Molekulare Stratifizierung von kolorektalen Karzinomen – was hat Relevanz für die klinische Praxis?

Die Therapiemöglichkeiten des kolorektalen Karzinoms (KRK) und die Indikation zur systemischen Chemotherapie im adjuvanten Stadium werden zunehmend durch molekulare Marker beeinflusst. Hierbei ergänzen molekular pathologische Veränderungen zunehmend die etablierte TNM-Klassifikation und eröffnen bestimmten Patientengruppen neue Therapiestrategien.

• Literatur

• 1 Neumann JH, Jung A, Kirchner T. Molecular pathology of colorectal cancer. Pathologe 2015; 36: 137-144
• 2 Schmiegel W, Buchberger B, Follmann M. et al. S3-Leitlinie – kolorektales Karzinom. Z Gastroenterol 2017; 55 (12) 1344-1498
• 3 Sargent DJ, Marsoni S, Monges G. et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010; 28: 3219-3226
• 4 Dalerba P, Sahoo D, Paik S. et al. CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer. N Engl J Med 2016; 374: 211-222
• 5 Liao X, Lochhead P, Nishihara R. et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 2012; 367: 1596-1606
• 6 You YN, Rustin RB, Sullivan JD. Oncotype DX colon cancer assay for prediction of recurrence risk in patients with stage II and III colon cancer: A review of the evidence. Surg Oncol 2015; 24: 61-66
• 7 Emile JF, Julié C, Le Malicot K. et al. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX. Eur J Cancer 2017; 82: 16-24
• 8 Cremolini C, Di Bartolomeo M, Amatu A. et al. BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann Oncol 2015; 26: 2092-2097
• 9 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 open-label, phase 3 TRIBE study. Lancet Oncol 2015; 16: 1306-1315
• 10 Modest DP. et al. Randomized phase III study of fluoropyrimidine (FP) plus bevacizumab (BEV) vs. FP plus irinotecan (IRI) and BEV as first-line therapy for metastatic colorectal cancer (mCRC): German AIO KRK0110 (ML22011)-study. Annal Oncol 2017; 28 (Suppl. 03) mdx262.025
• 11 Heinemann V, Rivera F, O’Neil BH. et al. A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer. Eur J Cancer 2016; 67: 11-20
• 12 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 2016; DOI: 10.1001/jamaoncol.2016.3797.
• 13 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
• 14 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
• 15 Kopetz S, McDonough SL, Morris VK. et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406). J Clin Oncol 2017; 35 (Suppl. 04) 520
• 16 Le DT, Uram JN, Wang H. et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 372: 2509-2520