Overall Survival In Esophageal Cancer Patients Research Articles

P4HA1 expression and function in esophageal squamous cell carcinoma.

This study aimed to explore the effect of P4HA1 (prolyl 4-hydroxylase subunit α1) and its ratio on the prognosis of esophageal squamous cell carcinoma. The expression data of P4HA1 in esophageal cancer in The Cancer Genome Atlas and Genotype-Tissue Expression were collected using the public database gene expression profiling interactive analysis. The expression levels of P4HA1 were examined by immunohistochemistry. The relationship between P4HA1 expression and clinicopathological parameters was analyzed the χ2 test. Survival analysis was performed to investigate the effect of P4HA1 and its ratio on prognosis. Compared with normal esophageal mucosal epithelium, there was higher P4HA1 gene mRNA in esophageal cancer tissue. Regarding the expression level, no significant difference was observed in patients with stage I-IV esophageal cancer. Immunohistochemistry showed that P4HA1 was highly expressed in esophageal squamous cell carcinoma (68.7%), while it was negatively expressed in paracancerous tissues. There was a significant difference in expression between cancer and adjacent tissues. The expression of P4HA1 associated with the degree of tumor differentiation, site, lymph node metastasis, and tumor node metastasis stage. The prognostic factors that affected the OS (overall survival) of esophageal cancer patients were the degree of differentiation, lymph node metastasis, and P4HA1 expression. Multivariate analysis of the OS results of patients showed that lymph node metastases and P4HA1 expression were independent prognostic factors that affected the OS of esophageal cancer patients. The prognostic factors affecting the PFS (progression-free survival) of esophageal cancer patients in the univariate survival analysis were as follows: degree of differentiation, lymph node metastasis, and P4HA1 expression. In addition, multivariate analysis of the PFS results of patients showed that lymph node metastasis and P4HA1 expression were independent prognostic factors that affected the PFS of esophageal cancer patients. P4HA1 may be a novel potential biomarker for the early diagnosis, prognosis, and targeted therapy of esophageal cancer.

Two novel clinical tools to predict the risk of bone metastasis and overall survival in esophageal cancer patients: a large population-based retrospective cohort study.

The aim of this study was to construct two web-based nomograms to predict the probability of bone metastasis (BM) in esophageal cancer (EC) patients and the prognostic of EC patients with BM (ECBM). We collected the data of EC and ECBM patients in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015. Independent risk variables for the development of BM in EC patients were identified using univariate and multivariate logistic regression analyses. Univariate and multivariate Cox regression analyses were used to assess independent prognostic variables in ECBM patients. And then, constructed two nomograms to predict the risk of bone metastases and overall survival (OS) of ECBM patients. Survival differences were studied by Kaplan-Meier (K-M) survival analysis. The predictive efficacy and clinical applicability of these two nomograms were assessed by using receiver operating characteristic (ROC) curve, the area under curve (AUC), calibration curve and decision curve analysis (DCA). We selected a total of 6839 patients with EC, of which 326 (4.77%) had BM at the time of initial diagnosis. The results of K-M survival and Cox regression analysis showed significant effects of BM on the OS in EC patients. Age, N stage, tumor size and brain/liver/lung organ metastasis were identified as BM-related risk variables. Chemotherapy and brain/liver organ metastasis were identified as ECBM-related prognostic variables. The ROC, AUC, calibration curves and DCA of two nomograms all showed excellent predictive efficacy and clinical applicability. These two nomograms were constructed and validated, which could objectively predict the risk of BM in EC patients and the prognostic in ECBM patients. These tools are expected to make valuable contributions in clinical work, informing surgeons in making decisions about patient care.

