Outcome Of Esophageal Cancer Patients Research Articles

Landscape of esophageal cancer in Northern Kenya: experience from Garissa Regional Cancer Center.

Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. More than 80% of cases and deaths from EC occur within developing countries. In Kenya, cancer is the second leading cause of non-communicable disease deaths, and the trend of cancer deaths is projected to increase as per the 2020 GLOBOCAN report showing 42,116 new cases annually with a mortality of 27,092 cases. EC is the leading cancer in men and the third most common in women in Kenya. The Garissa Regional Cancer Center (GRCC) is one of the three regional cancer centres in Kenya. Despite the rising EC incidence in the region, there is limited data about the clinicopathological features and treatment outcomes of EC, therefore, this is the first study to look at the landscape of EC in the northern Kenya region. This was a retrospective study involving patients' file review of confirmed EC cases diagnosed or treated at the GRCC from 2019 to 2023. Data collected from each patient's chart included age, sex, risk factors, family history of EC, histological type, stage at diagnosis, treatment type and survival outcomes. For patients who were no longer in contact with the staff through clinic visits, the patients or their next of kin were contacted through phone calls for patients' survival status. Data were collected and stored using the STATA software. Over the study period, 124 esophageal cases were identified, 64 (51.4%) were males and 60 (48.4%) were females with a mean age of 57.56 years. In terms of risk factors, hot beverage consumption was the highest (47 cases, 37.9%), followed by history of peptic ulcer disease (27 cases, 21.8%), smoking (8.9%) and gastresophageal reflux disease (2 cases, 1.6%). Stage of diagnosis at presentation was stage 1 (1 case, 0.8%), stage 2 (22 cases, 17.8%), stage 3 (25 cases, 20.2%), stage 4 (50 cases, 40.3%), not staged (26 cases, 21%). The majority had squamous cell carcinoma (SCC) (105 cases, 84.7%), followed by adenocarcinoma (5 cases, 4%), anaplastic (5 cases, 4%), SCC+ adenocarcinoma (1 case, 0.8%), unknown histology (8 cases, 3.2%). Nearly all patients had triple assessment (Endoscopy, histology and staging scans) accounting for 92 cases (74.2%), 24 cases (20%) had endoscopy+ histology only, and 8 cases (3.2%) had only imaging scans. In terms of family history of EC, 20 cases (16.1%) had a family history of EC.Most of the patients were of ethnic Kenyan-Somali background (108 cases, Kenyan Somali, 87.1%) and majority were from Garissa County 96 cases (77.4%), 12 cases (9.7%) Wajir County, 12 cases (9.7%) from Tana River County and 4 cases (3.2%) from other counties. Many patients lacked health insurance (27 cases, 25.8%), while the majority paid out of pocket (92 cases,74.1%). Only 21% (26 cases) received chemotherapy alone, 5 cases (4%) got radiotherapy alone, 12.9% (16 cases) got chemoradiotherapy and a significant number of patients (77 cases, 62.1%) did not receive hospital-based cancer treatment. This study is the first esophageal study at the GRCC and in northern Kenya in general. Our study confirmed the clinicopathological features of one of the most common cancers in Kenya and more so among Kenyan-Somalis.The study also validates the predominance of histological subtypes of esophageal SCC with the late presentation, short survival and significant loss of follow-up. We recommend future EC studies employing a large prospective design with a large sample size to determine the impact of the new GRCC on the outcomes of EC patients and the local community.

Body Composition and Clinical Outcomes in Esophageal Cancer Patients Treated with Immune Checkpoint Inhibitors.

Obesity is associated with increased mortality in various cancers, but the relationship between obesity and clinical outcomes in unresectable or recurrent esophageal cancer who receive immune checkpoint inhibitors (ICIs) remains unknown. This study investigated the association between body composition and clinical outcomes in patients with unresectable or recurrent esophageal cancer who received ICIs. Utilizing an unbiased database of 111 unresectable or recurrent esophageal cancers, we evaluated the relationships between body composition (body mass index, waist circumference, psoas major muscle volume, and subcutaneous and visceral fat areas) at the initiation of ICI treatment and clinical outcomes including the disease control rate and progression-free survival (PFS). Waist circumference was significantly associated with the disease control rate at the first assessment (P = 0.0008). A high waist circumference was significantly associated with favorable PFS in patients treated with nivolumab. In an univariable model, for 5-cm increase of waist circumference in the outcome category of PFS, univariable hazard ratio (HR) was 0.73 (95% confidence interval [CI], 0.61-0.87; P = 0.0002). A multivariable model controlling for potential confounders yielded a similar finding (multivariable HR, 0.56; 95% CI, 0.33-0.94; P = 0.027). We observed the similar finding in esophageal cancer patients treated with pembrolizumab+CDDP+5-FU (P = 0.048). In addition, waist circumference was significantly associated with the prognostic nutritional index (P = 0.0073). A high waist circumference was associated with favorable clinical outcomes in ICI-treated patients with unresectable or recurrent esophageal cancer, providing a platform for further investigations on the relationships among body composition, nutrition, and the immune status.

