Survival In Esophageal Cancer Research Articles

MS O09 - OGC Long-term oncological outcomes following totally minimally invasive, hybrid and open oesophagectomy for cancer

Abstract Background There has been a significant shift in the surgical management of oesophageal cancer, with increased popularity of minimally invasive oesophagectomy in comparison to open approaches. Data thus far has largely focused on the peri-operative and short-term benefits with limited study on long-term oncological outcomes. This study aims to explore patterns of oesophageal cancer recurrence and survival following minimally invasive and open oesophagectomy. Method This was a retrospective review of consecutive patients who underwent open (OO), hybrid (HO) and minimally invasive (MIO) oesophagectomy for cancer at a regional oesophago-gastric centre in the UK between 2014-2023. Follow-up data was obtained from the centre’s established surgical database, in addition to the regional radiology, MDT and electronic patient records to record survival, recurrence, and patterns of recurrence (locoregional, haematological, distal nodal, peritoneal and number of recurrence sites). Results 437 patients (170 OO; 132 HO; 135 MIO) were included. There was no difference in baseline data between the groups. Overall survival rates at 1-, 3-, and 5-year were 88%, 64% and 54%. Recurrence rates at 1-, 3-, and 5-year were 17%, 35% and 41%. Haematological and locoregional recurrence made up 37% and 33% of all recurrence types. 52% of patients had one type of recurrence at diagnosis. After adjusting for disease stage, there was no significant difference between operative approaches with respect to survival and recurrence rates (at 1,3 and 5 years), time to recurrence, or patterns of recurrence. Conclusion This study found no significant difference in long-term oncological outcomes when comparing different minimally invasive and open surgical approaches to oesophagectomy. MIO can continue to be offered to patients as a safe alternative to open surgery. Further multi-centre prospective research is required to validate these results.

Using high-repeatable radiomic features improves the cross-institutional generalization of prognostic model in esophageal squamous cell cancer receiving definitive chemoradiotherapy

ObjectivesRepeatability is crucial for ensuring the generalizability and clinical utility of radiomics-based prognostic models. This study aims to investigate the repeatability of radiomic feature (RF) and its impact on the cross-institutional generalizability of the prognostic model for predicting local recurrence-free survival (LRFS) and overall survival (OS) in esophageal squamous cell cancer (ESCC) receiving definitive (chemo) radiotherapy (dCRT).MethodsNine hundred and twelve patients from two hospitals were included as training and external validation sets, respectively. Image perturbations were applied to contrast-enhanced computed tomography to generate perturbed images. Six thousand five hundred ten RFs from different feature types, bin widths, and filters were extracted from the original and perturbed images separately to evaluate RF repeatability by intraclass correlation coefficient (ICC). The high-repeatable and low-repeatable RF groups grouped by the median ICC were further analyzed separately by feature selection and multivariate Cox proportional hazards regression model for predicting LRFS and OS.ResultsFirst-order statistical features were more repeatable than texture features (median ICC: 0.70 vs 0.42–0.62). RFs from LoG had better repeatability than that of wavelet (median ICC: 0.70–0.84 vs 0.14–0.64). Features with smaller bin widths had higher repeatability (median ICC of 8–128: 0.65–0.47). For both LRFS and OS, the performance of the models based on high- and low-repeatable RFs remained stable in the training set with similar C-index (LRFS: 0.65 vs 0.67, p = 0.958; OS: 0.64 vs 0.65, p = 0.651), while the performance of the model based on the low-repeatable group was significantly lower than that based on the high-repeatable group in the external validation set (LRFS: 0.61 vs 0.67, p = 0.013; OS: 0.56 vs 0.63, p = 0.013).ConclusionsApplying high-repeatable RFs in modeling could safeguard the cross-institutional generalizability of the prognostic model in ESCC.Critical relevance statementThe exploration of repeatable RFs in different diseases and different types of imaging is conducive to promoting the proper use of radiomics in clinical research.Key PointsThe repeatability of RFs impacts the generalizability of the radiomic model.The high-repeatable RFs safeguard the cross-institutional generalizability of the model.Smaller bin width helps improve the repeatability of RFs.Graphical

A2HTL: An Automated Hybrid Transformer-Based Learning for Predicting Survival of Esophageal Cancer Using CT Images.

