Esophageal Squamous Cell Carcinoma Research Articles

Neoadjuvant chemoradiotherapy versus neoadjuvant chemo-immunotherapy for locally advanced esophageal squamous cell carcinoma

Objective: To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC. Results: After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance (P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% (P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% (P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival (HR=0.58, 95% CI: 0.40-0.86) and overall survival (HR=0.53, 95% CI: 0.35-0.79). Conclusion: These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

Omission of lymph node dissection along the recurrent laryngeal nerve for lower thoracic esophageal squamous cell carcinoma with short esophageal invasion.

Esophagectomy with lymphadenectomy is the primary treatment for esophageal squamous cell carcinoma (ESCC). However, intensive dissection of lymph nodes (LNs) along the recurrent laryngeal nerve (RLN) is associated with RLN palsy and pulmonary complications leading to poor survival. Therefore, this study aimed identify the risk factors for LNs metastasis along the RLN in patients with ESCC. The present study included 168 patients with lower thoracic esophageal and esophagogastric junction (EGJ) squamous cell carcinoma who underwent esophagectomy with total mediastinal lymphadenectomy at Kobe University Hospital. Left/Right cervical paraesophageal (101L/R), left/right recurrent nerve (106 recL/R), and left tracheobronchial LNs (106 tbL) were defined as LNs along the RLN. We evaluated the pathological distance between the proximal tumor boundary and the EGJ using images of the fixed specimen (PB-EGJ length). LN metastasis along the RLN was observed in 19 (11%) patients. The percentage of patients with a longer PB-EGJ length and cLNs metastasis was higher in the LNs metastasis along the RLN positive-group than in the RLN-negative group (p=0.0075 and p=0.013, respectively). The incidence of LNs metastasis along the RLN was 0% (95% confidence interval [CI]=0-7.7%) when the PB-EGJ length was <4cm. Univariate analysis showed that patients with cLNs metastasis negative had a low risk for LNs metastasis along the RLN (odds ratio=0.26 and 95% CI=0.083-0.82). Patients with a PB-EGJ length <4cm and negative for cLNs metastasis may be candidates for the omission of lymphadenectomy along the RLN.

LncRNAs SOX2-OT and NEAT1 act as a potential biomarker for esophageal squamous cell carcinoma

Despite strides in diagnostic and therapeutic approaches for ESCC, patient survival rates remain relatively low. Recent studies highlight the pivotal role of long non-coding RNAs (lncRNAs) in regulating diverse cellular activities in humans. Dysregulated lncRNAs have emerged as potential diagnostic indicators across various cancers, including ESCC. However, further research is necessary to effectively leverage ESCC-associated lncRNAs in clinical settings. Understanding their clinical significance for ESCC diagnosis and their mechanisms can pave the way for more effective therapeutic strategies. Our qRT-PCR analysis revealed significant downregulation of SOX2-OT (~ 2.02-fold) and NEAT1 (~ 1.53-fold) in ESCC blood samples. These lncRNAs show potential as biomarkers for distinguishing ESCC patients from healthy individuals, with ROC curves and AUC values of 0.736 for SOX2-OT and 0.621 for NEAT1. Further analysis examined the correlation between SOX2-OT and NEAT1 expression and various clinicopathological factors, including age, gender, smoking, alcohol use, hot beverage intake, tumor grade, and TNM stages. In-silico studies highlighted their roles in miRNA sponging via mTOR and MAPK pathways, while co-expression network analysis identified associated genes. This research paves the way for future studies on ESCC prognosis using SOX2-OT and NEAT1 as predictive markers. By thoroughly investigating the functions of these lncRNAs, we aim to deepen our understanding of their potential as diagnostic markers and their role in facilitating effective therapeutic interventions for esophageal squamous cell carcinoma (ESCC) within clinical contexts.

Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common forms of malignancy worldwide. However, there is currently a lack of effective chemotherapeutic drugs for ESCC. Ivermectin is a broad-spectrum antiparasitic drug with notable antitumor activity. However, the cellular and molecular mechanisms by which ivermectin inhibits cancer growth remain unclear. In this study, we elucidate the role of ivermectin in ESCC suppression by activating the endoplasmic reticulum (ER) stress and autophagy pathways. In transcriptome analyses, we find that activating transcription factor 4 (ATF4) and DNA damage inducible transcript 3 (DDIT3) are involved in the activation of ER stress by ivermectin. Moreover, ivermectin treatment suppresses the growth of ESCC xenograft tumors in nude mice. Taken together, our results establish the antitumor molecular role of ivermectin in targeting the ER stress-autophagy pathway and suggest that ivermectin is a potential drug candidate for the treatment of ESCC.