Unveiling survival strategies: The impact of treatment modalities on patients with esophageal cancer and the role of racial disparities.

257 Background: Managing esophageal cancer (EC) involves neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy as the standard of care. However, some patients may remain unsuitable for esophagectomy. This study explores real-world outcomes in EC patients across different treatments, considers prognostic factors, and examines potential racial disparities. Methods: Data from 44,181 patients diagnosed with locally advanced EC between 2004-2017 were extracted from the National Cancer Database. The cohort was stratified into three groups: nCRT followed by esophagectomy, definitive RT (dCRT), single-modality RT. The dataset included 24,676 patients who received nCRT with esophagectomy or dCRT (N=17,534) and 1,971 patients who received single-modality RT. Endpoints included overall survival (OS). Cox Proportional Hazards Model was employed for multivariate survival analysis. Chi-square test was applied to the covariate demographic data. Results: nCRT followed by esophagectomy significantly improved OS compared to dCRT (mOS 43.5 vs. 20.1 months, p < 0.001). Single-modality RT had an mOS of 14.4 months. In the RT group, 73% were over 65 years old compared to 59% in the dCRT group (p < 0.001). Over 60% of patients had node-positive disease in both RT and dCRT groups (69% vs. 61.4%). More privately insured patients received multimodal treatment compared to publicly insured patients (27.3% vs. 16.8%, p < 0.001). Over 70% of patients were willing to travel within 20 miles for treatment, 60% underwent treatment in community programs. Racial disparities were observed, with Black patients experiencing worse outcomes compared to all other groups, while Asian and Hispanic patients had better outcomes (table1). In the squamous cell histology subset treated with dCRT, mOS was 22 (20.6 – 23.6 months) for Black patients, 27 (26 – 28) months for White patients, 36 (30-46) months for Hispanic patients, and 37 (30-44) months for Asian/Pacific Islander patients (p < 0.001). Conclusions: This real-world data analysis underscores the effectiveness of nCRT followed by esophagectomy in providing the best survival benefit for EC patients compared to dCRT or RT alone. Racial disparities emerged as significant factors influencing cancer survival outcomes. These identified factors including race and age can assist clinicians in making better-informed decisions regarding treatment pathways for specific patient populations. [Table: see text]

Comparative Analysis of Enteral and Parenteral Nutrition Impact on Outcomes in Esophageal Cancer Patients: A Paradigm for Nutritional Optimization in Oncology

Background: Individuals diagnosed with esophageal cancer face a pronounced risk of malnutrition, primarily attributed to the early onset of gastrointestinal obstruction. This risk persists and may even intensify following therapeutic interventions and the subsequent reconstruction of gastrointestinal passages. The current study focuses on elucidating the differential impact of enteral vs. parenteral nutrition on outcomes in patients hospitalized with esophageal cancer. Methods: The study analyzed adult discharges related to esophageal cancer from 2019 and 2020 using data from the National Inpatient Sample. Exclusion criteria included discharges involving minors and mixed nutritional regimens. Enteral nutrition and parenteral nutrition subgroups were identified using International Classification of Diseases, 10th revision codes. Outcome variables were determined through ICD-10 codes in the NIS dataset. Multivariable regression analyses were used to investigate associations between mode of nutrition and specified outcomes. Results: In this study involving 28,015 hospitalizations for esophageal cancer, 756(2.7%) received enteral nutrition, and 1064(3.8%) received parenteral nutrition. After adjusting for confounding variables, parenteral nutrition emerged as an independent predictor of mortality (OR 1.75, P=0.023), while enteral nutrition showed no association with higher mortality (OR 0.56, P=0.162). Both nutrition modes were associated with increased length of stay, with patients on parenteral nutrition having significantly longer stays (+9.07 days, P<0.001 vs 3.07 days, P=0.001). While both nutrition modes were linked to high total hospitalization charges, patients with parenteral nutrition experienced a significantly more significant increase in total treatment cost compared to those on enteral nutrition (112,093 USD, P<0.001 vs 54,953 USD, P=0.01) patients on enteral nutrition had lower odds of pneumonia compared to the parenteral nutrition group. The parenteral nutrition group had higher odds of various complications, including esophageal perforation, constipation, diarrhea, acute kidney injury, ICU admission, and acute respiratory failure, than those on enteral nutrition. Both forms of nutrition were associated with increased odds of malnutrition, fluid and electrolyte disorders, and septic shock. Conclusion: Parenteral nutrition has a higher risk of mortality compared to enteral nutrition. Both types are linked to longer hospital stays, increased treatment costs, and other adverse outcomes, with parenteral nutrition leading to more complications than enteral nutrition.