Esophageal cancer is a common malignant tumor, precisely predicting survival of esophageal cancer is crucial for personalized treatment. However, current region of interest (ROI) based methodologies not only necessitate prior medical knowledge for tumor delineation, but may also cause the model to be overly sensitive to ROI. To address these challenges, we develop an automated Hybrid Transformer based learning that integrates a Hybrid Transformer size-aware U-Net with a ranked survival prediction network to enable automatic survival prediction for esophageal cancer. Specifically, we first incorporate the Transformer with shifted windowing multi-head self-attention mechanism (SW-MSA) into the base of the U-Net encoder to capture the long-range dependency in CT images. Furthermore, to alleviate the imbalance between the ROI and the background in CT images, we devise a size-aware coefficient for the segmentation loss. Finally, we also design a ranked pair sorting loss to more comprehensively capture the ranked information inherent in CT images. We evaluate our proposed method on a dataset comprising 759 samples with esophageal cancer. Experimental results demonstrate the superior performance of our proposed method in survival prediction, even without ROI ground truth.

Improvement of esophageal cancer survival in Northeast Iran: A two-decade journey in a high-risk, low- resource region.

Two decades ago, an international initiative (GEMINI) was launched in a high-risk, low-resource region in Northeast Iran, aiming to investigate incidence, etiology, early detection, and treatment of esophageal squamous cell carcinoma (ESCC). An earlier report from this area, highlighted poor ESCC survival rates, with a 5-year survival probability of 3.3% and the median survival time of 7 months. Our study assesses whether ESCC survival has improved since the implementation of the GEMINI initiative in this region. 490 adult patients with histologically-confirmed ESCC were recruited from the Atrak clinic, Golestan, Iran, between 2007 and 2018. At recruitment, information on demographics and various exposures were collected. Active (telephone surveys) and passive (linkage to Golestan population-based cancer and death registries) follow-up methods were used to determine patients' vital status though March 2019. Survival estimates were obtained by Kaplan-Meier method and Cox proportional hazards regression models. Over the study period 340 deaths were recorded. Five-year ESCC survival probability was 23% (95% Confidence Interval: 19% to 28%), and the median survival time was 19 months. Five-year survival probability was higher among individuals who were younger (35% in <60-year-olds vs. 12% for >70-year-olds, p<0.001), educated (34% vs. 21% for no formal education, p = 0.027), never used opium (28% vs. 15%, p = 0.0016), and received cancer treatment (37% vs. 4%, p<0.001). In the adjusted models, a higher hazard of death was associated with older age [HR for each 10-year increase = 1.36 (95% CI = 1.22 to 1.51)], Turkman ethnicity [HR = 1.35 (95%CI: 1.07 to 1.70)], opium use [HR = 1.53 (95%CI: 1.20 to 1.94)],and receiving no cancer treatment [HR = 5.81 (95%CI: 3.97 to 8.52)]. Over the last two decades, ESCC survival in this population has significantly improved, highlighting the potential of enhancing healthcare infrastructure and ensuring access to affordable medical care in resource-limited, high-risk regions. Older age at diagnosis, Turkman ethnicity, opium use, and untreated cases (indicative of advanced disease at diagnosis) were identified as the main ESCC prognostic factors in this population.

An Ensemble Learning System Based on Stacking Strategy for Survival Risk Prediction of Patients with Esophageal Cancer

Background: Predicting the prognosis of esophageal cancer (EC) patients is crucial for optimizing the treatment plan and allocating medical resources effectively.Methods: This study proposes a novel ensemble learning-based EC survival prediction model. Firstly, recursive feature elimination (RFE) is used to determine the key feature subsets from the dataset. Based on the determined key features, the improved clustering by fast search and find of density peaks (IDPC) is proposed to construct a novel indicator related to EC survival risk. The cosine distance is introduced in IDPC to cluster samples with similar characteristics. Then, the adaptive synthetic (ADASYN) technique is used to generate more high-risk samples to balance high-risk and low-risk samples. Finally, the hyperparameters of the three models, including extreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), and random forest (RF), are optimized by whale optimization algorithm (WOA) and a new stacking model is constructed to evaluate the survival risk of patients.Results: The proposed stacking model achieved an area under the receiver operating characteristic curve (AUC) of 0.952 and Accuracy of 0.899, on the dataset from the First Affiliated Hospital of Zhengzhou University.Conclusions: The survival prediction model the proposed ensemble learning system is much more accurate and convenient, providing a basis clinical judgment and decision making and improving the survival status of esophageal cancer patients.

