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Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials.

ABSTRACT: BACKGROUND:The prognostic value of body composition in cancer patients has been widely studied during the last decade. The main finding of these studies is that sarcopenia, or skeletal muscle depletion, assessed by CT imaging correlates with a reduced overall survival (OS). By contrast, the prognostic value of fat mass remains ill-defined. This study aims to analyze the influence of body composition including both muscle mass and adipose tissue on OS in a homogeneous population of advanced colorectal cancer (CRC) patients. METHODS:Among 235 patients with chemorefractory advanced CRC included in the SoMore and RegARd-C trials, body composition was assessed in 217 patients on baseline CT images. The relationship between body composition (sarcopenia, muscle density, subcutaneous and visceral fat index and density), body mass index (BMI) and OS were evaluated. RESULTS:Patients with a higher BMI had a better OS (?30 versus

SUBMITTER: Charette N

PROVIDER: S-EPMC6371452 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials.

Charette Nicolas N Vandeputte Caroline C Ameye Lieveke L Bogaert Camille Van CV Krygier Jonathan J Guiot Thomas T Deleporte Amélie A Delaunoit Thierry T Geboes Karen K Van Laethem Jean-Luc JL Peeters Marc M Demolin Gauthier G Holbrechts Stéphane S Flamen Patrick P Paesmans Marianne M Hendlisz Alain A

BMC cancer 20190212 1

<h4>Background</h4>The prognostic value of body composition in cancer patients has been widely studied during the last decade. The main finding of these studies is that sarcopenia, or skeletal muscle depletion, assessed by CT imaging correlates with a reduced overall survival (OS). By contrast, the prognostic value of fat mass remains ill-defined. This study aims to analyze the influence of body composition including both muscle mass and adipose tissue on OS in a homogeneous population of advanc ...[more]

PMID: 30744591

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Project description:Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality globally and is the third most prevalent cancer. The effective treatment of CRC is challenged by tumor drug resistance, underscoring the urgent need for novel therapeutic strategies. It is well recognized that epigenetic modifications, particularly DNA methylation, significantly contribute to the initiation and advancement of CRC. Tumors frequently exhibit hypermethylation of specific gene promoters alongside a general hypomethylation of genomic DNA. In normal tissues, gene promoters, particularly those of tumor suppressor genes, are typically unmethylated, whereas they are often hypermethylated in cancerous tissues. Previous studies have identified the methylation status of the CpG island within the SLC30A10 gene as a reliable biomarker for CRC. Notably, a hypermethylated phenotype is inversely correlated with SLC30A10 expression. However, the precise functional implications of SLC30A10 suppression in the context of CRC progression remain to be elucidated.). The investigation of molecular pathways involved in metal metabolism in CRC has not been conducted previously at the transcriptomic level. Furthermore, the relationship between the mutational characteristics of tumors—such as individual mutations, mutational burden, and microsatellite instability—and the activity of genes related to metal metabolic pathways has not been explored. This project aims to be the first to examine the antitumor potential of modulating the transport systems for manganese and zinc ions in CRC. The molecular function of SLC30A10 is to export zinc (Zn) and manganese (Mn) ions from the cell. Additionally, SLC30A10 plays a crucial role in mitigating Mn-induced cytotoxicity and facilitates Zn transport to early endosomes while promoting endosomal recirculation to avert Zn toxicity. Our findings indicate that overexpression of SLC30A10 is correlated with the knockout of its functional antagonist, SLC39A14 in the HuTu80 and HCT-15 cell lines.

Project description:Abstract Background The potential of circulating tumour DNA (ctDNA) as a reliable biomarker for relapse/metastasis early detection and prognosis in esophageal squamous cell carcinoma (ESCC) after radiotherapy/chemoradiotherapy (RT/CRT) initiation requires comprehensive investigation. Methods Treatment‐naive locally advanced ESCC patients with available baseline plasma samples were prospectively enrolled from November 2018 to January 2020. RT/CRT was delivered with a simultaneous integrated boost of radiation dose. Serial plasma samples were collected at baseline (T0), week 4 of RT/CRT (T1), 1‐3 (T2) and 3‐6 months post‐RT/CRT (T3). ctDNA was analysed using next‐generation sequencing of 474 cancer‐relevant genes. Results A total of 128 plasma samples from 40 eligible patients were analysed (median age: 64 [range: 40‐78], 88% males, 95% stage III/IV), and the median follow‐up time was 20.6 months (range: 12.2‐33.3). During the post‐RT/CRT surveillance including 36 patients, radiological progression was observed in 16 patients, and 69% (11/16) had detectable post‐RT/CRT ctDNA prior to radiological progression, with a median lead time of 4.4 months compared with radiological imaging. ctDNA positivity at T1 (hazard ratio, HR: 3.60, 95% confidence interval, CI: 1.30‐10.01) or T2 (HR: 5.45, 95% CI: 1.72‐17.26) indicated inferior progression‐free survival (PFS). ctDNA clearance between T0‐T1 (HR: 0.31, 95% CI: 0.08‐1.13) or T0‐T2 (HR: 0.11; 95% CI: 0.02‐0.61) was associated with relatively favourable PFS. Similar results were obtained when focusing on patients without esophagectomy after RT/CRT. Notably, detectable ctDNA at T1 was a potential indicator of high local recurrence risks (HR: 4.43, 95% CI: 1.31‐15.04). Conclusions ctDNA was identified as a robust biomarker for early detection of disease progression and post‐RT/CRT prognosis stratification in ESCC. Detectable ctDNA at week 4 of RT/CRT might indicate higher local recurrence risks, implying the potential clinical utility of ctDNA tests in guiding post‐RT/CRT treatments for locoregional control in ESCC.

