Esophageal Carcinoma Patients Research Articles

Intra-luminal iodine-125 brachytherapy in patients with esophageal carcinoma and 3/4 dysphagia score: A feasibility study.

To evaluate the clinical results of nasal feeding nutritional tube (NFNT)-loaded iodine-125 (125I) seeds in intra-luminal brachytherapy (ILBT) for esophageal carcinoma (EC) patients with a 3/4 dysphagia score. From January 2019 to January 2020, 26 patients (female/male: 17/9, mean age: 75.3 years, dysphagia score 3/4: 6/20, mean Karnofsky score: 58.4) with EC underwent NFNT-loaded 125I seed placement for both nutrition and brachytherapy. Technical and clinical success, D90 (radiation dose received by 90% of tumor volume) and organ at risk (OAR) dose, complications, dysphagia-free time (DFT), and overall survival (OS) time were documented. Local tumor diameter, Karnofsky score, dysphagia score, and quality of life (QoL) were compared before and 6 weeks after tube placement. Technical and clinical success rates were 100% and 76.9%, respectively. The D90 and OAR doses were 39.7 Gy and 2.3 Gy, respectively. Eight cases (30.8%) experienced mild complications, but no seed loss, fistula, and massive bleeding were observed. Median DFT and OS were 3.1 months and 13.7 months, respectively. Tumor diameter and dysphagia score significantly decreased (p < 0.05), Karnofsky score significantly improved (p < 0.05), and QoL scores related to physical function, physical functioning, general health, vitality, and emotional functioning improved (p < 0.05). NFNT-loaded 125I brachytherapy for ILBT is technically a safe and effective strategy for EC patients with low Karnofsky scores, and can be a bridging therapy for advanced anti-cancer treatment.

Chloroquine Sensitizes Esophageal Carcinoma EC109 Cells to Paclitaxel by Inhibiting Autophagy.

As an autophagy inhibitor, chloroquine (CQ) showed anti-tumor effect on several types of cancer and paclitaxel (PTX) is widely used in the treatment of esophageal carcinoma patients, but chemoresistance remains a major hurdle for PTX application due to the cytoprotective autophagy. Therefore, the aim of this study was to investigate whether CQ could elevate the anti-tumor effect of PTX on esophageal carcinoma cell line EC109 and explore the potential molecular mechanisms. We confirmed the suppressive effect of PTX on EC109 by MTT, scratch test, transwell and soft agar assay. And, we detected the key proteins in Akt/mTOR pathway, as well as the autophagy marker LC3 and p62 through Western Blot. In addition, GFP-LC3 plasmid was transfected into EC109 cells to monitor the autophagosome after CQ and PTX treatment. Ultimately, we observed the alterations in the proliferation and colony formation abilities of EC109 after knocking down mTOR by shRNA. We confirmed PTX could suppress the proliferation, migration and colony formation (all P < 0.05) abilities of EC109, and CQ could sensitize the inhibition effect of PTX by inhibiting autophagy through Akt/mTOR pathway. Furthermore, inhibiting Akt/mTOR pathway initiated autophagy and enhanced the sensitivity of EC109 to CQ and PTX. In summary, we suggest CQ could be used as a potential chemosensitizer for PTX in esophageal carcinoma treatment.

The Impact of Pretreatment Esophageal Stenosis on Survival of Esophageal Cancer Patients.

Little is known about the survival impacts of pretreatment cancerous stenosis on patients with esophageal carcinoma (EC). The clinicopathologic characteristics of patients who underwent surgery for EC between January 2010 and December 2018 were retrospectively reviewed. Esophageal stenosis was defined as present when a thin endoscope could not be passed through the tumor site. The impacts of stenosis on overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox hazards analysis. Of the 496 EC patients in this study, 51 (10.3 %) had pretreatment esophageal stenosis. Stenosis was associated with lower body mass index (P < 0.001) and higher pStage (P < 0.001). The 3-year OS rate for the patients with stenosis was significantly poorer than for the patients without stenosis (40.2 % vs 69.6 %; hazard ratio [HR], 2.19; P < 0.001). The survival outcomes, especially CSS, for the patients with stenosis were significantly poorer than for the patients without stenosis for both pStage II-III (P = 0.009) and pStage IV (P = 0.006) disease. The OS and CSS curves were well stratified by the presence of stenosis even in early-stage (pStage II) patients (P = 0.04 and P < 0.01, respectively). Multivariable analysis showed esophageal stenosis, pStage III-IV disease, and non-curative resection to be independently associated with poor OS (HR, 1.61; P = 0.02) and poor CSS (HR,1.67; P = 0.02). Higher pStage was an independent predictor of poor CSS for patients without stenosis, but not for those with stenosis. Esophageal carcinoma patients with pretreatment stenosis had significantly poorer survival outcomes, especially poorer CSS, than those without stenosis in both early- and advanced-stage diseases.

