Curva de aprendizagem de dissecção endoscópica de submucosa por endoscopistas ocidentais treinados no Japão: Experiência na América Latina / Learning curve in esophageal endoscopic submucosal dissection by western endoscospists trained in japan: experience in latin america

ABSTRACT Background: Esophageal endoscopic submucosal dissection (EESD) is a complex and time-consuming procedure at which training are mainly available in Japan. There is a paucity of data concerning the learning curve to master EESD by Western endoscopists. Objective: This study aimed to assess the learning curve effect on patient's clinical outcome for EESD. Methods: This is a retrospective observational study. Enrolling patients that underwent EESD from 2009 to 2021. The analysis was divided into two periods; T1: case 1 to 49 and T2: case 50 to 98. The following features were analyzed for each group: patients and tumors characteristics, en-bloc, complete and curative resection rates, procedure duration and adverse events rate. Results: Ninety-eight EESD procedures were performed. Mean procedure time was 111.8 min and 103.6 min for T1 and T2, respectively (P=0.004). En bloc resection rate was 93.8% and 97.9% for T1 and T2, respectively (P=0.307). Complete resection rate was 79.5% and 85.7% for T1 and T2, respectively (P=0.424). Curative resection rate was 65.3% and 71.4% for T1 and T2, respectively (P=0.258). Four patients had complications; three during T1 period and one during T2 period. Overall mortality rate: 0%. Conclusion: The esophageal endoscopic submucosal dissection could be performed effectively and safely by an adequately trained Western endoscopist.

RESUMO Contexto: A dissecção endoscópica da submucosa do esôfago (DSEE) é um procedimento complexo, cujo treinamento está disponível principalmente no Japão. Há uma escassez de dados sobre a curva de aprendizado para se capacitar na realização da DSEE por endoscopistas ocidentais. Objetivo: Este estudo teve como objetivo avaliar o efeito da curva de aprendizado no resultado clínico dos pacientes submetidos a DSEE. Métodos: Trata-se de um estudo observacional retrospectivo. Foram incluídos pacientes submetidos a DSEE no período de 2009 a 2021. A análise foi dividida em dois períodos; T1: caso 1 a 49 e T2: caso 50 a 98. Os seguintes parâmetros foram analisados para cada grupo: características clínicas dos pacientes e dos tumores de esôfago, taxas de ressecção em bloco, completa e curativa, duração do procedimento e taxa de eventos adversos. Resultados: Noventa e oito procedimentos de DSEE foram realizados. O tempo médio do procedimento foi de 111,8 min e 103,6 min nos períodos T1 e T2, respectivamente (P=0,004). A taxa de ressecção em bloco foi de 93,8% e 97,9% nos períodos T1 e T2, respectivamente (P=0,307). A taxa de ressecção completa foi de 79,5% e 85,7% nos períodos T1 e T2, respectivamente (P=0,424). A taxa de ressecção curativa foi de 65,3% e 71,4% para T1 e T2, respectivamente (P=0,258). Quatro pacientes tiveram complicações; três durante o período T1 e um durante o período T2. Taxa de mortalidade geral: 0%. Conclusão: A DSEE pode ser realizada de forma eficaz e segura por um endoscopista ocidental adequadamente treinado.

Diagnóstico y tratamiento de los tumores de la unión esofagogástrica. Experiencia en el Instituto Nacional de Cancerología / Diagnosis and treatment of esophagogastric junction tumors. Experience at the National Cancer Institute

Introducción. El diagnóstico adecuado de los tumores de la unión esofagogástrica es esencial para el tratamiento de estos pacientes. La clasificación propuesta por Siewert-Stein define las características propias, factores de riesgo y estrategias quirúrgicas según la localización. El objetivo de este estudio fue describir las características de los pacientes con adenocarcinoma de la unión esofagogástrica tratados en nuestra institución. Métodos. Estudio retrospectivo, descriptivo, de corte longitudinal, que incluyó los pacientes con diagnóstico de adenocarcinoma de la unión esofagogástrica intervenidos quirúrgicamente en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre enero de 2012 y mayo de 2017. Resultados. Se operaron 59 pacientes (84,7 % hombres), con una edad media de 62,5 años. En su orden de frecuencia los tumores fueron tipo II (57,6 %), tipo III (30,7 %) y tipo I (11,9 %). El 74,6 % recibieron neoadyuvancia y se realizó gastrectomía total en el 73 % de los pacientes. La concordancia diagnóstica moderada con índice Kappa fue de 0,56, difiriendo con la endoscópica en 33,9 %. El 10,2 % de los pacientes presentó algún tipo de complicación intraoperatoria. La supervivencia a tres años en los tumores tipo II fue del 89,6 % y del 100 % en aquellos con respuesta patológica completa. Conclusión. Es necesario el uso de diferentes estrategias para un proceso diagnóstico adecuado en los tumores de la unión esofagogástrica. En esta serie, los pacientes Siewert II, aquellos que recibieron neoadyuvancia y los que obtuvieron una respuesta patológica completa, tuvieron una mejor supervivencia a tres años