Long-term Survival in Esophageal Cancer: Comparison of Minimally Invasive and Open Esophagectomy

BackgroundThoracoscopic esophagectomy is a less invasive surgical procedure; however, evidence of its effect on long-term survival is limited. We evaluated long-term survival after the procedure in patients with esophageal carcinoma. MethodsThis retrospective multicenter study involved 1559 consecutive patients with esophageal carcinoma who underwent thoracoscopic esophagectomy or open esophagectomy between 2012 and 2019 at 2 Japanese high-volume cancer centers. Propensity score matching analysis was performed to compare short- and long-term outcomes. In addition, stage-specific survival rates were compared between the groups. ResultsThere were 313 patients who were matched and analyzed. The 1-, 3-, and 5-year overall survival rates were 84.5%, 60.5%, and 52.1%, respectively, in the matched open esophagectomy group; and 87.2%, 68.6%, and 61.8%, respectively, in the matched thoracoscopic esophagectomy group. The weighted Cox regression model showed significantly better survival in the thoracoscopic esophagectomy group than in the open esophagectomy group (hazard ratio, 0.74; 95% CI, 0.582-0.941). Deaths from other causes occurred more frequently in the open esophagectomy group than in the thoracoscopic esophagectomy group. Stratified analysis showed no significant survival differences between clinical stage I or II and pathologic stage 0 or I subgroups. However, the thoracoscopic esophagectomy groups with clinical stage III or IV and pathologic stage II, III, or IV had significantly better overall survival. ConclusionsThis study demonstrated the survival benefits of thoracoscopic esophagectomy, particularly for highly advanced esophageal carcinoma.

1429P Differences in esophageal cancer incidence and survival by race/ethnicity: A SEER analysis

1429P Differences in esophageal cancer incidence and survival by race/ethnicity: A SEER analysis

Ten-Year Survivals of Right Thoracic vs Left Thoracic Approach for Esophageal Cancer

BackgroundEsophagectomy can be performed using various surgical techniques. The aim of this study was to understand the impact of surgery on long-term survival for esophageal cancer. MethodsBetween May 2010 and July 2012, 300 patients with esophageal cancer were randomly assigned to undergo esophagectomy with either a left or right thoracic approach. Disease-free survival (DFS) and overall survival (OS) were compared based on the per-protocol principle among 286 patients with esophageal squamous cell carcinoma determined by postoperative pathologic results (146 in the right and 140 in the left thoracic arms). ResultsThe median DFS was 92 months in the right thoracic arm and 41 months in the left thoracic arm (hazard ratio, 0.73; 95% CI, 0.54-0.99; P = .045), with a cumulative 10-year DFS of 47.6% and 37.5%, respectively. The median OS was 136 months in the right thoracic arm and 99 months in the left thoracic arm (hazard ratio, 0.75; 95% CI, 0.54-1.04; P = .081), with cumulative 10-year OS of 52.4% and 43.7%, respectively. DFS and OS were comparable between the 2 arms for patients without lymph node metastasis. Conversely, for patients with lymph node metastasis, 10-year DFS was 32.7% and 21.4%, respectively (P = .018), and 10-year OS of the right and left thoracic arms was 37.9% and 25.9%, respectively (P = .012). ConclusionsCompared with the left thoracic approach, patients who underwent esophagectomy through the right thoracic approach had better 10-year survival rates, and the survival benefit was significant for those with lymph node metastasis.

Carcinoma esophagus with small bowel metastasis: a case report with review of literature.

Small intestinal metastasis is extremely rare and only 13 cases have been reported till date and almost all such patients have presented with intestinal obstruction. The 5-year overall survival for metastatic esophageal cancer is as low as 5% while the patients with small intestinal metastasis have a median survival of only 3months (range 1-12months) despite undergoing radical resection of the small bowel. We present a case of a male in his 50's who presented with difficulty in swallowing for 4months. On evaluation, he was found to have squamous cell carcinoma in the mid thoracic esophagus. He underwent radical chemo-radiation up to 60Gy in 25 fractions over 5weeks. One week after completion of treatment he presented with ileal obstruction and omental nodules and surgical resection and evaluation of the respective ileal segment and omental biopsy revealed a metastatic squamous cell carcinoma. The patient expired 3months post-surgery. Carcinoma esophagus with small bowel metastasis has a very grave prognosis that patients rarely survive beyond 1year despite undergoing resection. Hence it is imperative to consider a small bowel metastasis when such patients present with clinical features of intestinal obstruction for early diagnosis and aggressive management.

