Survival In Esophageal Cancer Research Articles

Chemoradiotherapy Combined with Brachytherapy for the Definitive Treatment of Esophageal Carcinoma.

This study aims to investigate the effect of dose escalation with brachytherapy (BT) as an addition to definitive chemoradiotherapy (CRT) on local control and survival in esophageal cancer. From 2001 to 2020, 183 patients with locally limited or locally advanced esophageal cancer received definitive CRT with or without brachytherapy in a two-center study. External-beam radiotherapy was delivered at 50.4 Gy in 1.8 Gy daily fractions, followed by a sequential boost to the primary tumor of 9 Gy in 1.8 Gy daily fractions if indicated. Intraluminal high dose rate (HDR) Ir-192 brachytherapy was performed on 71 patients at 10 Gy in two fractions, with one fraction per week. The combined systemic therapy schedules used included 5-fluorouracil/cisplatin or 5-fluorouracil alone. Cisplatin was not administered in patients receiving brachytherapy. The median local progression-free survival was significantly extended in the BT group (18.7 vs. 6.0 months; p < 0.0001), and the median local control was also significantly prolonged (30.5 vs. 11.3 months, p = 0.008). Overall survival (OS) significantly increased in the BT group (median OS 22.7 vs. 9.1 months, p < 0.0001). No significant difference in the overall rate of acute toxicities was observed; however, the rate of acute esophagitis was significantly higher in the BT group (94.4% vs. 81.2%). Likewise, the overall rate of late toxicities (43.7% vs. 18.8%) was significantly higher in the BT group, including the rate of esophageal stenosis (22.5% vs. 9.8%). There was no difference in the occurrence of life-threatening or lethal late toxicities (grades 4 and 5). Brachytherapy, after chemoradiation with single-agent 5-FU, represents a safe and effective alternative for dose escalation in the definitive treatment of esophageal cancer.

A robust immune-related gene pairs signature for predicting the overall survival of esophageal cancer

BackgroundIdentifying reliable biomarkers could effectively predict esophagus carcinoma (EC) patients with poor prognosis. In this work, we constructed an immune-related gene pairs (IRGP) signature to evaluate the prognosis of EC.ResultsThe IRGP signature was trained by the TCGA cohort and validated by three GEO datasets, respectively. Cox regression model together with LASSO was applied to construct the overall survival (OS) associated IRGP. 21 IRGPs consisting of 38 immune-related genes were included in our signature, according to which patients were stratified into high- and low-risk groups. The results of Kaplan-Meier survival analyses indicated that high-risk EC patients had worse OS than low-risk group in the training set, meta-validation set and all independent validation datasets. After adjustment in multivariate Cox analyses, our signature continued to be an independent prognostic factor of EC and the signature-based nomogram could effectively predict the prognosis of EC sufferers. Besides, Gene Ontology analysis revealed this signature is related to immunity. ‘CIBERSORT’ analysis revealed the infiltration levels of plasma cells and activated CD4 memory T cells in two risk groups were significantly different. Ultimately, we validated the expression levels of six selected genes from IRGP index in KYSE-150 and KYSE-450.ConclusionsThis IRGP signature could be applied to select EC patients with high mortality risk, thereby improving prospects for the treatment of EC.

Validity of Using Pathological Response as a Surrogate for Overall Survival in Neoadjuvant Studies for Esophageal Cancer: A Systematic Review and Meta-analysis.