Impact of Lymphatic and Venous Invasion Patterns on Postoperative Prognosis and Distant Metastasis in Esophageal Squamous Cell Carcinoma After Preoperative Chemotherapy.

Lymphovascular invasion (LVI) is reported to correlate with postoperative prognosis in esophageal squamous cell carcinoma (ESCC). However, reports analyzing lymphatic and venous invasion separately are rare, and no studies have examined the correlation in resected specimens after neoadjuvant chemotherapy (NAC). This study evaluated the postoperative prognosis and distant metastatic recurrence patterns in ESCC patients who underwent esophagectomy after NAC. This retrospective study analyzed 427 ESCC patients who underwent radical esophagectomy after NAC. The study examined the association of LVI patterns with postoperative overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). The study also evaluated the correlation with postoperative distant metastasis patterns. Multivariate analyses showed that patients with venous invasion (VI) alone had significantly worse OS (HR, 2.99; p < 0.001), RFS (HR, 2.92; p < 0.001), and DMFS (HR, 3.63; p < 0.001) than patients without LVI. Patients with both lymphatic invasion (LI) and VI had the worst OS (HR, 4.23; p < 0.001), RFS (HR, 3.38; p < 0.001), and DMFS (HR, 4.59; p < 0.001) among all groups. For the ypN0 patients, VI positivity was the only independent risk factor for DMFS (HR, 5.33; p < 0.001). Regarding distant organ metastasis, liver, brain, and bone metastasis were more frequently detected in patients with both LI and VI than in patients with other LVI patterns. The study showed that ESCC patients treated with NAC who have resected specimens positive for VI, especially those also with positive lymphatic invasion, have a worse postoperative prognosis and a higher risk for postoperative distant metastases than those without LVI. More aggressive postoperative adjuvant therapy may be suitable for improving the prognosis of such patients.

Safety and Tolerability of Letetresgene Autoleucel (Lete-cel; GSK3377794): Pilot Studies in Patients With Advanced Non-Small Cell Lung Cancer.

To evaluate safety, tolerability, and anti-tumor response of lete-cel, genetically modified autologous T-cells expressing a T-cell receptor specific for NY-ESO-1/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in human leukocyte antigen HLA-A*02-positive (HLA-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-) patients with New York esophageal squamous cell carcinoma 1 (NY-ESO-1)- and/or LAGE-1a-positive non-small cell lung cancer (NSCLC). Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multi-arm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent NSCLC. Over 2500 patients were screened for target expression. In the multi-arm study, 738 (45%) of 1638 tested patients were HLA-A*02-positive. NY-ESO-1 and LAGE-1a testing was positive in 12% (62/525) and 4% (15/348) of tested patients, respectively. Forty-one patients positive for HLA-A*02 and antigen expression were screened in the single-arm study. Overall, 43 patients underwent leukapheresis and 18 received lete-cel across studies. Lete-cel demonstrated a manageable safety profile. No fatal treatment-related serious adverse events (AEs) were reported in either study. Cytopenias and cytokine release syndrome were the most common treatment-emergent AEs. Combining pembrolizumab with lete-cel did not appear to increase toxicity over lete-cel alone. Limited anti-tumor activity was observed; one of 18 patients had a durable response persisting for 18 months. Pharmacokinetic data showed similar T-cell expansion in all patients. Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Anti-tumor activity was observed in a limited number of patients.

Analysis of the pathogenesis of esophageal squamous cell carcinoma

Analysis of the pathogenesis of esophageal squamous cell carcinoma

Co-targeting TMEM16A with a novel monoclonal antibody and EGFR with Cetuximab inhibits the growth and metastasis of esophageal squamous cell carcinoma.

The chloride channel transmembrane protein 16A (TMEM16A) possesses a calcium-activated property linked to tumor-promoting malignant phenotype and electrophysiological stability. Numerous studies have shown that TMEM16A exhibits aberrant amplification in various squamous cell carcinomas such as esophageal squamous cell carcinoma (ESCC) and is correlated with unfavorable outcomes of ESCC patients. Therefore, TMEM16A is considered as a promising therapeutic target for ESCC. Because of its intricate structure, the development of therapeutic antibodies directed against TMEM16A has not been documented. In this study, we produced a series of novel monoclonal antibodies targeting TMEM16A and identified mT16#5 as an antibody capable of inhibiting ESCC cells migration, invasion and TMEM16A ion channel activity. Additionally, based on the validation that TMEM16A was positively correlated with expression of EGFR and the interaction between them, the mT16#5 exhibited a synergistic inhibitory effect on ESCC metastasis and growth when administered in combination with Cetuximab in vivo. In terms of mechanism, we found that mT16A#5 inhibited the phosphorylation of PI3K, AKT and JNK. These results highlight the anti-growth and anti-metastasis capacity of the combination of mT16A#5 and Cetuximab in the treatment of ESCC by targeting TMEM16A and EGFR, and provide a reference for combinational antibody treatment in ESCC.

