Prognostic impact of K-RAS mutational status and primary tumor location in patients undergoing resection for colorectal cancer liver metastases: an update

2019 ◽  
Vol 15 (27) ◽  
pp. 3149-3157
Author(s):  
Juan M O´Connor ◽  
Fernando Sanchez Loria ◽  
Victoria Ardiles ◽  
Jorge Grondona ◽  
Pablo Sanchez ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Mutation Status ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Kras Mutation Status

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.

scholarly journals Primary tumor location affects recurrence-free survival for patients with colorectal liver metastases after hepatectomy: A propensity score matching analysis

2020 ◽  
Author(s):  
Yuanping Zhang ◽  
Yongjin Wang ◽  
Yichuan Yuan ◽  
Jiliang Qiu ◽  
Yuxiong Qiu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Colorectal Liver Metastases ◽  
Tumor Location ◽  
Recurrence Free Survival ◽  
Primary Tumors ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Before And After

Abstract Background: Whether primary tumor location of colorectal cancer (CRC) affects survival of patients after resection of liver metastases remains controversial. This study was conducted to investigate the differences in clinicopathological characteristics and prognosis between right-sided CRC and left-sided CRC patients with liver metastases after hepatectomy. Methods: From 2002 to 2018, 611 patients with colorectal liver metastases (CRLM) who underwent hepatectomy at our center were reviewed. Primary tumors located from cecum to transverse colon were defined as right-sided group (n = 141); tumors located from splenic flexure to rectum were defined as left-sided group (n = 470). Patients were compared between two groups before and after a 1:1 propensity score matching (PSM) analysis. Results: Before PSM, median survival time and 5-year overall survival (OS) rate in right-sided group were 77 months and 56.3%, and those in left-sided group were 64 months and 51.1%, respectively. After PSM, median survival time and 5-year OS rate in right-sided group were 77 months and 55.9%, and those in left-sided group were 58.8 months and 47.3%, respectively. The OS rates did not differ between two groups before and after PSM (P = 0.575; P = 0.453). However, significant different recurrence-free survival (RFS) rate was found before and after PSM between right-sided and left-sided group (P = 0.028, P = 0.003). Conclusions: Compared to patients with left-sided primary tumors, patients with right-sided primary tumors had a worse RFS but similar OS. Careful preoperative evaluation, intensive preoperative chemotherapy and frequent follow-up to detect early recurrence might be justified for CRLM patients with right-sided primary tumors.

scholarly journals Primary tumor location affects recurrence-free survival for patients with colorectal liver metastases after hepatectomy: A propensity score matched analysis

2020 ◽  
Author(s):  
Yuanping Zhang ◽  
Yongjin Wang ◽  
Yichuan Yuan ◽  
Jiliang Qiu ◽  
Yuxiong Qiu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Median Survival Time ◽  
Colorectal Liver Metastases ◽  
Tumor Location ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Before And After

Abstract Background Whether primary tumor location of colorectal cancer (CRC) affects survival of patients after resection of liver metastases remains controversial. This study was conducted to investigate the differences in clinicopathological characteristics and prognosis between right-sided CRC and left-sided CRC patients with liver metastases after hepatectomy. Methods From 2002 to 2018, 611 patients with colorectal liver metastases (CRLM) who underwent hepatectomy at our center were reviewed. Primary tumors located from cecum to transverse colon were defined as right-sided group (n = 141); tumors located from splenic flexure to rectum were defined as left-sided group (n = 470). Patients were compared between two groups before and after a 1:1 propensity score analysis (PSM). Results Before PSM, median survival time and 5-year overall survival (OS) rate in right-sided group were 77 months and 56.3%, and those in left-sided group were 64 months and 51.1%, respectively. After PSM, median survival time and 5-year OS rate in right-sided group were 77 months and 55.9%, and those in left-sided group were 58.8 months and 47.3%, respectively. The OS rates did not differ between two groups before and after PSM ( P = 0.575; P = 0.453). However, significant different recurrence free survival (RFS) rate was found before and after PSM between right-sided and left-sided group ( P = 0.028, P = 0.003). Conclusions Primary tumor location of CRC impacts RFS for patients with liver metastases after resection. A more frequent follow up to detect early recurrence might be justified for CRLM patients with a right-sided CRC.

Association of KRAS mutation with worse recurrence-free survival and site of metastatic progression after resection of hepatic colorectal metastases.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3609-3609 ◽  
Author(s):  
Nancy E. Kemeny ◽  
Joanne F. Chou ◽  
Marinela Capanu ◽  
Alexandra N. Gewirtz ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Liver Metastases ◽  
Cumulative Incidence ◽  
Kras Mutation ◽  
Colorectal Metastases ◽  
Recurrence Free Survival ◽  
Mutation Status ◽  
Free Survival ◽  
Number Of Patients ◽  
Kras Mutation Status