The prognostic value of the controlling nutritional status (CONUT) score in predicting outcomes of esophageal cancer patients receiving radiotherapy with or without chemotherapy.

Controlling nutritional status (CONUT) scores and systemic immune-inflammation index (SII) values are associated with the prognosis of several common malignancies. The current study aimed to explore the prognostic value of CONUT scores and SII values in patients with esophageal cancer (EC) receiving radical radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). We calculated the pre-RT CONUT scores and SII values of 62 patients with EC receiving RT or CCRT. Receiver operating characteristic (ROC) curves were used to determine the adequate cut-off values. The Kaplan-Meier method and Cox proportional hazard model were used to analyze the association between CONUT scores and SII values and prognosis. The 1-year progression-free survival (PFS) and 1-year overall survival (OS) rates of the 62 patients were 51.61% and 66.13%, respectively. Based on the time-dependent ROC curve for the 1-year OS of all patients, the optimal cut-off value was 622.02 for the SII and a score of 1 for the CONUT score. The univariate analysis showed that the CONUT score (P=0.036), tumor-nodal-metastasis (TNM) stage (P<0.01), and CCRT (P=0.008) significantly affected the survival of EC patients. The multifactorial analysis showed that the CONUT score (P=0.041) and TNM stage (P<0.01) were independent prognostic factors affecting clinical outcomes in patients with EC undergoing radical RT or CCRT. The pre-RT CONUT score could be an effective predictor of prognosis in patients with EC receiving radical RT or CCRT; however, the pre-RT SII value had no clinical value in predicting survival in our study.

Survival outcomes of esophageal cancer patients with recurrence after curative treatments

BackgroundLittle is known about predictive factors for survival outcomes of esophageal carcinoma (EC) patients who developed recurrence after undergoing multimodal therapies. We aimed to investigate long-term outcomes and identify prognostic factors in patients with relapsed EC, focusing especially on those with oligometastasis (OM).MethodsEC patients who developed recurrence after curative treatments (radical esophagectomy or definitive chemoradiotherapy (dCRT)) between 2010 and 2017 were reviewed. Multivariate Cox hazards models were applied to determine independent predictors of poor post-recurrence survival (PRS).ResultsIn total, 178 patients were included. The median PRS was 12.9 months. Of the 178 patients, 98 had OM and 80 non-OM (NOM) disease. The survival outcomes of patients with OM were significantly better than those of patients with NOM (P < 0.01). Surgical treatments provided significantly better survival outcomes than CRT or chemo-/radiotherapy alone (3-year overall survival (OS); 78.1% vs. 42.5% vs. 28.9%, P < 0.01), mainly due to prolonging survival after the recurrence (3-year PRS 62.9% vs. 16.7% vs. 16.2%, P < 0.01). Multivariable analysis focusing on patients with OM revealed cStage III-IV disease (P < 0.01), high GPS at the time of recurrence (P = 0.02) and non-curative treatments (P < 0.01), to be independently associated with poor PRS. In contrast, in patients with NOM, no independent predictors for poor PRS were identified.ConclusionsThe survival outcomes of patients with relapsed EC remain poor. Surgical treatments could provide survival benefits for patients with recurrent EC, especially for patients with OM.

