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Association between Primary Tumor Location and Prognostic Survival in Synchronous Colorectal Liver Metastases after Surgical Treatment: A Retrospective Analysis of SEER Data.

ABSTRACT: The prognostic and predictive role of primary tumor location (PTL) in localized and metastatic colorectal cancer (CRC) is a hotspot issue in recent years. However, its prognostic role is still unclear in synchronous colorectal liver metastases (sCRLM), especially in those receiving surgical treatment of primary tumor and liver metastases. Here, a retrospective survival analysis was performed using the Surveillance, Epidemiology, and End Results Program (SEER) database between 2010 and 2014, on patients who were pathologically confirmed sCRLM, and received surgical treatment of both primary tumor and liver metastases. After stringent exclusive procedure, a total of 1508 patients with sCRLM (872 men [57.8%] and 636 women [42.2%]; mean age, 60.9 years) were eligible for the final study. Compared with sCRLM with left-sided PTL, cases with right-sided PTL were more likely to be T4 (31.3% vs. 20.1%, p<0.001), N2 (42.5% vs. 31.8%, p<0.001) and poorly differentiated (30.5% vs. 15.1%, p<0.001). Furthermore, right-sided sCRLM showed significantly shorter cancer specific survival (CSS) than those from left-side (p<0.001). After Cox hazard regression analysis, right-sided PTL still remained to be a strong independent predictor for poor prognosis in this cohort of sCRLM patients (OS, HR=1.75, 95% CI 1.34-2.29; CSS, HR=1.76, 95% CI 1.33-2.35). In conclusion, according to this population-based cohort from the SEER database, PTL was a critical prognostic factor that affect long-term OS and CSS in patients with sCRLM after surgical treatment of primary tumor and liver metastases.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6547995 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Strong immune responses in primary colorectal cancer correspond with better patient survival following surgery compared with tumors with predominantly stromal microenvironments. However, biomarkers to identify patients with colorectal cancer liver metastases (CRLM) with good prognosis following surgery for oligometastatic disease remain elusive. The aim of this study was to determine the practical application of a simple histological assessment of immune cell infiltration and stromal content in predicting outcome following synchronous resection of primary colorectal cancer and CRLM and to interrogate the underlying functional biology that drives disease progression. Samples from patients undergoing synchronous resection of primary colorectal cancer and CRLM were evaluated in detail through histological assessment, panel genomic and bulk transcriptomic assessment, IHC, and GeoMx spatial transcriptomics (ST) analysis. High immune infiltration of metastases was associated with improved cancer-specific survival. Bulk transcriptomic analysis was confounded by stromal content, but ST demonstrated that the invasive edge of the metastases of long-term survivors was characterized by adaptive immune cell populations enriched for type II IFN signaling and MHC-class II antigen presentation. In contrast, patients with poor prognosis demonstrated increased abundance of regulatory T cells and neutrophils with enrichment of Notch and TGFβ signaling pathways at the metastatic tumor center. In summary, histological assessment can stratify outcomes in patients undergoing synchronous resection of CRLM, suggesting that it has potential as a prognostic biomarker. Furthermore, ST analysis has revealed significant intratumoral and interlesional heterogeneity and identified the underlying transcriptomic programs driving each phenotype.SignificanceSpatial transcriptomics uncovers heterogeneity between patients, between matched lesions in the same patient, and within individual lesions and identifies drivers of metastatic progression in colorectal cancer with reactive and suppressed immune microenvironments.

Project description:ImportanceIschemia-reperfusion injury during hepatic resection has been shown to accelerate progression of liver cancer. However, the prognostic relevance of remnant liver ischemia (RLI) after resection of colorectal liver metastases (CLMs) is unknown to date.ObjectivesTo assess the prognostic influence of RLI after resection of CLMs and to identify correlates of greater extent of RLI.Design, setting, and participantsThis study was a retrospective analysis at The University of Texas MD Anderson Cancer Center based on prospectively collected data. The study identified 202 patients who underwent curative resection of CLMs between January 1, 2008, and December 31, 2014, and had enhanced computed tomographic images obtained within 30 days after surgery.Main outcomes and measuresRemnant liver ischemia was defined as reduced or absent contrast enhancement during the portal phase. Postoperative RLI was classified as grade 0 (none), 1 (marginal), 2 (partial), 3 (segmental), or 4 (necrotic) as previously defined. Experienced members of the surgical team retrospectively performed imaging assessments. Team members were masked to the postoperative outcomes. Survival after resection was stratified by RLI grade. Predictors of RLI grade 2 or higher and survival were identified.ResultsAmong 202 patients (median [range] age, 56 [27-87] years; 84 female), the RLI grades were as follows: grade 0 (105 patients), grade 1 (47 patients), grade 2 (45 patients), grade 3 (5 patients), and grade 4 (0 patients). Recurrence-free survival (RFS) and cancer-specific survival (CSS) rates after hepatic resection were worse in patients with RLI grade 2 or higher vs grade 1 or lower (RFS at 3 years, 6.4% [3 of 50] vs 39.2% [60 of 152]; P < .001 and CSS at 5 years, 20.7% [10 of 50] vs 63.7% [97 of 152]; P < .001). A largest metastasis at least 3 cm (OR, 2.74; 95% CI, 1.35-5.70; P = .005), multiple CLMs (OR, 2.51; 95% CI, 1.25-5.24; P = .009), and nonanatomic resection (odds ratio [OR], 3.29; 95% CI, 1.52-7.63; P = .002) were associated with RLI grade 2 or higher. A largest metastasis at least 3 cm (hazard ratio [HR], 1.70; 95% CI, 1.01-2.88; P = .045), mutant RAS (HR, 2.15; 95% CI, 1.27-3.64; P = .005), and RLI grade 2 or higher (HR, 2.90; 95% CI, 1.69-4.84; P < .001) were associated with worse CSS.Conclusions and relevanceIn this study, remnant liver ischemia grade 2 or higher was associated with worse CSS after resection of CLMs. High-quality anatomic surgery to minimize RLI after resection is essential.

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Association between Primary Tumor Location and Prognostic Survival in Synchronous Colorectal Liver Metastases after Surgical Treatment: A Retrospective Analysis of SEER Data.

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