Pathological response is a critical factor in predicting long-term survival of patients with esophageal cancer after preoperative therapy. However, the validity of using pathological response as a surrogate for overall survival (OS) for esophageal cancer has not yet been established. In this study, a literature-based meta-analysis was conducted to evaluate pathological response as a proxy endpoint for survival in esophageal cancer. Three databases were systematically searched to identify relevant studies investigating neoadjuvant treatment for esophageal cancer. The correlation between pathological complete response (pCR) and OS were assessed using a weighted multiple regression analysis at the trial level, and the coefficient of determination (R2) was calculated. The research design and histological subtypes were considered in the performance of subgroup analysis. In this meta-analysis, a total of 40 trials, comprising 43 comparisons and 55,344 patients were qualified. The surrogacy between pCR and OS was moderate (R2 = 0.238 in direct comparison, R2 = 0.500 for pCR reciprocals, R2 = 0.541 in log settings). pCR could not serve as an ideal surrogate endpoint in randomized controlled trials (RCTs) (R2 = 0.511 in direct comparison, R2 = 0.460 for pCR reciprocals, R2 = 0.523 in log settings). A strong correlation was observed in studies comparing neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy (R2 = 0.595 in direct comparison, R2 = 0.840 for pCR reciprocals, R2 = 0.800 in log settings). A lack of surrogacy of pathological response for long-term survival at trial level is established in this study. Hence, caution should be exercised when using pCR as the primary endpoint in neoadjuvant studies for esophageal cancer.

Diabetes, metformin use, and survival in esophageal cancer: a population-based cohort study.

It is unclear how diabetes and metformin use is associated with survival of esophageal cancer. This population-based cohort study included new cases of esophageal cancer reported in Sweden from 2006 to 2018 with follow-up through 2019. Diabetes status and metformin use were analyzed in relation to all-cause and disease-specific mortality using multivariable Cox regression. The hazard ratios (HRs) with 95% confidence intervals (CIs) were adjusted for age, sex, calendar year, obesity, comorbidity, and use of nonsteroidal anti-inflammatory drugs or statins. For comparison reasons, 3 other antidiabetic medications were also analyzed (ie, sulfonylureas, insulin, and thiazolidinedione). Among 4851 esophageal cancer patients (8404 person-years), 4072 (84%) died during follow-up. Compared with esophageal cancer patients with diabetes but not using metformin, decreased all-cause mortality was indicated among nondiabetic patients (without metformin) (HR = 0.86, 95% CI = 0.77 to 0.96) and diabetic patients who used metformin (HR = 0.86, 95% CI = 0.75 to 1.00). The hazard ratios of all-cause mortality decreased with a higher daily dose of metformin (Ptrend = .04). The corresponding hazard ratios for disease-specific mortality were similar but slightly attenuated. The results were also similar in separate analyses of esophageal cancer patients with adenocarcinoma or squamous cell carcinoma, with tumor stage I-II or III-IV, and in those who had or had not undergone surgery. No associations with mortality outcomes were found for use of sulfonylureas, insulin, or thiazolidinedione. Diabetes was associated with an increased all-cause mortality, whereas metformin use was associated with decreased all-cause mortality among esophageal cancer patients. More research is needed to determine if metformin affects survival in esophageal cancer.

Change in stage after neoadjuvant chemoradiation is associated with survival in patients with esophageal cancer.

The aim of this study was to determine if change in stage after neoadjuvant chemoradiation (CRT) was associated with improved survival in esophageal cancer using a national database. Using the National Cancer Database, patients with non-metastatic, resectable esophageal cancer who received neoadjuvant CRT and surgery were identified. Comparing clinical to the pathologic stage, change in stage was classified as pathologic complete response (pCR), downstaged, same-staged, or upstaged. Univariable and multivariable Cox regression models were used to identify factors associated with survival. A total of 7745 patients were identified. The median overall survival (OS) was 34.9 months. Median OS was 60.3 months if pCR, 39.1 months if downstaged, 28.3 months if same-staged, and 23.4 months if upstaged (p < 0.0001). On multivariable analysis, pCR was associated with improved OS compared to the other groups (downstaged: hazard ratio [HR]:1.32 [95% confidence interval [CI]: 1.18-1.46]; same-staged: HR: 1.89 [95% CI: 1.68-2.13]; upstaged: HR: 2.54 [95% CI: 2.25-2.86]; all p < 0.0001). In this large database study, change in stage after neoadjuvant CRT was strongly associated with survival for patients with non-metastatic, resectable esophageal cancer. There was a significant stepwise decline in survival, in descending order of pCR, downstaged tumor, same-staged tumor, and upstaged tumor.

