Neoadjuvant Chemotherapy or Adjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chemotherapy and chemoradiation have become essential adjuncts to improve the survival of patients with resectable esophageal squamous cell carcinoma (ESCC) in the perioperative period. Although preoperative treatment plus surgery is commonly used, controversy remains regarding the optimal treatment strategy for patients with locally advanced ESCC. METHODS: A retrospective review of clinical stage II and III ESCC patients who underwent esophagectomy at Henan Cancer Hospital between October 2014 and October 2017 was performed. The patients were divided into a neoadjuvant chemotherapy (NAC) group and an adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was used to exclude confounders. Survival was estimated using Kaplan‒Meier analysis and compared by the log-rank test. The Cox proportional hazards regression model was used for both the univariate and multivariate analyses. RESULTS: A total of 684 patients were enrolled, including 365 (53.4%) patients in the NAC group. After PSM, 294 pairs of patients were left. NAC prolonged the OS (not reached versus 57.3 months, P = 0.002) and DFS (57.2 vs. 36.4 months, P = 0.010) and decreased the total rate of recurrence (50.1% vs. 59.2%, P = 0.025) and local recurrence (27.9% vs. 36.7%, P = 0.022) compared with AC. The multivariable analyses showed that NAC plus surgery modality was an independent predictor for improved OS (HR: 0.582, 95% CI: 0.467-0.786, P = 0.001). CONCLUSION: NAC plus surgery prolonged OS and DFS, and significantly decreased the total rate of recurrence compared with surgery plus AC in patients with clinical stage II and III ESCC.

The prognostic impact of tumor length on pathological stage IA-IC esophageal adenocarcinoma.

This study was completed to evaluate the relationship between tumor length and the prognosis of patients with pathological stage IA-IC esophageal adenocarcinoma (EAC). Patients were identified from the Surveillance, Epidemiology, and End Results Program database (United States, 2006-2015). X-tile software and ROC analysis were mainly used to explore the best threshold of tumor length for dividing patients into different groups, and then propensity score matching (PSM) was used to balance other variables between groups. The primary outcome assessed was overall survival (OS). A total of 762 patients were identified, and 500 patients were left after PSM. Twenty millimeters were used as the threshold of tumor length. Patients with longer tumor lengths showed worse OS (median: 93 vs. 128 months; P = 0.006). Multivariable Cox regression analysis showed that longer tumor length was an independent risk factor (hazard ratio 1.512, 95% confidence interval, 1.158-1.974, P = 0.002). Tumor length has an impact on patients with pathological stage IA-IC EAC who undergo surgery alone. The prognostic value of the pathological stage group may be improved after combining it with tumor length and age.

Patterns and Influence of Lymph Nodal Metastases After Neoadjuvant Chemotherapy and Surgery for Thoracic Esophageal Squamous Cell Carcinoma.

PURPOSE: The purpose of this retrospective study was to define the pattern of lymph nodal metastases in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy (NCT) followed by esophagectomy and to evaluate its influence on prognosis. METHODS: A total of 398 patients with clinical stage T3N0 or T1-3N+ ESCC who underwent NCT and radical esophagectomy with two-field lymphadenectomy were included. The distribution and frequency of metastases were counted separately for each lymph node station. The ypN stage, number of positive lymph node stations and lymph node stations with a metastasis rate greater than 5% were analyzed by using univariate Cox regression, followed by separate multivariable Cox regression analyses after adjusting for various clinical factors. RESULTS: Lymph node metastases were most frequently observed in the right upper paratracheal (16.8%) and left gastric artery (13.1%) stations. Multivariable models controlling for clinical factors showed that ypN stage remained a significant independent predictor of survival (N1 vs. N0: hazard ratio [HR], 2.30, 95% confidence interval [CI] 1.38-3.83, P < 0.001; N2 vs. N0: HR, 3.76, 95% CI 2.21-6.38, P < 0.001; N3 vs. N0: HR, 7.14, 95% CI 3.78-13.48, P < 0.001). The model from the multivariable analysis with the highest c-index score, indicating superior discriminatory preference, was ypN stage (c-index, 0.72). CONCLUSIONS: The pattern and influence of lymph node metastases after NCT will provide guidance on the extent of lymphadenectomy. Common positive lymph node stations for thoracic ESCC after NCT include the paratracheal, subcarinal, paraesophageal, paracardial, and left gastric artery stations.