346. IMPACT OF VIRTUAL POST-OPERATIVE CARE ON ESOPHAGECTOMY PATIENTS DURING THE COVID-19 PANDEMIC

Abstract Background The SARS-CoV-2 pandemic has resulted in disruptions to oncology practices amongst healthcare institutions globally. To adapt, telehealth has been increasingly implemented into oncologic care, including that of esophageal cancer patients, which has been met with overall success. However, there remains a lack of evidence in the literature pertaining to the outcomes of virtual postoperative appointments for esophagectomy patients. Methods We conducted a retrospective cohort study to assess the clinical outcomes of esophageal cancer patients attending phone call follow-up (virtual) visits compared to standard in person care after esophagectomy. Demographic data, clinical and disease characteristics, and hospital visit data within 6 months of operation were collected. This included surgical clinic visits, endoscopies, and emergency room (ER) admissions. Results 168 esophagectomy patients underwent follow-up care between March 2020 to May 2022; 70 virtual and 98 in-person. Patients attending virtual appointments had significantly fewer ED admissions (−0.48, p = 0.005*, 95%CI [−0.80, −0.14]). Number of endoscopy visits (0.36, p = 0.110, 95%CI [−0.08, 0980]) and the number of clinic visits (0.42, p = 0.118, 95%CI [−0.11, 0.93]) were similar between the two cohorts. ER visits for virtual cohort included feeding tube complications (20.0%), dysphagia (20.0%), and abdominal pain (13.3%). For the in-person cohort, feeding tube complications (12.8%) and chest pain or cardiac features (9.3%) were the most common reasons. Conclusion The results of this study provide evidence for the increased use of telehealth following esophagectomy. The reduction in emergency admissions in the virtual cohort may be due to increased comfort with phone call appointments or increased fear of hospital visitation during the pandemic.

230. SURVIVAL OUTCOMES OF ROBOT-ASSISTED TRANS-MEDIASTIONAL ESOPHAGECTOMY IN PATIENTS WITH CT1N0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background We have developed a robot-assisted trans-mediastinal esophagectomy (RATME) to reduce the surgical invasiveness of open trans-thoracic esophagectomy (oTTE). However, the long-term outcome of esophageal cancer patients who underwent RATME remains unclear. Methods Patients who underwent RATME or oTTE for clinical T1N0 esophageal squamous cell carcinoma were enrolled in this study. The clinicopathological and surgical details, overall survival (OS), disease-free survival (DFS), and cause-specific survival (CSS) were compared between the RATME and oTTE groups. Results Forty-three and 47 patients who underwent RATME and oTTE, respectively, were included in this analysis. The RATME group included more male patients and had a significantly lower comorbidity index. There was no significant difference in age, tumor location, preoperative ESD rates, and pathological TNM factors between the two groups. The RATME group showed a longer operation time, less blood loss, low incidence of pneumonia, and shorter hospital stays. The OS and DFS rates in the RATME tended to be higher than in the oTTE group; The 5-year OS rates were 88.4 vs 71.5%, and the 5-year DFS rates were 81.4 vs 62.8% (RATME vs oTTE group, p = 0.09 and p = 0.11). The CSS in both groups were equivalent; The 5-year CSS rates were 93.7 vs 92.4% in the RATME and oTTE groups respectively. The RATME group had significantly fewer deaths than the oTTE group (p = 0.032). Conclusions The RATME group tended to show better OS and DFS than the oTTE group. The OS of the RATME group was equivalent to that of the comprehensive registry data in Japan, indicating that RATME radicality is guaranteed.

The gap before real clinical application of imaging-based machine-learning and radiomic models for chemoradiation outcome prediction in esophageal cancer: a systematic review and meta-analysis.

Due to tumoral heterogeneity and the lack of robust biomarkers, the prediction of chemoradiotherapy response and prognosis in patients with esophageal cancer (EC) is challenging. The goal of this study was to assess the study quality and clinical value of machine learning and radiomic-based quantitative imaging studies for predicting the outcomes of EC patients after chemoradiotherapy. PubMed, Embase, and Cochrane were searched for eligible articles. The methodological quality and risk of bias were evaluated using the Radiomics Quality Score (RQS), Image Biomarkers Standardization Initiative (IBSI) Guideline, and Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement, as well as the modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. A meta-analysis of the evidence focusing on predicting chemoradiotherapy response and outcome in EC patients was implemented. Forty-six studies were eligible for qualitative synthesis. The mean RQS score was 9.07, with an adherence rate of 42.52%. The adherence rates of the TRIPOD and IBSI were 61.70 and 43.17%, respectively. Ultimately, 24 studies were included in the meta-analysis, of which 16 studies had a pooled sensitivity, specificity, and area under the curve (AUC) of 0.83 (0.76-0.89), 0.83 (0.79-0.86), and 0.84 (0.81-0.87) in neoadjuvant chemoradiotherapy datasets, as well as 0.84 (0.75-0.93), 0.89 (0.83-0.93), and 0.93 (0.90-0.95) in definitive chemoradiotherapy datasets, respectively. Moreover, radiomics could distinguish patients from the low-risk and high-risk groups with different disease-free survival (DFS) (pooled hazard ratio: 3.43, 95% CI 2.39-4.92) and overall survival (pooled hazard ratio: 2.49, 95% CI 1.91-3.25). The results of subgroup and regression analyses showed that some of the heterogeneity was explained by the combination with clinical factors, sample size, and usage of the deep learning (DL) signature. Noninvasive radiomics offers promising potential for optimizing treatment decision-making in EC patients. However, it is necessary to make scientific advancements in EC radiomics regarding reproducibility, clinical usefulness analysis, and open science categories. Improved model reporting of study objectives, blind assessment, and image processing steps are required to help promote real clinical applications of radiomics in EC research.