Overexpression of CENPL mRNA potentially regulated by miR-340-3p predicts the prognosis of pancreatic cancer patients

BackgroundIn our previous study it was found that CENPL was overexpressed in hepatocellular carcinoma and significantly predicted patient's prognosis. However, the expression and prognostic value of CENPL in other gastrointestinal tumors remain unknown. Therefore, we investigated the expression and prognostic value of CENPL in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ).MethodsIn this study, Oncomine, GEPIA, OncoLnc, TIMER, cBioPortal, miRWalk and ENCORI databases were used to analyze the level of CENPL mRNA, prognostic value and potential regulatory mechanism of CENPL mRNA in tumors. The CENPL expression and clinicopathological data regarding PAAD were from the UCSC Xena database and univariate and multivariate Cox regression analyses were performed using R (Version 3.6.3). Immunohistochemical staining was used to verify the expression of CENPL protein in clinical specimens. Cytoscape (Version: 3.7.2) was used to visualize microRNA (miRNA) that potentially regulates CENPL.ResultsGene differential expression analysis showed that CENPL mRNA was significantly overexpressed in ESCA, STAD, PAAD, COAD and READ (p < 0.01). The overexpression of CENPL mRNA was significantly correlated with the poor prognosis of PAAD patients (p < 0.05). However, there was no significant correlation between the level of CENPL mRNA and the prognosis of ESCA, STAD, COAD and READ patients (p > 0.05). Univariate and multivariate Cox regression analyses suggested that CENPL was a prognostic risk factor for PAAD. The mutation rate of CENPL in PAAD was 2.2% (17/850). There was no significant correlation between the CENPL expression and the infiltration levels of immune cells in PAAD (|Cor|< 0.5). Immunohistochemical staining showed that CENPL was overexpressed in 42% (11/26) of PAAD specimens, which was significantly higher compared with that in the normal tissues. The expression of miR-340-3p and miR-484 in PAAD were significantly lower than in the normal tissues (p < 0.05) and PAAD patients with lower expression of miR-340-3p had poorer prognosis (p < 0.05).ConclusionCENPL potentially regulated by miR-340-3p, is overexpressed in PAAD and predicts patient’s prognosis, suggestive of a diagnostic and prognostic value in PAAD patients.

Left versus right approach for middle and lower esophageal squamous cell carcinoma: A propensity score-matched study.

Despite superior short-term outcomes, there is considerable debate about the oncological efficacy of the left approach esophagectomy for middle and lower squamous esophageal carcinoma (ESCC). A propensity score-matched retrospective study was conducted to evaluate the left approach's short- and long-term effects. We recorded data from patients with ESCC who underwent curative resection via the left or right approach between January 2010 and December 2015. Propensity score matching (PSM) was performed, and maximally selected rank statistics (MSRS) were utilized to determine the appropriate number of lymph nodes to resect during esophagectomy. One hundred and forty-eight ESCC patients underwent esophagectomy via the right approach, and 108 underwent the left approach esophagectomy. After PSM, the left approach esophagectomy showed statistically significant superiority in operative time and time to oral intake, and there was a trend toward a shorter length of hospital stay. Fewer cervical, upper thoracic, and recurrent laryngeal nerve lymph nodes were harvested via the left approach than the right approach; the total number of lymph nodes harvested via the left and right approaches was similar. Similar long-term survival outcomes were achieved. MSRS suggested that at least 25 lymph nodes are needed to be resected during esophagectomy to improve survival in N0 patients. The left approach esophagectomy might facilitate postoperative recovery in patients with middle and lower ESCC. With adequate lymphadenectomy, the left approach esophagectomy might achieve similar long-term outcomes for middle and lower ESCC patients.

The Role of Alternative Splicing Factors hnRNP G and Fox-2 in the Progression and Prognosis of Esophageal Cancer.