Introduction: Proper diagnosis of gastroesophageal junction tumors is essential for the treatment of these patients. The classification proposed by Siewert-Stein defines its own characteristics, risk factors and surgical strategies according to the location. This study describes the characteristics of patients with adenocarcinoma of the esophagogastric junction treated at our institution. Methods. Retrospective, descriptive, longitudinal study, which includes patients diagnosed with adenocarcinoma of the esophagogastric junction who underwent surgery at the National Cancer Institute in Bogotá, Colombia, between January 2012 and May 2017. Results. Fifty-nine patients (84.7% men) were operated on, with a mean age of 62.5 years. In their order of frequency, the tumors were type II (57.6%), type III (30.7%) and type I (11.9%). 74.6% received neoadjuvant therapy and total gastrectomy was performed in 73% of the cases. The moderate diagnostic concordance with the Kappa index was 0.56, differing from the endoscopic one in 33.9%. 10.2% of the patients presented some type of intraoperative complication. Three-year survival in type II tumors was 89.6% and 100% in those with complete pathologic response. Conclusion. The use of different strategies is necessary for an adequate diagnostic process in tumors of the esophagogastric junction. In this series, Siewert II patients, those who received neoadjuvant therapy, and those who obtained a complete pathological response had a better three-year survival

Does neoadjuvant chemoradiotherapy for esophageal and gastroesophageal junction cancer patients affect postoperative outcomes? a study using the becker tumor regression grade system and lymph node regression / A radioterapia e quimioterapia neoadjuvantes para pacientes com câncer de esôfago e junção gastro-esofágica afetam os resultados pós-operatórios? um estudo usando o sistema de regressão tumoral de becker e regressão de linfonodos

ABSTRACT BACKGROUND: The effect of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal cancer can be determined by assessing the Becker tumor regression grade in the primary tumor, as well as in lymph nodes. AIMS: The aim of this study was to investigate the anatomopathological changes caused by neoadjuvant chemoradiotherapy and their impact on clinical parameters. Specifically, we analyzed the Becker tumor regression grade, lymph node status, and regression changes and evaluated their association with the Clavien-Dindo classification of surgical complications and overall patient survival. METHODS: This is a retrospective and observational study including 139 patients diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus and treated with either neoadjuvant chemoradiotherapy followed by surgery or surgery alone. For the 94 patients who underwent neoadjuvant chemoradiotherapy, we evaluated tumor regression by Becker tumor regression grade in primary tumors. We also analyzed lymph node status and regression changes on lymph nodes with or without metastases. Overall survival analysis was performed using Kaplan-Meier curves. RESULTS: Becker tumor regression grade is associated with lower lymphatic permeation (p<0.01) and vascular invasion (p<0.001), but not with lymph node regression rate (p=0.10). Clavien-Dindo classification was associated neither with lymph node regression rate (odds ratio=0.784, p=0.795) nor with tumor regression grade (p=0.68). Patients who presented with lymphatic permeation and vascular invasion had statistically significantly lower median survival (17 vs. 30 months, p=0.006 for lymphatic permeation, and 14 vs. 29 months, p=0.024 for vascular invasion). CONCLUSION: In our series, we were unable to demonstrate an association between Becker tumor regression grade and lymph node regression rate with any postoperative complications. Patients with lower lymphatic permeation and vascular invasion have higher overall survival, correlating with a better response in the Becker tumor regression grade system.

RESUMO RACIONAL: O efeito da quimioradioterapia neoadjuvante em pacientes com câncer de esôfago localmente avançado pode ser determinado pela avaliação do grau de regressão tumoral de Becker no tumor primário, bem como nos linfonodos. OBJETIVOS: Investigar as alterações anatomopatológicas causadas pela quimioradioterapia neoadjuvante e seu impacto nos parâmetros clínicos. Especificamente, analisamos o grau de regressão tumoral de Becker, o status linfonodal e as alterações de regressão e avaliamos sua associação com a Classificação Clavien-Dindo de complicações cirúrgicas e a sobrevida geral dos pacientes. MÉTODOS: Estudo retrospectivo e observacional incluindo 139 pacientes diagnosticados com carcinoma espinocelular de esôfago ou adenocarcinoma da junção esofagogástrica, tratados com quimioradioterapia neoadjuvante seguido de cirurgia ou cirurgia isolada. Para os 94 pacientes submetidos a quimioradioterapia neoadjuvante, avaliamos a grau de regressão tumoral de Becker em tumores primários. Também analisamos o status linfonodal e as alterações de regressão em linfonodos com ou sem metástases. A análise de sobrevida global foi realizada usando curvas de Kaplan-Meier. RESULTADOS: O grau de regressão tumoral de Becker está associado a menor permeação linfática (p<0,01) e invasão vascular (p<0,001), mas não à taxa de regressão linfonodal (p=0,10). A classificação de Clavien-Dindo não foi associada à taxa de regressão linfonodal (OR=0,784; p=0,795) nem ao grau de grau de regressão tumoral (p=0,68). Os pacientes que apresentavam permeação linfática e invasão vascular tiveram sobrevida mediana menor estatisticamente significativa (17 vs 30 meses; p=0,006 para a permeação linfátiva e 14 vs 29 meses; p=0,024, para a invasão vascular, respectivamente). CONCLUSÕES: Em nossa série não conseguimos demonstrar associação entre grau de regressão tumoral de Becker e taxa de regressão linfonodal com quaisquer complicações pós-operatórias. Pacientes com menor permeação linfática e invasão vascular apresentam maior sobrevida global, correlacionando-se com uma melhor resposta no sistema Becker.

