Surgical vs nonsurgical treatment for esophageal squamous cell carcinoma in patients older than 70 years: a propensity score matching analysis.

PURPOSE: With the rising life expectancy and an aging population, it has become increasingly important to investigate treatments suitable for older adult patients with esophageal cancer. This study investigated whether older adult patients who underwent esophagectomy had better clinical outcomes than those who were nonsurgically treated. METHODS: We retrospectively analyzed patients with esophageal squamous cell carcinoma (ESCC) who were 70 years or older and underwent esophagectomy, radiotherapy (RT), and/or chemoradiotherapy (CRT) between January 2018 and December 2019. Patients were divided into 2 groups: the surgery group (S group) and the nonsurgery group (NS group). We then compared the clinical outcomes of the 2 groups. RESULTS: After a median follow-up duration of 36.6 months, the S group showed better overall survival (OS). The 3-year OS was 59% in the S group and 27% in the NS group (hazard ratio [HR], 0.397; 95% CI, 0.278-0.549; P < .0001). In the S group, the median progression-free survival was 38.3 months (95% CI, 30.6-46.1) compared with 12.3 months in the NS group (HR, 0.511; 95% CI, 0.376-0.695; P < .0001). In addition, the number of adverse events in the NS group was higher than that in the S group (P < .001). CONCLUSION: Overall, patients with ESCC at the age of ≥70 years who underwent esophagectomy had significantly better clinical outcomes than those who underwent nonsurgical treatment with RT and/or CRT.

Effect of cervical paraesophageal lymph node metastasis versus supraclavicular lymph node metastasis on the overall survival of patients with thoracic esophageal squamous cell carcinoma: an observational study.

Background: Esophageal cancer (EC) is a major global health burden, with a particularly high incidence in East Asia. The authors aimed to investigate the effect of metastasis in cervical paraesophageal lymph nodes (station 101) and supraclavicular lymph nodes (station 104) on the survival of patients who underwent esophagectomy for esophageal squamous cell carcinoma (ESCC). Materials and Methods: Data were obtained from the database of the authors' hospital. The authors retrospectively analyzed the patients with EC who underwent esophagectomy from January 2010 to December 2017. These patients were allocated into two groups based on the presence of lymph node metastasis (LNM) in the cervical paraesophageal or supraclavicular regions. Clinical outcomes and survival data were compared using the TNM staging system of the 8th edition of the American Joint Committee on Cancer (AJCC). Results: After a median follow-up of 62.1 months, 122 patients with LNM in the supraclavicular region were included in the study. Among these patients, 53 showed cervical paraesophageal LNM and an overall survival (OS) of 19.9 months [95% confidence interval (CI): 16.3-23.5]. In contrast, 69 patients showed supraclavicular LNM with an OS of 34.9 months (95% CI 25.7-44.1). The OS rates at 1, 3, and 5 years were 77%, 29%, and 21%, respectively, for patients with cervical paraesophageal LNM. Moreover, patients with supraclavicular LNM demonstrated OS rates of 88%, 48%, and 34%, respectively [Hazard ratio (HR): 0.634, 95% CI: 0.402-1.000, P=0.042]. Conclusions: Patients with ESCC with cervical paraesophageal LNM had significantly worse OS than those with supraclavicular LNM. This study underscores the importance of accurately identifying and managing ESCC with cervical paraesophageal LNM, as it may require more tailored and aggressive treatment strategies to prolong patient survival.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Impact of Metastatic Lymph Nodes on Survival of Patients with pN1-Category Esophageal Squamous Cell Carcinoma: A Long-Term Survival Analysis.

BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.

