The predictors of lymphopenia and its effects on survival in locally advanced esophageal squamous cell carcinoma.

To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (r= -0.389, p < .001) and GTV (r= -0.211, p < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group (p = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm3 group (p = .242) and GTV ≤ 68.8 cm3 group(p = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.

CircRNA_101491 regulated the radiation sensitivity of esophageal squamous cell carcinomas via sponging miR-125a-5p.

BACKGROUND: At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism. METHODS: We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo. RESULTS: According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC. CONCLUSION: In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma.

We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.

Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II clinical trial.

OBJECTIVE: To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). METHODS: Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. RESULTS: (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4-5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. CONCLUSIONS: The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).

Kinetics of plasma cell-free DNA as a prospective biomarker to predict the prognosis and radiotherapy effect of esophageal cancer.

PURPOSE: The lack of reliable biomarkers for the prognosis and radiotherapy efficacy in esophageal cancer (EC) necessitates further research. The aim of our study was to investigate the predictive utility of plasma cell-free DNA (cfDNA) kinetics in patients with EC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and cfDNA levels (pre-radiotherapy [pre-RT] and post-radiotherapy [post-RT]) and the cfDNA kinetics (cfDNA ratio: post-RT cfDNA/pre-RT cfDNA) of 88 patients. We employed Kaplan-Meier curves to examine the relationship between cfDNA and overall survival (OS) as well as progression-free survival (PFS). Univariate and multivariate Cox regression analyses were executed to ascertain the independent risk factors in EC. RESULTS: The pre-RT cfDNA levels were positively correlated with clinical stage (P=0.001). The pre-RT cfDNA levels (cutoff value=16.915ng/mL), but not the post-RT cfDNA levels, were linked to a diminished OS (P<0.001) and PFS (P=0.0137). CfDNA kinetics (cutoff value=0.883) were positively associated with OS (P=0.0326) and PFS (P=0.0020). Notably, we identified independent risk factors for OS in EC treated with RT, including cfDNA ratio (high/low) (HR=0.447 [0.221-0.914] P=0.025), ECOG (0/1/2) (HR=0.501 [0.285-0.880] p=0.016), and histological type (esophagal squamous cell carcinoma [ESCC]/non-ESCC) (HR=3.973 [1.074-14.692] P=0.039). CONCLUSION: Plasma cfDNA kinetics is associated with prognosis and radiotherapy effect in EC undergoing RT, suggesting potential clinical application of a cheap and simple blood-based test.

Expression of Glutathione Peroxidase4 in Patients with Esophageal Squamous Carcinoma and Its Impact on the Radiosensitivity of Esophageal Squamous Carcinoma.

OBJECTIVE: Glutathione peroxidase-4 (GPX4) is a member of Ferroptosis and lipid circulation. This study aims to investigate the expression of GPX4 in esophageal squamous cell carcinoma and its impact on radiosensitivity. METHOD: Immunohistochemistry staining was used to detect GPX4 expression in 180 samples of ESCC tissues and adjacent tissues. We analyzed the relationship between GPX4 expression and ESCC clinical parameters. In vitro experiments were conducted using apoptosis assays and colony formation assays to investigate the effect of GPX4 on the radiosensitivity of ESCC cells. In vivo experiments were carried out using a nude mouse xenograft model to evaluate the impact of GPX4 on the radiosensitivity of ESCC. RESULTS: GPX4 expression was lower in adjacent tissues than tumor tissues. The expression of GPX4 was significantly associated with the pathological grade of ESCC. The overall survival time (OS) of ESCC patients with low GPX4 expression was significantly longer than that of patients with high GPX4 expression. GPX4 could be used as independent prognostic factors in patients with ESCC. In vivo experiments, silencing of GPX4 or using GPX4 inhibitors significantly inhibits the viability and colony formation of ESCC cells after radiation exposure while increasing intracellular reactive oxygen species (ROS) levels, and significantly suppresses the tumorigenic ability of ESCC cells in subcutaneous xenografts after radiation exposure. CONCLUSION: GPX4 is highly expressed in ESCC, which has the potential value for prognostic assessment of ESCC. Silencing or inhibiting GPX4 can enhance the radiosensitivity of ESCC.

Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Influence of radiotherapy interruption on esophageal cancer with intensity-modulated radiotherapy: a retrospective study.