A multicenter randomized, controlled clinical trial of adjuvant sintilimab for esophageal squamous cell carcinoma.

No adjuvant treatment has been established for patients who remain at high risk of recurrence and incidental pathologic lymph node metastasis for esophageal squamous cell carcinoma (ESCC). In this open-label, multicenter, phase III, randomized controlled trial, ESCC patients who did not achieve pathologic complete response after neoadjuvant chemotherapy plus surgery and clinical T1-2 N0 patients with incidental pathologic lymph node metastasis following initial surgery were randomized at a 2:1 ratio to receive either a sintilimab regimen or observational management (NCT05495152). The primary end point was disease-free survival for all randomized patients. The results of this randomized controlled trial addressed controversy regarding the survival benefits of adjuvant sintilimab treatment for patients with resected locally advanced ESCC. Clinical Trial Registration: NCT05495152 (ClinicalTrials.gov).

Stratification of lymph node metastasis improves diagnostic efficiency in thoracic esophageal squamous cell carcinoma.

INTRODUCTION: Difference of the short diameter of lymph nodes in the main regions of esophageal squamous cell carcinoma (ESCC) and its value in the diagnosis of lymph nodes need to explore. METHODS: The clinical data of patients with thoracic ESCC who underwent surgical treatment in our hospital were collected. The short diameters of the largest lymph node in each region of the patient were measured by preoperative enhanced computed tomography (CT) and were compared with the postoperative pathology. RESULTS: A total of 477 patients with thoracic ESCC who did not receive neoadjuvant therapy were enrolled in this study. The receiver operating characteristic curve suggested that the short diameters of the paracardial nodes, the left gastric nodes, the right recurrent laryngeal nerve nodes, and the left recurrent laryngeal nerve nodes could well predict the postoperative pathology of the lymph nodes, with area under curve (AUC) of 0.958, 0.937, 0.931, and 0.915, the corresponding cut-off values of 5.7 mm, 5.7 mm, 5.5 mm, and 4.8 mm, the corresponding sensitivities of 94.7%, 85.4%, 88.7%, and 79.4%, and the corresponding specificities of 93.7%, 96.3%, 86.2%, and 95.0%, respectively. The AUC of the thoracic paraesophageal lymph nodes, the subcarinal nodes and all regional lymph nodes were 0.845, 0.688, and 0.776, respectively. CONCLUSION: Region-based criterion for lymph node metastasis of thoracic ESCC is beneficial to improve the diagnostic efficiency of preoperative CT.

Survival impact of the number of lymph nodes dissection in patients receiving neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

This study aimed to investigate the survival impact of the number of lymph nodes dissection (LND) in patients receiving neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed the clinical pathological data and survival of 407 ESCC patients who underwent esophagectomy after NCT between January 2015 and December 2016. The relationship between the number of LNDs and 5-year overall survival (OS) or disease-free survival (DFS) was plotted by using restricted cubic spline analysis. A Cox proportional hazards regression model was used to identify prognostic factors of OS and DFS. We observed an obvious non-linear relationship between LND and the hazard ratios (HRs) for OS (P = 0.0015) and DFS (P < 0.001) of all the patients. In the multivariate analysis of OS and DFS, the number of LNDs (greater than 28 and less than 46) had a significant protective effect on survival (OS: HR: 0.61, 95% CI: 0.42-0.88, P = 0.007; DFS: HR: 0.50, 95% CI: 0.36-0.70, P < 0.001). For patients with nodal metastases, it was also an independent prognostic factor for OS (HR, 0.56, 95% CI, 0.35-0.90, P = 0.017) and DFS (HR, 0.42, 95% CI, 0.28-0.65, P < 0.001). Some degree of lymphadenectomy after NCT was beneficial in improving 5-year OS and DFS for ESCC patients with nodal metastases. For patients with nodal negativity, more extended lymphadenectomy did not improve patient survival.

Exosome-derived miR-200a promotes esophageal cancer cell proliferation and migration via the mediating Keap1 expression.

Previous studies have reported that exosomes bearing certain microRNAs (miRNAs) are related to the physiological functions of different types of cancer cells. Our study aimed to elucidate the role of miR-200a in esophageal squamous cell carcinoma (ESCC). We observed that miR-200a expression is higher in esophageal carcinoma cells, tissues, and exosomes than in normal cells and healthy tissues. We showed that exosome-shuttled miR-200a promotes the proliferation, migration, and invasion of esophageal cells and inhibits apoptosis, thereby leading to the progression of ESCC. We showed that miR-200a exerts its effects through its interaction with Keap1, thus altering the Keap1/Nrf2 signaling pathway. Our results suggest that exosome-shuttled miR-200a might be useful as a biomarker for prognosis in patients with ESCC.