Comparison of complications and long-term survival after minimally invasive esophagectomy versus open esophagectomy in patients with esophageal cancer and chronic obstructive pulmonary disease

ObjectiveTo compare the complications and long-term survival of esophageal cancer patients with chronic obstructive pulmonary disease (COPD) after minimally invasive esophagectomy (MIE) versus open esophagectomy (OE) using propensity score matching (PSM).MethodsEsophageal cancer patients who underwent esophagectomy at the Thoracic Surgery Department of the First Affiliated Hospital of Hebei North University from January 2010 to December 2018 were retrospectively enrolled. The incidence of postoperative complications and prognosis of the MIE (n = 132) and OE (n = 138) groups were compared. To reduce bias, 1:1 PSM was adopted for the analysis.ResultsThe median disease-free survival (DFS) of the MIE and OE groups were 24 months and 26 months, respectively, and neither group reached median survival. There was no significant difference between the two groups in terms of 3-year DFS and overall survival (OS). The stratification of the patients on the basis of the percentage of estimated forced expiratory volume in the first second (%FEV1) did not result in significant differences in the survival rates. A total of 42 patients (50%) in the MIE group and 55 patients (65.48%) in the OE group experienced complications, and the difference was statistically significant (OR=0.527, 95% CI: 0.283–0.981, P=0.042). The incidence of acute COPD exacerbation (OR=0.213, 95% OR, CI: 0.068–0.666, P=0.004) and pulmonary atelectasis requiring bronchoscopic aspiration (OR=0.232, 95% OR, CI: 0.082–0.659, P=0.004) were significantly higher in the OE versus the MIE group. In addition, the distribution of the various grades of complications also differed significantly between the two groups (P=0.016). While the incidence of minor complications (≤Grade II) was similar in both groups (P=0.503), that of severe complications (≥Grade III) was markedly higher in the OE group (P=0.002) and the Grade-IIIa complications were predominant (P=0.001). The severity of complications was correlated with the postoperative duration of hospital stay in both groups (r=0.187, P=0.015). No significant difference was observed in the incidence of minor complications (≤Grade II) between the two groups following stratification on the basis of %FEV1, whereas severe complications were more frequent in the OE group among patients with %FEV1 between 60% and 70% (P=0.001<0.05).ConclusionThere was no significant difference in the postoperative DFS and OS of esophageal cancer patients with COPD after undergoing MIE or OE. However, MIE significantly reduced the incidence of severe postoperative complications among patients with %FEV1 between 60% and 70%.

Lymph Node Ratio Improves Prediction of Overall Survival in Esophageal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy: A National Cancer Database Analysis.

This study aimed to propose a revised ypN (r-ypN) classification based on lymph node ratio (LNR) and to examine its prognostic value in postneoadjuvant esophageal cancer. A new postneoadjuvant pathologic (ypTNM) staging classification has been introduced for esophageal cancer. However, the ypN classification currently defined by the number of positive lymph nodes is influenced by the extent of lymphadenectomy. Data on 7195 esophageal cancer patients receiving neoadjuvant chemoradiation were extracted from the National Cancer Database (NCDB). Four r-ypN stages were defined by 3 LNR thresholds (0%, 10%, and 20% using X-tile software). A revised ypTNM (r-ypTNM) classification was developed by solely changing N categories. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Akaike information criterion (AIC) and Harrell's concordance index ( C -index) were used to compare the predictive performance of the current and the revised classification. External validation was performed using an independent cohort from the NEOCRTEC5010 clinical trial. Both ypN ( P <0.001) and r-ypN ( P <0.001) were independent prognostic factors of overall survival (OS) for esophageal cancer patients. Kaplan-Meier curves demonstrated a better discrimination with r-ypN than ypN categories. Within each ypN category (except ypN3), OS was significantly different comparing r-ypN strata; however, there were no differences between ypN strata within each r-ypN category (except r-ypN3). r-ypN (AIC: 60752 vs 60782; C -index: 0.591 vs 0.587) and r-ypTNM (AIC: 60623 vs 60628; C -index: 0.613 vs 0.610) showed better predictive performance than the current staging system, with a lower AIC (better calibration) and higher C -index (improved discrimination). This advantage was also confirmed by external validation using the NEOCRTEC5010 cohort. LNR showed better performance than ypN in predicting OS of esophageal cancer patients after neoadjuvant chemoradiation and may be an improvement on the current staging system.