Sex differences in survival following surgery for esophageal cancer: A systematic review and meta-analysis.

The impact of sex on the prognosis of patients with esophageal cancer remains unclear. Evidence supports that sex- based disparities in esophageal cancer survival could be attributed to sex- specific risk exposures, such as age at diagnosis, race, socioeconomic status, smoking, drinking, and histological type. The aim of our study is to investigate the role of sex disparities in survival of patients who underwent surgery for esophageal cancer. A systematic review and meta-analysis of the existing literature in PubMed, EMBASE, and CENTRAL from December 1966 to February 2023, was held. Studies that reported sex-related differences in survival outcomes of patients who underwent esophagectomy for esophageal cancer were identified. A total of 314 studies were included in the quantitative analysis. Statistically significant results derived from 1-year and 2-year overall survival pooled analysis with Relative Risk (RR) 0.93 (95% Confidence Interval (CI): 0.90-0.97, I2= 52.00) and 0.90 (95% CI: 0.85-0.95, I2= 0.00), respectively (RR < 1 = favorable for men). In the postoperative complications analysis, statistically significant results concerned anastomotic leak and heart complications, RR: 1.08 (95% CI: 1.01-1.16) and 0.62 (95% CI: 0.52-0.75), respectively. Subgroup analysis was performed among studies with <200 and > 200 patients, histology types, study continent and publication year. Overall, sex tends to be an independent prognostic factor for esophageal carcinoma. However, unanimous results seem rather obscure when multivariable analysis and subgroup analysis occurred. More prospective studies and gender-specific protocols should be conducted to better understand the modifying role of sex in esophageal cancer prognosis.

Phase III randomized trial comparing palliative systemic therapy to best supportive care in advanced esophageal/GEJ cancer.

No study has unequivocally proven that chemotherapy prolongs overall survival (OS) in advanced esophageal cancer. We conducted a Phase III randomized study in first-line advanced unresectable/metastatic esophageal/GEJ cancer. Patients aged 18-70 years, with performance status 0-2, were randomized to best supportive care (BSC) alone, or BSC with weekly paclitaxel 80 mg/m2. BSC comprised, as indicated, education, counselling, radiation, stenting, feeding tube placement, nutritional supplementation, medications like analgesics, and referral to a support group and palliative care. The primary endpoint was OS; secondary endpoints included progression free survival (PFS), response, toxicity, and QoL. Between May 2016-December 2020, we recruited 281 patients: 143 to chemotherapy and 138 to BSC. Histopathology was squamous in 269 (95.7%) patients. Median number of paclitaxel doses was 12 (IQR, 7-23). Median OS was 4.2 months (95% CI, 3.42-5.32) in BSC, and 9.2 months (95% CI, 8.02-10.48) in chemotherapy; HR, 0.49 (95% CI, 0.39-0.64); p < .001. As compared to BSC, chemotherapy increased response (2.9% to 39%), median PFS (2.1 to 4.2 months), 1-year OS (11% to 32%), 2-year OS (0 to 9%), median dysphagia-free survival (2.9 to 14.8 months), and global and esophagus-specific QoL, without significantly increasing all-grade or grade ≥3 toxicities. Using ESMO clinical benefit scale and ASCO Value Framework, palliative chemotherapy scored as having "substantial value." Our study provides the first level 1 evidence that chemotherapy prolongs survival in advanced esophageal/GEJ carcinoma. BSC alone is no longer appropriate. Weekly paclitaxel is an attractive option, especially in LMICs with limited access to immunotherapy.

Survival improvements in esophageal and gastric cancers in the Nordic countries favor younger patients.