Alternative splicing (AS) has been widely demonstrated in the occurrence and progression of many cancers. Nevertheless, the involvement of cancer-associated splicing factors in the development of esophageal carcinoma (ESCA) remains to be explored. RNA-Seq data and the corresponding clinical information of the ESCA cohort were downloaded from The Cancer Genome Atlas database. Bioinformatics methods were used to further analyzed the differently expressed AS (DEAS) events and their splicing network. Kaplan-Meier, Cox regression, and unsupervised cluster analyses were used to assess the association between AS events and clinical characteristics of ESCA patients. The splicing factors screened out were verified in vitro at the cellular level. A total of 50,342 AS events were identified, of which 3,988 were DEAS events and 46 of these were associated with overall survival (OS) of ESCA patients, with a 5-year OS rate of 0.941. By constructing a network of AS events with survival-related splicing factors, the AS factors related to prognosis can be further identified. In vitro experiments and database analysis confirmed that the high expression of hnRNP G in ESCA is related to the high invasion ability of ESCA cells and the poor prognosis of ESCA patients. In contrast, the low expression of fox-2 in esophageal cancer is related to a better prognosis. ESCA-associated AS factors hnRNP G and Fox-2 are of great value in deciphering the underlying mechanisms of AS in ESCA and providing clues for therapeutic goals for further validation.

Super-enhancers in esophageal carcinoma: Transcriptional addictions and therapeutic strategies.

The tumorigenesis of esophageal carcinoma arises from transcriptional dysregulation would become exceptionally dependent on specific regulators of gene expression, which could be preferentially attributed to the larger non-coding cis-regulatory elements, i.e. super-enhancers (SEs). SEs, large genomic regulatory entity in close genomic proximity, are underpinned by control cancer cell identity. As a consequence, the transcriptional addictions driven by SEs could offer an Achilles' heel for molecular treatments on patients of esophageal carcinoma and other types of cancer as well. In this review, we summarize the recent findings about the oncogenic SEs upon which esophageal cancer cells depend, and discuss why SEs could be seen as the hallmark of cancer, how transcriptional dependencies driven by SEs, and what opportunities could be supplied based on this cancer-specific SEs.

The Treatment Outcomes of Patients with Cervical Esophageal Carcinoma Undergoing Definitive Chemoradiotherapy: A Multi-Institutional Analysis TROD 01-005

<h3>Purpose/Objective(s)</h3> To investigate the clinical outcomes of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy (CRT). <h3>Materials/Methods</h3> The clinical data of 180 patients received concurrent CRT between April 2005 and September 2021 at 17 institutions were retrospectively analyzed. All patients were treated with curative intent CRT. Only patients treated with definitive intent, and squamous histology were analyzed. Patients who were treated with adjuvant or neoadjuvant setting or adenocarcinoma histology were excluded. The primary endpoint was LC, and the secondary endpoints were PFS and OS. <h3>Results</h3> Median age was 56 years (range; 26-87 years). Mean tumor size was 4.9 ± 2.1 cm. Majority of patients (60.6%) are female, had extensive T stage (78.9%), and regional lymph node metastasis (60.6%). Median fraction and total radiation doses were 2 Gy (range, 1.8-2.3 Gy) and 60 Gy (45-72 Gy), respectively delivered in median 30 fractions (range, 23-38 fr). Thirty-six patients (20%) were treated with 3-D conformal radiotherapy (RT) and 144 patients (80%) received intensity modulated RT (IMRT). Majority of the patients (49.4%) received concurrent cisplatin-based chemotherapy with a median 5 cycles (range, 1-8). Median follow-up was 20.7 months (range, 2.4-155.2 months). The 2-year OS and PFS rates were 58.7% and 47%, respectively. The 2-year LC was 69.5%. In univariate analysis ECOG performance score (p:0.01) and treatment response (p<0.001) were significant prognostic factors for OS and PFS. In multivariate analysis ECOG score 2 (HR=1.94, 95%CI, 1.18-3.18, p=0.009) and incomplete treatment response (HR=4.42, 95%CI, 2.80-6.99, p<0.001) were independent predictors for worse OS. In multivariate analysis ECOG score 2 (HR=1.73, 95%CI, 1.0.7-3.79, p=0.003) and incomplete treatment response (HR=4.42, 95%CI, 2.88-6.74, p<0.001) were independent predictors for worse PFS. <h3>Conclusion</h3> We found that CRT is a safe and effective treatment modality in patients with cervical esophageal carcinoma. The treatment response and patient performance status were predictive for survival. Further prospective studies with larger cohorts are warranted to confirm our findings.