Effectiveness of the Tailored, Early Comprehensive Rehabilitation Program (t-ECRP) based on ERAS in improving the physical function recovery for patients following minimally invasive esophagectomy: a prospective randomized controlled trial.

BACKGROUND: Perioperative rehabilitation management is essential to enhanced recovery after surgery (ERAS). Limited reports, however, have focused on quantitative, detailed early activity plans for patients receiving minimally invasive esophagectomy (MIE). The purpose of this research was to estimate the effectiveness of the Tailored, Early Comprehensive Rehabilitation Program (t-ECRP) based on ERAS in the recovery of bowel and physical functions for patients undergoing MIE. METHODS: In this single-blind, 2-arm, parallel-group, randomized pilot clinical trial, patients admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2019 to February 2020 were selected and randomly assigned to an intervention group (IG) or a control group (CG). The participants in the IG received medical care based on the t-ECRP strategy during perioperative period, and participants in the CG received routine care. The recovery of bowel and physical functions, readiness for hospital discharge (RHD), and postoperative hospital stay were evaluated on the day of discharge. RESULTS: Two hundred and fifteen cases with esophageal cancer (EC) were enrolled and randomized to the IG (n = 107) or CG (n = 108). The mean age was 62.58 years (SD 9.07) and 71.16% were male. For EC, 53.49% were mid-location cancers and 79.07% were classified as pathological stage II and III cancers. There were no significant differences between the two groups in terms of demographic and clinical characteristics and baseline physical functions. Participants in the IG group presented significantly shorter lengths of time to first flatus (P < 0.001), first postoperative bowel movement (P = 0.024), and for up and go test (P < 0.001), and lower scores of frailty (P < 0.001). The analysis also showed that participants in the IG had higher scores of RHD and shorter lengths of postoperative stay than in the CG (P < 0.05). CONCLUSIONS: The t-ECRP appears to improve bowel and physical function recovery, ameliorate RHD, and shorten postoperative hospital stay for patients undergoing MIE. Clinicians should consider prescribing quantitative, detailed, and individualized early activity plans for these patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01998230).

Minimally Invasive Versus Open McKeown for Patients with Esophageal Cancer: A Retrospective Study.

INTRODUCTION: McKeown minimally invasive esophagectomy (McKeown-MIE) offers advantages in short-term outcomes compared with McKeown open esophagectomy (McKeown-OE); however, debate as to whether MIE is equivalent or better than OE regarding survival outcomes is ongoing. OBJECTIVE: The aim of this study was to compare long-term survival between McKeown-MIE and McKeown-OE in a large cohort of esophageal cancer (EC) patients. METHODS: We used a prospective database (independently managed by LinkDoc company) of the Thoracic Surgery Department at Henan Cancer Hospital and included patients who underwent McKeown-MIE and McKeown-OE for EC from 1 January 2015 to 6 January 2018. The perioperative data and overall survival (OS) rate in the two groups were retrospectively compared. RESULTS: We included 502 patients who underwent McKeown-MIE (n = 306) or McKeown-OE (n = 196) for EC. The median age in the total patient population was 63 years. All baseline characteristics were well-balanced between the two groups. There was a significantly shorter mean operative time (269.76 min vs. 321.14 min, p < 0.001) in the OE group. The 30-day and in-hospital mortality rates were 0, and there was no difference in 90-day mortality (p = 0.053) between the groups. The postoperative stay was shorter in the MIE group and was 14 days and 18 days in the MIE and OE groups, respectively (p < 0.001). The OS at 60 months was 58.8% and 41.6% in the MIE and OE groups, respectively (p < 0.001) [hazard ratio 1.783, 95% confidence interval 1.347-2.359]. CONCLUSIONS: These results showed that McKeown-MIE was associated with better long-term survival than McKeown-OE for patients with resectable EC.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a single-Centre, open-label, randomized, controlled, clinical trial (HCHTOG1903).