Esophageal cancer (EC) and gastric cancer (GC) are fatal cancers with a relatively late age of onset. Age is a negative risk factor for survival in many cancers and our aim was to analyze age-specific survival in EC and GC using the recently updated NORDCAN database. NORDCAN data originate from the Danish, Finnish, Norwegian, and Swedish nationwide cancer registries covering years 1972 through 2021 inviting for comparison of 50-year survival trends between the countries. Relative 1- and 5-year survival and 5/1-year conditional survival (i.e., survival in those who were alive in Year 1 to survive additional 4 years) were analyzed. Survival in EC showed large gains for patients below age 80 years, 5-year survival in Norwegian men reaching 30% and in women over 30% but for 80-89 year old survival remained at 10%. In contrast, hardly any gain was seen among the 80-89 year patients for 1-year survival and small gains in 5 year and 5/1-year survival. Survival gaps between age-groups increased over time. For GC there was also a clear age-related negative survival gradient but the survival gaps between the age groups did not widen over time; Norwegian male and female 5-year survival for 80-89 year old was about 20%. The age-specific survival difference in GC arose in Year 1 and did not essentially increase in 5-year survival. While there were differences in survival improvements between the countries, poor survival of the 80-89 year old patients was shared by all of them. To conclude, survival has improved steadily in younger GC and EC patients in most Nordic countries. While the 80-89 year old population accounts for nearly a quarter of all patients and their poor survival depressed overall survival, which can therefore be increased further by improving diagnostics, treatment and care of elderly EC and GC patients.

Does Radical Lymphadenectomy Improve Survival in Esophageal and Gastroesophageal Junction Cancer?

Background: Esophageal carcinoma is one of the deadliest cancer in gastrointestinal system with 5-years survival of only 24%. Lymphnode metastasis has been associated with worse outcome. But the extent of lymphnode dissection has been a debate among surgeons worldwide. This study aimed to compare the overall survival of patients undergoing radical and non-radical lymphadenectomy in a tertiary referral cancer hospital in Nepal. Methodology: This study included 634 patients of esophageal and gastroesophageal junction cancer who underwent surgical resection at our institution over a period of 2001- 2019. The patients were divided into 2 groups; radical lymphadenectomy (RLN) and non-radical lymphadenectomy (NRLN) groups. RLN group underwent two-field or three field lymphadenectomy for esophageal cancer and D2 or D2 + lower mediastinal lymphadenectomy for GEJ cancer. NRLN group underwent nodal sampling or D1 dissection. Results: RLN was performed in 85.9%. NRLN was done in 14.1%. Surgery alone was performed in 47.1% and multimodality approach in 52.9% cases. Median survival for RLN and NRLN groups was 34 and 15 months, respectively (p &lt; .001). Conclusion: Improved median survival has been observed after radical lymphadenectomy for esophageal and GEJ cancer.

PANoptosis-based molecular subtype and prognostic model predict survival and immune landscape in esophageal cancer

PurposeTo establish a prognostic model to predict the survival of patients with esophageal cancer (EC).MethodsWe extracted the expression profiles of prognostic-related genes and clinicopathological data from TCGA and GEO databases. Subsequently, a comprehensive bioinformatics analysis was conducted to construct a prognostic model utilizing LASSO and multivariate Cox regression. The stability of the risk signature was validated through Kaplan-Meier and ROC curve analyses on the training, internal testing, and external testing sets. Furthermore, we developed a nomogram that incorporates the risk score and clinical features to predict the suvival. Additionally, a nomogram incorporating the risk score and relevant clinical parameters was developed to enhance survivorship prediction. Furthermore, we delved into exploring the correlation between the risk score and immune cell abundance, expression of cancer checkpoints, as well as responses to immunotherapy and chemotherapeutic agents.ResultsIn this study, we successfully identified 19 prognosis-related genes out of a pool of 65 PANoptosis-related genes (PRGs) sourced from existing literature. Through consensus clustering analysis, we classified patients into two distinct groups as PANcluster A and B. Furthermore, the risk score derived from the five PANoptosis-related signatures emerged as an independent prognostic factor among patients with EC. To enhance the prognostic accuracy, we devised a nomogram integrating the risk score with clinical risk characteristics, enabling the prediction of 1-year, 2-year, and 3-year overall survival (OS) rates. Notably, individuals classified in the high-risk group demonstrated poorer prognoses compared to their low-risk counterparts. Furthermore, the risk score displayed substantial correlations with immune cell abundance, expression levels of cancer checkpoints, and responses to immunotherapy and chemotherapeutic agents. These pivotal findings underscore the significance of considering PANoptosis-related patterns in improving prognostic assessment and predicting treatment responses in patients diagnosed with esophageal cancer.ConclusionWe constructed a reliable prognostic risk model for EC utilizing five PRGs. The developed nomogram serves as a valuable tool in predicting patient outcomes, offering crucial insights that can inform and guide treatment decisions for individuals diagnosed with EC.