S2435 A Rare Case of Plummer-Vinson Syndrome Treated With Pneumatic Dilations and Iron Supplementation

Introduction: Plummer-Vinson Syndrome (PVS), also known as Paterson-Kelly syndrome, presents with a classic triad of dysphagia, iron-deficiency anemia and esophageal webs. Although this triad of disease is increasingly less prevalent, early detection and intervention are imperative to reduce mortality given increased risk of malignant transformation.1 Case Description/Methods: A 22-year-old female with a history of iron deficiency anemia presented to the emergency department with syncope in the setting of palpitations and dyspnea. The patient endorsed alarm symptoms including hematochezia over the past 6 weeks, 20-lb unintentional weight loss and dysphagia. Initial labs were remarkable for a hemoglobin of 11.1 g/dL, and microcytic indices, with an MCV of 72.4 fL. The patient underwent esophagogastroduodenoscopy (EGD) to investigate the etiology of iron deficiency anemia. EGD revealed a prominent esophageal web (Figure A) in the proximal esophagus with associated erythema and mucosal friability. Significant narrowing impeded safe passage of the endoscope and thus serial pneumatic dilations to 10 mm were performed. Following pneumatic dilation, the endoscope was successfully advanced beyond the web (Figure B) to the gastroesophageal junction. The patient tolerated the procedure well and had immediate resolution of dysphagia following EGD with pneumatic dilation. She was then continued on iron supplementation as previously prescribed at discharge. Discussion: Plummer-Vinson Syndrome comprises the pathological triad of dysphagia, esophageal web, and iron deficiency anemia. Other signs and symptoms can include glossitis, angular cheilitis, and koilonychia. The decreased incidence of this syndrome parallels the decreased prevalence of iron deficiency in the developed world. Iron deficiency induces an iron-dependent enzyme dysfunction which causes oxidative stress, mucosal DNA damage and ultimately potentiates the formation of esophageal webs. 2 Without intervention, patients with this syndrome may develop absolute dysphagia, aspiration pneumonia and other complications. Due to increased risk of malignancy, surveillance EGDs are necessary to screen for esophageal carcinoma in patients with PVS.Figure 1.: Esophageal Web pre dilation (a) and post dilation (b).

526. SALVAGE SURGERY FOR ESOPHAGEAL CANCER: IS IT TIME TO REFINE SURVEILLANCE CRITERIA?

Abstract There is no accepted surveillance strategy following curative oesophageal cancer management, with reinvestigation often relying on symptom development. Lack of a surveillance standard may impact on outcome and survival. We hypothesized that strict surveillance was more likely to detect curable recurrent disease. This study compared the outcome for salvage surgery for recurrent disease, detected on a strict surveillance program, with survival of patients that had undergone immediate surgery following an incomplete response to neoadjuvant chemoradiotherapy. A prospective database of oesophageal carcinoma patients who were treated with curative intent (Surgery alone, Neoadjuvant Chemoradiotherapy (NeoCR) plus surgery, Definitive Chemoradiotherapy or Neoadjuvant Chemoradiotherapy with surveillance by choice), was interrogated for patients with recurrent disease amenable to salvage surgery. Surveillance for all consisted of 3-monthly endoscopy and 6-monthly CT scanning for 3 years, followed by 6-monthly endoscopy and yearly CT scanning to 5 years, and both yearly thereafter. If recurrence was diagnosed patients were restaged and, if suitable, underwent salvage surgery. Their outcome was compared with patients undergoing neoadjuvant chemoradiotherapy and having immediate surgery for an incomplete response. Of 205 patients treated with curative intent, 18 (9%) underwent salvage surgery for locoregional recurrence. They had a median survival of 61.6 months (range 10.32 to 136.08) and a 3-year survival of 50%. This compares to 115 patients who underwent surgery following incomplete response to NeoCR, who had a median survival of 38.3 months (range 2.20 to 254.26) and a 3 year survival of 44%, which was statistically insignificant between the groups (p= 0.975). The overall mean survivals were 57.84 months and 57.9 months respectively. Intensive surveillance identified a cohort of patients (9% of total) with recurrence amenable to salvage surgery and with outcomes non-inferior to immediate surgery following NeoCR. As most were asymptomatic, it is suggested that without surveillance the opportunity for curative intervention would have been lost. Even novel treatments will require detection of recurrence before disease becomes unmanageable. It is suggested that surveillance guidelines be updated to standardize interval endoscopy/imaging, as for other GI malignancies.

