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MRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy.

ABSTRACT: BACKGROUND:Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy. METHODS:CRLM from two patient groups were collected: I) with recurrent disease ?12 months after surgery (N = 33), and II) without recurrences and disease free for ?36 months (N = 30). The patients were clinically homogeneous; all had a low clinical risk score (0-2) and did not receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a prognostic gene expression signature. RESULTS:LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease ?12 months after partial hepatectomy. This signature had a sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences (?12 months) versus no recurrences for at least 36 months after surgery (X2 P < 0.0001). CONCLUSION:The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.

SUBMITTER: van der Stok EP

PROVIDER: S-EPMC5423127 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy.

van der Stok E P EP Smid M M Sieuwerts A M AM Vermeulen P B PB Sleijfer S S Ayez N N Grünhagen D J DJ Martens J W M JW Verhoef C C

Molecular oncology 20160920 10

<h4>Background</h4>Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy.<h4>Methods</h4>CRLM from two patient groups were collected: I) with recurrent dise ...[more]

PMID: 27692894

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Project description:BackgroundThe purpose of this study was to determine the optimal definition and elucidate the predictive factors of early recurrence after surgery for colorectal liver metastases (CRLM).MethodsAmong 987 patients who underwent curative surgery for CRLM from 1990 to 2012, 846 with a minimum follow-up period of 24 months were eligible for this study. The minimum p value approach of survival after initial recurrence was used to determine the optimal cutoff for the definition of early recurrence. The predictive factors of early recurrence and prognostic factors of survival were analyzed.ResultsFor 667 patients (79%) who developed recurrence, the optimal cutoff point of early recurrence was determined to be 8 months after surgery. The impact of early recurrence on survival was demonstrated mainly in patients who received preoperative chemotherapy. Among the 691 patients who received preoperative chemotherapy, recurrence was observed in 562 (81%), and survival in patients with early recurrence was significantly worse than in those with late recurrence (5-year survival 18.5% vs. 53.4%, p < .0001). Multivariate logistic analysis identified age ≤57 years (p = .0022), >1 chemotherapy line (p = .03), disease progression during last-line chemotherapy (p = .024), >3 tumors (p = .0014), and carbohydrate antigen 19-9 >60 U/mL (p = .0003) as independent predictors of early recurrence. Salvage surgery for recurrence significantly improved survival, even in patients with early recurrence.ConclusionThe optimal cutoff point of early recurrence was determined to be 8 months. The preoperative prediction of early recurrence is possible and crucial for designing effective perioperative chemotherapy regimens.Implications for practiceIn this study, the optimal cutoff point of early recurrence was determined to be 8 months after surgery based on the minimum p value approach, and its prognostic impact was demonstrated mainly in patients who received preoperative chemotherapy. Five factors, including age, number of preoperative chemotherapy lines, response to last-line chemotherapy, number of tumors, and carbohydrate antigen 19-9 concentrations, were identified as predictors of early recurrence. Salvage surgery for recurrence significantly improved survival, even in patients with early recurrence. For better selection of patients who could truly benefit from surgery and should also receive strong postoperative chemotherapy, the accurate preoperative prediction of early recurrence is crucial.

Project description:The aim of this study was to assess safety, efficacy and survival outcomes of repeat thermal ablation as compared to repeat partial hepatectomy in patients with recurrent colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study of two cohorts, repeat thermal ablation versus repeat partial hepatectomy, analyzed 136 patients (100 thermal ablation, 36 partial hepatectomy) and 224 tumors (170 thermal ablation, 54 partial hepatectomy) with recurrent CRLM from May 2002 to December 2020. The primary and secondary endpoints were overall survival (OS), distant progression-free survival (DPFS) and local tumor progression-free survival (LTPFS), estimated using the Kaplan-Meier method, and complications, analyzed using the chi-square test. Multivariable analyses based on Cox proportional hazards model were used to account for potential confounders. In addition, subgroup analyses according to patient, initial and repeat local treatment characteristics were performed. In the crude overall comparison, OS of patients treated with repeat partial hepatectomy was not statistically different from repeat thermal ablation (p = 0.927). Further quantification of OS, after accounting for potential confounders, demonstrated concordant results for repeat local treatment (hazard ratio (HR), 0.986; 95% confidence interval (CI), 0.517-1.881; p = 0.966). The 1-, 3- and 5-year OS were 98.9%, 62.6% and 42.3% respectively for the thermal ablation group and 93.8%, 74.5% and 49.3% for the repeat resection group. No differences in DPFS (p = 0.942), LTPFS (p = 0.397) and complication rate (p = 0.063) were found. Mean length of hospital stay was 2.1 days in the repeat thermal ablation group and 4.8 days in the repeat partial hepatectomy group (p = 0.009). Subgroup analyses identified no heterogeneous treatment effects according to patient, initial and repeat local treatment characteristics. Repeat partial hepatectomy was not statistically different from repeat thermal ablation with regard to OS, DPFS, LTPFS and complications, whereas length of hospital stay favored repeat thermal ablation. Thermal ablation should be considered a valid and potentially less invasive alternative for small-size (0-3 cm) CRLM in the treatment of recurrent new CRLM. While, the eagerly awaited results of the phase III prospective randomized controlled COLLISION trial (NCT03088150) should provide definitive answers regarding surgery versus thermal ablation for CRLM.