Early postoperative outcomes of the esophagectomy minimally invasive in esophageal cancer / Resultados pós-operatórios precoces da esofagectomia minimamente invasiva no câncer do esôfago

ABSTRACT BACKGROUND: The incidence of esophageal cancer is high in some regions and the surgical treatment requires reference centers, with high volume, to make surgery feasible. AIMS: To evaluate patients undergoing minimally invasive esophagectomy by thoracoscopy in prone position for the treatment of esophageal cancer and to recognize the experience acquired over time in our service after the introduction of this technique. METHODS: From January 2012 to August 2021, all patients who underwent the minimally invasive esophagectomy for esophageal cancer were retrospectively analyzed. In order to assess the factors associated with the predefined outcomes as fistula, pneumonia, and intrahospital death, we performed univariate and multivariate logistic regression analyses, accounting for age as an important factor. RESULTS: Sixty-six patients were studied, with mean age of 59.5 years. The main histological type was squamous cell carcinoma (81.8%). The incidence of postoperative pneumonia and fistula was 38% and 33.3%, respectively. Eight patients died during this period. The patient's age, T and N stages, the year the procedure was performed, and postoperative pneumonia development were factors that influenced postoperative death. There was a 24% reduction in the chance of mortality each year, associated with the learning curve of our service. CONCLUSIONS: The present study presented the importance of the team's experience and the concentration of the treatment of patients with esophageal cancer in reference centers, allowing to significantly improve the postoperative outcomes.

RESUMO RACIONAL: A incidência do câncer de esôfago é elevada em algumas regiões e o tratamento cirúrgico requer centros de referência com alto volume para viabilizar a cirurgia. OBJETIVOS: Avaliar os pacientes submetidos à esofagectomia minimamente invasiva, por toracoscopia na posição prona, para o tratamento do câncer de esôfago e conhecer a experiência adquirida ao longo do tempo em nosso serviço após a introdução desta técnica. MÉTODOS: De janeiro de 2012 a agosto de 2021, foram analisados retrospectivamente todos os pacientes submetidos à esofagectomia minimamente invasiva para câncer de esôfago. Para avaliar os fatores associados aos desfechos predefinidos de fístula, pneumonia e óbito intra-hospitalar, realizamos análises de regressão logística univariada e multivariada considerando a idade como fator importante. RESULTADOS: Foram estudados 66 pacientes, com idade média de 59,5 anos. O tipo histológico mais frequente foi carcinoma espinocelular (81,8%). A incidência de pneumonia pós-operatória e fístula foi de 38% e 33,3%, respectivamente. Oito pacientes morreram durante este período. A idade do paciente, os estágios T e N, o ano da realização do procedimento e o desenvolvimento de pneumonia pós-operatória foram fatores que influenciaram o óbito. Houve uma redução de 24% na chance de mortalidade, ano a ano, associada à curva de aprendizado do nosso serviço. CONCLUSÕES: O presente estudo mostrou a importância da experiência da equipe e da concentração do tratamento de pacientes com câncer de esôfago em centros de referência, possibilitando melhorar significativamente o resultado pós-operatório.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Distribution features of resident CD8 + T cells in human esophageal cancer tissues and its effects on the prognosis / 中华消化杂志