Demonstration of quasi-real-time intrafractional motion in esophageal cancer radiotherapy provided by ExacTrac X-ray snap verification.

To investigate the following hypotheses: (1) ExacTrac X-ray Snap Verification (ET-SV) is an alternative to CBCT for positioning patients with esophageal carcinoma (EC), (2) ET-SV can detect displacement in EC patients during radiotherapy (RT) and (3) EC patients can be feasibly monitored in quasi-real-time with ET-SV during RT. Anthropomorphic phantoms and 13 patients were included in this study. CBCT and ET-SV were both implemented before treatment delivery to detect displacement, and their correction results were compared. For the patient tests, positional correction in 3 translational directions and the yaw direction were applied using the ET-SV correction results. The residual error was detected immediately using ET-SV. Finally, to acquire the intrafractional motion, ET-SV was implemented when the gantry was at 0°, 90°, 180° and 270°, respectively. In phantom tests, the maximum value of the difference in displacement between the CBCT and ET systems was 1.16 mm for translation and 0.31° for yaw. According to Bland-Altman analysis of the patient test results, 5% (5/98), 5% (5/98), 5% (5/98), and 4% (4/98) of points were beyond the upper and lower limits of agreement in the AP, SI, LR and yaw directions, respectively. The mean residual error was -0.482 mm, 1.215 mm, 1.0 mm, -0.487°, 0.105°, and 0.003° in the AP, SI, LR, pitch, roll and yaw directions, respectively. The intrafractional displacement ranged from -0.21 mm to 0 mm for translation and from -0.63° to 0.21° for rotation. The mean total translational error for intrafractional motion increased from 0.47 mm to 1.14 mm during the treatment. The accuracy of ET-SV for EC RT positional correction is comparable to that of CBCT. Thus, Quasi-real-time intrafractional monitoring can be used to detect EC patient displacement during radiotherapy.

Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma

Esophageal carcinoma (ESCA) is a common type of cancer with high mortality. Cuproptosis is a new type of cell death and is characterized by the dependence on mitochondrial respiration and protein lipoylation. However, the potential roles of cuproptosis-related genes (CRGs) in ESCA remain elusive. Here, we systematically assessed the transcriptional and genetic alterations of CRGs in ESCA. We identified a CRGs signature for ESCA patients. A 6-CRGs signature was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis along with the univariate cox regression analysis and differential genes analysis. The CRGs score could significantly stratify ESCA patients’ survival and a high CRGs score was significantly correlated with worse overall survival. Moreover, higher CRGs score indicated higher pathology grades and aberrant cell adhesion, possibly via the PI3K-AKT pathway, which could also underly their increased sensitivity to PI3K-AKT pathway inhibitors. In addition, patients with high CRGs tend to hold more mutation load and abnormal APOBEC mutation. Notably, a higher CRGs score was anomalously associated with more immune infiltration, which could explain its malignancy by increased PD-L1 stability and a higher proportion of bystander T cells. In conclusion, our report revealed the significance of cuproptosis in ESCA and may have therapeutic potential in activating the bystander T cells.

MiR-145-3p Hampers the Malignant Progression of Esophageal Carcinoma via CXCL5 Downregulation.

Esophageal carcinoma (EC) is the most prevalent malignant tumor that occurs frequently worldwide. The early diagnostic biomarkers are crucial for EC treatment. miRNA can regulate EC progression, with diagnostic and prognostic value. Herein, differentially expressed miRNAs and mRNAs (DEmRNAs) in EC were predicted based on TCGA database. The target mRNAs of miRNA were predicted through databases, which were then intersected with DEmRNAs. Next, the correlation between miRNA and candidate mRNAs was analyzed. qRT-PCR was introduced to analyze expression of miR-145-3p and CXCL5 mRNA in EC cell lines, and western blot was performed to assess protein expression of CXCL5. Cell proliferation, migration, invasion, and apoptosis in EC were examined through CCK-8, wound healing, Transwell invasion, and flow cytometry assays. Moreover, targeting relationship between miR-145-3p and CXCL5 was verified through luciferase reporter gene analysis. The experimental results revealed a decreased miR-145-3p expression and an increased CXCL5 expression in EC. Enforced expression of miR-145-3p hindered proliferation, migration, invasion, and stimulated apoptosis of EC cells by repressing CXCL5. This study manifested that miR-145-3p may be a tumor suppressor in EC, and miR-145-3p/CXCL5 axis restrained the malignant progression of EC. These results supply an underlying target for prognosis and treatment of EC patients.

