Frank Makowiec1,2, Peter Bronsert3,4, Andrea Klock5, Ulrich T Hopt5, Hannes P Neeff5,3. 1. Department of Surgery, University of Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany. frank.makowiec@uniklinik-freiburg.de. 2. Comprehensive Cancer Center, University of Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany. frank.makowiec@uniklinik-freiburg.de. 3. Comprehensive Cancer Center, University of Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany. 4. Institute of Pathology, University of Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany. 5. Department of Surgery, University of Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany.
Abstract
PURPOSE: Modern chemotherapy (CTX) increases survival in stage IV colorectal cancer. In colorectal liver metastases (CLM), neoadjuvant (neo) CTX may increase resectability and improve survival. Due to widespread use of CTX in CLM, recent studies assessed the role of the hepatic margin after CTX, with conflicting results. We evaluated the outcome after resection of CLM in relation to CTX and hepatic resection status. METHODS: Since 2000, 334 patients with first hepatic resection for isolated CLM were analyzed. Thirty-two percent had neoadjuvant chemotherapy (targeted therapy in 42%). Sixty-eight percent never had CTX before hepatectomy or longer than 6 months before resection. The results were gained by analysis of our prospective database. RESULTS: Positive hepatic margins occurred in 8% (independent of neoCTx). Patients after neoCTX had higher numbers of CLM (p < 0.01) and a longer duration of surgery (p < 0.03). After hepatectomy, 5-year survival was 45% and correlated strongly with the margin status (47% in R-0 and 21% in R-1; p < 0.001). Survival also correlated with margin status in the subgroups with neoCTX (p < 0.01) or without neoCTx (p < 0.01). In multivariate analysis of the entire group, hepatic margin status (RR 3.2; p < 0.001) and age > 65 years (RR 1.6; p < 0.01) were associated with poorer survival. In the subgroup of patients after neoCTX (n = 106), only the resection margin was an independent predictor of survival (p < 0.001). CONCLUSION: In patients with isolated colorectal liver metastases undergoing resection, the hepatic margin status was the strongest independent prognostic factor. This effect was also present after neoadjuvant chemotherapy for CLM.
PURPOSE: Modern chemotherapy (CTX) increases survival in stage IV colorectal cancer. In colorectal liver metastases (CLM), neoadjuvant (neo) CTX may increase resectability and improve survival. Due to widespread use of CTX in CLM, recent studies assessed the role of the hepatic margin after CTX, with conflicting results. We evaluated the outcome after resection of CLM in relation to CTX and hepatic resection status. METHODS: Since 2000, 334 patients with first hepatic resection for isolated CLM were analyzed. Thirty-two percent had neoadjuvant chemotherapy (targeted therapy in 42%). Sixty-eight percent never had CTX before hepatectomy or longer than 6 months before resection. The results were gained by analysis of our prospective database. RESULTS: Positive hepatic margins occurred in 8% (independent of neoCTx). Patients after neoCTX had higher numbers of CLM (p < 0.01) and a longer duration of surgery (p < 0.03). After hepatectomy, 5-year survival was 45% and correlated strongly with the margin status (47% in R-0 and 21% in R-1; p < 0.001). Survival also correlated with margin status in the subgroups with neoCTX (p < 0.01) or without neoCTx (p < 0.01). In multivariate analysis of the entire group, hepatic margin status (RR 3.2; p < 0.001) and age > 65 years (RR 1.6; p < 0.01) were associated with poorer survival. In the subgroup of patients after neoCTX (n = 106), only the resection margin was an independent predictor of survival (p < 0.001). CONCLUSION: In patients with isolated colorectal liver metastases undergoing resection, the hepatic margin status was the strongest independent prognostic factor. This effect was also present after neoadjuvant chemotherapy for CLM.
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