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Metabolic Parameters as Predictors for Progression Free and Overall Survival of Patients with Metastatic Colorectal Cancer.

ABSTRACT: We tested the prognostic relevance of metabolic parameters and their relative changes in patients with metastatic colorectal cancer (mCRC) treated with monoclonal antibody and chemotherapy. SUV_max (standardized uptake volume), SAM (standardized added metabolic activity) and TLG (total lesion glycolysis) are assessed with ¹⁸F-fluorodeoxyglucosepositron emission tomography and computed tomography (FDG-PET/CT) to evaluate total metabolic activity of malignant processes. Our purpose was to investigate the change of glucose metabolism in relation to PFS (progression free survival) and OS (overall survival). Fifty-three patients with mCRC with at least one measurable liver metastasis were included in this prospective, multi-center, early exploratory study. All patients were treated with first-line chemotherapy and targeted therapy. Metabolic parameters, like SUV_max, SAM, normalized SAM (NSAM) and TLG were assessed by FDG-PET/CT, carried out at baseline (scan-1) and after two therapeutic cycle (scan-2). Our results suggested neither SUVmax nor TLG have such prognostic value as NSAM in liver metastases of colorectal cancer. The parameters after the two cycles of chemotherapy proved to be better predictors of the clinical outcome. NSAM after two cycles of treatment has a statistically significant predictive value on OS, while SAM was predictive to the PFS. The follow up normalized SAM after 2 cycles of first line oncotherapy was demonstrated to be useful as prognostic biomarkers for OS in metastatic colorectal cancer. We should introduce this measurement in metastatic colorectal cancer if there is at least one metastasis in the liver.

SUBMITTER: Nemeth Z

PROVIDER: S-EPMC7772167 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Metabolic Parameters as Predictors for Progression Free and Overall Survival of Patients with Metastatic Colorectal Cancer.

Nemeth Zsuzsanna Z Wijker Wouter W Lengyel Zsolt Z Hitre Erika E Borbely Katalin K

Pathology oncology research : POR 20200713 4

We tested the prognostic relevance of metabolic parameters and their relative changes in patients with metastatic colorectal cancer (mCRC) treated with monoclonal antibody and chemotherapy. SUV<sub>max</sub> (standardized uptake volume), SAM (standardized added metabolic activity) and TLG (total lesion glycolysis) are assessed with <sup>18</sup>F-fluorodeoxyglucosepositron emission tomography and computed tomography (FDG-PET/CT) to evaluate total metabolic activity of malignant processes. Our pu ...[more]

PMID: 32661836

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Project description:BackgroundMetastatic colorectal cancer (mCRC) is a highly heterogeneous disease from a clinical, molecular, and immunological perspective. Current predictive models rely primarily in tissue based genetic analysis, which not always correlate with inflammatory response. Here we evaluated the role of a circulating inflammatory signature as a prognostic marker in mCRC.MethodsTwo hundred eleven newly diagnosed patients with mCRC were enrolled in the study. One hundred twenty-one patients had unresectable metastases, whereas ninety patients had potentially resectable liver metastases at presentation. Analysis of miR-21, IL-6, and IL-8 in the plasma of peripheral blood was performed at baseline. Patients with high circulating levels of ≥2 of the three inflammation markers (miR-21, IL-6, and IL-8) were considered to have the "Inflammation phenotype-positive CISIG".ResultsPositive CISIG was found in 39/90 (43%) and 50/121 (45%) patients in the resectable and unresectable cohort, respectively. In the resectable population the median relapse-free survival was 18.4 compared to 31.4 months (p = 0.001 HR 2.09, 95% CI 1.2-3.67) for positive vs. negative CISIG. In contrast, the individual components were not significant. In the same population the median overall survival was 46.2 compared to 66.0 months (p = 0.0003, HR 2.57, 95% CI 1.26-5.27) for positive vs. negative CISIG, but not significant for the individual components. In the unresectable population, the median overall survival was 13.5 compared to 25.0 months (p = 0.0008, HR 2.49, 95% CI 1.46-4.22) for positive vs. negative CISIG. IL-6 was independently prognostic with overall survival of 16.2 compared to 27.0 months (p = 0.004, HR 1.96, 95% CI 1.24-3.11) for high vs. low IL-6, but not the other components. Using a Cox regression model, we demonstrated that CISIG is an independent predictive marker of survival in patients with unresectable disease (HR 1.8, 95% CI 1.2, 2.8, p < 0.01).ConclusionIn two different cohorts, we demonstrated that CISIG is a strong prognostic factor of relapse-free and overall survival of patients with mCRC. Based on these data, analysis of circulating inflammatory signaling can be complimentary to traditional molecular testing.

Project description:BackgroundThe purpose of this study was to investigate the prognostic significance of sarcopenia diagnosed based on anthropometric equations for progression-free survival (PFS) and overall survival (OS) in patients with colorectal cancer (CRC).MethodsA total of 1,441 CRC patients who underwent surgical treatment between January 2012 and December 2016 were enrolled in this study. Sarcopenia was diagnosed according to validated anthropometric equations. The Kaplan-Meier method with the log-rank test was used to estimate the survival curve. Cox proportional hazards regression models with forward selection were used to evaluate risk factors affecting the prognosis of CRC patients. R package "survival" was used to build the prognostic nomograms to predict 1-5 years of PFS and OS in CRC patients. The concordance index (C-index) and calibration curve were used to evaluate the prognostic accuracy of the prognostic nomogram.ResultsTwo hundred and seventy-one patients (18.8%) were diagnosed with sarcopenia. Sarcopenia was significantly associated with advanced age, large tumor size, and high mortality. Compared with the non-sarcopenia patients, the PFS of sarcopenia patients was worse (5-year PFS, 48.34 vs. 58.80%, p = 0.003). Multivariate survival analysis showed that patients with sarcopenia had a higher risk (23.9%) of adverse PFS (HR, 1.239; 95%CI: 1.019-1.505, p = 0.031) than patients without sarcopenia. The OS of patients with sarcopenia was significantly worse than that of patients without sarcopenia (5-year OS: 50.92 vs. 61.62%, p = 0.001). In CRC patients, sarcopenia was independently associated with poor OS (HR: 1.273, 95%CI: 1.042-1.556, p < 0.001). Moreover, sarcopenia effectively differentiated the OS of CRC patients in the normal carcinoembryonic antigen (CEA) subgroup but not in the high CEA subgroup. Notably, sarcopenia can provide effective prognostic stratification in CRC patients at different pathological stages. Nomograms that integrated prognostic features were built to predict the risk of adverse outcomes in CRC patients. The C-index and calibration curves showed that these nomograms had good prediction accuracy. Internal validation confirmed that our nomogram has wide application potential.ConclusionSarcopenia diagnosed based on anthropometric equations is an independent risk factor for PFS and OS in CRC patients.

Dataset Information

Metabolic Parameters as Predictors for Progression Free and Overall Survival of Patients with Metastatic Colorectal Cancer.

Publications

Metabolic Parameters as Predictors for Progression Free and Overall Survival of Patients with Metastatic Colorectal Cancer.

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