Cost-effectiveness analysis of nivolumab combination therapy in the first-line treatment for advanced esophageal squamous-cell carcinoma.

ObjectiveWe aimed to investigate the cost-effectiveness of nivolumab plus chemotherapy and nivolumab plus ipilimumab versus chemotherapy in the first-line treatment for advanced esophageal squamous-cell carcinoma (ESCC) patients from a healthcare system perspective in China.MethodsOn the basis of the CheckMate 648 trial, a partitioned survival model was constructed to estimate economic costs and health outcomes among overall and PD-L1-positive advanced ESCC patients over a 10-year lifetime horizon. The health-related costs and utilities were obtained from the local charges and published literature. The lifetime costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were measured. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of the model.ResultsIn the base-case analysis, in overall and PD-L1-positive advanced ESCC patients, the ICERs were $415,163.81/QALY and $216,628.00/QALY for nivolumab plus chemotherapy, and$430,704.11/QALY and $185,483.94/QALY for nivolumab plus ipilimumab, respectively, compared with chemotherapy. One-way sensitivity analyses revealed that patients’ weight was the most influential parameter on ICER. The PSA demonstrated that the probability of nivolumab combination therapy being cost-effective was 0% over chemotherapy at the current price and willingness-to-pay threshold ($38,351.20/QALY). When the price of nivolumab and ipilimumab decreased 80%, the cost-effective probability of nivolumab plus ipilimumab increased to 40.44% and 86.38% in overall and PD-L1-positive advanced ESCC patients, respectively.ConclusionNivolumab combination therapy could improve survival time and health benefits over chemotherapy for advanced ESCC patients, but it is unlikely to be a cost-effective treatment option in China.

EIF6 is potential diagnostic and prognostic biomarker that associated with 18F-FDG PET/CT features and immune signatures in esophageal carcinoma

BackgroundAlthough eukaryotic initiation factor 6 (eIF6) is a novel therapeutic target, data on its importance in the development of esophageal carcinoma (ESCA) remains limited. This study evaluated the correlation between eIF6 expression and metabolic analysis using fluorine-18 fluorodeoxyglucose (18F-FDG) -Positron emission tomography (PET) and immune gene signatures in ESCA.MethodsThis study employed The Cancer Genome Atlas (TCGA) to analyze the expression and prognostic value of eIF6, as well as its relationship with the immune gene signatures in ESCA patients. The qRT-PCR and Western blot analyses were used to profile the expression of eIF6 in ESCA tissues and different ESCA cell lines. The expression of tumor eIF6 and glucose transporter 1 (GLUT1) was examined using immunohistochemical tools in fifty-two ESCA patients undergoing routine 18F-FDG PET/CT before surgery. In addition, the cellular responses to eIF6 knockdown in human ESCA cells were assessed via the MTS, EdU, flow cytometry and wound healing assays.ResultsOur data demonstrated that compared with the normal esophageal tissues, eIF6 expression was upregulated in ESCA tumor tissues and showed a high diagnostic value with an area under curve of 0.825 for predicting ESCA. High eIF6 expression was significantly correlated with shorter overall survival of patients with esophagus adenocarcinoma (p = 0.038), but not in squamous cell carcinoma of the esophagus (p = 0.078). In addition, tumor eIF6 was significantly associated with 18F-FDG PET/CT parameters: maximal and mean standardized uptake values (SUVmax and SUVmean) and total lesion glycolysis (TLG) (rho = 0.458, 0.460, and 0.300, respectively, p < 0.01) as well as GLUT1 expression (rho = 0.453, p < 0.001). A SUVmax cutoff of 18.2 led to prediction of tumor eIF6 expression with an accuracy of 0.755. Functional analysis studies demonstrated that knockdown of eIF6 inhibited ESCA cell growth and migration, and fueled cell apoptosis. Moreover, the Bulk RNA gene analysis revealed a significant inverse association between eIF6 and the tumor-infiltrating immune cells (macrophages, T cells, or Th1 cells) and immunomodulators in the ESCA microenvironment.ConclusionOur study suggested that eIF6 might serve as a potential prognostic biomarker associated with metabolic variability and immune gene signatures in ESCA tumor microenvironment.