Objective:To explore the distribution features of resident CD8 + T cells infiltration in human esophageal cancer tissues and its clinical significance. Methods:Data from the Cancer Genome Atlas database were retrieved, the correlation between CD103 + CD8 + T cells and infiltration degree of conventional type 1 dendritic cell (cDC1), conventional type 2 dendritic cell (cDC2), type 3 dendritic cell(DC3) was investigated. From January 2006 to December 2008, 78 esophageal cancer tissues and 75 adjacent normal tissues from 78 esophageal cancer patients were collected by Shanghai Outdo Biotechnology Co., Ltd, the clinical data of patients was followed up by telephone until July 2015. The distribution of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues was detected by multi-color labeling techniques and multispectral tissue imaging. The differences of the number and the ratio of CD8 + T cells and CD103 + CD8 + T cells in cancer tissues and adjacent normal tissues were compared. The Kaplan-Meier survival curves of patients with tissue infiltration of CD8 + T cells and CD103 + CD8 + T cells at different levels were drawn through the R language " survminer" package, and the best cut-off value was obtained. TNM stage, pathological stage and other clinical parameters of patients with high and low infiltration of CD8 + T cells, CD103 + CD8 + T cells were compared. Wilcoxon rank sum test, chi-square test, log-rank test and Cox proportional risk regression model statistical analysis were used to evaluate the prognostic value of the above indicators. Spearman correlation analysis was used for correlation analysis. Results:In the cancer tissues of patients with esophageal cancer, the infiltration degree of CD103 + CD8 + T cells was positively correlated with the infiltration degree of cDC1 cells, cDC2 cells and DC3 cells ( r=0.67, 0.53 and 0.47, all P<0.001). The percentage of CD8 + T cells in all cells in the whole tissue core of tumor tissues (63.09% (42.14%, 76.21%)) was higher than that of adjacent normal tissues (2.56% (1.68%, 5.38%)), and the difference was statistically significant ( U=41.00, P<0.001). The proportion of CD103 + CD8 + T cells in all cells in the whole tissue core of tumor tissues (7.92% (1.60%, 20.61%)) was higher than that of adjacent normal tissues (0.04% (0.01%, 0.10%)), and the difference was statistically significant ( U=857.50, P<0.001). The percentage of high CD8 + T cells infiltration in esophageal cancer tissues of patients with pathological stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (57.9%, 33/57 vs. 85.7%, 18/21); the percentage of high CD103 + CD8 + T cells in CD8 + T cells in esophageal cancer tissues of patients with TNM stage Ⅰ+ Ⅱ was lower than that of patients with stage Ⅲ+ Ⅳ (21.6%, 8/37 vs. 48.8%, 20/41), and the differences were both statistically significant ( χ2=5.25 and 6.23, P=0.022 and 0.013). The results of Kaplan-Meier survival analysis and univariate Cox proportional risk regression model showed that the overall survival (OS) of patients with high CD8 + T cell infiltration was longer than that of patients with low CD8 + T cell infiltration ( HR=0.57, 95% confidence interval (95% CI) 0.34 to 0.96, P=0.034). There was no significant difference in OS between patients with high CD103 + CD8 + T cell infiltration and patients with low CD103 + CD8 + T cell infiltration ( HR=0.66, 95% CI 0.40 to 1.08, P>0.05). Conclusion:The high infiltration of CD103 + CD8 + T cells in esophageal cancer tissues are expected to be used as a prognostic predictor for patients with esophageal cancer, which is an important component of anti-tumor immune response in tumor microenvironment of esophageal cancer.

Effects of circ_0063865 silencing on the malignant phenotype of esophageal squamous cell carcinoma / 中华老年医学杂志

Objective:To investigate the expression of circ_0063865 in esophageal squamous cell carcinoma(ESCC)tissues and cells and its effect on the biological properties of the cells.Methods:The loop structure and stability of circ_0063865 were identified by Sanger sequencing, back-to-back primer validation and the ribonuclease R(Rnase R)tolerance assay.The expression of circ_0063865 was detected by RNA fluorescence in situ hybridization in an ESCC tissue microarray and its clinical relevance was analyzed.The expression levels of circ_0063865 in a normal esophageal epithelial cell line and ESCC cell lines were measured by real-time quantitative polymerase chain reaction(RT-qPCR). Cell counting Kit-8, the colony formation assay, the scratch assay, the transwell invasion assay and flow cytometry were used to detect the effects of circ_0063865 on cell proliferation, migration, invasion abilities and apoptosis, respectively.Results:The loop formation of circ_0063865 was verified by Sanger sequencing, back-to-back primer and Rnase R tolerance assays.The results of RNA fluorescence in situ hybridization showed that the mean fluorescence intensity of circ_0063865 expressed in ESCC tissues was significantly higher than in its paired paracancerous normal tissues( t=2.267, P<0.05). The expression of circ_0063865 was significantly associated with lymph node metastasis( χ2=4.356, P<0.05). The average overall survival time of patients with high circ_0063865 expression ESCC was lower than that of patients with low circ_0063865 expression ESCC.RT-qPCR results demonstrated that, compared with HEEC, circ_0063865 expression was elevated in ESCC cell lines( F=18.413, P<0.05). In addition, after circ_0063865 knockdown, the proliferation, migration and invasion abilities of KYSE-30 and KYSE-150 cells were significantly decreased, and the level of apoptosis was significantly increased(both P<0.05). Conclusions:The expression of circ_0063865 in ESCC is high, and changes in its expression are significantly correlated with lymph node metastasis.Additionally, circ_0063865 can promote the proliferation, migration and invasion of ESCC cells.

Effects of niraparib on the radiosensitivity of human esophageal cancer cells and its mechanism / 中华放射肿瘤学杂志

Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.