BACKGROUND: Radiotherapy interruption (RTI) prolongs the overall total treatment time and leads to local control loss in many cancers, but it is unclear in esophageal cancer. We aimed to evaluate the influence of RTI on the overall survival (OS), progression-free survival (PFS), and local-regional recurrence-free survival (LRFS) of patients with esophageal cancer undergoing chemoradiotherapy. METHODS: A total of 299 patients with esophageal squamous cell carcinoma from 2017 to 2019 were retrospectively analyzed to investigate the effect of RTI on OS, PFS, and LRFS. The delayed time of radiotherapy interruption was calculated as the actual radiation treatment time minus the scheduled time. The univariate and multivariate analyses were performed by the COX proportional hazards regression models, and the survival analysis was performed through the Kaplan‒Meier method, and compared with the log-rank test. RESULTS: The 3-year OS, PFS, and LRFS rates were 53.0%, 42.0%, and 48.0%, respectively. The univariate and multivariate analyses showed that the delayed time > 3 days was an independent adverse prognostic factor for OS (HR = 1.68, 95% CI 1.10-2.55, p = 0.016), and LRFS (HR = 1.74, 95% CI 1.18-2.57, p = 0.006). The patient with a delayed time of > 3 days had poorer survival rates of OS, and LRFS than patients with a delayed time of ≤ 3 days (OS, p = 0.047; LRFS, p = 0.013), and the survival outcomes of patients with shorter delayed time (1-3 days) were slightly different from the patients without interruptions. The impact of delay time on PFS is not statistically significant, but the survival outcomes of the two groups were slightly different. CONCLUSION: There was a significant correlation between delayed time and local control of esophageal cancer. The delayed time for more than 3 days might decrease the survival outcome, and increase the local recurrence risk.

Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1.

BACKGROUND: While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure. METHODS: FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1. RESULTS: Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival. CONCLUSIONS: Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma.

BACKGROUND AND AIM: There has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. METHODS: A systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. RESULTS: Ninety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5-3.125Gy per fraction (total dose 50-60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6-88.0%. CONCLUSION: These data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. REGISTRATION DETAILS: PROSPERO; CRD42023457791.

Survival benefits of human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy: A retrospective cohort study.

The role of human papillomavirus 16 (HPV 16) in esophageal squamous cell carcinoma (ESCC) remains uncertain. Therefore, this study aimed to investigate the prevalence of HPV 16 in patients with ESCC and its impact on theirprognosis. HPV 16 was detected using FISH, and TP53 status was evaluated via immunohistochemistry. The factors influencing prognosis were ananalyzed using the Log-rank test and Cox regression analyses. Among 178 patients with ESCC, 105 and 73 patients were categorized into concurrent chemoradiotherapy (CCRT) and postoperative chemoradiotherapy (POCRT) cohorts, respectively. Among 178 patients, 87 (48.87%) tested positive for HPV 16. Log-rank tests revealed that the overall survival (OS) of patients with ESCC who were HPV 16-positive was longer than that of those who were HPV 16-negative (median OS: 57 months vs. 27 months, p < 0.01**). HPV 16 infection and TP53 mutation status were identified as independent events. The OS of patients with mutant TP53 who were HPV 16-positive was longer than that of those who were HPV 16-negative in both CCRT and POCRT cohorts (p = 0.002** for CCRT cohorts and p = 0.0023** for POCRT cohorts). Conversely, HPV 16 infection had no effect on OS in the wild-type TP53 subgroup (p = 0.13 and 0.052 for CCRT and POCRT cohorts, respectively). As a conclusion, the positive rate of HPV 16 in ESCC in this study was 48.87% (87/178). Among the patients with ESCC who had TP53 mutation, those who were HPV 16-positive exhibited a better prognosis than those who were HPV 16-negative.

HRU-Net: A high-resolution convolutional neural network for esophageal cancer radiotherapy target segmentation.

BACKGROUND AND OBJECTIVE: The effective segmentation of esophageal squamous carcinoma lesions in CT scans is significant for auxiliary diagnosis and treatment. However, accurate lesion segmentation is still a challenging task due to the irregular form of the esophagus and small size, the inconsistency of spatio-temporal structure, and low contrast of esophagus and its peripheral tissues in medical images. The objective of this study is to improve the segmentation effect of esophageal squamous cell carcinoma lesions. METHODS: It is critical for a segmentation network to effectively extract 3D discriminative features to distinguish esophageal cancers from some visually closed adjacent esophageal tissues and organs. In this work, an efficient HRU-Net architecture (High-Resolution U-Net) was exploited for esophageal cancer and esophageal carcinoma segmentation in CT slices. Based on the idea of localization first and segmentation later, the HRU-Net locates the esophageal region before segmentation. In addition, an Resolution Fusion Module (RFM) was designed to integrate the information of adjacent resolution feature maps to obtain strong semantic information, as well as preserve the high-resolution features. RESULTS: Compared with the other five typical methods, the devised HRU-Net is capable of generating superior segmentation results. CONCLUSIONS: Our proposed HRU-NET improves the accuracy of segmentation for squamous esophageal cancer. Compared to other models, our model performs the best. The designed method may improve the efficiency of clinical diagnosis of esophageal squamous cell carcinoma lesions.