The Application of Nimotuzumab Combined With Definitive Chemoradiotherapy Toward the Treatment of Locally Advanced Cervical Esophageal Carcinoma: A Retrospective Study.

ObjectiveTo evaluate the safety and effectiveness of nimotuzumab in combination with chemoradiotherapy for locally advanced cervical esophageal squamous cell carcinoma.MethodsRetrospective analysis was conducted from September 2012 to February 2017 among 50 locoregional-advanced cervical esophageal carcinoma (CEC) patients who received concurrent chemoradiotherapy (CRT) combined with or without nimotuzumab at Ningbo Medical Center Lihuili Hospital. Intensity-modulated radiotherapy (IMRT) was administrated on all patients. All patients were divided into two groups, of which 26 (Group A) received 200 mg (22 of 50) or 400 mg (4 of 50) of nimotuzumab per week with CRT and 24 (Group B) received definitive CRT.ResultsThe median follow-up time was 23 months. The median overall survival (OS) and progression-free survival (PFS) were 40.6 and 21.1 months for all, respectively. The 1-, 2-, and 3-year OS rates on the whole were 79.6%, 62.1%, and 47.8%. There was no statistical difference in overall response rate and disease control rate between the two groups. Patients treated with nimotuzumab (group A) had better PFS than the definitive CRT group (group B) (P < 0.05). However, the median OS was 41.4 months in group A and 32.4 months in group B, respectively (P = 0.517). Multivariate analysis showed that PFS among those with lower Eastern Cooperative Oncology Group (ECOG) score (HR = 5.11; P < 0.01), stage II (HR = 9.52; P < 0.01) and the application of nimotuzumab combined with CRT (HR = 0.16; P < 0.01) was much longer. Furthermore, ECOG, stage, C-reactive protein (CRP) baseline, and histological grade can also be used as independent predictors of OS. Grade >3 adverse reactions were not observed. The most common adverse event related to nimotuzumab was mild fever and the occurrence rate was 19% (5 of 26). The incidence of anemia was 65.4% in group A and 87.5% in group B (P < 0.05).ConclusionsFor locoregional-advanced CEC, nimotuzumab combined with IMRT and concomitant chemotherapy was tolerated and effective. In addition, patients with a normal pretherapeutic serum CRP level (CRP < 10 mg/L) can achieve better OS.

Serological markers associated with response and adverse events in patients of esophageal squamous carcinoma with toripalimab combined with nab-paclitaxel and S-1 as neoadjuvant therapy.

e16017 Background: Immune checkpoint inhibitor (ICI) combined with chemotherapy as a neoadjuvant therapy has been applied to the treatment of patients with esophageal squamous carcinoma (ESCC), however, there were a limited number of predictive biomarkers for response and adverse events. Methods: 60 patients diagnosed with ESCC and considered propable for surgical treatment were enrolled from October 2019 to September 2020 in the first medical center of Chinese PLA General Hospital and received Toripalimab combined with nab-Paclitaxel and S-1 as neoadjuvant therapy. Serum samples were collected at baseline and performed with 92 proteins using proximity extension assay technology. Results: In total, 50 patients were examined, and 3 patients did not pass quality control. Patients with IFN-Y-L, LAMP3-L and Gal.1-H at baseline were associated with longer overall survival. Furthermore, 21 proteins were found to be significantly lower in patients with severe side effects than in patients without serious adverse events. Conclusions: Our study found that serum levels of several proteins were associated with clinical benefit and severe side effects, and these proteins may be useful biomarkers for predicting response and severe side effects in ESCC treated with ICI and chemotherapy.

REGOMUNE: A phase II study of regorafenib plus avelumab in solid tumors—Results of the oesophageal or gastric carcinoma (OGC) cohort.