Performance of radiomics-based artificial intelligence systems in the diagnosis and prediction of treatment response and survival in esophageal cancer: a systematic review and meta-analysis of diagnostic accuracy.

Radiomics can interpret radiological images with more detail and in less time compared to the human eye. Some challenges in managing esophageal cancer can be addressed by incorporating radiomics into image interpretation, treatment planning, and predicting response and survival. This systematic review and meta-analysis provides a summary of the evidence of radiomics in esophageal cancer. The systematic review was carried out using Pubmed, MEDLINE, and Ovid EMBASE databases-articles describing radiomics in esophageal cancer were included. A meta-analysis was also performed; 50 studies were included. For the assessment of treatment response using 18F-FDG PET/computed tomography (CT) scans, seven studies (443 patients) were included in the meta-analysis. The pooled sensitivity and specificity were 86.5% (81.1-90.6) and 87.1% (78.0-92.8). For the assessment of treatment response using CT scans, five studies (625 patients) were included in the meta-analysis, with a pooled sensitivity and specificity of 86.7% (81.4-90.7) and 76.1% (69.9-81.4). The remaining 37 studies formed the qualitative review, discussing radiomics in diagnosis, radiotherapy planning, and survival prediction. This review explores the wide-ranging possibilities of radiomics in esophageal cancer management. The sensitivities of 18F-FDG PET/CT scans and CT scans are comparable, but 18F-FDG PET/CT scans have improved specificity for AI-based prediction of treatment response. Models integrating clinical and radiomic features facilitate diagnosis and survival prediction. More research is required into comparing models and conducting large-scale studies to build a robust evidence base.

Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study

Background We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. Methods This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. Results Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). Conclusion This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

Health Disparities and Precision Oncology in Foregut Malignancies

Health disparities exist in incidence, treatment, and survival of esophageal and gastric cancer based on socioeconomic and minority racial/ethnic group status. How socioeconomic and minority status affect access and utilization of precision oncology in foregut malignancies is not well understood. Based on other cancer types, multiple intrinsic and extrinsic factors influence utilization of cancer genetic testing, participation in precision oncology clinical trials, and access to molecularly targeted therapies. As precision oncology becomes more common in the treatment of foregut malignancies, health equity will require ongoing identification of sources of disparities and proposal of practical solutions.

Prediction of conditional survival in esophageal cancer in a Population-based cohort study.

We aimed to produce a prediction model for survival at any given date after surgery for esophageal cancer (conditional survival), which has not been done previously. Using joint density functions, we developed and validated a prediction model for all-cause and disease-specific mortality after surgery with esophagectomy, for esophageal cancer, conditional on post-surgery survival time. The model performance was assessed by the area under the receiver operating characteristic curve (AUC) and risk calibration, with internal cross-validation. The derivation cohort was a nationwide Swedish population-based cohort of 1027 patients treated in 1987-2010, with follow-up throughout 2016. This validation cohort was another Swedish population-based cohort of 558 patients treated in 2011-2013, with follow-up throughout 2018. The model predictors were age, sex, education, tumor histology, chemo(radio)therapy, tumor stage, resection margin status, and reoperation. The medians of AUC after internal cross-validation in the derivation cohort were 0.74 (95% confidence interval [95%CI] 0.69-0.78) for 3-year all-cause mortality, 0.76 (95%CI 0.72-0.79) for 5-year all-cause mortality, 0.74 (95%CI 0.70-0.78) for 3-year disease-specific mortality, and 0.75 (95%CI 0.72-0.79) for 5-year disease-specific mortality. The corresponding AUC values in the validation cohort ranged from 0.71 to 0.73. The model showed good agreement between observed and predicted risks. Complete results for conditional survival any given date between 1 and 5 years of surgery are available from an interactive web-tool: https://sites.google.com/view/pcsec/home. This novel prediction model provided accurate estimates of conditional survival any time after esophageal cancer surgery. The web-tool may help guide post-operative treatment and follow-up.