The role of spleen radiomics model for predicting prognosis in esophageal squamous cell carcinoma patients receiving definitive radiotherapy.

BACKGROUND: The spleen plays an important role in systemic antitumor immune response, but whether spleen imaging features have predictive effect for prognosis and immune status was unknown. The aim of this study was to investigate computed tomography (CT)-based spleen radiomics to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC) underwent definitive radiotherapy (dRT) and to try to find its association with systemic immunity. METHODS: This retrospective study included 201 ESCC patients who received dRT. Patients were randomly divided into training (n = 142) and validation (n = 59) groups. The pre- and delta-radiomic features were extracted from enhanced CT images. LASSO-Cox regression was used to select the radiomics signatures most associated with progression-free survival (PFS) and overall survival (OS). Independent prognostic factors were identified by univariate and multivariate Cox analyses. The ROC curve and C-index were used to evaluate the predictive performance. Finally, the correlation between spleen radiomics and immune-related hematological parameters was analyzed by spearman correlation analysis. RESULTS: Independent prognostic factors involved TNM stage, treatment regimen, tumor location, pre- or delta-Rad-score. The AUC of the delta-radiomics combined model was better than other models in the training and validation groups in predicting PFS (0.829 and 0.875, respectively) and OS (0.857 and 0.835, respectively). Furthermore, some spleen delta-radiomic features are significantly correlated with delta-ALC (absolute lymphocyte count) and delta-NLR (neutrophil-to-lymphocyte ratio). CONCLUSIONS: Spleen radiomics is expected to be a useful noninvasive tool for predicting the prognosis and evaluating systemic immune status for ESCC patients underwent dRT.

Effects of intensity-modulated radiotherapy combined with chemotherapy and prognostic factors in patients with locally advanced oesophageal cancer.

PURPOSE: We explored the efficacy and influencing factors of chemoradiotherapy and radiotherapy alone in patients with locally advanced oesophageal squamous cell carcinoma. METHODS: We retrospectively analysed 226 locally advanced oesophageal squamous cell carcinoma patients who underwent chemoradiotherapy and radiotherapy alone. Univariate and multivariate Cox regression analyses were used to analyse the impact of relevant factors. The endpoint was overall survival and progression-free survival. RESULTS: Compared with the radiotherapy group, the chemoradiotherapy group had a significant difference in the overall survival rate and the progression-free survival rate between 3 and 5 years (both p â€‹< â€‹0.05). The incidences of radiation pneumonitis and radiation oesophagitis were analysed, and the differences were not significant (all p â€‹> â€‹0.05). The incidence of haematological toxicity in the chemoradiotherapy group was significantly higher than that in the radiotherapy group (p â€‹= â€‹0.001). There was a significant difference in the incidence of haematological toxicity between the ≤65 and the >65 age groups (p â€‹< â€‹0.05). Tumour location, T stage, tumour length, tumour target volume, and short-term curative effect were the main factors affecting the prognosis (all p â€‹< â€‹0.05). T stage, gross tumour volume, and short-term curative effect were all independent factors affecting the prognosis (all p â€‹< â€‹0.05). CONCLUSIONS: Patients with locally advanced oesophageal cancer who received intensity-modulated radiotherapy (IMRT) combined with chemotherapy had significant survival benefits compared with radiotherapy alone. Haematological toxicity was the main adverse reaction. T-stage, gross tumour volume and short-term curative effect were independent factors influencing the prognosis.

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.

Exosome-transported of circ_0081069 induces SPIN1 production by binding to miR-195-5p to inhibit radiosensitivity in esophageal squamous cell carcinoma.

