Christine Koch1, Niklas Schmidt2, Ria Winkelmann3, Katrin Eichler4, Ursula Pession5, Wolf Otto Bechstein5, Stefan Zeuzem2, Oliver Waidmann2, Jörg Trojan2. 1. Department of Gastroenterology, University Liver and Cancer Centre, Frankfurt University Clinic, Frankfurt am Main, GermanyChristine.koch@kgu.de. 2. Department of Gastroenterology, University Liver and Cancer Centre, Frankfurt University Clinic, Frankfurt am Main, Germany. 3. Senckenberg Institute for Pathology, Frankfurt University Clinic, Frankfurt am Main, Germany. 4. Institute for Diagnostic and Interventional Radiology, Frankfurt University Clinic, Frankfurt am Main, Germany. 5. Department of General and Visceral Surgery, Frankfurt University Hospital and Clinics, Frankfurt am Main, Germany.
Abstract
BACKGROUND: Initially unresectable colorectal liver metastases can become resectable after chemotherapy. Combination chemotherapy with epidermal growth factor receptor (EGFR) antibodies has shown consistent high response rates in patients with all rat sarcoma (RAS) wild-type tumors. METHODS: Out of a cohort of 424 patients with metastatic colorectal cancer, we identified 30 patients with initially unresectable Kirsten RAS (KRAS) exon 2 wild-type colorectal liver metastases who received neoadjuvant chemotherapy with anti-EGFR agents between January 2008 and February 2014. In all patients, extended RAS analysis (KRAS and NRAS exon 3 codon 59/61 and exon 4 codon 117/146) was carried out retrospectively. RESULTS: RAS mutation analysis identified further KRAS mutations in 4/30 patients (13.3%). In none of these 4 patients a R0 resection was achieved. In contrast, 15/26 (57.7%) RAS wild-type patients were R0 resected. Median overall survival was > 63.3 months in R0-resected patients versus 30.0 months in those with a R1 or R2 resection (HR 0.23; [95% CI 0.10-0.75; p = 0.008). CONCLUSION: Our data suggest that a RAS wild-type and a R0 resection are the strongest predictors for overall survival.
BACKGROUND: Initially unresectable colorectal liver metastases can become resectable after chemotherapy. Combination chemotherapy with epidermal growth factor receptor (EGFR) antibodies has shown consistent high response rates in patients with all ratsarcoma (RAS) wild-type tumors. METHODS: Out of a cohort of 424 patients with metastatic colorectal cancer, we identified 30 patients with initially unresectable Kirsten RAS (KRAS) exon 2 wild-type colorectal liver metastases who received neoadjuvant chemotherapy with anti-EGFR agents between January 2008 and February 2014. In all patients, extended RAS analysis (KRAS and NRAS exon 3 codon 59/61 and exon 4 codon 117/146) was carried out retrospectively. RESULTS: RAS mutation analysis identified further KRAS mutations in 4/30 patients (13.3%). In none of these 4 patients a R0 resection was achieved. In contrast, 15/26 (57.7%) RAS wild-type patients were R0 resected. Median overall survival was > 63.3 months in R0-resected patients versus 30.0 months in those with a R1 or R2 resection (HR 0.23; [95% CI 0.10-0.75; p = 0.008). CONCLUSION: Our data suggest that a RAS wild-type and a R0 resection are the strongest predictors for overall survival.