The clinical impacts of lymphocyte-to-C-reactive protein ratio for esophageal cancer patients who receive curative treatment.

We investigated the impact of the lymphocyte-to-C-reactive protein ratio (LCR) on esophageal cancer survival and recurrence after curative treatment. This study included 89 patients who underwent curative surgery followed by adjuvant treatment for esophageal cancer between 2008 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. LCR of 12,177 was regarded to be the optimal critical point of classification considering the 1-year, 3-year, and 5-year survival rates. The OS rates at 3 and 5 years after surgery were 33.2% and 29.9% in the LCR low group, respectively, and 74.0% and 60.9% in the LCR high group, which amounted to a statistically significant difference (P = 0.001). The RFS rates at 3 and 5 years after surgery were 25.3% and 21.7% in the LCR low group, respectively, and 52.1% and 47.4% in the LCR high group, which amounted to a statistically significant difference (P = 0.001). A multivariate analysis demonstrated that the LCR was a significant independent risk factor for both the OS and RFS. LCR was a risk factor for survival in patients who underwent curative treatment for esophageal cancer. It is necessary to develop the effective plan of the perioperative care and the surgical strategy according to the LCR.

Prognostic Value of Radiomics Analysis of Skeletal Muscle After Radical Irradiation of Esophageal Cancer.

Sarcopenia is an independent survival predictor in several tumor types. Computed tomography (CT) is the standard measurement for body composition assessment. Radiomics analysis of CT images allows for the precise evaluation of skeletal muscles. This study aimed to construct a prognostic survival model for patients with esophageal cancer who underwent radical irradiation using skeletal muscle radiomics. We retrospectively identified patients with esophageal cancer who underwent radical irradiation at our institution between April 2008 and December 2017. Skeletal muscle radiomics were extracted from an axial pretreatment CT at the third lumbar vertebral level. The prediction model was constructed using machine learning coupled with the least absolute shrinkage and selection operator (LASSO). The predictive nomogram model comprised clinical factors with radiomic features. Three prediction models were created: clinical, radiomics, and combined. Ninety-eight patients with 98 esophageal cancers were enrolled in this study. The median observation period was 57.5 months (range=1-98 months). Thirty-five radiomics features were selected by LASSO analysis, and a prediction model was constructed using training and validation data. The average of the accuracy, specificity, sensitivity, and area under the concentration-time curve for predicting survival in esophageal cancer in the combined model were 75%, 92%, and 0.86, respectively. The C-indices of the clinical, radiomics, and combined models were 0.76, 0.80, and 0.88, respectively. A prediction model with skeletal muscle radiomics and clinical data might help determine survival outcomes in patients with esophageal cancer treated with radical radiotherapy.

Trends in best-case, typical and worst-case survival scenarios of patients with non-metastatic esophagogastric cancer between 2006 and 2020: A population-based study.

New treatment options and centralization of surgery have improved survival for patients with non-metastatic esophageal or gastric cancer. It is unknown, however, which patients benefitted the most from treatment advances. The aim of this study was to identify best-case, typical and worst-case scenarios in terms of survival time, and to assess if survival associated with these scenarios changed over time. Patients with non-metastatic potentially resectable esophageal or gastric cancer diagnosed between 2006 and 2020 were selected from the Netherlands Cancer Registry. Best-case (20th percentile), upper-typical (40th percentile), typical (median), lower-typical (60th percentile) and worst-case (80th percentile) survival scenarios were defined, and regression analysis was used to investigate the change in survival time for each scenario across years. For patients with esophageal cancer (N=24 352) survival time improved on average 12.0 (until 2011), 1.5 (until 2018), 0.7, 0.4 and 0.2months per year for the best-case, upper-typical, median, lower-typical and worst-case scenario, respectively. For patients with gastric cancer (N=9993) survival time of the best-case scenario remained constant, whereas the upper-typical, median, lower-typical and worst-case scenario improved on average with 1.0 (until 2018), 0.5, 0.2 and 0.2months per year, respectively. Subgroup analyses showed that, survival scenarios improved for nearly all patients across treatment groups and for patients with squamous cell carcinomas or adenocarcinomas. Survival improved for almost all patients suggesting that in clinical practice the vast majority of patients benefitted from treatment advances. The clinically most meaningful survival advantage was observed for the best-case scenario of esophageal cancer.