Prognostic value of pre-treatment prognostic nutrition index in patients with cervical and thoracic upper esophageal squamous cell carcinoma and radiation induced esophagitis / 中华放射肿瘤学杂志

Objective:To investigate the prognostic value of Onodera's prognostic nutrition index (PNI) before treatment in patients with cervical and upper thoracic esophageal squamous cell carcinoma (CUTESCC) undergoing definitive chemoradiotherapy (dCRT) and its predictive value in the occurrence of ≥ grade 2 radiation esophagitis (RE).Methods:The data of 163 CUTESCC patients eligible for inclusion criteria admitted to the Fourth Hospital of Hebei Medical University from January 2012 to December 2017 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to calculate the best cut-off value of PNI for predicting the prognosis of patients. The prognosis of patients was analyzed by univariate and Cox multivariate analyses. Logistics binary regression model was adopted to analyze the risk factors of ≥ grade 2 RE in univariate and multivariate analyses. The significant factors in logistic multivariate analysis were used to construct nomogram for predicting ≥ grade 2 RE.Results:The optimal cut-off value of PNI was 48.57 [area under the curve (AUC): 0.653, P<0.001]. The median overall survival (OS) and progression-free survival (PFS) were 26.1 and 19.4 months, respectively. The OS ( χ2=6.900, P=0.009) and PFS ( χ2=9.902, P=0.003) of patients in the PNI ≥ 48.57 group ( n=47) were significantly better than those in the PNI < 48.57 group ( n=116). Cox multivariate analysis showed that cTNM stage and PNI were the independent predictors of OS ( HR=1.513, 95% CI: 1.193-1.920, P=0.001; HR=1.807, 95% CI: 1.164-2.807, P=0.008) and PFS ( HR=1.595, 95% CI: 1.247-2.039, P<0.001; HR=2.260, 95% CI: 1.439-3.550, P<0.001). Short-term efficacy was another independent index affecting PFS ( HR=2.072, 95% CI: 1.072-4.003, P=0.030). Logistic multivariate analysis showed that the maximum transverse diameter of the lesion ( OR=3.026, 95% CI: 1.266-7.229, P=0.013), gross tumor volume (GTV) ( OR=3.456, 95% CI: 1.373-8.699, P=0.008), prescription dose ( OR=3.124, 95% CI: 1.346-7.246, P=0.009) and PNI ( OR=2.072, 95% CI: 1.072-4.003, P=0.030) were the independent factors affecting the occurrence of ≥ grade 2 RE. These four indicators were included in the nomogram model, and ROC curve analysis showed that the model could properly predict the occurrence of ≥ grade 2 RE (AUC=0.686, 95% CI: 0.585-0.787). The calibration curve indicated that the actually observed values were in good agreement with the predicted RE. Decision curve analysis (DCA) demonstrated satisfactory nomogram positive net returns in most threshold probabilities. Conclusions:PNI before treatment is an independent prognostic factor for patients with CUTESCC who received definitive chemoradiotherapy. The maximum transverse diameter of the lesion, GTV, prescription dose and PNI are the risk factors for ≥ grade 2 RE in this cohort. Establishing a prediction model including these factors has greater predictive value.

Radiotherapy strategy for advanced esophageal cancer / 中华放射肿瘤学杂志

Advanced esophageal cancer accounts for a large proportion of all esophageal cancer cases, and the treatment modality recommended by the current guidelines is systemic treatment. Radiotherapy is an important treatment option for malignant tumors, which is widely applied in clinical practice. Retrospective analysis and small-sample prospective studies have shown that combination of radiotherapy with chemotherapy, targeted therapy, and immunotherapy has the advantages of improving disease control rate, symptom remission rate and prolonging survival of advanced esophageal cancer patients. Therefore, it is an important clinical topic issue to make better use of the advantages of radiotherapy for esophageal cancer, such as rapid relief of symptoms, durable efficacy, and stimulation of immune neoantigens, etc. To optimize the treatment strategy of advanced esophageal cancer, the radiotherapy strategy for esophageal cancer with oligometastases or multiple metastases, and the screening method for the eligible population for radiotherapy were reviewed, aiming to provide reference for improving the status of radiotherapy in comprehensive treatment of advanced esophageal cancer.

Research progress on neoadjuvant immunotherapy for esophageal cancer / 中华放射肿瘤学杂志

Neoadjuvant therapy, especially neoadjuvant chemoradiotherapy, has become the standard preoperative treatment for locally advanced resectable esophageal cancer, whereas the recurrence and distant metastasis rates after surgery remain high. In recent years, programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors have been widely adopted in immunotherapy for cancer. Whether PD-1/PD-L1 immune checkpoint inhibitors combined with neoadjuvant chemotherapy / neoadjuvant chemoradiotherapy could further improve clinical efficacy, increase the complete surgical resection rate and safety are current research hotspots. In this article, neoadjuvant immunotherapy combined with chemotherapy / radiochemotherapy for esophageal cancer was reviewed.