BACKGROUND: Neoadjuvant therapy plus oesophagectomy has been accepted as the standard treatment for patients with potentially curable locally advanced oesophageal cancer. No completed randomized controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation in patients with oesophageal squamous cell carcinoma (ESCC). The aim of the current RCT is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiotherapy plus surgery on overall survival for patients with resectable locally advanced ESCC. METHODS: This open label, single-centre, phase III RCT randomized patients (cT2-T4aN + M0 and cT3-4aN0M0) in a 1:1 fashion to receive either the CROSS regimen (paclitaxel 50 mg/m2; carboplatin (area under the curve = 2), q1w, 5 cycles; and concurrent radiotherapy, 41.4 Gy/23 F, over 5 weeks) or neoadjuvant chemotherapy (paclitaxel 175 mg/m2; and cisplatin 75 mg/m2, q21d, 2 cycles). Assuming a 12% 5-year overall survival difference in favour of the CROSS regimen, 80% power with a two-sided alpha level of 0.05 and a 5% dropout each year for an estimated 3 years enrolment, the power calculation requires 456 patients to be recruited (228 in each group). The primary endpoint is 5-year overall survival, with a minimum 5-year follow-up. The secondary endpoints include 5-year disease-free survival, toxicity, pathological complete response rate, postoperative complications, postoperative mortality and quality of life. A biobank of pre-treatment and resected tumour tissue will be built for translational research in the future. DISCUSSION: This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies. TRIAL REGISTRATION: NCT04138212, date of registration: October 24, 2019.

Predictive Value of Body Mass Index for Short-Term Outcomes of Patients with Esophageal Cancer After Esophagectomy: A Meta-analysis.

BACKGROUND: The association between body mass index (BMI) and short-term outcomes after esophagectomy remains controversial. METHODS: A meticulous search for articles describing the association between BMI and perioperative outcomes after esophagectomy was conducted using PubMed, EMBASE, and the Cochrane Library. The study classified BMI according to the World Health Organization definitions and Asian-specific BMI cutoff values. Normal weight was selected as the comparator, and the odds ratio (OR) was calculated as the primary effect. RESULTS: This meta-analysis included 13 studies with 5480 patients. Obese patients exhibited higher risks of overall complication (OR 1.37; P = 0.013), anastomotic leakage (OR 1.74; P = 0.001), and thromboembolic complications (OR 2.05; P = 0.039). Subgroup analysis indicated that obese patients from Western countries had a higher risk of wound infection (OR 2.22; P = 0.022), whereas obese Asians were more likely to experience pulmonary complications (OR 1.64; P = 0.002). Overweight patients displayed no significant differences in major complications relative to normal-weight patients, except for the increased risk of overall complications (OR 1.32; P = 0.030). Additionally, underweight patients showed increased incidence of pulmonary complications (OR 1.92; P = 0.020 and anastomotic leakage (OR 1.64; P = 0.034). Morbid obesity also was analyzed separately with limited data, and this group displayed a higher risk of wound infection (OR 1.62; P = 0.027) and thromboembolic complications (OR 2.65; P = 0.003). No significant differences in mortality were observed among patients in different BMI categories. CONCLUSIONS: Obesity and underweight statuses were confirmed risk factors for several complications after esophagectomy, whereas overweight patients tended to experience greater benefit from surgery.

Early Oral Feeding Following McKeown Minimally Invasive Esophagectomy: An Open-label, Randomized, Controlled, Noninferiority Trial.

OBJECTIVE: Our objective was to evaluate the impact of early oral feeding (EOF) on postoperative cardiac, respiratory, and gastrointestinal (CRG) complications after McKeown minimally invasive esophagectomy for esophageal cancer. SUMMARY BACKGROUND DATA: Nil-by-mouth with enteral tube feeding is routinely practiced after esophagectomy. METHODS: Patients were randomly allocated to receive oral feeding on the first postoperative day (EOF group) or late oral feeding (LOF group) 7 days after surgery. The primary endpoint was the occurrence of postoperative CRG complications, and the secondary outcomes included bowel function recovery and short-term quality of life (QOL). RESULTS: Between February 2014 and October 2015, 280 patients were enrolled in this study. There were 140 patients in the EOF group and 140 patients in the LOF group. EOF was noninferior to LOF for CRG complications (30.0% in the EOF group vs. 32.9% in the LOF group; 95% confidence interval of the difference: -13.8% to 8.0%). Compared with the LOF group, the EOF group showed significantly shorter time to first flatus (median of 2 days vs. 3 days, P = 0.001) and bowel movement (median of 3 vs. 4 days, P < 0.001). Two weeks after the operation, patients in the EOF group reported higher global QOL and function scores and lower symptom scores than patients in the LOF group. CONCLUSIONS: In patients after McKeown minimally invasive esophagectomy is noninferior to the standard of care with regard to postoperative CRG complications. In addition, patients in the EOF group had a quicker recovery of bowel function and improved short-term QOL.