Construction a new nomogram prognostic model for predicting overall survival after radical resection of esophageal squamous cancer.

Esophageal cancer is one of the deadliest malignancies in the world, and 5-year overall survival (OS) of esophageal cancer ranges from 12% to 20%. Surgical resection remains the principal treatment. The American Joint Commission on Cancer (AJCC) TNM (tumor, node, and metastasis) staging system is a key guideline for prognosis and treatment decisions, but it cannot fully predict outcomes. Therefore, targeting the molecular and biological features of each patient's tumor, and identifying key prognostic biomarkers as effective survival predictors and therapeutic targets are highly important to clinicians and patients. In this study, three different methods, including Univariate Cox regression, Lasso regression, and Randomforest regression were used to screen the independent factors affecting the prognosis of esophageal squamous cell carcinoma and construct a nomogram prognostic model. The accuracy of the model was verified by comparing with TNM staging system and the reliability of the model was verified by internal cross validation. Preoperative neutrophil lymphocyte ratio(preNLR), N-stage, p53 level and tumor diameter were selected to construct the new prognostic model. Patients with higher preNLR level, higher N-stage, lower p53 level and larger tumor diameter had worse OS. The results of C-index, Decision Curve Analysis (DCA), and integrated discrimination improvement (IDI) showed that the new prognostic model has a better prediction than the TNM staging system. The accuracy and reliability of the nomogram prognostic model were higher than that of TNM staging system. It can effectively predict individual OS and provide theoretical basis for clinical decision making.

Survival in gastric and esophageal cancers in the Nordic countries through a half century.

Gastric cancer (GC) and esophageal cancer (EC) are among the most fatal cancers and improving survival in them is a major clinical challenge. Nordic cancer data were recently released up to year 2019. These data are relevant for long-term survival analysis as they originate from high-quality national cancer registries from countries with practically free access to health care, thus documenting 'real-world' experience for entire populations. Data were obtained for Danish (DK), Finnish (FI), Norwegian (NO), and Swedish (SE) patients from the NORDCAN database from years 1970 through 2019. Relative 1- and 5-year survival were analyzed, and additionally the difference between 1- and 5-year survival was calculated as a measure of trends between years 1 and 5 after diagnosis. Relative 1-year survival for Nordic men and women in GC was 30% in period 1970-74 and it increased close to 60%. Early 5-year survival ranged between 10 and 15% and the last figures were over 30% for all women and NO men while survival for other men remain below 30%. Survival in EC was below that in GC, and it reached over 50% for 1-year survival only for NO patients; 5-year survival reached over 20% only for NO women. For both cancers, the difference between 1- and 5-year survival increased with time. Survival was worst among old patients. GC and EC survival improved over the 50-year period but the increase in 5-year survival was entirely explained by gains in 1-year survival, which improved at an accelerated pace in EC. The likely reasons for improvements are changes in diagnosis, treatment, and care. The challenges are to push survival past year 1 with attention to old patients. These cancers have a potential for primary prevention through the avoidance of risk factors.