Linkage of time interval from neoadjuvant chemoradiotherapy to surgery with pathological response and survival profile in resectable esophageal cancer patients.

e16071 Background: The optimal time interval from neoadjuvant chemoradiotherapy (nCRT) to surgery remains controversial in esophageal cancer (ESC) patients. Hence, this study aimed to evaluate the relationship of the time interval from nCRT to surgery with the prognosis in ESC patients. Methods: Totally, 166 ESC patients treated with nCRT followed by surgical resection were reviewed. Their pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS) were analyzed. Based on the median duration from nCRT to surgery, patients were classified into duration from nCRT to surgery ≥66 days group or &lt;66 days group. Results: The pCR rate was elevated in duration from nCRT to surgery ≥66 days group compared to &lt;66 days group (48.3% vs. 25.3%, P = 0.002), while DFS ( P = 0.316) and OS ( P = 0.883) were of no difference between these two groups. The duration from nCRT to surgery (≥66 days vs. &lt;66 days) (odds ratio (OR): 2.149, P = 0.039) was independently related to improved pCR rate as validated by multivariate logistic regression, while it did not correlate with DFS or OS (both P &gt; 0.05) by univariate and multivariate Cox’s regression analyses. Moreover, female gender ( P=0.001) and radiation dose ≥40 Gy. ( P = 0.039) could independently predict better pCR rate; and pCR rate was independently related to longer DFS ( P = 0.003) and OS ( P = 0.008). Conclusions: The prolonged time interval from nCRT to surgery relates to a higher pCR rate but does not correlate with DFS or OS in ESC patients.

Detection of Circulating and Disseminated Tumor Cells and Their Prognostic Value under the Influence of Neoadjuvant Therapy in Esophageal Cancer Patients

Detection of circulating (CTC) or disseminated tumor cells (DTC) are correlated with negative prognosis in esophageal cancer (EC) patients. In this study, DTC- and CTC-associated markers CK20 and DEFA5 were determined by RT-PCR in EC patients and correlated with clinical parameters to determine their prognostic impact. The blood and bone marrow (BM) of 216 EC patients after tumor resection with or without neoadjuvant therapy and as control blood samples from 38 healthy donors and BM from 24 patients with non-malignant diseases were analyzed. Both markers were detected in blood and BM of EC patients and the control cohort. A cut-off value was determined to define marker positivity for correlation with clinical data. CK20 expression was detected in 47/206 blood samples and in 49/147 BM samples of EC patients. DEFA5 positivity was determined in 96/206 blood samples and 98/147 BM samples, not correlating with overall survival (OS). However, CK20 positivity in BM and DEFA5 negativity in blood were associated with reduced OS in EC patients without neoadjuvant therapy, while in patients with neoadjuvant therapy DEFA5 positivity in BM was associated with improved OS. Overall, our study suggests DEFA5 as a prognostic biomarker in liquid biopsies of EC patients which requires further validation.

Immunotherapy for Esophageal Cancer: State-of-the Art in 2021

Simple SummaryThe aim of this review was to describe the rationale for immunotherapy in different stages of esophageal cancer (EC) treatment, with a particular accent on curative intent treatment of locally advanced disease for the two predominant histological types (adenocarcinoma and squamous cell cancer). In addition to the already existing literature on immunotherapy for advanced and metastatic stages of EC, the current study provides a comprehensive review of the leading ongoing trials in 2021 with a focus on earlier stages of treatment in neo adjuvant and adjuvant settings.The management of esophageal cancer (EC) has experienced manifold changes during the last decades. Centralization of EC treatment has been introduced in many countries, subsequently allowing the development of specialized high-volume centers. Minimal invasive surgery has replaced open surgery in many centers, whereas more potent systemic treatments have been introduced in clinical practice. Newer chemotherapy regimens increase long-term survival. Nevertheless, the overall survival of EC patients remains dismal for advanced tumor stages. In this direction, a wide range of targeted biologic agents (immunotherapy) is currently under assessment. Anti- Human Epidermal Growth Factor Receptor-2 (HER-2) monoclonal antibodies are used in HER2 (+) tumors, predominantly well-differentiated adenocarcinomas, and are currently assessed in the neoadjuvant setting (TRAP, INNOVATION trials). Immune checkpoint inhibitors Nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181), have demonstrated a survival benefit compared with conventional chemotherapy in heavily pre-treated progressive disease. More recently, CheckMate-577 showed very promising results for nivolumab in a curative adjuvant setting, improving disease-free survival mainly for esophageal squamous cell carcinoma. Several ongoing trials are investigating novel targeted agents in the preoperative setting of locally advanced EC. In addition, other immunomodulatory approaches such as peptide vaccines and tumor infiltrating lymphocytes (TILs) are currently under development and should be increasingly integrated into clinical practice.