Development and validation of a prognostic nomogram for predicting cancer-specific survival in lymph node-negative elderly esophageal cancer patients: A SEER-based study.

In this study, we explored the prognostic risk factors of elderly patients (≥65 years old) with lymph node-negative esophageal cancer (EC) and established a nomogram to evaluate the cancer-specific survival of patients. The surveillance, epidemiology, and end results database was used to collect data on patients diagnosed with EC. Univariate and multivariate Cox analyses were used to determine independent prognostic factors, and the nomogram for predicting cancer-specific survival of EC patients was constructed based on the independent prognostic factors obtained from the multivariate Cox analysis. To evaluate the predictive ability of the nomogram, calibration curves, concordance index (C-index), receiver operating characteristic curves, and decision curve analysis were conducted. Kaplan-Meier method was used to analyze the long-term outcomes of EC patients with different risk stratifications. A total of 3050 cases with lymph node-negative EC were randomized into the training cohort (1525) and the validation cohort (1525). Cancer-specific mortality at 1, 3, and 5 years in the entire cohort was 30.7%, 41.8%, and 59.2%, respectively. In multivariate Cox analysis, age (P < .001), marital status (P < .001), tumor size (P < .001), Tumor-node-metastasis stage (P < .001), chemotherapy (P = .011), radiotherapy (P < .001), and surgery (P < .001) were independent prognostic factors. The C-index for the training cohort was 0.740 (95% confidence interval [CI]: 0.722-0.758), and the C-index for the validation cohort was 0.738 (95% CI: 0.722-0.754). The calibration curve demonstrated the great calibration ability of the nomogram. Based on the area under the receiver operating characteristic curve, the nomogram demonstrated a higher sensitivity than the tumor-node-metastasis stage. Decision curve analysis showed the good clinical utility of the nomogram. The risk stratification system was established using the Kaplan-Meier curve and verified by the log-rank test (P < .001). The nomogram and risk stratification system can improve the accuracy of prediction to help clinicians identify high-risk patients and make treatment decisions.

TRIM29 hypermethylation drives esophageal cancer progression via suppression of ZNF750

Esophageal cancer (ESCA) is the seventh most frequent and deadly neoplasm. Due to the lack of early diagnosis and high invasion/metastasis, the prognosis of ESCA remains very poor. Herein, we identify skin-related signatures as the most deficient signatures in invasive ESCA, which are regulated by the transcription factor ZNF750. Of note, we find that TRIM29 level strongly correlated with the expression of many genes in the skin-related signatures, including ZNF750. TRIM29 is significantly down-regulated due to hypermethylation of its promoter in both ESCA and precancerous lesions compared to normal tissues. Low TRIM29 expression and high methylation levels of its promoter are associated with malignant progression and poor clinical outcomes in ESCA patients. Functionally, TRIM29 overexpression markedly hinders proliferation, migration, invasion, and epithelial–mesenchymal transition of esophageal cancer cells, whereas opposing results are observed when TRIM29 is silenced in vitro. In addition, TRIM29 inhibits metastasis in vivo. Mechanistically, TRIM29 downregulation suppresses the expression of the tumor suppressor ZNF750 by activating the STAT3 signaling pathway. Overall, our study demonstrates that TRIM29 expression and its promoter methylation status could be potential early diagnostic and prognostic markers. It highlights the role of the TRIM29-ZNF750 signaling axis in modulating tumorigenesis and metastasis of esophageal cancer.

Efficacy and adverse events of immune checkpoint inhibitors in esophageal cancer patients: Challenges and perspectives for immunotherapy.

Esophageal cancer (EC) is the seventh most common cancer worldwide. Patients with EC have a generally poor prognosis mainly due to the lack of effective treatments. Cancer immunotherapy is a promising novel treatment option for EC. This literature review investigated the clinical efficacy of immunotherapy either alone or in combination with chemotherapy or targeted therapy. In addition, we analyzed the adverse events associated with immune checkpoint inhibitors (ICIs). In conclusion, ICIs increase the efficacy of EC treatments, thereby improving the outcomes of EC patients. The findings of this study may help enhance the response to immunotherapy, diminish toxicity, and thus eventually improve medical care for patients with EC.