Endoscopic therapy replaces surgery for clinical T1 oesophageal cancer in the Netherlands: a nationwide population-based study

BackgroundEndoscopic resection for early oesophageal cancer was introduced around 2000 in the Netherlands. The scientific question was how the treatment and survival of early oesophageal and gastro-oesophageal junction cancer has changed over time in the Netherlands.MethodsData were obtained from the nationwide population-based Netherlands Cancer Registry. All patients diagnosed with clinical in situ or T1 oesophageal or GOJ cancer without lymph node or distance metastasis during the study period (2000–2014) were extracted. Primary outcome parameters were the trends in treatment modalities over time and relative survival of each treatment regime.ResultsA total of 1020 patients were diagnosed with a clinical in situ or T1 oesophageal or gastro-oesophageal junction cancer without lymph node or distance metastasis. The proportion of patients who received endoscopic treatment increased from 2.5% in 2000 to 58.1% in 2014. During the same period the proportion of patients who received surgery decreased from 57.5 to 23.1%. Five-year relative survival of all patients was 69%. Five-year relative survival after endoscopic therapy was 83% and after surgery 80%. Relative excess risk analyses showed no significant difference in survival between patients in the endoscopic therapy group and patients in the surgery group after adjustment for age, sex, clinical TNM classification, morphology and tumour location (RER 1.15; CI 0.76–1.75; p 0.76).ConclusionOur results demonstrate an increase in endoscopic treatment and a decrease of surgical treatment for in situ and T1 oesophageal/GOJ cancer between 2000–2014 in the Netherlands. The relative 5-year survival after endoscopic treatment is high (83%) and comparable with surgery (80%).

Experience in Locally Advanced Esophageal Cancer with Definitive Chemoradiotherapy at the National Oncology Institute in the Period 2012-2022

<i>Introduction: </i>The World Health Organization (WHO) estimates 18 million people were diagnosed with cancers in 2020, of these 600,000 were esophageal cancer and ranks 6th in mortality. In Panama, in 2020, 58 new cases were diagnosed, with a lethality of 90%. Despite advances in the therapeutic approach and survival of localized esophageal cancer, we are unaware of the survival results associated with concomitant chemoradiotherapy treatment. <i>Methodology: </i>We conducted a retrospective study, reviewing the electronic medical records of patients with locally advanced esophageal cancer treated with Chemotherapy-Radiotherapy at the National Institute of Oncology from 2012 to 2022. Results were evaluated using the Kaplan Meier method, long rank test and a multivariate analysis with Cox regression. <i>Objective: </i>to evaluate the survival results in patient with locally advanced esophageal cancer treated with chemotherapy-radiotherapy. <i>Results: </i>94 patients were evaluated, with a mean age of 64 years. The median time to progression (TPP) was 6 months and the median overall survival (OS) was 9 months. 69% patient has Eastern Cooperative Oncology Group (ECOG) 1, with a predominance of squamous histology in 89% and the degree of differentiation moderately differentiated in 55.3%. The main chemotherapy treatment was based on a scheme of weekly Carboplatin plus Paclitaxel in 41.5%, of which 66% received a dose of radiotherapy ≥45 Gy, with a 5-week extension time. A post-treatment radiographic response was evidenced with a clinical benefit of 36.2% and an objective response of 27.7%. The main adverse effects were dysphagia (16%), neutropenia (8.3%), nausea and vomiting (7.4%), and weight loss (7.4%). When analyzing the associated factors in relation to OS, in the multivariate analysis, the ECOG and the well-differentiated histological grade turned out to be significant association factors for better OS; but for the TTP, there were no associated factors identified when performing multivariate analysis. <i>Conclusions: </i>In this retrospective analysis, we found a median TTP of 6 months and a median OS of 9 months, which is below the values in the literature. The ECOG and the degree of differentiation were the factors associated with a better overall survival. Hematological and gastrointestinal adverse events were the most reported. It is important to choose patients in the best clinical condition for concomitant treatment with CT/RT to achieve better clinical results.

