management. Semin Radiat Oncol 2018; 28: 288-294 DOI: 10.1016/j.semradonc.2018.06.009.
• 41 Gani C, Boeke S, McNair H. et al Marker-less online MR-guided stereotactic body radiotherapy of liver metastases at a 1.5 T MR-Linac – Feasibility, workflow data and patient acceptance. Clin Transl Radiat Oncol 2021; 26: 55-61 DOI: 10.1016/j.ctro.2020.11.014.
• 42 Ohri N, Tomé WA, Méndez Romero A. et al Local Control After Stereotactic Body Radiation Therapy for Liver Tumors. Int J Radiat Oncol Biol Phys 2021; 110: 188-195 DOI: 10.1016/j.ijrobp.2017.12.288.
• 43 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 DOI: 10.1200/jco.2015.66.1181.
• 44 Gibbs P, Heinemann V, Sharma NK. et al Effect of Primary Tumor Side on Survival Outcomes in Untreated Patients With Metastatic Colorectal Cancer When Selective Internal Radiation Therapy Is Added to Chemotherapy: Combined Analysis of Two Randomized Controlled Studies. Clin Colorectal Cancer 2018; 17: e617-e629 DOI: 10.1016/j.clcc.2018.06.001.
• 45 Garlipp B, Gibbs P, Van Hazel GA. et al Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial. Br J Surg 2019; 106: 1837-1846 DOI: 10.1002/bjs.11283.