High Serum Levels of Wnt Signaling Antagonist Dickkopf-Related Protein 1 Are Associated with Impaired Overall Survival and Recurrence in Esophageal Cancer Patients.

Dickkopf-related protein 1 (DKK1), an antagonist of the canonical Wnt pathway, has received tremendous attention over the past years as its dysregulation is said to be critically involved in a wide variety of gastrointestinal cancers. However, the potential clinical implications of DKK1 remain poorly understood. Although multimodal treatment options have been implemented over the past years, esophageal cancer (EC) patients still suffer from poor five-year overall survival rates ranging from 15% to 25%. Especially prognostic factors and biomarkers for risk stratification are lacking to choose the most beneficial treatment out of the emerging landscape of different treatment options. In this study, we analyzed the serum DKK1 (S-DKK1) levels of 91 EC patients prior to surgery in a single center study at the University Medical Center Hamburg-Eppendorf by enzyme-linked immunosorbent assay. High levels of S-DKK1 could be especially observed in patients suffering from esophageal adenocarcinoma which may promote the hypothesis of a crucial role of DKK1 in inflammation. S-DKK1 levels of ≥5800 pg/mL were shown to be associated with unfavorable five-year survival rates and the presence of CTCs. Interestingly, significantly lower S-DKK1 levels were detected in patients after neoadjuvant treatment, implying that S-DKK1 may serve as a useful biomarker for treatment monitoring. Multivariate analysis identified S-DKK1 as an independent prognostic marker with respect to overall survival in EC patients with a hazard ratio of 2.23. In conclusion, our data implicate a negative prognostic role of DKK1 with respect to the clinical outcome in EC patients. Further prospective studies should be conducted to implement S-DKK1 into the clinical routine for risk stratification and treatment monitoring.

M6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1.

N6-methyladenosine (m6A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m6A modification and m6A RNA methylation regulators were involved in cancer progression. However, the m6A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m6A regulators using The Cancer Genome Atlas data and found 14 of 19 m6A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of m6A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m6A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m6A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

The Expression of Tripartite Motif Protein 36 and β-Catenin Correlates with the Prognosis of Esophageal Cancer.

Aims Tripartite motif protein 36 (TRIM36) plays a tumor-suppressive role in prostate cancer. However, there is little information on the clinical relevance of TRIM36 expression in esophageal cancer (ESCA). Methods TRIM36 expression was analyzed by using The Cancer Genome Atlas (TCGA) ESCA dataset as well as by quantitative real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining on samples from our hospital. Results In the current study, the analysis of TCGA ESCA dataset suggested the decreased expression of TRIM36 in ESCA tissues. Further analyses on samples from our hospital demonstrated that TRIM36 was significantly downregulated in ESCA tissues than in the noncancerous controls at both the mRNA and protein levels. Moreover, gene set enrichment analysis on TCGA ESCA dataset suggested that TRIM36 expression was inversely correlated with the β-catenin pathway. IHC staining data showed that 66.25% (53/80) and 51.25% (41/80) of ESCA cases had a low expression of TRIM36 and a high expression of β-catenin, respectively. By Fisher's exact test, we found that TRIM36 protein expression was significantly correlated with tumor size (P = 0.0104), tumor stage (P = 0.0169), lymph node metastasis (P = 0.0021), vital status (P = 0.0443), and β-catenin expression (P = 0.0329). These findings suggest the potential clinical significance of TRIM36 in ESCA. Kaplan–Meier and log-rank test demonstrated that a low expression of TRIM6 and a high expression of β-catenin were associated with poor overall survival of ESCA patients. Conclusions Our study provides evidence for the prognostic value of TRIM36 in ESCA.

Oncogenic microRNA-301b regulates tumor repressor dystrobrevin alpha to facilitate cell growth, invasion and migration in esophageal cancer.