Circ_0081069 plays a key role in tumor growth; however, its effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unknown. The study is performed to reveal the association of circ_0081069 expression and radiosensitivity in ESCC and the underlying mechanism. Circ_0081069, miR-195-5p, and spindlin 1 (SPIN1) RNA expression were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell viability, proliferation, cell apoptosis, migration, and invasion were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test, and transwell assays, respectively. The sensitivity of ESCC cells to radiation was investigated by cell colony formation assay. The interactions among circ_0081069, miR-195-5p, and SPIN1 were identified by dual-luciferase reporter assay and RNA Immunoprecipitation assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on radiosensitivity in vivo. Circ_0081069 and SPIN1 expression were upregulated, whereas miR-195-5p was downregulated in ESCC tissues, ESCC cells, and radiation-stimulated ESCC cells. Circ_0081069 silencing inhibited ESCC cell proliferation, invasion, and migration but improved cell apoptosis. In addition, circ_0081069 knockdown enhanced ESCC cell radiosensitivity in vitro and in vivo. Circ_0081069 bound to miR-195-5p and regulated radiosensitivity by binding to miR-195-5p in ESCC cells. Moreover, SPIN1, a target of miR-195-5p, rescued miR-195-5p-mediated effects in ESCC cells. Circ_0081069 was secreted from ESCC cells by being packaged into exosomes. Further, circ_0081069-Exo inhibited radiosensitivity in ESCC cells. Exosome-mediated transfer of circ_0081069 induced SPIN1 production by binding to miR-195-5p, further inhibiting radiosensitivity in ESCC.

A retrospective cohort study to observe the efficacy and safety of Endoscopic Submucosal Dissection (ESD) with adjuvant radiotherapy for T1a-MM/T1b-SM Esophageal Squamous Cell Carcinoma (ESCC).

BACKGROUND AND AIM: The clinical outcome of endoscopy submucosal dissection with subsequent radiotherapy for esophageal squamous cell carcinoma remain unclear. In this study we aim to investigate the efficacy and safety of endoscopic submucosal dissection with adjuvant radiotherapy in the treatment of superficial esophageal squamous cell carcinoma involving the muscularis mucosae (T1a-MM) or the submucosa < 200 µm (T1b-SM1). METHODS: We analyzed 20 patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell carcinoma treated by endoscopic submucosal dissection from 2016 to 2020 in Lihuili Hospital, 9 patients received adjuvant radiotherapy (RT group) and 11 patients received did not (non-RT group). RESULTS: All 20 patients underwent en bloc resection, and both the vertical and horizontal margins were negative. There was no recurrence or lymph node metastasis in the RT group, and no serious complications or death were observed. In the non-RT group, 2 patients had local recurrence and 1 had distant metastasis. None of the 20 patients died of esophageal carcinoma. CONCLUSIONS: Adjuvant radiotherapy following endoscopic submucosal dissection may be a safe and effective method for the treatment of T1a-MM/T1b-SM1 superficial esophageal squamous cell carcinoma.

Nuclear factor erythroid 2-related factor 2 promotes radioresistance by regulating glutamate-cysteine ligase modifier subunit and its unique immunoinvasive pattern.

The enzyme glutamate-cysteine ligase modifier subunit (GCLM) serves as the initial rate-limiting factor in glutathione (GSH) synthesis. GSH is the preferred substrate for glutathione peroxidase 4 (GPX4), directly impacting its activity and stability. This study aims to elucidate the expression of GCLM and its correlation with the nuclear factor erythroid 2-related factor 2 (NFE2L2), commonly referred to as NRF2, in esophageal squamous cell carcinoma (ESCC) and further investigate the potential signaling axis of radiotherapy resistance caused by NRF2-mediated regulation of ferroptosis in ESCC. The expression of NRF2, GCLM, and GPX4 in ESCC was analyzed by bioinformatics, and their relationship with ferroptosis was verified through cell function experiments. Their role in radioresistance was then investigated through multiple validation steps. Bioinformatics analysis was employed to determine the immune infiltration pattern of NRF2 in ESCC. Furthermore, the effect of NRF2-mediated massive macrophage M2 infiltration on radiotherapy and ferroptosis was validated through in vivo experiments. In vitro assays demonstrated that overactivated NRF2 promotes radioresistance by directly binding to the promoter region of GCLM. The Tumor Immune Estimation Resource (TIMER) and quanTIseq analyses revealed NRF2 enrichment in M2 macrophages with a positive correlation. Co-culturing KYSE450 cells with M2 macrophages demonstrated that a significant infiltration of macrophages M2 can render ESCC cells resistant to radiotherapy but restore their sensitivity to ferroptosis in the process. Our study elucidates a link between the NRF2-GCLM-GSH-GPX4 signaling axis in ESCC, highlighting its potential as a therapeutic target for antagonistic biomarkers of resistance in the future. Additionally, it provides a novel treatment avenue for ESCC metastasis and radioresistance.