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Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases.

ABSTRACT: Colorectal cancer (CRC) is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs). During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as "mild" or "severe" based on the 5-year survival. The study was performed on 85 CRLM tumor samples. Firstly, to evaluate any distinct tumor proteomic signatures between mild and severe CRLM patients, a training group of 57 CRLM tumor samples was characterized by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and a classification and regression tree (CART) analysis was subsequently performed. Finally, 28 CRLM tumor samples were used to confirm and validate the results obtained. Based on all the protein peaks detected in the training group, the CART analysis was generated, and four peaks were considered to be the most relevant to construct a diagnostic algorithm. Indeed, the multivariate model yielded a sensitivity of 85.7% and a specificity of 86.1%, respectively. In addition, the receiver operating characteristic (ROC) curve showed an excellent diagnostic accuracy to discriminate mild from severe CRLM patients (area under the ROC: 0.903). Finally, the validation process yielded a sensitivity and specificity of 68.8% and 83.3%, respectively. We identified a proteomic profile potentially useful to determine the prognosis of CRLM patients based on the 5-year survival.

SUBMITTER: Marfa S

PROVIDER: S-EPMC5067925 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTextbook outcome is a valuable tool for assessing surgical outcomes. The aim of this study was to analyse textbook-outcome rates in the prospective Spanish National Registry of the Liver-First Approach (RENACI Project) and the factors influencing textbook-outcome achievement. Additionally, a model for assessing a procedure-specific textbook outcome for the liver-first approach was proposed.MethodsA retrospective analysis of a prospective and multicentre database that included consecutive patients with colorectal cancers and synchronous liver metastases who underwent a liver-first approach between June 2019 and August 2020 was performed. Two types of textbook outcome were measured: classic textbook outcome and liver-first-approach-specific textbook outcome (which included negative margins, no perioperative transfusion, no postoperative major surgical complications, no prolonged length of hospital stay, no readmissions, no mortality, and full treatment completion). The primary endpoint was textbook-outcome rate for a liver-first approach at 90 days.ResultsA total of 149 patients were included in the analysis. Classic and liver-first-approach-specific textbook-outcome rates were 71.8 per cent (107 patients) and 46 per cent (69 patients) respectively. Factors significantly associated with liver-first-approach-specific textbook-outcome achievement in the multivariable analysis were the number of metastases (OR 0.82 (95 per cent c.i. 0.73 to 0.92); P = 0.001) and intraoperative blood loss (OR 0.99 (95 per cent c.i. 0.99 to 1.00); P = 0.007). Prolonged length of hospital stay (33 patients, 41 per cent), positive margins (31 patients, 39 per cent), perioperative transfusion (27 patients, 34 per cent), and no full treatment completion (18 patients, 23 per cent) were the items that most frequently prevented liver-first-approach-specific textbook-outcome achievement.ConclusionLiver-first-approach-specific textbook outcome is a promising tool for measuring the quality of care when using the liver-first approach for synchronous colorectal liver metastases.

Project description:ImportanceColorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic.ObjectiveTo examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs.Design, setting, and participantsThis prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021.ExposuresLiving-donor liver transplant.Main outcomes and measuresPerioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients.ResultsOf 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III).Conclusions and relevanceThis study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

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Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases.

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