Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phaseⅡstudy

Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this therapy.Therefore,there is a need for a more suitable radiotherapy combination regimen for this population.This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)score.Methods:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled.They were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive radiotherapy.The primary endpoint was the locoregional control(LRC)rate.Results:A total of 55 patients who met the study criteria were enrolled.After completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 patients.The median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]months.The LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire population.The overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,respectively.Surgery was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events occurred.Conclusions:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

Nomograms and prognosis for superficial esophageal squamous cell carcinoma

In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.

Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy

BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used classification.Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different shapes.However,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'infiltration.AIM To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'infiltration.METHODS Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023.Patients first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical treatment.Pathological images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and t-tests.RESULTS The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and B3.Statistical analyses revealed significant differences(aP<0.05)in the short and long calibers,area,location,and density between types A and B.Notably,there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3(P>0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP<0.05);no significant differences were found in the density or location(P>0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy,especially between the types A and B.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Rare esophageal carcinoma-primary adenoid cystic carcinoma of the esophagus: A case report

BACKGROUND Esophageal adenoid cystic carcinoma(EACC)is an exceedingly rare malignant tumor of the esophagus,posing significant challenges in the clinic.CASE SUMMARY This report detailed the case of a 72-year-old male whose diagnosis of EACC was confirmed through postoperative histopathological examination.The patient underwent thoracoscopy-assisted radical resection of the esophageal tumor,coupled with lymph node dissection.Pathological findings revealed an adenoid cystic carcinoma infiltrating the entire layer of the muscularis propria,locally extending into the outer membrane of the esophageal fiber,involving the cardia and exhibiting no lymph node metastasis.The patient’s condition was classified as primary EACC,T3N0M0,per the American Joint Committee on Cancer(2017;8th edition).One month after surgery,the patient received postoperative adjuvant radiation therapy.CONCLUSION In addressing the rarity and high potential for biopsy misdiagnosis of EACC,this study delved into its diagnostic methods and treatment.

Novel milestones for early esophageal carcinoma:From bench to bed

Esophageal cancer(EC)is the seventh most common cancer worldwide,and esophageal squamous cell carcinoma(ESCC)accounts for the majority of cases of EC.To effectively diagnose and treat ESCC and improve patient prognosis,timely diagnosis in the initial phase of the illness is necessary.This article offers a detailed summary of the latest advancements and emerging technologies in the timely identification of ECs.Molecular biology and epigenetics approaches involve the use of molecular mechanisms combined with fluorescence quanti-tative polymerase chain reaction(qPCR),high-throughput sequencing technology(next-generation sequencing),and digital PCR technology to study endogenous or exogenous biomolecular changes in the human body and provide a decision-making basis for the diagnosis,treatment,and prognosis of diseases.The invest-igation of the microbiome is a swiftly progressing area in human cancer research,and microorganisms with complex functions are potential components of the tumor microenvironment.The intratumoral microbiota was also found to be connected to tumor progression.The application of endoscopy as a crucial technique for the early identification of ESCC has been essential,and with ongoing advancements in technology,endoscopy has continuously improved.With the advancement of artificial intelligence(AI)technology,the utilization of AI in the detection of gastrointestinal tumors has become increasingly prevalent.The implementation of AI can effectively resolve the discrepancies among observers,improve the detection rate,assist in predicting the depth of invasion and differentiation status,guide the pericancerous margins,and aid in a more accurate diagnosis of ESCC.

Regulation of TMEM100 expression by epigenetic modification,effects on proliferation and invasion of esophageal squamous carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a prevalent malignancy with a high morbidity and mortality rate.TMEM100 has been shown to be suppressor gene in a variety of tumors,but there are no reports on the role of TMEM100 in esophageal cancer(EC).AIM To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion.METHODS Firstly,we found the expression of TMEM100 in EC through The Cancer Genome Atlas database.The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis.We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification.To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100.Finally,we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases(MAPK)pathway.RESULTS In the present study,by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects.Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC.Then,we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells[quantitative real-time PCR(qRT-PCR)and western blotting].Subsequently,we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells(qRT-PCR and western blotting).Overexpression of TMEM100 also inhibited proliferation,invasion and migration of ESCC cells(cell counting kit-8 and clone formation assays).Next,by enrichment analysis,we found that the gene set was significantly enriched in the MAPK signaling pathway.The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting.CONCLUSION TMEM100 is a suppressor gene in ESCC,and its low expression may lead to aberrant activation of the MAPK pathway.Promoter methylation may play a key role in regulating TMEM100 expression.

Comparative efficacy and safety between endoscopic submucosal dissection,surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer

BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.

VEGF, HIF-1α, and Metabolic Indicators in Esophageal Squamous Cell Carcinoma

Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.

Efficacy of concurrent chemoradiotherapy with thalidomide and S-1 for esophageal carcinoma and its influence on serum tumor markers