Esophageal cancer (EC) ranks the eighth in morbidity and the sixth in mortality around the whole world, which is an aggressive malignancy. To authenticate potential therapeutic targets for EC is therefore imperative. Although miR-301b might display changed expression in esophageal adenocarcinoma by utilizing Taqman miRNA profiling analysis, much less is known about the impact of miR-301b in EC. By analyzing the data of 187 cancer tissues and 13 normal samples from TCGA database, we discovered that miR-301b was highly expressed in EC tissues. Then, RT-qPCR determined that miR-301b was up-regulated in EC cell lines (ECA109, JAR, TE-1 and OE33). Besides, miR-301b expression level was higher in ESCC cell line-TE-1 cells and lower in ESCC cell line-ECA109 cells compared to other EC cell lines. Hence, ECA109 cell line was used to up-regulate miR-301b expression while TE-1 cell line was applied to down-regulate miR-301b expression in the subsequent experiments. Additionally, OE33, as an ECA cell line, was applied to upregulate miR-301b expression to reflect the influence of miR-301b overexpression on EC progression. More interestingly, miR-301b appeared to act as a promoting effect on the proliferation of EC cells, which was tested by CCK8. Dystrobrevin alpha (DTNA) was a targeting gene of miR-301b, which was predicted by the websites of miRanda, miRWalk and TargetScan. Additionally, DTNA was low expressed in EC tissues and was an independent predictor of EC. Meanwhile, the low expression of DTNA was related to worse overall survival in EC patients. The Pearson correlation coefficient analyzed that DTNA expression was negatively correlated with miR-301b. Furthermore, RT-qPCR and western blotting assays ulteriorly indicated that DTNA was negatively modulated by miR-301b. The facilitating impact of miR-301b re-expression on ECA109 and OE33 cell growth, invasion and migration was receded by DTNA over-expression, whilst the repressive effect of miR-301b ablation on TE-1 cell growth, invasion and migration was inversed by DTNA silencing. Overexpression of miR-301b accelerated EC cell growth, migration and invasion through targeting DTNA. Above all, we concluded that miR-301b was concerned with the progression of EC via regulating DTNA, suggesting that miR-301b and its target gene, DTNA, might serve as predictive biomarkers for EC therapy.

Characterization of gene expression profiles of esophageal cancer patients with different nonsynonymous tumor mutation burden.

BackgroundNonsynonymous tumor mutation burden (NSTMB) could affect the prognosis of esophageal cancer (EC) patients, but differentially expressed genes between EC patients with different NSTMB have not been explored. Our study aimed to compare differentially expressed genes between EC patients with different NSTMB (high vs. low).MethodsRNA‐seq data for EC patients were downloaded from The Cancer Genome Atlas (TCGA). The edgeR package was used to identify differentially expressed genes between patients with different NSTMB. Cell type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) software was employed to underscore immune cell differences between patients with different NSTMB.ResultsIn total, we discovered 2215 differentially expressed genes between patients with different NSTMB, among which 842 genes were upregulated and 1373 downregulated in patients with high NSTMB. The differentially expressed genes were enriched in pathways such as heme binding and structural molecule activity. We built a logistic model that may be used to predict patients' NSTMB. We found that tumors with high NSTMB had a significantly higher percentage of resting natural killer (NK) cells than those with low NSTMB (P = 0.028). The percentages of regulatory T (Treg) and CD8+ T cells were also higher in those with high NSTMB, although it was not statistically significant (P = 0.064 for Treg cells and P = 0.12 for CD8+ T cells).ConclusionsNSTMB may cause changes in gene expression and immune cell infiltration in EC patients, and affect the overall survival of EC patients.Key points Significant findings of the study This study found differentially expressed genes and differences in infiltration of immune cells between esophageal cancer (EC) with different NSTMB. What this study adds This study highlights differences between EC patients with different NSTMB.

The Significance of Negative Lymph Nodes in Esophageal Cancer After Curative Resection: A Retrospective Cohort Study.