4060 Background: Combination VEGF and PD-1/PD-L1 axis blockade has shown benefit in various tumors and is emerging as a promising combination strategy. Methods: This is a single-arm open-label multicentric phase II trial assessing the efficacy and safety of regorafenib (R) (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in advanced or metastatic oesophageal or gastric carcinoma (OGC) patients (pts). The primary endpoint was the confirmed objective response rate, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Dec. 2018 and Mar. 2021, 49 pts were enrolled in 6 centers: 33 adenocarcinoma (ADK), 16 squamous cell carcinoma (SCC). Median age was 63.9 (range 33 – 80). Median follow-up was 14.5 months. Median number of previous treatment lines was: 2 (range 1 – 6). 29 (59.2%) pts experienced at least 1 dose modification or treatment interruption due to an adverse event related to treatment. The most common grade 3/4 adverse events were : Hypertension (12.2% of pts), palmar-plantar erythrodysesthesia syndrome (10.2%), and hypophosphatemia (8.2%). No death was related to the treatment. Among the 42 (29 ADK and 13 SCC) pts who had at least one imaging tumor assessment, 8 (19.1%) achieved a partial response, 5 (17.2%) and 3 (23.1%) in the ADK and SCC group respectively. 12 pts (28.6%) demonstrated stable disease and 22 pts (52.3%) had progressive disease. The median PFS and OS were 1.9 months (95%CI 1.8 – 3.5) and 7.5 months (95%CI 4.5 – 15.7) respectively. Conclusions: The R+A combination is associated with encouraging antitumor activity in patients with OGC. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

The analysis of CCND1 amplification in Chinese patients with esophageal carcinoma.

e16073 Background: The CCND1 gene is considered an oncogene located on human chromosome 11q13.3, Cyclin D1 protein encoded by the CCND1 gene is the critical gatekeeping protein in charge of regulating the transition. Previous studies have reported that CCND1 amplification associated with a negative response to immune checkpoint inhibitors (ICIs) in pancancers, but the association with clinical and molecular characteristics in esophageal carcinoma (ESCA) have not been researched. Herein, we explore CCND1 amplification profiles in Chinese patients with ESCA. Methods: A total of 59 patients of ESCA with paired tumor-normal samples were collected into the study. All samples were detected by DNA based sequencing with a 1021 gene panel. Results: Firstly, the frequency of CCND1 amplification in Chinese ESCA patients was 32.20% (19/59). Then, all the samples were divided into two groups according to whether CCND1 was amplified or not. In the CCND1 amplification group, the top8 co-mutated genes were TP53, FGF4, FGF3, FGF19, MYC, NOTCH1, CDKN2A, CDKN2B. We calculated the clinical and molecular characteristics between the two groups, the results showed there were no difference in gender, age and TNM stage. Meanwhile, the CCND1 amplification group had more somatic mutations (median 19 vs. 11, P = 0.0003), higher TMB value (median 8.64 vs. 5.76, P = 0.0199) and more TMB-H patients (47.37% vs. 17.50%, P = 0.018). Indicating the CCND1 amplification is associated with TMB-H in ESCA. However, previous studies have reported the negative impact of CCND1 amplification on the efficacy of ICIs in pancancer (including ESCA), these results suggesting the efficacy of ICIs in ESCA may be affected by multiple biomarkers, especially for TMB-H patients should be concerned about the high frequency CCND1 amplification, the patients may have a poorer benefit from immunotherapy. Conclusions: The efficacy of ICIs in ESCA may be affected by multiple biomarkers, especially for TMB-H patients should be concerned about the higher frequency of CCND1 amplification, these patients may have a poorer benefit from immunotherapy.[Table: see text]

Comparison of Long-Term Survival Between cT1N0 Stage Esophageal Cancer Patients Receiving Endoscopic Dissection and Esophagectomy: A Meta-Analysis.

BackgroundEndoscopic dissection (ED) shows relatively high clinical value in early esophageal cancer (cT1N0) such as lower incidence of postoperative complications and hospitalization costs and enhanced recovery. However, whether ED still has certain advantages over esophagectomy in terms of long-term survival remains unclear.PurposeThe aim of this meta-analysis was to compare the long-term outcomes of ED and surgery in the treatment of cT1N0 esophageal cancer.MethodsSeveral electronic databases including the PubMed, EMBASE, Web of Science and Cochrane Library databases were searched up to April 7, 2022 for studies which compared the overall survival (OS) and disease-specific survival (DSS) of cT1N0 esophageal cancer patients receiving the ED or esophagectomy. The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined and all statistical analysis was conducted through STATA 15.0 software.ResultsA total of 12 studies involving 3,732 patients were enrolled. No significant difference in the OS between ED and surgery groups was observed (HR = 0.78, 95% CI, 0.59–1.04, p = 0.089). However, the DSS of the ED group was significantly longer than that of the surgery group (HR = 0.56, 95% CI, 0.39–0.82, p = 0.003).ConclusionIn overall, the current evidence manifested that the long-term survival of cT1N0 esophageal cancer patients undergoing ED was not worse than that of patients undergoing esophagectomy. ED may be considered as the primary treatment for cT1N0 esophageal carcinoma patients.