BACKGROUND Although the current conventional treatment strategies for esophageal carcinoma(EC)have been proven effective,they are often accompanied by serious adverse events.Therefore,it is still necessary to continue to explore new therapeutic strategies for EC to improve the clinical outcome of patients.AIM To elucidate the clinical efficacy of concurrent chemoradiotherapy(CCRT)with thalidomide(THAL)and S-1(tegafur,gimeracil,and oteracil potassium capsules)in the treatment of EC as well as its influence on serum tumor markers(STMs).METHODS First,62 patients with EC treated at the Zibo 148 Hospital between November 2019 and November 2022 were selected and grouped according to the received treatment.Among these,30 patients undergoing CCRT with cis-platinum and 5-fluorouracil were assigned to the control group(Con),and 32 patients receiving CCRT with THAL and S-1 were assigned to the research group(Res).Second,inter-group comparisons were carried out with respect to curative efficacy,incidence of drug toxicities,STMs[carbohydrate antigen 125(CA125)and macrophage inflammatory protein-3α(MIP-3α)],angiogenesis-related indicators[vascular endothelial growth factor(VEGF);VEGF receptor-1(VEGFR-1);basic fibroblast growth factor(bFGF);angiogenin-2(Ang-2)],and quality of life(QoL)[QoL core 30(QLQ-C30)]after one month of treatment.RESULTS The analysis showed no statistical difference in the overall response rate and disease control rate between the two patient cohorts;however,the incidences of grade I–II myelosuppression and gastrointestinal reactions were significantly lower in the Res than in the Con.Besides,the post-treatment CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels in the Res were markedly lower compared with the pre-treatment levels and the corresponding post-treatment levels in the Con.Furthermore,more evident improvements in QLQ-C30 scores from the dimensions of physical,role,emotional,and social functions were determined in the Res.CONCLUSION The above results demonstrate the effectiveness of THAL+S-1 CCRT for EC,which contributes to mild side effects and significant reduction of CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels,thus inhibiting tumors from malignant progression and enhancing patients’QoL.

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma(CEC)patients who underwent definitive chemoradiotherapy(CRT).The clinical data of 175 biopsyconfirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed.The prognostic factors predicting overall survival(OS),progression-free survival(PFS),and local recurrence-free survival(LRFS)were assessed in uni-and multivariable analyses.The median age of the entire cohort was 56 years(range:26–87 years).All patients received definitive radiotherapy with a median total dose of 60 Gy,and 52%of the patients received cisplatin-based concurrent chemotherapy.The 2-year OS,PFS,and LRFS rates were 58.8%,46.9%,and 52.4%,respectively,with a median follow-up duration of 41.6 months.Patients’performance status,clinical nodal stage,tumor size,and treatment response were significant prognostic factors for OS,PFS,and LRFS in univariate analysis.Non-complete treatment response was an independent predictor for poor OS(HR=4.41,95%CI,2.78–7.00,p<0.001)and PFS(HR=4.28,95%CI,2.79–6.58,p<0.001),whereas poor performance score was a predictor for worse LRFS(HR=1.83,95%CI,1.12–2.98,p=0.02)in multivariable analysis.Fifty-two patients(29.7%)experienced grade II or higher toxicity.In this multicenter study,we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC.Higher radiation doses were found to have no effect on treatment outcomes,but a better response to treatment and a better patient performance status did.

Is Escalated Radiation Dose in Definitive Chemoradiotherapy Better for Inoperable Esophageal Carcinoma? A Meta-Analysis and Systematic Review

Purpose: This study aimed to compare the survival benefits between different total radiation doses in definitive chemoradiotherapy (dCRT) for inoperable esophageal carcinoma (EC) based on modern radiotherapy techniques. Methods: A systematic review was performed by searching the databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. All studies published prior to November 30, 2022, comparing radiation dose and disease-related outcomes in EC patients. The hazard ratio (HR) and odds ratio (OR) were used to describe the risk of outcomes and toxicities. Results: Seven prospective trials involving 1124EC patients were enrolled for analyses. The results revealed that the effect on overall survival (HR = 0.99, 95% CI = 0.85 - 1.16, P = 0.94), local progression-free survival (HR = 0.83, 95% CI = 0.58 - 1.17, P = 0.29), local regional progression-free survival (HR = 0.94, 95% CI = 0.76 - 1.17, P = 0.61), progression-free survival (HR = 0.90, 95% CI = 0.71 - 1.13, P = 0.35) was similar in the high-dose and standard-dose groups. Additionally, a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose (4.8% vs 2.2%, OR 2.11, P = 0.06). Conclusions: The efficacy of the HD group (≥60 Gy) and the SD group (approximately 50 Gy) for inoperable local advanced EC was similar. However, the HD group exhibited a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose. Simultaneously, the final results of several ongoing prospective trials regarding the optimal radiation dose in dCRT are awaited.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor

BACKGROUND Targeting DNA damage response(DDR)pathway is a cutting-edge strategy.It has been reported that Schlafen-11(SLFN11)contributes to increase chemosensitivity by participating in DDR.However,the detailed mechanism is unclear.AIM To investigate the role of SLFN11 in DDR and the application of synthetic lethal in esophageal cancer with SLFN11 defects.METHODS To reach the purpose,eight esophageal squamous carcinoma cell lines,142 esophageal dysplasia(ED)and 1007 primary esophageal squamous cell carcinoma(ESCC)samples and various techniques were utilized,including methylationspecific polymerase chain reaction,CRISPR/Cas9 technique,Western blot,colony formation assay,and xenograft mouse model.RESULTS Methylation of SLFN11 was exhibited in 9.15%of(13/142)ED and 25.62%of primary(258/1007)ESCC cases,and its expression was regulated by promoter region methylation.SLFN11 methylation was significantly associated with tumor differentiation and tumor size(both P<0.05).However,no significant associations were observed between promoter region methylation and age,gender,smoking,alcohol consumption,TNM stage,or lymph node metastasis.Utilizing DNA damaged model induced by low dose cisplatin,SLFN11 was found to activate non-homologous end-joining and ATR/CHK1 signaling pathways,while inhibiting the ATM/CHK2 signaling pathway.Epigenetic silencing of SLFN11 was found to sensitize the ESCC cells to ATM inhibitor(AZD0156),both in vitro and in vivo.CONCLUSION SLFN11 is frequently methylated in human ESCC.Methylation of SLFN11 is sensitive marker of ATM inhibitor in ESCC.