Project description:BackgroundCancer recurrence is an important predictor of survival outcomes in patients with colorectal cancer-associated liver metastasis (CRLM), who undergo radical hepatectomy. Therefore, identification of patients with the greatest risk of recurrence is critical for developing a precision oncology strategy that might include frequent surveillance (in low-risk patients) or a more aggressive treatment approach (in high-risk patients). We performed genome-wide expression profiling, to identify and develop a transcriptomic signature for predicting recurrence in patients with CRLM.MethodsWe analysed a total of 383 patients with CRLM, including 63 patients from a publicly available data set (the NCBI's Gene Expression Omnibus with accession number GSE81423). and 320 patients from whom surgical specimens were collected for independent training (n = 169) and validation (n = 151) of identified biomarkers. Using Cox's proportional hazard regression analysis, we evaluated the clinical significance of the identified gene signature by comparing its performance with several key clinical factors.ResultsWe identified a six-gene panel that robustly categorised patients with recurrence in the discovery (area under the curve (AUC) = 0.90). We showed that the panel was a significant predictor of recurrence in the clinical training (AUC = 0.83) and validation cohorts (AUC = 0.81). By combining our panel with key clinical factors, we established a risk-stratification model that emerged as an independent predictor of recurrence (AUC = 0.85; univariate: hazard ratio (HR) = 4.34, 95% confidence interval (CI) = 2.71-6.93, P < 0.001; multivariate: HR = 3.40, 95% CI = 1.76-6.56, P < 0.001). The stratification model revealed recurrence prediction in 89% of high-risk group and non-recurrence in 62% of low-risk group.ConclusionsWe established a novel transcriptomic signature that robustly predicts recurrence, which has significant implications for the management of patients with CRLM.

Project description:BackgroundThe objective of this study was to compare the results of laparoscopic hepatectomy with those of open hepatectomy for colorectal cancer liver metastases (CCLM) using a propensity score matching (PSM) in two university hospital settings.MethodsA patient in the laparoscopic approach (LA) surgery group was randomly matched with another patient in the open approach (OA) group using a 1:1 allocated ratio with the nearest estimated propensity score. No patients of the LA group were excluded for the matching. Matching criteria included age, gender, body mass index (BMI), American society anesthesiologists score, potential co-morbidities, hepatopathies, synchronous or metachronous lesions, size and number of CCLM, preoperative chemotherapy, minor or major liver resections. Intraoperative, postoperative data, and survival were compared in both groups.ResultsFrom January 2012 to January 2015, a total of 242 hepatectomies were consecutively performed, of which 119 for CCLM, namely 101 in the OA group (84.9%) and 18 in the LA group (15.1%). The conversion rate was 5.6% (n=1). The mortality rate was 1% in the OA group and 0% in the LA group. Prior to PSM, there was a statistically significant difference favorable to the LA group regarding operative time, blood loss, length of hospital stay and the rate of medical complications. After PSM, there was no difference regarding operative time or length of hospital stay. However, there was a trend towards less blood loss (P=0.066) and fewer medical complications (44.4% vs.16.7%, P=0.07). The R0 resection rate was 94.4% (n=17) in the two groups. In addition, there was no difference regarding overall survival (P=0.358) and recurrence-free survival [HR =0.99 (0.1-12.7); P=0.99].ConclusionsLaparoscopic liver resections for CCLM seem to yield short- and long-term results, which are similar to open hepatectomies, and could well be considered an alternative to open surgery and become the gold standard in carefully selected patients.

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MRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy.

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mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy.

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