Outcome prediction in resectable esophageal adenocarcinoma based on clinical variables, radiomics, and ctDNA.

423 Background: Despite the advent of precision medicine, prediction of survival outcome of esophageal cancer patients remains a challenge. Here we aim to investigate the value of prediction models integrating multi-signal data including radiomics and circulating tumor DNA (ctDNA) data in addition to clinical data for the prediction of resectable esophageal adenocarcinoma (rEAC) related outcomes. Methods: In total n=111 rEAC patients treated with neoadjuvant chemoradiotherapy (nCRT; n=71) +/- anti-PD-L1 (n=40) were included. Baseline clinical variables (n=9) were based on the SOURCE survival prediction model (van den Boorn et al. JNCCN. 2021). The baseline ctDNA data from plasma was derived from fragmentomic and copy number aberrations (ichorCNA) from shallow whole genome sequencing (&lt;5-fold coverage) and a custom next-generation sequencing panel (n=23 genes). Baseline radiomic original features were extracted by the pyradiomics package from CT-image delineated tumor volumes. An initial redundancy filtering was performed to remove correlating variables (r&gt;0.6). We evaluated the predictive performance of baseline ctDNA and radiomics features on overall survival (OS), progression free survival (PFS), and time to progression (TTP), through fitting Cox-regression models. Four ctDNA features were included in the models: P20-150, ichorCNA, fragment end score and mutation detection. For the radiomics features we performed an additional back- and forward variable selection based on Akaike’s Information Criterion. Using the likelihood ratio test we tested if the model fit changed after adding ctDNA and radiomics features to a model with clinical variables. Results: The addition of radiomics to clinical variables improved model fit for OS (p=0.017). Baseline prediction of OS resulted in a C-index of 0.65 using clinical variables only, 0.65 with ctDNA, 0.68 with radiomics and 0.68 with ctDNA and radiomics combined. For PFS model fit improved after adding radiomics (p=0.020) and ctDNA and radiomics combined (p=0.017). Baseline prediction of PFS resulted in a C-index of 0.64 using clinical variables, 0.65 with ctDNA, 0.67 with radiomics, and 0.68 with ctDNA and radiomics combined. For TTP model fit improved after adding radiomics (p=0.008) and radiomics and ctDNA combined (p=0.002). Baseline prediction of TTP resulted in a C-index of 0.64 with clinical variables, 0.65 with ctDNA, 0.71 with radiomics, and 0.72 with ctDNA and radiomics combined. Based on the cox-regression models using clinical variables and radiomics, risk stratification by splitting the cohort in a high and low risk group was possible for OS, PFS and TTP (p&lt;0.001). Conclusions: Combining clinical variables from SOURCE with radiomics data improved predictions of OS, PFS, and TTP among patients with rEAC. Multi-signal integration of clinical and radiomics variables could potentially be used to identify risk groups.

Efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy in esophageal cancer: A systematic review and meta-analysis.

Significant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy. A search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed. A total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups. Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.

Concomitant preoperative airflow obstruction confers worse prognosis after trans-thoracic surgery for esophageal cancer.

Airflow obstruction is a critical element of chronic airway diseases. This study aimed to evaluate the impact of preoperative airflow obstruction on the prognosis of patients following surgery for esophageal carcinoma. A total of 821 esophageal cancer patients were included and classified into two groups based on whether or not they had preoperative airflow obstruction. Airflow obstruction was defined as a forced expiration volume in the first second (FEV1)/forced vital capacity (FVC) ratio below the lower limit of normal (LLN). A retrospective analysis of the impact of airflow obstruction on the survival of patients with esophageal carcinoma undergoing esophagectomy was performed. Patients with airflow obstruction (102/821, 12.4%) had lower three-year overall (42/102, 58.8%) and progression-free survival rate (47/102, 53.9%) than those without airflow obstruction (P < 0.001). Multivariate analyses showed that airflow obstruction was an independent risk factor for overall survival (Hazard Ratio = 1.66; 95% CI: 1.17-2.35, P = 0.004) and disease progression (Hazard Ratio = 1.51; 95% CI: 1.1-2.08; P = 0.01). A subgroup analysis revealed that the above results were more significant in male patients, BMI < 23 kg/m2 patients or late-stage cancer (stage III-IVA) (P = 0.001) patients and those undergoing open esophagectomy (P < 0.001). Preoperative airflow obstruction defined by FEV1/FVC ratio below LLN was an independent risk factor for mortality in esophageal cancer patients after trans-thoracic esophagectomy. Comprehensive management of airflow obstruction and more personalized surgical decision-making are necessary to improve survival outcomes in esophageal cancer patients.