Project description:Low skeletal muscle mass is a well-known prognostic factor for patients treated for a non-small-cell lung cancer by surgery or chemotherapy. However, its impact in patients treated by exclusive radiochemotherapy has never been explored. Our study tries to evaluate the prognostic value of low skeletal muscle mass and other antropometric parameters on this population. Clinical, nutritional and anthropometric date were collected for 93 patients treated by radiochemotherapy for a NSCLC. Anthropometric parameters were measured on the PET/CT by two methods. The first method was a manual segmentation at level L3, used to define Muscle Body Area (MBAL3), Visceral Fat Area (VFAL3) and Subcutaneous Fat Area (SCFAL3). The second method was an software (Anthropometer3D), allowing an automatic multislice measurement of Lean Body Mass (LBMAnthro3D), Fat Body Mass (FBMAnthro3D), Muscle Body Mass (MBMAnthro3D), Visceral Fat Mass (VFMAnthro3D), and Sub-Cutaneous Fat Mass (SCFMAnthro3D) on the PET/CT. All anthropometrics parameters were normalised by the patient's height. The primary end point was overall survival time. Univariate and then stepwise multivariate cox analysis were performed for significant parameters. Finally, Spearman's correlation between MBAL3 and MBMAnthro3D was assessed. Forty-one (44%) patients had low skeletal muscle mass. The median overall survival was 18 months for low skeletal muscle mass patients versus 36 months for non-low skeletal muscle mass patients (p = 0.019). Low skeletal muscle mass (HR = 1.806, IC95% [1.09-2.98]), serums albumin level < 35 g/l (HR = 2.203 [1.19-4.09]), Buzby Index < 97.5 (HR = 2.31 [1.23-4.33]), WHO score = 0 (HR = 0.59 [0.31-0.86] and MBMAnthro3D < 8.56 kg/m2 (HR = 2.36 [1.41-3.90]) were the only significant features in univariates analysis. In the stepwise multivariate Cox analysis, only MBMAnthro3D < 8.56 kg/m2 (HR = 2.16, p = 0.003) and WHO score = 0 (HR = 0.59, p = 0.04) were significant. Finally, muscle quantified by MBAL3 and MBMAnthro3D were found to be highly correlated (Spearman = 0.9). Low skeletal muscle mass, assessed on the pre-treatment PET/CT is a powerful prognostic factor in patient treated by radiochemotherapy for a NSCLC. The automatic software Anthropometer3D can easily identify patients a risk that could benefit an adapted therapy.

Project description:BackgroundIdentifying patients with low muscle mass is crucial for the diagnosis of sarcopenia. Although the Creatinine/Cystatin C (Cr/CysC) is recommended as a simplified indicator to identify patients with low muscle mass, its ability to assess muscle mass and predict a poor prognosis has not been validated. We aimed to determine the diagnosis value of Cr/CysC for low muscle mass and examine the association of Cr/CysC with mortality.MethodsIn this cohort study we analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2002. Follow-up was conducted up to December, 2015. Appendicular skeletal mass was calculated based on dual-energy X-ray absorptiometry (DXA) scans. Low muscle mass was defined referring to five international diagnostic criteria. The diagnostic value of Cr/CysC as a replacement indicator of muscle mass was measured using area under the curve, positive percent agreement, negative percent agreement and kappa. Cox proportional hazards regression models were developed to examine the association between Cr/CysC and risk of mortality.ResultsThis cohort study of 3,741 adults comprised 1,823 females (48.73%), with a weighted mean (SE) age of 44.46 (0.43) years. The positive percent agreement of Cr/CysC for the diagnosis of low muscle mass was poor (40.23-58.74%), except for Foundation of the National Institute of Health (FNIH) criteria (80.90-58.97%). But the negative percent agreement of Cr/CysC for the diagnosis of low muscle mass was high (males: 62.15-88.17%; females: 55.26-82.30%). Moreover, the risk of death was reduced by 2% per 0.01 unit increase in Cr/CysC (aHR, 0.98; 95% CI, 0.98-0.99, P < 0.001).ConclusionsCr/CysC performed well not only in identifying non-sarcopenia cases, especially when based on FNIH diagnostic criteria, but also in revealing a positive association with higher risk of mortality. The optimal cut-off values for Cr/CysC were <1.0 in males and <0.8 in females. Expanding the use of Cr/CysC would allow for early and targeted treatment of sarcopenia.

Dataset Information

Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials.

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Prognostic value of adipose tissue and muscle mass in advanced colorectal cancer: a post hoc analysis of two non-randomized phase II trials.

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