Optimal Time-to-Surgery Recommendations Based on Primary Tumor Volume Regression for Patients with Resectable Esophageal Cancer after Neoadjuvant Chemoradiotherapy: A Retrospective Study.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) has shown promise in improving the prognosis of individuals with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the factors influencing tumor response and long-term survival in these patients remain unknown. The optimal timing for surgery after the completion of radiotherapy in LA-ESCC remains controversial. Therefore, this study was designed to identify biomarkers and to determine the optimal post-NCRT time-to-surgery (TTS) for patients with LA-ESCC. METHODS: This retrospective study included patients with resectable LA-ESCC who underwent NCRT between May 2017 and June 2021. The tumor shrinkage rate was calculated as the difference between the pre- and post-primary gross tumor volume (GTVp) divided by the pre-GTVp. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival (PFS). RESULTS: We collected data from 248 patients with resectable LA-ESCC who underwent computed tomography (CT) scans before the initiation of treatment. The median follow-up time was 37.7 months. The optimal cutoff of tumor shrinkage was 45%. In the univariate and multivariate analyses, we found a significant association between the tumor shrinkage rate and PFS (p = 0.001). Among the subgroup of patients who responded to treatment, extending the TTS was associated with improved OS (p = 0.037) and PFS (p = 0.028). CONCLUSIONS: For patients with resectable LA-ESCC, the tumor shrinkage rate is an independent prognostic factor for PFS. Thus, for responders, prolonging TTS is recommended to obtain a better OS.

Refining postoperative monitoring of recurrent laryngeal nerve injury in esophagectomy patients through transcutaneous laryngeal ultrasonography.

BACKGROUND: Recurrent laryngeal nerve injury (RLNI) leading to vocal cord paralysis (VCP) is a significant complication following minimally invasive esophagectomy (MIE) with upper mediastinal lymphadenectomy. Transcutaneous laryngeal ultrasonography (TLUSG) has emerged as a non-invasive alternative to endoscopic examination for evaluating vocal cord function. Our study aimed to assess the diagnostic value of TLUSG in detecting RLNI by evaluating vocal cord movement after MIE. METHODS: This retrospective study examined 96 patients with esophageal cancer who underwent MIE between January 2021 and December 2022, using both TLUSG and endoscopy. RESULTS: VCP was observed in 36 out of 96 patients (37.5%). The incidence of RLNI was significantly higher on the left side than the right (29.2% vs. 5.2%, P < 0.001). Postoperative TLUSG showed a sensitivity and specificity of 88.5% (31/35) and 86.5% (45/52), respectively, with an AUC of 0.869 (P < 0.001, 95% CI 0.787-0.952). The percentage agreement between TLUSG and endoscopy in assessing VCP was 87.4% (κ = 0.743). CONCLUSIONS: TLUSG is a highly effective screening tool for VCP, given its high sensitivity and specificity. This can potentially eliminate the need for unnecessary endoscopies in about 80% of patients who have undergone MIE.

Collaborative multidisciplinary management and expertise of cT2-3 locally advanced operable esophageal squamous cell carcinoma: a report of two cases.

Background: The accurate clinical staging of esophageal squamous cell carcinoma (ESCC) is pivotal for guiding treatment strategies. However, the current precision in staging for clinical T (cT)2 and cT3 stages remains unsatisfactory. This article discusses the role of multidisciplinary teams (MDTs) in the clinical staging and formulation of neoadjuvant treatment strategies for locally advanced operable ESCC. These challenges underscore the importance of precise staging in the decision-making process for appropriate therapeutic interventions. Case Description: Through the lens of two patient case studies with locally advanced resectable ESCC, the article showcases the intricate process of treatment planning undertaken by MDTs. It captures a range of expert perspectives from Japan, China, Hong Kong (China), Korea, the USA, and Europe, focusing on the challenges of differentiating between cT2 and cT3 stages of the disease, which is a critical determinant in the management and therapeutic approach for patients. Conclusions: The article concludes that the accurate staging of ESCC is a cornerstone in determining the most suitable treatment strategies. It underscores the vital role that MDTs play in both clinical staging and the decision-making process for treatment. Highlighting the limitations in current diagnostic methods, the article emphasizes the urgent need for advanced research and the refinement of diagnostic tools to improve the precision of staging, particularly between the cT2 and cT3 stages. It suggests that future research should consider whether a reclassification of these stages could be warranted to enhance treatment planning and outcomes for patients with ESCC.

Clinical value of folate receptor-positive circulating tumor cells in patients with esophageal squamous cell carcinomas: a retrospective study.