Galectins in Esophageal Cancer: Current Knowledge and Future Perspectives

Esophageal cancer is a disease with poor overall survival. Despite advancements in therapeutic options, the treatment outcome of esophageal cancer patients remains dismal with an overall 5-year survival rate of approximately 20 percent. To improve treatment efficacy and patient survival, efforts are being made to identify the factors that underlie disease progression and that contribute to poor therapeutic responses. It has become clear that some of these factors reside in the tumor micro-environment. In particular, the tumor vasculature and the tumor immune micro-environment have been implicated in esophageal cancer progression and treatment response. Interestingly, galectins represent a family of glycan-binding proteins that has been linked to both tumor angiogenesis and tumor immunosuppression. Indeed, in several cancer types, galectins have been identified as diagnostic and/or prognostic markers. However, the role of galectins in esophageal cancer is still poorly understood. Here, we summarize the current literature with regard to the expression and potential functions of galectins in esophageal cancer. In addition, we highlight the gaps in the current knowledge and we propose directions for future research in order to reveal whether galectins contribute to esophageal cancer progression and provide opportunities to improve the treatment and survival of esophageal cancer patients.

Impact of oral nutrition supplementation on outcomes of esophageal cancer patients treated with chemotherapy: A retrospective cohort study with propensity score matching.

There is a lack of evidence regarding the outcomes of oral nutrition supplementation (ONS) in patients with esophageal cancer (EC) who received chemotherapy treatment. The aim of this study was to perform a retrospective cohort study by comparing an adequate ONS group with a control group. The study was performed in the Oncology Department of West China Hospital of Sichuan University. Patients at nutritional risk were identified from March 2016 to June 2019, and divided into an ONS group and a control group. To control for potential confounding variables, the propensity score method with matching was carried out. The main outcomes were length of stay (LOS) and hospitalization cost. Secondary outcomes included the incidence of pulmonary infection and myelosuppression. Out of 5,316 hospitalizations, a one-to-one matched sample was created (N = 229). The pathological tumor, node, metastasis (pTNM) stage of patients ranged from II to IV. A total of 69 patients received ONS, and 160 patients did not receive ONS. The incidence of myelosuppression in the ONS group and the control group was 4.3 vs. 17.4% (P = 0.014), respectively. However, ONS was associated with a 2 days increase in LOS, from 7 to 9 days (P < 0.000) and a hospitalization cost increase of $731, from $1134 to $1865 (P = 0.005). No statistical differences were observed in the incidence of pulmonary infection between the two groups. Further subgroup analysis based on body mass index (BMI) showed that at BMI ≤ 18.5 kg/m2, the incidence of myelosuppression in the ONS group was lower than that in the control group (3.0 vs. 20.8%, P = 0.022). At BMI > 18.5 kg/m2, no statistical differences were observed in the incidence of myelosuppression between the two groups. Although ONS increases hospitalization cost and LOS, it may be associated with reduced myelosuppression incidence, especially for patients with a BMI ≤ 18.5 kg/m2.