Identification of a stable immunosuppressive molecular subtype in esophageal squamous cell carcinoma based on inflammation‐related genes

Identification of a stable immunosuppressive molecular subtype in esophageal squamous cell carcinoma based on inflammation‐related genes

Effects of Neoadjuvant Therapy on Tumour Target Expression of Oesophageal Cancer Tissue for NIR Fluorescence Imaging.

Oesophaegal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiotherapy (nCRT) are candidates for an active surveillance strategy. Regrowth rates of 40% after initial clinical CR indicate that identification of a true complete response to nCRT remains challenging. Near-infrared tumour-specific fluorescence endoscopic imaging might help to discriminate patients with a true complete response from patients with residual disease. This study aims to find potential markers to enable molecular imaging in oesophageal cancer and to assess the effect of nCRT on marker expression. Oesophageal cancer tissue slides of diagnostic biopsies (n = 41) (pre-treatment) and paired surgical specimens (n = 31) (post-treatment) were collected. Tissue slides of patients with adenocarcinoma (n = 29) and squamous cell carcinoma (n = 12)) were included. Immunohistochemistry was performed to assess expression of the tumour markers CEA, EpCAM, VEGF-α, EGFR, and c-MET in the tumour and compared to the expression of these markers in surrounding healthy tissue. A total immunostaining score (TIS, range 0-12), which combines the percentage and intensity of stained cells, was calculated. The TIS of pre-treated biopsies were compared with the TIS of the post-treatment surgical specimens to assess the effect of neoadjuvant therapy on the marker expression. The median TIS of EpCAM in adenocarcinomas was 10, vs. 0 in healthy mucosa (p < 0.001). The median TIS of EGFR in squamous cell carcinoma was 12, vs. 4 in healthy mucosa (p < 0.001). Neoadjuvant therapy did not affect the expression of the markers. EpCAM and EGFR appear to be the most suitable targets for tumour-specific NIR fluorescence imaging of oesophageal adenocarcinoma and squamous cell carcinoma, respectively. Unaffected expression of all suitable markers by neoadjuvant therapy implies that the diagnostic biopsy can be used to select a patient-specific target for response evaluation by molecular imaging.

MiR-101-3p Promotes Tumor Cell Proliferation and Migration via the Wnt Signal Pathway in MNNG-Induced Esophageal Squamous Cell Carcinoma.

N-methyl-n'-nitroso-n'-nitroso guanidine (MNNG) can induce esophageal squamous cell carcinoma (ESCC), and microRNAs are associated with the development of ESCC and may serve as potential tumor prognostic markers. Thus, the aim of this study was to evaluate the potential function of miR-101-3p in MNNG-induced ESCC. An investigation of risk factors in patients with ESCC was carried out and the concentration of nine nitrosamines in urine samples was detected by the SPE-GC-MS technique. Then, we performed cancer tissue gene sequencing analysis, and RT-qPCR verified the expression level of miR-101-3p. Subsequently, the relationship between miR-101-3p potential target genes and the ESCC patients' prognosis was predicted. Finally, we investigated the function of miR-101-3p in MNNG-induced ESCC pathogenesis and the regulatory mechanism of the signaling pathway by in vivo and in vitro experiments. The results revealed that high dietary nitrosamine levels are high-risk factors for ESCC. MiR-101-3p is down-regulated in ESCC tissues and cells, and its potential target genes are enriched in cell migration and cancer-related pathways. MiR-101-3p target genes include AXIN1, CK1, and GSK3, which are involved in the regulation of the Wnt signaling pathway. MiR-101-3p overexpression promotes apoptosis and inhibits the proliferation and migration of Eca109 cells. The Wnt pathway is activated after subchronic exposure to MNNG, and the Wnt pathway is inhibited by the overexpression of miR-101-3p in Eca109 cells. Down-regulated miR-101-3p may exert tumor suppressive effects by regulating the Wnt pathway and may be a useful biomarker for predicting ESCC progression.

NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination

The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers. Here, we reported that NEDD4L, an E3 ubiquitin ligases, inhibited esophageal squamous cell carcinoma (ESCC) tumor growth and facilitated ferroptosis by ubiquitination of xCT. NEDD4L expression was declined in ESCC and was associated with tumor invasion, lymph node metastasis and distant metastasis. Silencing NEDD4L triggered ESCC tumor growth. Meanwhile, knock down of NEDD4L prevented the accumulation of ROS, elevated the level of GSH, reduced the content of MDA in ESCC cells, thereby inhibiting ferroptosis. Mechanistically, NEDD4L directly bound to the ∆CT domain of xCT through its WW and HECT domain. More importantly, NEDD4L promoted xCT degradation by facilitating its polyubiquitination in ESCC cells. Collectively, these findings suggest that NEDD4L is crucial in governing the stability of xCT and mediating ferroptosis in ESCC.

Prospective multicenter study of camrelizumab in real-world settings for asian patients with esophageal squamous cell carcinoma

BackgroundIn this study, we aimed to evaluate the real-world efficacy and safety of camrelizumab and identify clinicolaboratory factors that predict treatment outcomes in patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) receiving camrelizumab.MethodsHerein, 174 patients with unresectable advanced, recurrent, or metastatic ESCC treated with camrelizumab monotherapy (n = 30), camrelizumab + chemotherapy (CT; n = 91), and camrelizumab + radiotherapy (RT; n = 53) between October 1, 2019 and October 1, 2022 were included.ResultsThe median follow-up time was 20 months (range, 1–34 months). The median progression-free survival (PFS) and overall survival (OS) of the whole cohort were 8 months [95% confidence interval (CI), 6.5–9.5 months] and 14 months (95% CI, 11.2–16.8 months), respectively. After multivariate analysis, receiving > 4 cycles of camrelizumab was identified as an independent predictor of better PFS [hazard ratio (HR), 0.56; 95% CI, 0.38–0.827; P = 0.004] and OS (HR, 0.532; 95% CI, 0.341–0.83; P = 0.005). An intermediate-to-poor lung immune prognostic index (LIPI) was identified as an independent predictor of worse PFS (HR, 1.505; 95% CI, 1.032–2.196; P = 0.034) and OS (HR, 1.657; 95% CI, 1.094–2.51; P = 0.017). The disease control rate of patients in the camrelizumab monotherapy group, camrelizumab + CT group, and camrelizumab + RT group was 92.3% (95% CI, 74.9–99.1%), 90.6% (95% CI, 82.3–95.9%), and 96.1% (95% CI, 86.8–99.5%), respectively. The treatment-related adverse events (AEs) of grade 3 or higher were reported in 67 patients (38.5%). The most common treatment-related AEs were decreased neutrophil count (23.0%), decreased white blood cell count (19.5%), anemia (7.5%), and pneumonitis (4.6%). One patient (0.6%) died from a treatment-related AE of immune checkpoint inhibitor-induced myocarditis.ConclusionCamrelizumab was safe and effective as both monotherapy and part of a combination therapy. Longer PFS and OS were associated with receiving > 4 cycles of camrelizumab and having a good LIPI. LIPI can be used as a prognostic biomarker for ESCC patients receiving camrelizumab + RT.Trial registrationClinicalTrial.gov Identifier: CHICTR2000039499. Registered: 19th October 2020.

Abstract A030: Polycomb repressive complex 2 (PRC2) mediates the epigenetic regulation of cancer-associated fibroblasts in esophageal cancer

Abstract Cancer-associated fibroblasts (CAFs) are a heterogenous cell population that can promote esophageal cancer progression through multiple molecular mechanisms including increased cancer cell proliferation and migration, immunosuppression, and therapeutic resistance. Despite the divergence of CAFs from normal fibroblasts with regards to phenotype and functions, CAFs rarely exhibit widespread genetic alterations. Instead, it is proposed that CAFs are regulated at the epigenetic level. Our objective is to delineate this epigenetic regulation of CAFs in esophageal cancer. Ultimately, we aim to identify the epigenetic regulatory complexes that mediate CAF heterogeneity and pro-tumorigenic functions. To this end, we completed RNA-seq and ATAC-seq on fibroblasts isolated from esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and non-cancerous esophageal tissue. Enrichment analysis identified the polycomb repressive complex 2 (PRC2) as a potential regulator of ESCC and EAC CAFs. PRC2 catalyzes the methylation (mono-, di- or tri-) of lysine 27 on histone 3 (H3K27me1/2/3) resulting in transcriptional repression. Inhibition of two key proteins of PRC2 (EZH2 and SUZ12) through either pharmacological or genetic modulation, altered expression of multiple CAF phenotype related proteins and inhibited CAF functions including CAF proliferation. Ongoing studies, using co-cultures of fibroblasts and tumor cells, seek to identify if inhibition of PRC2 can prevent the initial transition of normal esophageal fibroblasts into CAFs. Importantly, we are conducting in vivo studies to determine if selective PRC2 inhibition in CAFs can inhibit esophageal tumor progression with specific focus on primary tumor growth and metastatic spread. In summary, initial studies have identify that PRC2 complex mediates CAF phenotype and functions, and we aim to establish the larger impact of these CAF specific effects on esophageal cancer. Citation Format: Karen J. Dunbar, Raul Navaridas Fernandez de Bobadil, Katherine M. Cunningham, Emily Esquea, Gizem Efe, Anil K. Rustgi. Polycomb repressive complex 2 (PRC2) mediates the epigenetic regulation of cancer-associated fibroblasts in esophageal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A030.