FA01.03: USE OF 'NON-TUBE NO FASTING' ERAS PROTOCOL IN PATIENTS AFTER MIE WITH LI'S ANASTOMOSIS: OUTCOMES IN THE FIRST 113 PATIENTS PERFORMED BY A SURGEON AFTER TRAINING COURSE.

BACKGROUND: Use of enhanced recovery after surgery(ERAS) protocol in the patients after esophagectomy is reported to be feasible and safe in recent studies. And in Prof. Yin Li's research, patients after minimally invasive esophagectomy(MIE) with Li's anastomosis took oral feeding on the 1st day after operation (POD1). However, all the esophagectomy-procedures were proceeded by experienced experts. There was no report regarding whether ERAS protocol after MIE with Li's anastomosis could be safely proceeded by a young surgeon after training course. The aim of this study was to evaluate the feasibility and safety of 'Non-Tube No Fasting' ERAS Protocol in patients after MIE with Li's Anastomosis proceeded by a surgeon after the training course. METHODS: We retrospectively reviewed the clinical data of patients who underwent MIE for cancer from December 2015 to September 2017 by a new surgical team finished MIE training course in our department. During the study period, the new team performed Mckeown MIE with Li's anastomosis for 127 esophageal cancer patients. We analyzed the data of 113 patients who followed the protocol of 'Non-tube No Fasting' ERAS. The primary end-points were the incidence of anastomotic fistula, the injury of recurrent laryngeal nerve, pneumonia, and postoperative length of hospital-stay. RESULTS: All the 113 patients began oral feeding on POD1. Two patients exited the ERAS protocol on account of bucking caused by recurrent laryngeal nerve injury on POD3. The incidence of anastomotic fistula, recurrent laryngeal nerve injury and pneumonia were 3.5% (4/113), 12.4%(14/113) and 18.5%(21/113). The average length of postoperative hospital-stay was 8.6 ± 6.9 days. Both of the in-hospital mortality and 30-day mortality were 0. CONCLUSION: Our date indicated that it was feasible and safe for a selected surgeon after 'Non-tube no fasting' ERAS and MIE training courses to proceed the protocol. Of course, more clinical researches are needed to confirm this result. DISCLOSURE: All authors have declared no conflicts of interest.

[Patterns of lymphatic spread in thoracic esophageal squamous cell carcinoma: a study of 313 cases].

OBJECTIVE: We analyzed the lymph node (MLNs) metastasis of thoracic esophageal squamous cell carcinoma (ESCC) to explore the patterns of lymphatic spread and the rational surgical procedure and extent of lymph node dissection for ESCC. METHODS: We retrospectively evaluated 313 consecutive patients treated in our hospital between January 2010 and May 2014 who underwent minimally invasive esophagectomy (MIE) for ESCC. The information of lymph node status was obtained and the features of lymph node metastasis were analyzed. RESULTS: Of the 313 cases, 122 (39.0%) were found to have lymph node metastasis. In the 4461 dissected lymph nodes, metastasis was identified in 294 (6.6%) lymph nodes. The recurrent laryngeal nerve lymph nodes were the most frequent metastatic nodes with a metastasis rate of 25.2%, followed by the paracardiac and left gastric artery lymph nodes (18.2%). Chi-square test showed that the lymph node metastasis is associated with tumor invasion and tumor differentiation (P<0.001 for both). Metastases were more frequently found in the recurrent laryngeal nerve lymph nodes in patients with tumors in the upper third esophagus and with histologically poor differentiation (P<0.05 for both). The metastasis rate of para-cardiac and left gastric artery lymph nodes was associated with tumor in the lower third of esophagus, T stage and differentiation (all P<0.05). Logistic regression analysis showed that tumor differentiation and location are independent factors affecting the metastasis of recurrent laryngeal nerve lymph nodes (P<0.05 for all). T stage, tumor differentiation and location were independent factors associated with metastasis of para-cardiac and left gastric artery lymph nodes (P<0.05 for all). CONCLUSIONS: (1) Metastases of thoracic esophageal carcinoma are often found in the recurrent laryngeal nerve lymph nodes, para-cardiac and left gastric artery lymph nodes. (2) Extensive lymph node dissection should be performed for ESCC with poor differentiation and deep tumor invasion.