3609 Background: There are conflicting results regarding the influence of KRAS mutation status and outcome in patients (pts) with colorectal cancer. A recent report suggested worse outcome in KRAS mutated (MUT) pts who underwent resection of hepatic metastases (Karagkounis et al, ASCO 2012). Methods: Recurrence patterns and survival were evaluated in 169 patients who had undergone resection of liver metastases, then received adjuvant hepatic arterial infusion and systemic chemotherapy, and for whom KRAS data were available. Kaplan-Meier methods were used to estimate recurrence free survival (RFS) and overall survival (OS). Log-rank test was used to determine whether survival functions differed by KRAS mutation status. Cumulative incidence function was used to estimate the probability of time from adjuvant therapy to bone, brain, lung and liver metastases separately. Mutations in KRAS (codons 12, 13) were detected using the iPLEX assay (Sequenom, Inc). Results: Median follow-up for the entire cohort was 38.8 months. 118 were KRAS wildtype (WT), and 51 were KRAS MUT (45 G12, 5 G13, 1 K117N). The 3 year RFS was 48% [95%CI: 37-58%] for KRAS WT pts and 30% [15-44%] for MUT pts (p<0.01). OS at 3 years was 96% [88-98%] for KRAS WT and 80% [61-90%] for MUT pts (p=0.08). Cumulative incidence of developing bone, brain, lung, and liver metastases by 2 years is presented in Table 1. The cumulative incidence of metastases to bone at 2 years was 0% and 13.7% in KRAS WT versus MUT pts (p<0.01), to brain 0% versus 4.6% for KRAS WT versus MUT (p=0.05), and to lung 27% versus 47.5% in KRAS WT versus MUT pts (p<0.01). Conclusions: In pts who have had liver resection followed by adjuvant therapy, those with KRAS MUT have a worse RFS and seemingly worse OS than those who are KRAS WT. Also, patients with KRAS MUT appear more likely to develop bone, brain, and lung metastases. Further investigation of a larger number of patients is warranted. [Table: see text]

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Prognostic impact of primary tumor location on survival time in patients (pts) with metastatic colorectal cancer (mCRC) treated with cetuximab plus oxaliplatin-based chemotherapy: A subgroup analysis of the JACCRO CC-05/06.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 613-613 ◽  
Author(s):  
Yu Sunakawa ◽  
Wataru Ichikawa ◽  
Akihito Tsuji ◽  
Tadamichi Denda ◽  
Yoshihiko Segawa ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Prognostic Impact ◽  
Wild Type ◽  
Phase Ii Trials ◽  
Exon 2 ◽  
Free Survival ◽  
Primary Tumor Location ◽  
Kras Exon

613 Background: Sub-analyses of US and European randomized trials have demonstrated that primary tumor location is a critical prognostic factor in mCRC treated with 1st-line chemotherapy; moreover, left-sided tumor location may be a predictor of cetuximab efficacy in KRAS exon 2 wild-type tumors (Loupakis F, et al. J Natl Cancer Inst 2015; von Einem JC, et al. J Cancer Res Clin Oncol 2014). We therefore investigated the prognostic impact of primary tumor location on outcomes of Japanese pts enrolled in JACCRO CC-05 or CC-06 trial, which evaluated efficacy of cetuximab in combination with FOLFOX or SOX, respectively, for mCRC with KRAS exon 2 wild-type tumors. Methods: This study evaluated the association of tumor location with overall survival (OS) and progression-free survival (PFS) in mCRC pts from 2 phase II trials of 1st-line therapy; JACCRO CC-05 of cetuximab plus FOLFOX (n= 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n= 67, UMIN000007022). Tumors proximal or from left flexure to rectum were defined as right-sided or left-sided, respectively. Results: In total of 124 pts of the 2 trials, 110 pts were assessable for the primary tumor location: 90 pts with left-sided tumors and 20 pts with right-sided tumors. In the population consists of 110 evaluable pts, median PFS was 9.4 months, and median OS was 33.9 months. Left-sided tumors were significantly associated with longer OS (36.2 months vs. 12.6 months, HR 0.28, 95%CI 0.15-0.53, p< 0.0001) and PFS (11.1 months vs. 5.6 months, HR 0.47, 95%CI 0.29-0.82, p= 0.0041) compared to right-sided tumors. The association was evident in the group of FOLFOX (p< 0.0001 for OS and p= 0.0002 for PFS), while there was a trend in OS of the group of SOX (p= 0.079). In the FOLFOX-group, median OS and PFS were 5.7 and 3.0 months, respectively, for right-sided tumors (n= 9) and 42.8 and 11.3 months, respectively, for left-sided tumors (n= 43). Conclusions: Our study demonstrates that primary tumor location may serve as a predictor of prognosis of mCRC pts treated with cetuximab plus oxaliplatin-based therapy, potentially confirming the prognostic impact of tumor location.

scholarly journals Primary tumor location and the prognosis of patients after local treatment of colorectal liver metastases: a systematic review and meta-analysis

HPB ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 351-357 ◽  
Author(s):  
Florian E. Buisman ◽  
Boris Galjart ◽  
Stefan Buettner ◽  
Bas Groot Koerkamp ◽  
Dirk J. Grünhagen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Colorectal Liver Metastases ◽  
Meta Analysis ◽  
Local Treatment ◽  
Tumor Location ◽  
Primary Tumor Location
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