Surgical and endoscopic management of clinical T1b esophageal cancer

ObjectiveEsophageal cancers that invade the submucosa (T1b) have increased risk for occult lymph node metastases. To avoid the morbidity and recovery from esophagectomy, patients with cT1bN0 tumors have been increasingly managed endoscopically. We hypothesized that tumor attributes could predict upstaging and outcome associated with surgical and endoscopic treatment. Our objective was to evaluate the comparative effectiveness of esophagectomy across different cT1bN0 tumor attributes. MethodsTreatment-naïve patients who underwent endoscopic management or esophagectomy for a clinical stage cT1bN0 esophageal cancer diagnosed between 2010 and 2018 in the National Cancer Database were identified. Factors associated with upstaging were assessed by logistic regression. Adjusted survival was assessed by Kaplan-Meier analysis of 528 propensity-matched pairs and accelerated time failure models, stratified across tumor attributes. ResultsOverall, 1469 patients classified as cT1bN0 were identified; 926 underwent esophagectomy and 543 were managed endoscopically. In general, patients who were managed endoscopically were older (median, 71; interquartile range, 63-78; vs 66; interquartile range, 60-72; P < .0001) with smaller tumors compared with the patients who were managed with esophagectomy. Nodal upstaging was associated with lymphovascular invasion (odds ratio [OR], 6.88; confidence interval [CI], 4.39-10.77; P < .0001), poor tumor differentiation (OR, 2.77; CI, 1.30-5.88; P = .0081), and tumor size >1 cm (OR, 3.19; CI, 1.49-6.83, P = .0028). Overall survival was better among propensity-matched patients who underwent esophagectomy (5-year 68.4% vs 59.7% endoscopic, P < .001). However, accelerated time failure models suggested similar outcomes among patients with well-differentiated tumors managed surgically or endoscopically. ConclusionsEsophagectomy was associated with improved survival for cT1bN0 esophageal cancer; however, endoscopic treatment may achieve similar survival in patients with favorable tumor attributes. Further study is warranted.

Predictive role of Naples prognostic score for survival in esophageal cancer: A meta-analysis.

To further clarify the predictive value of pretreatment Naples prognostic score (NPS), calculating based on the serum albumin concentration, total cholesterol level, neutrophil to lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR), among esophageal cancer patients based on available evidence. The PubMed, EMBASE, Web of Science and CNKI databases were searched up to December 1, 2023 for relevant studies. Overall survival (OS), progression-free survival (PFS) and cancer-specific survival (CSS) were endpoints and the hazard ratio (HR) with 95% confidence interval (CI) was combined to evaluate the predictive role of NPS for survival. Subgroup analysis based on pathological type and treatment were further conducted. Ten retrospective studies with 2250 cases were included in our analysis. Pooled results demonstrated that higher pretreatment NPS predicted poorer OS (HR = 2.24, 95% CI: 1.57-3.20, P < .001), PFS (HR = 3.03, 95% CI: 1.84-4.98, P < .001) and CSS (HR = 2.90, 95% CI: 1.80-4.68, P < .001). Then subgroup analysis for the OS and PFS stratified by the pathological type (squamous cell carcinoma vs esophageal cancer) and treatment (surgery vs non-surgery) were further conducted, which showed similar results. Pretreatment NPS is significantly associated with prognosis in esophageal cancer and higher NPS predicts worse survival among patients with esophageal cancer.

923: Defining the optimal radiation-induced lymphopenia metric to discern survival in esophageal cancer

923: Defining the optimal radiation-induced lymphopenia metric to discern survival in esophageal cancer

The promoting effects of Grin2d expression in tumorigenesis and the aggressiveness of esophageal cancer.