Prediction model of radiation pneumonitis after chemoradiotherapy for esophageal cancer based on dosiomics / 中华放射肿瘤学杂志

Objective:To study the risk factors and prediction model of radiation pneumonitis (RP) after radical chemoradiotherapy for locally advanced esophageal cancer based on dosiomics.Methods:Clinical data of 105 patients with esophageal cancer undergoing radical chemoradiotherapy at Zhejiang Cancer Hospital between January 2020 and August 2021 were retrospectively analyzed. RP was scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Clinical factors, traditional dosimetric features and dosiomics features were collected, respectively. The features for predicting PR were analyzed by limma package. Support vector machine, k-nearest neighbor, decision tree, random forest and extreme gradient boosting were used to establish the prediction model, and the ten-fold cross-validation method was employed to evaluate the performance of the model. The differences of this model when different features were chosen were analyzed by delong test.Results:The incidence of RP in the whole group was 21.9%. One clinical factor, 6 traditional dosimetric features and 42 dosiomics features were significantly correlated with the occurrence of RP (all P<0.05). Support vector machine using linear kernel function yielded the optimal prediction performance, and the area under the receiver operating characteristic (ROC) without and with dosiomics features was 0.72 and 0.75, respectively. The models established by support vector machine, random forest and extreme gradient boosting were significantly different with and without dosiomics features (all P<0.05). Conclusion:The addition of dosiomics features can effectively improve the performance of the prediction model of RP after radiotherapy for esophageal cancer.

Feasibility study of automatic uARC planning for esophageal cancer using simultaneous integrated boost radiotherapy / 中华放射肿瘤学杂志

Objective:To compare dosimetric and radiobiological parameters between automatic and manual uARC plans in the treatment of esophageal cancer patients, aiming to provide reference for clinical application.Methods:High-quality uARC plans of 100 patients with esophageal cancer were selected, and the mean values of the dosimetric parameters in the target area and organs at risk (OAR) were counted, and the goal table of uRT-TPOIS intelligent plan was established. Automatic and manual uARC plans were generated with UIH (United Imaging) treatment planning system (TPS) for 21 esophageal cancer patients. The differences in mean dose (D mean), approximate minimum (D 98%) and maximum (D 2%) dose of planning target volume (PTV), homogeneity index (HI) and conformity index (CI), dose of OAR, mean planning time, monitor unit (MU), tumor control probability (TCP) and normal tissue complication probability (NTCP) were compared between automatic and manual uARC plans. Normally distributed data between two groups were compared by paired t-test, and non-normally distributed data were assessed by nonparametric Wilcoxon test. Results:The D 98% (PTV 60 Gy: P<0.001, PTV 54 Gy: P=0.001) , CI (PTV 60 Gy: P<0.001, PTV 54 Gy: P=0.002) and target volume of area covered by prescription dose (V 54 Gy: P<0.001) of the automatic uARC plans were better than those of manual uARC plans (all P<0.05). There was no significant difference in D mean or HI between the two plans [PTV 54 Gy (59.32±1.87) Gy vs. (59.13±1.64) Gy, (0.19±0.02) vs. (0.18±0.02), all P>0.05]. The D mean and D max of spinal cord of the automatic plan were better than those of the manual plan [(13.22±4.27) Gy vs. (13.75±4.44) Gy, P=0.020 and (36.99±1.67) Gy vs. (38.14±1.31) Gy, P=0.011]. There was no significant difference in the mean dose of V 20 Gy of the lung between two plans ( P>0.05), whereas the mean doses of V 5 Gy and V 10 Gy of the lung of the manual plan were less than those of the automatic plan ( both P<0. 001). Automatic uARC plan had a significantly shorter mean planning time than manual uARC plan [(11.79±1.71) min vs. (53.36±8.23) min, P<0.001]. MU did not significantly differ between two plans [(762.84±74.83) MU vs. (767.41±80.63) MU, P>0.05]. The TCP of the automatic plan was higher than that of the manual plan (PTV 60 Gy 89.15%±0.49% vs. 86.75%±6.46%, P=0.004 and PTV 54 Gy 79.79%±3.48% vs. 77.51%±5.04%, P=0.006). However, manual plan had a lower NTCP of the lung than automatic uARC plan (0.46%±0.40% vs. 0.35%±0.32%, P<0.001). There was no significant difference in NTCP of heart and spinal cord between two plans (all P>0.05). Conclusion:It is feasible to generate automatic uARC plan with uRT-TPOIS TPS for esophageal cancer patients, which can increase the target CI and shorten the plan design time.

