KRAS status and outcome of liver resection after neoadjuvant chemotherapy including bevacizumab

Abstract

This study provided further evidence for the prognostic importance of KRAS status in terms of recurrence-free and overall survival. Neoadjuvant chemotherapy including bevacizumab elicited a response, irrespective of KRAS status, in this selected group of patients with CLM.

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis

“…Indeed it's possible that both KRAS and BRAF mutations are associated with a worse biology and a more rapid and aggressive metastatic behavior of CLM, discouraging surgeons to perform surgical resection, independently of clinical resectability. This interpretation is consistent with the evidence that the percentage of KRAS mutated patients ranged from 14% (Stremitzer et al, 2012) to 37% (Teng et al, 2012) in all seven included studies, compared to 35-45% reported in metastatic and unresectable CRC, suggesting a significant association between KRAS mutations rates and tumor behavior, as described in preclinical studies (Suchy et al, 1992;Tanaka et al, 1994;Varghese et al, 2002;Webb et al, 1998). Some clinical series have also shown that KRAS mutations are associated with an increased risk of developing lung and liver metastases compared to wild-type population (Vauthey et al, 2013;Kemeny et al, 2014).…”

“…Three of these studies were retrospective series (Vauthey et al, 2013;Kemeny et al, 2014;Francesca Bergamo and Loupakis et al, 2014), while the others were prospective studies (Nash et al, 2010;Karagkounis et al, 2013;Stremitzer et al, 2012;Teng et al, 2012). In these 7 studies, sample sizes of the analyzed population ranged from 60 (Stremitzer et al, 2012) to 309 (Schirripa et al, 2015), while the percentage of KRAS mutated patients ranged from 14% (Stremitzer et al, 2012) to 37% (Teng et al, 2012). BRAF mutations were analysed in four of the seven included studies (Karagkounis et al, 2013;Stremitzer et al, 2012;Teng et al, 2012), and it was found in 2-4% of patients who underwent surgery for CLM.…”

“…In these 7 studies, sample sizes of the analyzed population ranged from 60 (Stremitzer et al, 2012) to 309 (Schirripa et al, 2015), while the percentage of KRAS mutated patients ranged from 14% (Stremitzer et al, 2012) to 37% (Teng et al, 2012). BRAF mutations were analysed in four of the seven included studies (Karagkounis et al, 2013;Stremitzer et al, 2012;Teng et al, 2012), and it was found in 2-4% of patients who underwent surgery for CLM. In nearly every trial, patients' characteristics were well balanced between the two arms.…”

“…Five studies reported HRs with 95% CI data for both RFS and OS (Karagkounis et al, 2013;Vauthey et al, 2013;Stremitzer et al, 2012;Kemeny et al, 2014), while two studies reported only HRs with 95% CI data for OS (Nash et al, 2010;Teng et al, 2012). Pooled analysis showed that KRAS mutations predicted a significant worse both RFS (HR: 1.53; 95% CI: 1.27-1.83) and OS (HR: 1.7; 95% CI: 1.38-2.10) in patients who underwent surgical resection of CLM (Figs.…”

“…The majority of such studies have shown that both KRAS and BRAF, respectively detected in about 30% and 3% of CLM, are associated with worse survival outcomes of patients undergoing liver resection (Nash et al, 2010;Karagkounis et al, 2013;Vauthey et al, 2013;Stremitzer et al, 2012), while some other studies have not found a significant association (Kemeny et al, 2014;Teng et al, 2012;Schirripa et al, 2015). The aim of this meta-analysis is to combine and analyze simultaneously all the studies reporting the survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status, in order to provide a more precise estimation of the prognostic value of both KRAS and BRAF, in patients undergoing surgical therapy for CLM.…”