An indirect assessment of individual-level association between disease-free survival (DFS) and overall survival (OS) for resectable esophageal or gastroesophageal junction cancer (EC/GEJC): A pooled analysis of randomized controlled trials (RCTs) by an illness-death model.

369 Background: Validation of intermediate endpoints such as DFS as surrogates for overall survival (OS) in RCTs at individual-level remains as a challenge due to difficulty of collection of individual-level patient data. This study explores the individual-level correlation between DFS and OS indirectly using reconstructed Kaplan-Meier (KM) curves from the RCTs assessing therapies for (neo)adjuvant and perioperative treatment of EC/GEJC. Methods: An illness-death model previously validated in estimating individual-level association between DFS and OS for four correlation meta-analyses, two of which were published by the GASTRIC group, in early and late stage treatment of gastric cancer was employed. Reconstructed DFS and OS data from 25 RCTs published between 1994 - 2020 was pooled separately for each arm and each endpoint. Pooled data was analyzed to estimate the correlation between DFS and OS, as measured by Pearson’s r, Spearman’s rho, and Kendall’s tau. Predictive accuracy of the approach was evaluated by comparing its OS and restricted mean survival time (RMST) predictions to their counterparts obtained from the reported OS data from the RCTs. Sensitivity of correlation measures were assessed with respect to pre-specified variations in pre-recurrence death probability, post-recurrence mortality rate, and choice of the survival model used to extrapolate reported DFS curves from the RCTs. Results: Across all RCTs, the primary cancers covered were EC (n=13), EC/GEJC(n=9), GEJC (n=2) and GEJC/gastric cancer (n=1). According to the histology, 10 RCTs studied only squamous cell carcinoma (SCC) and 9 RCTs studied only adenocarcinoma (AC) of the disease, whereas the remaining 6 RCTs included varying mixtures of SCC and AC patients. The follow-up duration ranged between 27 and 72 months across RCTs. Comparator and intervention arms of the pooled data had 2499 and 2490 patients, respectively. Predicted Pearson’s r, Spearman’s rho, Kendall’s tau were 0.67, 0.79, and 0.70, respectively with negligibly narrow 95% CIs. Across both arms of the pooled data, on average, predicted OS curves laid within the 95% CIs of the pooled OS KM-curves 92% of the time. Average deviation between the RMSTs under the model-predicted OS curves and pooled OS KM curves was 2%. In sensitivity analyses, the ranges for r, r, and t were (0.56-0.88), (0.69-0.89), and (0.61-0.80), respectively. Conclusions: Results indicate moderate-to-strong correlation between DFS and OS in early-stage treatment of EC/GEJC providing supportive evidence for the validation of DFS as a surrogate for OS. Our approach mitigates the lack of patient level data in endpoint correlation assessment but may be prone to changes in the predicted value of pre-recurrence death probability.

MiR-139 Affects Radioresistance in Esophageal Cancer by Targeting the PDK1/AKT/Cyclin D1 Signaling Pathway.

We explored the mechanism by which miR-139 modulates radioresistance of esophageal cancer (EC). The radioresistant cell line KYSE150R was obtained from the parental KYSE150 cell line by fractionated irradiation (15×2 Gy; total dose of 30 Gy). The cell cycle was assessed by flow cytometry. A gene profiling study was conducted to detect the expression of genes related to the radioresistance of EC. In the KYSE150R line, flow cytometry revealed increased number of G1-phase cells and decreased number of G2-phase cells; the expression of miR-139 increased. Knockdown of miR-139 decreased radioresistance and changed the distribution of cell cycle phases in KYSE150R cells. Western blotting showed that miR-139 knockdown increased the expression levels of cyclin D1, p-AKT, and PDK1. However, PDK1 inhibitor GSK2334470 reversed this effect for p-AKT and cyclin D1 expression. A luciferase reporter assay indicated that miR-139 directly bound to the PDK1 mRNA 3'-UTR. Analysis of the clinical data from 110 patients with EC showed an association of miR-139 expression with the TNM stage and the effect of therapy. MiR-139 expression significantly correlated with EC and progression-free survival. In conclusion, miR-139 enhances the radiosensitivity of EC by regulating the cell cycle through the PDK1/Akt/Cyclin D1 signaling pathway.