[Clinical implications of the concentration and EGFR/KRAS mutations of plasma cell free DNA of patients with lung cancer and esophageal cancer].

OBJECTIVE: To analyze the correlation between the concentration of plasma cell free DNA (cfDNA) of patients with lung cancer or esophageal cancer and clinical features, and to assess the coincidence rate of the EGFR/KRAS mutations between the cfDNA and tumor tissue DNA. METHODS: A total of 30 cases lung cancer and esophageal cancer (including 15 lung cancer, 15 esophageal cancer) were enrolled in this study. The tumor tissue and plasma sample of patients were collected. The tumor tissue DNA and plasma cfDNA were extracted. The EGFR/KRAS mutations of the tumor tissue DNA and plasma cfDNA were detected by fluorescence PCR. RESULTS: The concentration of cfDNA of patients with lung cancer (5.0 ± 1.4) µg/L and esophageal cancer (7.0 ± 0.8) µg/L were positively correlated with tumor size (r = 0.574, P = 0.01). There was no significant correlation between the concentration of cfDNA and TNM stage of tumor, gender, and age of patients. There was no EGFR/KRAS gene mutations in tumor tissue DNA and plasma cfDNA of esophageal cancer. A total of 6 tumor tissue samples of lung cancer patients were detected EGFR mutation, and 1 tumor tissue sample was detected KRAS mutation. Meanwhile, 4 plasma cfDNA samples of lung cancer patients were detected EGFR mutation, and 1 plasma cfDNA sample was detected KRAS mutation. CONCLUSION: The concentration of cfDNA of patients with lung cancer and esophageal cancer was positively correlated with tumor burden. There was high coincidence rate of the EGFR/KRAS mutations between the cfDNA and tumor tissue DNA.

Biofunctional study on chemoresistance in esophageal squamous carcinoma cells induced by missense mutation of NOTCH1 p.E450K.

Background: Neoadjuvant chemotherapy (nCT) combined with surgery is one of the main strategies for the treatment of resectable locally advanced esophageal squamous cell carcinoma (ESCC). However, nearly 40% of patients did not benefit from nCT, and the detection rate of NOTCH1 missense mutation was significantly increased in patients who did not respond to chemotherapy, suggesting that the missense mutation may be related to tumor chemoresistance. We aim to explore the effect of a NOTCH1 missense mutation on cell phenotype, to interpret the biofunctional changes in cell lines with a NOTCH1 missense mutation and to analyze the effect of a NOTCH1 missense mutation on drug resistance in ESCC cell lines. Methods: Sanger sequencing was used to evaluate the exon mutations in the NOTCH1 ligand binding region of candidate ESCC cell lines. After screening, KYSE450 and KYSE140 cells were selected as the research objects, and point mutation cell lines [KYSE140-mutant-type (MT) and KYSE450-MT] were constructed by CRISPR/Cas9 technology. Then, functional experiments were performed with the four cell lines [KYSE450-MT/wild-type (WT) and KYSE140-MT/WT]. The drug resistance of ESCC cell lines was assessed with a drug sensitivity test, and the proliferation, invasion and migration of ESCC lines were evaluated by proliferation test, scratch test and Transwell test. The cell cycle status of ESCC cells was assessed using flow cytometry. Results: Drug sensitivity tests showed that the NOTCH1 p.E450K point mutation caused chemotherapy resistance in KYSE140 and KYSE450 ESCC cell lines. Cell proliferation, Wound scratch and Transwell assays showed that the NOTCH1 p.E450K point mutation enhanced the proliferation, invasion and migration abilities of KYSE140 and KYSE450 cells. Flow cytometry analysis showed that the NOTCH1 p.E450K point mutation caused an increase in KYSE140 and KYSE450 cells in S phase. Conclusions: The NOTCH1 p.E450K point mutation causes chemotherapy resistance in KYSE140 and KYSE450 ESCC cells. Cell functional experiments showed that the NOTCH1 p.E450K point mutation enhanced the proliferation, migration and invasion abilities of KYSE140 and KYSE450 cells and increased the number of cells in S phase.