441. ESOPHAGEAL CANCER MANAGEMENT IN A SWISS REFERRAL CENTER; A 20-YEAR EXPERIENCE

Abstract In the past decades, management of esophageal cancer (EC) has significantly changed with the widespread use of oncological treatments, as well as minimally invasive surgery and enhanced recovery protocols. Concurrently, the histological type, comorbidity status and life expectency of the ‘typical’ EC patient have also evolved. The aim of this study was to assess the evolution in epidemiology, management and outcomes of EC patients treated in a Swiss tertiary referral center the last 20 years. Baseline demographics, clinico-pathological data, treatment details and postoperative outcomes were retrieved from our institutional prospective database for all consecutive patients operated for esophageal cancer with curative intent. Emergency surgery and endoscopic treatment of early EC were excluded, hence 332 patients (265 male, 67 female) were included in the final analysis. Patients were divided in 3 groups: ‘historical group’: 2000–2007, n = 73; ‘transition group’: 2008–2014, n = 108; ‘modern group’: 2015–2020, n = 151. Comparison was performed with the x2 test for discrete and the ANOVA tests for continuous variables, with the Bonferroni method to determine significance in pairwise comparisons (p &amp;lt; 0.05). The annual caseload doubled (10 to 25 cases/y). Alcohol consumption (57.5% to 28.5%, p &amp;lt; 0.001), active smoking (64.4% to 38.4%, p = 0.001) and COPD (41.1% to 35.1%, p = 0.05) decreased. Squamous cell carcinoma (58.9% historic, 34.4% modern group) was replaced by adenocarcinoma as the most prevalent type (35.6% vs 64.2%, p = 0.001). Detection of locally advanced disease increased from 58.8% to 75.8% (p = 0.022), along with the use of neoadjuvant treatment (34.2% historic, 83.4% modern group, p &amp;lt; 0.001). Major postoperative morbidity was documented in 34.2% of patients (historic group) versus 58.3% (modern group, p = 0.002), but mortality remained stable. No differences were observed in long-term survival. Centralization significantly increased the annual caseload. Improved preoperative workup enabled more accurate detection of locally advanced disease and subsequently appropriate multimodal treatment that is currently used in most patients. The ‘typical’ EC patient has shifted from the squamous cell to the adenocarcinoma type, but males are still more concerned. Postoperative complications are nowadays more rigorously detected and managed, keeping mortality rates low. Long-term survival remained unchanged over time.

Current perspectives of the Japanese Esophageal Oncology Group on the development of immunotherapy for esophageal cancer.

Esophageal cancer is the seventh most common cancer worldwide and continues to have a poor prognosis. Starting with the development of immune checkpoint inhibitors for patients with metastatic melanoma, many clinical trials have been conducted to evaluate the efficacy and safety of immune checkpoint inhibitors against various malignancies. Although few effective drugs are available for patients with advanced esophageal cancer, two immune checkpoint inhibitors, nivolumab and pembrolizumab, have been approved as second-line treatments for advanced esophageal squamous cell carcinoma. Recently, immune checkpoint inhibitors have shown promising results as post-operative therapies and first-line treatments for advanced esophageal cancer. Nivolumab has been approved as a post-operative therapy based on the CheckMate-577 trial, and nivolumab, ipilimumab and pembrolizumab have been approved as first-line treatments based on the CheckMate-648 trial and the KEYNOTE-590 trial. In addition, many trials of immune checkpoint inhibitors plus pre-operative treatment or definitive chemoradiotherapy are ongoing. The Japan Esophageal Oncology Group was established in 1978 and has conducted numerous clinical trials, most of which have examined multimodality treatments. In the era of immunotherapy, Japan Esophageal Oncology Group is conducting a clinical trial studying multimodality treatment with an immune checkpoint inhibitor. JCOG1804E (FRONTiER) is a phase I trial to evaluate the safety and efficacy of nivolumab plus pre-operative chemotherapy followed by surgery. These results might improve the clinical outcomes of esophageal cancer patients.

YAP1 acts as a negative regulator of pro-tumor TAZ expression in esophageal squamous cell carcinoma

PurposeAlthough YAP1 and TAZ are believed to be equivalent downstream effectors of the Hippo pathway, differential expression of YAP1 or TAZ suggests distinct functions during cancer progression. The exact role of YAP1 and TAZ in esophageal cancer, the 6th leading cancer-related mortality in the world, remains elusive.MethodsFollowing single or double manipulation of YAP1 or TAZ expression, we subjected these manipulated cells to proliferation, migration, invasion, and xenograft tumorigenesis assays. We used RT-qPCR and Western blotting to examine their expression in the manipulated cells with or without inhibition of transcription or translation. We also examined the impact of YAP1 or TAZ deregulation on clinical outcome of esophageal cancer patients from the TCGA database.ResultsWe found that YAP1 functions as a tumor suppressor whereas TAZ exerts pro-tumor functions in esophageal cancer cells. We also found a significant increase in TAZ mRNA expression upon YAP1 depletion, but not vice versa, despite the downregulation of CTGF and CYR61, shared targets of YAP1 and TAZ, in xenografted tissue cells. In addition to transcriptional regulation, YAP1-mediated TAZ expression was found to occur via protein synthesis. Restored TAZ expression mitigated YAP1-mediated suppression of cellular behavior. By contrast, TAZ silencing reduced the promoting effect exerted by YAP1 depletion on cellular behaviors. The observed anti-tumor function of YAP1 was further supported by a better overall survival among esophageal cancer patients with a high YAP1 expression.ConclusionFrom our data we conclude that YAP1 functions as a suppressor and negatively regulates pro-tumor TAZ expression via transcriptional and translational control in esophageal cancer.