Preliminary analysis of immunotherapy combined with second-line treatment for esophageal squamous cell carcinoma patients / 中华放射肿瘤学杂志

Objective:To investigate the efficacy of camrelizumab combined with second-line therapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the real-world settings.Methods:Clinical data of 48 patients with esophageal cancer who met the inclusion criteria were retrospectively analyzed. The types of failure after first-line treatment, clinical efficacy, side effects and prognostic factors of second-line treatment were analyzed. SPSS 25.0 software was used for statistical analysis. Count data were expressed by composition ratio and analyzed by Chi-square test or Fisher's exact test. Survival analysis was conducted by Kaplan-Meier curve and log-rank test. Non-normally distributed data were recorded with the median, range and quartile. Results:There were 26, 14, and 4 cases of combined chemoradiotherapy, chemotherapy and radiotherapy in the treatment of second-line camrelizumab, and 4 cases received immunotherapy alone. The median duration of immunotherapy was 6 cycles (range, 2-39 cycles). After second-line treatment, the short-term efficacy of 17, 27 and 4 cases was partial remission (PR), stable disease (SD) and progressive disease (PD), respectively. The overall response rate (ORR) was 35.4% and disease control rate (DCR) was 91.7%. The 1- and 2-year OS rates were 42.9% and 22.5%, and 1- and 2-year PFS rates were 29.0% and 5.8%. The median OS and PFS were 9.0 months (95% CI=6.4-11.7) and 8.5 months (95% CI=1.5-5.6), respectively. Multivariate analysis showed that combined immunotherapy mode, number of cycles of immunotherapy and short-term efficacy were the independent prognostic indicators affecting OS in this group of patients ( HR=2.598, 0.222, 8.330, P=0.044, <0.001, <0.001). Lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), combined immunotherapy mode and short-term efficacy were the independent prognostic indicators affecting PFS in this group ( HR=3.704, 3.598, 6.855, 2.159, 2.747, P=0.009, 0.008, <0.001, 0.049, 0.012). Conclusions:Camrelizumab combined with second-line therapy can bring survival benefit to patients with recurrent or metastatic ESCC after first-line therapy, especially immunotherapy combined with chemoradiotherapy can significantly provide survival benefit. Peripheral blood inflammatory biomarkers are independent indicators affecting clinical prognosis of patients. Patients with better short-term efficacy also achieve better prognosis. The final conclusion remains to be validated by a large number of randomized controlled studies.

Advances and the status of radiotherapy in advanced esophageal cancer / 中华放射肿瘤学杂志

Radiotherapy plays an important role in the treatment of advanced esophageal cancer. Under the premise of effective systemic treatment, selecting patients who may benefit from local radiotherapy can effectively relieve symptoms and improve quality of life, and it is expected to prolong the survival time of patients. Moreover, immunotherapy plays an increasingly significant role in advanced esophageal cancer, and the efficacy of radiotherapy combined with immunotherapy is promising.

Involved-field irradiation and elective nodal irradiation for esophageal squamous cell carcinoma: a systematic review and meta-analysis / 中华放射肿瘤学杂志

Objective:To analyze whether involved-field irradiation (IFI) was associated with improved survival and reduced treatment-related adverse events compared with elective nodal irradiation (ENI) in Chinese patients with esophageal squamous cell carcinoma receiving radiotherapy.Methods:Literature review was conducted from CNKI, Wanfang Data, PubMed, Embase, Web of Science and Cochrane Central databases (until July 31, 2022). Relevant data were collected according to the inclusion and exclusion criteria. Primary outcomes included overall survival (OS) rate and treatment-related adverse events. Secondary outcomes included progression-free survival (PFS) rate and local control rate (LCR). Risk of bias was assessed using the Cochrane Risk of Bias tool. The quality of the results was assessed by using the meta analysis of Evidence Evaluation and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methods.Results:A total of 7 articles with 918 patients were included of which 465 received IFI and 453 received ENI. The 1-, 2-, 3-and 5-year OS rates in the IFI group were not significantly different from those in the ENI group (1-year OS rate: RR=1.00, 95% CI=0.94-1.07, P=0.97, high certainty; 2-year OS rate: RR=1.01, 95% CI=0.90-1.13, P=0.90, high certainty; 3-year OS rate: RR=0.86, 95% CI=0.71-1.05, P=0.14, high certainty; 5-year OS rate: RR=0.76, 95% CI=0.42-1.37, P=0.36, low certainty). In the IFI group, patients with ≥grade 2 acute radiation esophagitis ( RR=0.71, 95% CI=0.58-0.87, P=0.001, high certainty), ≥grade 3 acute radiation esophagitis ( RR=0.39, 95% CI=0.24-0.64, P<0.001, high certainty) and ≥grade 2 acute radiation pneumonitis ( RR=0.72, 95% CI=0.52-0.99, P=0.04, high certainty) were significantly lower compared with those in the ENI group. However, no significant differences were observed in the incidence of ≥grade 3 late radiation esophagitis, ≥grade 3 acute radiation pneumonitis and ≥grade 3 late radiation pneumonitis between two groups. No significant differences were noted in the 1-, 2-, 3-PFS rates and LCR between two groups. Conclusions:For Chinese patients with esophageal squamous cell carcinoma, IFI and ENI yield similar efficacy in terms of OS, PFS and LCR. However, IFI has a lower incidence of ≥grade 2 acute radiation esophagitis, ≥grade 3 acute radiation esophagitis and ≥grade 2 acute radiation pneumonitis than ENI.