Grin2d is an ionotropic NMDA receptor, a subunit of glutamate-dependent, and a facilitator of cellular calcium influx in neuronal tissue. In this study, we found that Grin2d expression was higher in esophageal cancer than in normal mucosa at both the mRNA and protein level using RT-PCR, bioinformatics analysis, and western blotting (p<0.05). Grin2d mRNA expression was positively correlated with old age, white race, heavy weight, distal location, adenocarcinoma, cancer with Barrett's lesion, or high-grade columnar dysplasia (p<0.05). The differential genes associated with Grin2d mRNA were involved in fat digestion and absorption, cholesterol metabolism, lipid transfer, lipoproteins, synaptic membranes, and ABC transporters (p<0.05). The Grin2d-related genes were classified into the following categories: metabolism of glycerolipids, galactose, and O-glycan, cell adhesion binding, actin binding, cadherin binding, the Hippo signaling pathway, cell-cell junctions, desmosomes, DNA-transcription activator binding, and skin development and differentiation (p<0.05). Grin2d immunoreactivity was positively correlated with distal metastasis and unfavorable overall survival in esophageal cancer (p<0.05). Grin2d overexpression promoted proliferation, migration, and invasion in esophageal cancer cells but blocked apoptosis (p<0.05) and increased the expression of PI3K, Akt and p-mTOR. Grin2d knockout caused the opposite effects. These findings indicated that upregulated Grin2d expression played an important role in esophageal carcinogenesis via the PI3K/Akt/mTOR pathway and might be a biological marker for aggressive tumor behavior and poor prognosis. Its silencing might represent a targeted therapy approach against esophageal cancer.

Treatment patterns and survival in T4b esophageal cancer: a retrospective cohort study.

This study aims to evaluate the efficacy of various treatment approaches in stage T4b esophageal cancer patients. Data were extracted from the Surveillance, Epidemiology, and End Results databases, covering patients diagnosed with esophageal cancer between 2000 and 2020. Kaplan-Meier analysis was used to assess cancer-specific survival (CSS) and overall survival (OS) across different treatment patterns. The study included 482 patients: 222 (46.1%) received chemoradiotherapy, 58 (12.0%) underwent radiotherapy alone, 37 (7.7%) received chemotherapy alone, 50 (10.4%) underwent surgery, and 115 (23.8%) received no treatment. Median CSS were 12, 4, 6, 18, and 1 month for chemoradiotherapy, radiotherapy alone, chemotherapy alone, surgery, and non-treatment groups. Median OS for these groups were 11, 3, 6, 17, and 1 month, respectively. Multivariable proportional hazard regression analysis revealed that patients who underwent surgery experienced significantly improved CSS (hazard ratio [HR] = 0.42, 95% confidence interval [CI]: 0.24-0.72; P = 0.002) and OS (HR = 0.45, 95% CI: 0.28-0.74; P = 0.002) compared to those receiving chemoradiotherapy after propensity score matching. Esophagectomy, with or without radiotherapy and/or chemotherapy, results in better survival outcomes than chemoradiotherapy in patients with stage T4b esophageal cancer.

Effect of longitudinal changes of cachexia on the efficacy and toxicity of immune checkpoint inhibitors in esophageal squamous cell cancer (ESCC) patients

PurposeImmune checkpoint inhibitors (ICIs) have enhanced survival in advanced esophageal squamous cell cancer (ESCC) patients, but their efficacy varies. Cachexia, characterized by muscle loss and significant weight loss, might influence ICI response. This study examines the relationship between cachexia's longitudinal changes and ICI outcomes in ESCC patients. MethodsESCC patients undergoing at least two ICI cycles from 2017 to 2021 were studied. Cachexia's baseline and evolving patterns during ICI treatment were observed. Kaplan-Meier and Cox regression analyses were used to assess cachexia's effect on ICI efficacy. Chi-square tests were used to determine cachexia's link to immune-related adverse effects (irAEs). ResultsTwo hundred seventy-eight ICI-treated patients had a median progression-free survival (PFS) of 5.78 months and overall survival (OS) of 8.3 months. Pretreatment cachexia led to worse outcomes: PFS 7.87 versus 5.3 months, time to progression (TTP) 10.9 versus 6.1 months, and OS 14.3 versus 9.2 months. Irreversible cachexia showed the poorest results. Cachexia's changes weren't associated with irAEs. ConclusionBaseline and evolving cachexia significantly impact ICI efficacy in ESCC patients. Continuous cachexia monitoring during ICI therapy is crucial for optimal ESCC management.