ObjectiveThe impact of negative lymph nodes (NLNs) count on prognosis in esophageal cancer (EC) was analyzed using two institutions surgical database.MethodsWe conducted a retrospective study of 768 EC patients treated by surgical resection between January 2010 and December 2012. The effects of the NLNs count on prognosis was analyzed. Cox regression model was conducted to determine the significant prognostic elements.ResultsThe number of NLNs was studied as a categorical variable based on the quartiles (Q1: ≤15, Q2: 16–21, Q3: 22–30, Q4: ≥31). And a better overall survival (OS) was observed with increasing number of NLNs (HR= 0.762; 95% CI, 0.596–0.974 for Q2, HR= 0.666; 95% CI, 0.516–0.860 for Q3 and HR= 0.588; 95% CI, 0.450–0.768 for Q4) (all P<0.05). Multivariate regression analysis revealed that the NLNs count was an independent prognostic factor. Besides, for patients in T2 or T3 stage, a high number of NLNs was found to be significantly associated with a favorable OS (log rank P<0.001).ConclusionA higher number of NLNs is independently related to the better OS in EC patients after surgical resection.

Identification of LCA-binding Glycans as a Novel Biomarker for Esophageal Cancer Metastasis using a Lectin Array-based Strategy.

Esophageal cancer (EC) is a unique and heterogeneous disease diagnosed mostly at advanced stages. Altered glycans presented on cell surfaces are involved in the occurrence and development of malignancy. However, the effects of glycans on EC progression are largely unexplored. Here, a lectin array was utilized to detect the glycan profiling of the normal esophageal mucosal epithelial cell line and two EC cell lines. The binding of Lens culinaris lectin (LCA) to EC cells was found to be stronger than that of the normal cells. Lectin immunohistochemical staining revealed that LCA-binding glycans were markedly elevated in EC tissues compared to adjacent non-cancerous tissues. LCA staining was significantly associated with lymph node metastasis, depth of invasion, TNM stage and poor overall survival of EC patients. Added LCA to block LCA recognized glycans could inhibit the migration and invasion of EC cells. Further analysis revealed that blocking the biosynthesis of LCA-binding glycans by tunicamycin attenuated cellular migratory and invasive abilities. Additionally, a membrane glycoprotein CD147 was recognized as a binder of LCA. There was a positive correlation between LCA-binding glycans and CD147 expression in clinical samples. Interestingly, CD147 inhibition also reduced cell migration and invasion. These findings indicated that LCA-binding glycans may function as a novel indicator to predict metastasis for patients with EC.

Abstract 1610: Getting under the skin: Fat quality in esophageal cancer prognosis

Abstract INTRODUCTION The last few years have seen an increased interest in the role of body mass composition parameters in cancer survival. this study sought to assess the impact of the body mass composition (BMC) on prognosis of locally advanced esophageal cancer (EC) patients beyond the usual quantitative weight loss associated with this condition. METHODS Diagnostic CT scans were assessed for BMC in 155 all-stage EC patients at diagnosis. The index (area/height2) of skeletal muscle (SMI), subcutaneous (SFI) and visceral fat (VFI) were delineated on two adjacent slides at the third lumbar vertebra level by two independent investigators using PLANET ONCO® software (DOSIsoft, France). Mean attenuation (or density) of fat tissue was measuring to assess the quality of adipose compartments. Survival and relapse free survival (RFS) were calculated from date of baseline CT-scan. RESULTS Interobserver correlations were excellent for all BMC parameters measured (r = 0.94 to 0.99). Remarkably, low subcutaneous fat density (SFD) was associated to better outcome, as were low disease stages. Low C-reactive protein (CRP) levels were also associated with better overall survival (OS). In contrast, low BMI did not affect the patients’ outcome. Relapse free survival (RFS) analysis showed that only high disease stages and SFD remained associated with poor RFS. Stepwise regression showed that the combination of SFD, stage and CRP was an effective model for OS prediction. No parameter was retained for RFS in the multivariate analysis. Detailed results are shown in Table 1. CONCLUSION SFD, stages and CRP appeared as robust prognostic factors of OS in EC patients, in contrast with BMI. While SFD and stages were significant in RFS univariate analysis, none of these two parameters were retained in multivariate analyses. These results confirm the validity of BMC assessment for evaluating patient prognosis and show for the first time that adipose tissues and inflammation may have a preponderant impact on cancer prognosis. ParametersThresholdOSmalefemalep valueHR (95 CI)Low SFD&amp;lt; -95,7&amp;lt; -99,40,000282,2 (1,4-3,5)Low disease stages1+2A vs 2B+3+40,00472,2 (1,2-3,7)Low CRP&amp;lt; 3,200,00532,2 (1,2-3,8)Low BMI&amp;lt;250,130,71 (0,46-1,1)ParametersThresholdRFSmalefemalep valueHR (95 CI)Low SFD&amp;lt; -95,7&amp;lt; -99,40,041,6 (1-2,6)Low disease stages1+2A vs 2B+3+40,0441,8 (1-3,1)N.B. Thresholds for SFD are the sex-specific medians. Thresholds for CRP is the median Citation Format: Maelle Anciaux, Lieveke Ameye, Thomas Guiot, Patrick Flamen, Serge Goldman, Pieter Demetter, Amélie Deleporte, André Van Gossum, Marianne Paesmans, Vincent Donckier, Alain Hendlisz, Caroline Vandeputte. Getting under the skin: Fat quality in esophageal cancer prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1610.