Efficacy of chemoradiotherapy versus surgery in cervical esophageal cancer: a population-based competing risk analysis / 中华放射肿瘤学杂志

Objective:To evaluate the value of chemoradiotherapy and surgery in cervical esophageal cancer (CEC).Methods:Data of 459 patients with CEC from 2004 to 2017 were collected and retrospectively analyzed from the surveillance, epidemiology, and end results (SEER) database of National Cancer Institute (US). All patients were divided into the chemoradiotherapy group ( n=379) and surgery group ( n=80) according to the treatment methods. Survival analysis was performed by Kaplan-Meier method and survival curve was drawn. Multivariate survival analysis was conducted by Cox proportional hazards regression model. The death rate of different causes between two groups was calculated by cumulative incidence function (CIF). The differences of death rate between two groups were evaluated by Fine-Gray competing risk model. By analyzing the clinical characteristics and survival of CEC patients, the overall survival (OS) was compared between the surgery and chemoradiotherapy groups. Results:The 2- and 5-year survival rates in the chemoradiotherapy group were 43.1% and 22.4%, while those of the surgical group were 46.8% and 26.0%, respectively. No significant difference was observed in the OS between the chemoradiotherapy and surgery groups ( P=0.750). Cox multivariate analysis showed that treatment (surgery group vs. chemoradiotherapy group) was not an independent prognostic factor for OS. Based on the results of competing risk analysis, the risk of esophageal cancer-specific death in the chemoradiotherapy group was higher than that in the surgery group, and the difference was statistically significant between two groups ( P<0.001). The risk of other cause-specific death in the chemoradiotherapy group was lower than that in the surgery group ( P<0.001). The proportion of patients who died of oral, oropharyngeal, hypopharyngeal and laryngeal diseases in the surgery group was significantly higher than that in the chemoradiotherapy group(all P<0.001). Conclusions:No significant difference is observed in the OS of CEC patients treated with chemoradiotherapy or surgery. In the surgery group, the risk of esophageal cancer-specific death is lower, whereas the risk of other cause-specific death is higher compared with those in the chemoradiotherapy group.

Research progress on the application of radiomics in prognostic prediction of esophageal cancer / 中华放射肿瘤学杂志

Esophageal cancer is a tumor with high morbidity and mortality in China, which is generally diagnosed at late stage and yields poor prognosis. Early diagnosis and correct staging are the basis, and reasonable treatment is the most important. Radiomics can make use of existing imaging resources for deeper mining, and make secondary use of its potential high-throughput data through deep learning or machine learning, thereby establishing a radiomics prediction model. This may become an essential marker of tumor prognosis to predict overall survival or tumor progression, thus stratifying patients at different risk for individualized treatment. In this article, the basic concepts of radiomics, its application in prognostic prediction of esophageal cancer and its combination with clinical and genetic studies were reviewed.

Failure mode and long-term survival after neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Pathological evaluation of 30 cases of esophageal squamous cell carcinoma after two neoadjuvant therapies / 中华放射肿瘤学杂志

Objective:To explore the pathological differences of surgically resected specimens of advanced esophageal squamous cell carcinoma (ESCC) to different neoadjuvant therapies (neoadjuvant radiochemotherapy and toripalimab combined with neoadjuvant radiochemotherapy).Methods:Thirty patients diagnosed with advanced ESCC who underwent surgical operation after neoadjuvant therapy in Jiangsu Cancer Hospital from October 2020 to September 2021 were included. Among them, 15 patients received neoadjuvant radiochemotherapy (radiochemotherapy group) and 15 patients were treated with toripalimab combined with radiochemotherapy (immunotherapy combined with radiochemotherapy group). Surgically resected specimens were collected. The histopathological features of primary esophageal lesions and the responses of involved lymph nodes were analyzed and compared between two groups.Results:The major pathological response (MPR) rate in the radiochemotherapy group was 10/15, and 14/15 in the immunotherapy combined with radiochemotherapy group ( P=0.17). The pathological complete response (pCR) rate of the primary lesions in the radiochemotherapy group was 7/15, and 10/15 in the immunotherapy combined with radiochemotherapy group ( P=0.46). In the radiochemotherapy group, the incidence rate of tertiary lymphoid structure (TLS) was 7/15, and 12/15 in the immunotherapy combined with radiochemotherapy group ( P=0.02). The incidence rate of necrosis in the radiochemotherapy group was 6/15, and 1/15 in the immunotherapy combined with radiochemotherapy group ( P=0.03). In addition, the incidence rate of foam cell infiltration in the radiochemotherapy group was 6/15, and 13/15 in the immunotherapy combined with radiochemotherapy group ( P=0.01). Furthermore, the pCR rate of involved lymph nodes in the radiochemotherapy group was 7/33, and 11/12 in the immunotherapy combined with radiochemotherapy group ( P<0.001). Conclusion:Compared with the radiochemotherapy group, the incidence of TLS and foam cell infiltration is higher, the incidence of necrosis is lower and clinical efficacy of involved lymph nodes is higher in the immunotherapy combined with radiochemotherapy group, prompting that toripalimab combined with neoadjuvant radiochemotherapy exert higher synergistic immune effect.