Clinical usefulness of the lymphocyte-to-monocyte ratio and aggregate index of systemic inflammation in patients with esophageal cancer: a retrospective cohort study

BackgroundMultiple perioperative inflammatory markers are considered important factors affecting the long-term survival of esophageal cancer (EC) patients. Hematological parameters, whether single or combined, have high predictive value.AimTo investigate the inflammatory status of patients with preoperative EC using blood inflammatory markers, and to establish and validate competing risk nomogram prediction models for overall survival (OS) and progression-free survival (PFS) in EC patients.MethodsA total of 508 EC patients who received radical surgery (RS) treatment in The First Affiliated Hospital of Zhengzhou University from August 5, 2013, to May 1, 2019, were enrolled and randomly divided into a training cohort (356 cases) and a validation cohort (152 cases). We performed least absolute shrinkage and selection operator (LASSO)-univariate Cox- multivariate Cox regression analyses to establish nomogram models. The index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, time-dependent area under curve (AUC) and calibration curves were used to evaluate the discrimination and calibration of the nomograms, and decision curve analysis (DCA) was used to evaluate the net benefit of the nomograms. The relative integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to evaluate the improvement in predictive accuracy of our new model compared with the AJCC staging system and another traditional model. Finally, the relationship between systemic inflammatory response markers and prognostic survival was explored according to risk plot, time-dependent AUC, Kaplan–Meier and restricted cubic spline (RCS).ResultsBased on the multivariate analysis for overall survival (OS) in the training cohort, nomograms with 10 variables, including the aggregate index of systemic inflammation (AISI) and lymphocyte-to-monocyte ratio (LMR), were established. Time-dependent ROC, time-dependent AUC, calibration curves, and DCA showed that the 1-, 3-, and 5 year OS and PFS probabilities predicted by the nomograms were consistent with the actual observations. The C-index, NRI, and IDI of the nomograms showed better performance than the AJCC staging system and another prediction model. Moreover, risk plot, time-dependent AUC, and Kaplan–Meier showed that higher AISI scores and lower LMR were associated with poorer prognosis, and there was a nonlinear relationship between them and survival risk.ConclusionAISI and LMR are easy to obtain, reproducible and minimally invasive prognostic tools that can be used as markers to guide the clinical treatment and prognosis of patients with EC.

Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma.

Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status. In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006-2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3. Sarcopenia was determined using published cutoffs, based on sex and height. Of 202 MEC patients, most were male (166/82%), < 65years (116/57%), and had adenocarcinoma histology (141/70%); 110/54% had recurrent MEC after initial curative-intent treatment; 92/46% presented with de novo MEC. At stage IV diagnosis, 20/10% were underweight, 97/48% were normal-weight and 84/42% were overweight/obese; 103/51% were sarcopenic. Sarcopenia was associated with worse median OS (4.6 vs. 7.9months; log-rank p = 0.03) and 1-year survival, even after adjusting for other body composition variables (e.g., BMI, VA, and SA): adjusted-HR 1.51 [95% CI 1.1-2.2, p = 0.02]. In post hoc analysis, sarcopenia was highly prognostic in adenocarcinomas (p = 0.003), but not squamous cell carcinomas (SCC). In patients receiving palliative systemic treatment (104/51%), sarcopenia was associated with shorter PFS (p = 0.004) in adenocarcinoma patients (75/72%). In metastatic esophageal adenocarcinomas, sarcopenia is associated with worse PFS and OS. In metastatic esophageal SCC, there was a non-significant trend for worse PFS but no association with OS. In order to offset the poor prognosis associated with sarcopenia particularly in metastatic esophageal adenocarcinoma patients, future research should focus on possible countermeasures.