A Study of the Risk Factors for 402 Patients with Esophageal Squamous Cell Carcinoma - A Retrospective Comparison with Health Checkup Participants.

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

Multimodality deep learning radiomics predicts pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma

ObjectivesThis study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT).Materials and methodsPatients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models’ performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis.ResultsThe study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766–0.959), sensitivity of 88% (95% CI: 73.9–100), and specificity of 78.4% (95% CI: 63.6–90.2) in the testing cohort. This model outperformed single-modality models and the clinical model.ConclusionA multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT.Critical relevance statementOur research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy.Key PointsAfter neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%.The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy.The multimodality radiomics can be helpful in personalized treatment of esophageal cancer.Graphical

ASO Visual Abstract: Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

ASO Visual Abstract: Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy.

Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial.

This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate. Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS. Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

The application of statistical techniques in assessing the impact of medical interventions: A case study of diabetes management

Abstract. Esophageal cancer (EC) ranks seventh among all cancers in terms of frequency and is the sixth leading cause of cancer-related deaths worldwide. The 5-year relative survival rate for esophageal cancer stands at a dismal 21%, which is nearly the lowest among all cancers. In China alone, over 477,900 individuals are diagnosed with EC annually. Advances in whole-genome sequencing technologies have enabled researchers to identify numerous gene mutations across the entire gene sequence in EC patients. This paper aims to consolidate current knowledge on several key genes implicated in EC, as revealed by whole-genome sequencing of patient biopsies. By examining research papers published within the last decade, this study captures the main findings and elucidates the influence of mutations in SOX2, TP53, NOTCH1, SMAD4, and CDKN2A on the formation, progression, and prognosis of both esophageal adenocarcinomas and squamous cell carcinomas. The insights gained are expected to contribute positively to the overall comprehension of esophageal cancer.

Characteristics of multiple esophageal squamous cell carcinomas detected in the surveillance after endoscopic resection.

Endoscopic resection (ER) of esophageal squamous cell carcinoma (ESCC) is an organ-preserving treatment; however, heterochronic carcinomas are often encountered. Most patients are treated using ER; however, for some, this is inadequate and requires additional treatment. We sought to identify the characteristics and frequency of lesions at high risk of metastasis during surveillance based on Lugol-voiding lesion (LVL) grading and esophagogastroduodenoscopy (EGD) intervals. Of the 1301 patients who underwent ER, 956 underwent surveillance EGD at our hospital for at least 1year (median, 59months). We analyzed identified multiple ESCCs to reveal the characteristic of high-metastasis-risk lesions, which was defined ESCC with submucosal or lymphovascular invasion. In the 956 patients, 444 multiple ESCCs were identified in 216 patients and the cumulative incidence of multiple ESCCs was 15.4% and 22.9% at 3 and 5years, respectively, while for high-risk lesions, it was 1.0% and 1.8%. The risk factors for high-metastasis-risk lesions were being female (odds ratio (OR):5.58, 95% confidence interval (CI):1.96-15.9), lesions located in the cervical/upper thoracic esophagus (OR: 4.81, 95% CI:1.80-12.8), and the presence of submucosal tumor (SMT)-like marginal elevation (OR:65.4, 95% CI:11.0-390). No significant differences in the frequency of high-risk lesions were found based on LVL grade at any EGD intervals. During endoscopic surveillance, attention should be given to the cervical/upper thoracic esophagus and lesions with SMT-like marginal elevation. The frequency of high-metastasis-risk lesions was not different by LVL grade or EGD intervals.