Clinical significance of systemic immune-inflammation index (SII) and C-reactive protein-to-albumin ratio (CAR) in patients with esophageal cancer: a meta-analysis.

Background: Numerous studies have reported that systemic immune-inflammation index (SII) and C-reactive protein-to-albumin ratio (CAR) correlate with tumor progression and prognosis in various types of human cancer. The aim of this study is to systematically investigate the clinical significance of SII and CAR in esophageal cancer (EC).Methods: We searched a number of databases for articles reporting the effect of pretreatment SII and CAR on the survival of EC patients. Review Manager 5.3 and STATA/SE 14.1 were applied in this meta-analysis. The multivariable-adjusted hazard ratio (HR) was used for calculating the relationship between SII and CAR and overall survival (OS), and the odds ratio (OR) was applied for the clinical pathology.Results: Five original studies for SII and seven original datasets for CAR were included for analysis. Increased SII showed a significant association with shorter OS in EC patients after surgery (HR: 1.34, 95% CI: 1.15–1.53, P<0.001) and high CAR indicated worse long-term OS in EC (HR: 1.60, 95% CI: 1.29–1.90, P<0.001). Different subgroup analyses were also confirmed the prognostic roles in EC patients. Furthermore, the adverse impacts of elevated SII and CAR on tumor progression were revealed in the infiltration depth, lymph node metastasis, and clinical stage.Conclusions: Both pretreatment SII and CAR might be promising predictors of cancer survival and tumor progression in EC. Further studies are warranted to verify the clinical usefulness in patients with EC.

Prognostic value of tumor length in predicting survival for patients with esophageal cancer

Background: To determine the prognostic value of tumor length in predicting overall survival (OS) for patients with esophageal cancer. Methods: Patients who were diagnosed with esophageal cancer between 2010 and 2014 were identified from the Surveillance Epidemiology and End Results (SEER) data. We performed Kaplan-Meier survival analysis and developed a Cox regression proportional hazard model to explore the effect of tumor length on survival. Results: A total of 6,897 esophageal cancer patients were identified. The patients were classified according to tumor length: 2,334 patients had a tumor length ≤3 cm, and 4,563 patients had a tumor length >3 cm. Patients with a tumor length >3 cm were more likely to have poorer histological grade (P 3 cm than in those with a tumor length ≤3 cm both in the Cox regression univariate analysis [hazard ratio (HR): 1.790; 95% CI: 1.667–1.922; P=0.000] and the multivariate analysis (HR: 1.447; 95% CI: 1.341–1.561; P=0.000). A stratified analysis based on different T stages showed that the HR for death was 1.84 (P=0.000) for T1 stage patients, 1.227 (P=0.046) for T2 stage patients, and 1.157 (P=0.012) for T3 stage patients; there was no difference in survival for T4 stage patients. Conclusions: Tumor length significantly influences the OS of esophageal cancer patients, especially in early T stage patients. Further prospective trials are needed to validate the prognostic value of tumor length among esophageal cancer patients.

Overexpression of VEGF-C correlates with a poor prognosis in esophageal cancer patients

The prognostic value of vascular endothelial growth factor C (VEGF-C) in patients with esophageal cancer (EC) remains controversial. The aim of this meta-analysis was to clarify the association of VEGF-C with survival in EC patients. We performed a meta-analysis that included eligible studies to expound the effect of VEGF-C in EC survival. Eligible studies published until November 2015 was identified using available databases. STATA 12.0 was performed in this meta-analysis. We identified 13 studies, including 1203 patients, in this meta-analysis. The combined hazard ratio of 1.70 (95% CI, 1.43-2.03, P < 0.001) shows that VEGF-C overexpression was significantly correlated with poor overall survival in EC patients. Furthermore, the results suggested a significant relationship between VEGF-C expression and overall survival was also showed in studies with patient source, patient number ≥ 70, methods detecting VEGF-C by reverse transcription PCR (RT-PCR) or ELISA and histology type. Moreover, combined odds ratio of VEGF-C displayed that VEGF-C overexpression was significantly association with stage, depth of tumor invasion, lymph node status and metastasis of EC (P < 0.05). However, it has no correlation with differentiation degree of EC (P > 0.05). VEGF-C overexpression shows an unfavorable prognosis for EC patients.

Increased MALAT1 expression predicts poor prognosis in esophageal cancer patients

This study was designed to determine the expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in patients with esophageal cancer (EC). In addition, we attempted to seek the prognostic value of MALAT1 in EC based on its expression. The expression of MALAT1 in EC tissues and cell lines were measured by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). The association between MALAT1 expression and the clinical characteristics was analyzed using Chi-square test. Kaplan-Meier survival curves were plotted to describe the overall survival of EC patients with different expression of MALAT1. Cox regression analysis was per formed to evaluate the prognostic value of MALAT1 for EC patients. Expression levels of MALAT1 were significantly higher in EC tissues and cells than the controls (P<0.05). MALAT1 expression was tightly related to lymphatic invasion (P=0.018), distant metastasis (P=0.033) and tumor differentiation (P=0.025), but shared no association with age, gender and tumor location (P>0.05). In addition, patients with high MALAT1 expression had a shorter overall survival than those with low MALAT1 (P<0.001). The results of Cox analysis shown that MALAT1 was significantly linked with the prognosis of EC patients (HR=6.638; P=0.000; 95% CI=2.948-14.947). Taken together, the expression of MALAT1 could be a predictor for prognosis of EC patients.

DNA repair gene ERCC1 C118T polymorphism predicts sensitivity of recurrent esophageal cancer to radiochemotherapy in a Chinese population

BackgroundDNA repair gene polymorphisms could alter DNA repair capacity and therefore associate with tumor sensitivity to radiochemotherapy. This study assessed excision repair cross-complementing group 1 (ERCC1) C118T and X-ray cross-complementing group 1 (XRCC1) G399A single-nucleotide polymorphisms in esophageal patients for an association with sensitivity to radiation and chemotherapy.MethodsEsophageal squamous cell carcinoma patients (n = 118) who relapsed after surgery were enrolled for assessment of ERCC1 C118T and XRCC1 G399A polymorphisms by direct DNA sequencing.ResultsThe response rate of treatments was 48.30%: 14 complete response (CR, 11.86%), 43 partial response (PR, 36.44%), 49 stable disease (SD, 41.53%), and 12 progressive disease (PD, 10.17%). ERCC1 C118T was significantly associated with treatment response (C/T vs. C/C + T/T, odds ratio [OR] = 6.035, 95% confidence interval [CI]: 2.114–17.226, P = 0.001) after adjusting for other clinicopathological factors. Patients carrying the C/T genotype had significantly prolonged overall survival (OS) compared with C/C and T/T (median OS 43.00 vs. 27.00, P = 0.027). Multivariate Cox regression showed that a response was only an independent prognostic factor for OS (CR + PR vs. SD+PD, HR = 0.471 95% CI 0.269–0.826, P = 0.009). Grade III and IV adverse events occurred in 12 of 118 patients (10.17%). Only concurrent radiochemotherapy significantly increased these adverse events (OR = 26.529, 95% CI 2.312–304.389, P = 0.008).ConclusionERCC1 C118T could be a predictive factor for the response to radiotherapy and chemotherapy, but not a prognostic factor for OS in esophageal cancer patients after surgery.