BACKGROUND: The aim of the study is to explore the role of preoperative folate receptor-positive circulating tumor cell (FR+CTC) levels in predicting disease-free survival (DFS) and overall survival (OS) in patients with esophageal squamous cell carcinomas (ESCC). METHODS: Three ml blood samples were prospectively drawn from ESCC patients, and ligand-targeted polymerase chain reaction (LT-PCR) was used for the quantification of FR+CTCs. Other serum indicators were measured by traditional methods. Clinicopathological characteristics were obtained from the hospital medical record system, DFS and OS data were obtained by follow-up. The correlation between clinico-pathological characteristics, DFS, and OS and FR+CTCs were analyzed, respectively. Risk factors potentially affecting DFS and OS were explored by Cox regression analysis. RESULTS: there were no significant correlations between FR+CTCs and patient age, sex, albumin, pre-albumin, C-reactive protein (CRP), ferritin and CRP/Albumin ratio, tumor size, grade of differentiation, lymph node metastasis, TNM stage, perineural invasion/vessel invasion (all P > 0.05). Nevertheless, preoperative FR+CTCs were an independent prognostic factor for DFS (HR 2.7; 95% CI 1.31-, P = 0.007) and OS (HR 3.37; 95% CI 1.06-, P = 0.04). DFS was significantly shorter for patients with post-operative FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml (P = 0.0012). For OS, it was shorter for patients with FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml, however, the difference did not reach statistical significance (P = 0.51). CONCLUSIONS: ESCC patients with high FR+CTCs tend to have a worse prognosis. FR+CTCs may monitor the recurrence of cancers in time, accurately assess patient prognosis, and guide clinical decision-making. TRIAL REGISTRATION: The study was approved by the Sichuan Cancer Hospital & Institute Ethics Committee (No. SCCHEC-02-2022-050).

EUS-derived maximum tumor thickness and tumor shrinkage rate as independent prognostic factors in locally advanced esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy.

Background and Objectives: EUS-derived maximum tumor thickness (MTT) pre- and post-neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) indicates treatment response. However, the accuracy of predicting long-term survival remains uncertain. This study aimed to investigate the association between EUS-derived MTT pre- and post-NCRT and tumor shrinkage rate as well as long-term survival in patients with LA-ESCC receiving NCRT. Methods: We retrospectively enrolled patients with LA-ESCC who underwent EUS examination from 2017 to 2021. Tumor shrinkage rate was the ratio of the difference between pre- and post-MTT to pre-MTT. The most fitted cutoff values were determined by the receiver operating characteristic curve. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival. Data from another center were also used for external validation testing. Results: Two hundred thirty patients were enrolled. Of the patients, 178 completed the first EUS pre-NCRT and obtained pre-MTT, 200 completed the reexamined EUS post-NCRT and obtained post-MTT, and 148 completed both EUS and achieved tumor shrinkage. For all the patients, the 1- and 3-year OS rates were 93.9% and 67.9%, and progression-free survival rates were 77.7% and 54.1%, respectively. The median follow-up period was 30.6 months. Thinner post-MTT (≤8.8 mm) and EUS responder (tumor shrinkage rate ≥52%) were independently associated with better OS. Conclusions: EUS-derived MTT and tumor shrinkage post-NCRT are independent prognostic factors for long-term survival and may be an alternative method for evaluating tumor response in patients with LA-ESCC after NCRT.

Advantages of Totally Stapled Collard Over Circular Stapled Technique for Cervical Esophagectomy Anastomosis.

BACKGROUND: The quality of life between the totally stapled Collard (TSC) and circular stapled (CS) techniques from the patient's perspective has not been assessed. This longitudinal patient-reported outcome and objective data assessment study aimed to compare the effects of TSC vs CS for cervical anastomosis with minimally invasive esophagectomy (MIE) on the quality of life. METHODS: This single-center, retrospective study included patients with esophageal cancer who underwent MIE and cervical anastomosis between April 2019 and February 2021; of whom, 105 and 216 patients received TSC and CS anastomosis, respectively. The objective metrics were evaluated based on postoperative complications. Patient-reported outcomes instruments using the European Organization for Research and Treatment of Cancer modules were assessed preoperatively. The Quality of Life Questionnaire (QLQ) Core 30 and the QLQ-Oesophagus Module 18 assessed the quality of life. Mixed-effects models examined changes in questionnaire scores. RESULTS: The stenosis rate in the TSC group was significantly lower than that in the CS group. There were no significant differences in other postoperative complications between the groups. In the QLQ Core 30 scale, the TSC group had better emotional function, less fatigue, less appetite loss, and better function than the CS group, with significant differences in different time points between the groups. QLQ-Oesophagus Module 18 revealed that the TSC group had significantly less appetite loss, dysphagia, dry mouth, pain, and obstruction, and better eating and speech than the CS group. CONCLUSIONS: TSC has significant advantages over the CS technique in lowering postoperative symptom burden and improving quality of life for cervical anastomosis on patient-reported outcomes.

Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma.

Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of ß-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy. SIGNIFICANCE: Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration. See related commentary by Sfanos, p. 2985.

Histone Deacetylases HD2A and HD2B Undergo Feedback Regulation by ABA and Modulate Drought Tolerance via Mediating ABA-Induced Transcriptional Repression.

Histone deacetylation catalyzed by histone deacetylase plays a critical role in gene silencing and subsequently controls many important biological processes. It was reported that the expression of the plant-specific histone deacetylase subfamily HD2s is repressed by ABA in Arabidopsis. However, little is known about the molecular relationship between HD2A/HD2B and ABA during the vegetative phase. Here, we describe that the hd2ahd2b mutant shows hypersensitivity to exogenous ABA during the germination and post-germination period. Additionally, transcriptome analyses revealed that the transcription of ABA-responsive genes was reprogrammed and the global H4K5ac level is specifically up-regulated in hd2ahd2b plants. ChIP-Seq and ChIP-qPCR results further verified that both HD2A and HD2B could directly and specifically bind to certain ABA-responsive genes. As a consequence, Arabidopsis hd2ahd2b plants displayed enhanced drought resistance in comparison to WT, which is consistent with increased ROS content, reduced stomatal aperture, and up-regulated drought-resistance-related genes. Moreover, HD2A and HD2B repressed ABA biosynthesis via the deacetylation of H4K5ac at NCED9. Taken together, our results indicate that HD2A and HD2B partly function through ABA signaling and act as negative regulators during the drought resistance response via the regulation of ABA biosynthesis and response genes.

Arabidopsis histone deacetylase HD2A and HD2B regulate seed dormancy by repressing DELAY OF GERMINATION 1.

Seed dormancy is a crucial developmental transition that affects the adaption and survival of plants. Arabidopsis DELAY OF GERMINATION 1 (DOG1) is known as a master regulator of seed dormancy. However, although several upstream factors of DOG1 have been reported, the exact regulation of DOG1 is not fully understood. Histone acetylation is an important regulatory layer, controlled by histone acetyltransferases and histone deacetylases. Histone acetylation strongly correlates with transcriptionally active chromatin, whereas heterochromatin is generally characterized by hypoacetylated histones. Here we describe that loss of function of two plant-specific histone deacetylases, HD2A and HD2B, resulted in enhanced seed dormancy in Arabidopsis. Interestingly, the silencing of HD2A and HD2B caused hyperacetylation of the DOG1 locus and promoted the expression of DOG1 during seed maturation and imbibition. Knockout of DOG1 could rescue the seed dormancy and partly rescue the disturbed development phenotype of hd2ahd2b. Transcriptomic analysis of the hd2ahd2b line shows that many genes involved in seed development were impaired. Moreover, we demonstrated that HSI2 and HSL1 interact with HD2A and HD2B. In sum, these results suggest that HSI2 and HSL1 might recruit HD2A and HD2B to DOG1 to negatively regulate DOG1 expression and to reduce seed dormancy, consequently, affecting seed development during seed maturation and promoting seed germination during imbibition.

Mapping of Lymph Node Metastasis and Efficacy Index in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Retrospective Analysis.

BACKGROUND: Esophageal squamous cell carcinoma has a high mortality rate in China. The metastatic pattern in the lymph nodes and the value of their dissection on the overall survival of these patients remain controversial. The primary aim of this study was to provide a basis for accurate staging of esophageal cancer and to identify the relationship between esophageal cancer surgery, lymph node dissection, and overall survival rates. METHODS: We utilized our hospital database to retrospectively review the data of 1727 patients with esophageal cancer who underwent R0 esophagectomy from January 2010 to December 2017. The lymph nodes were defined according to Japanese Classification of Esophageal Cancer, 11th Edition. The Efficacy Index (EI) was calculated by multiplying the frequency (%) of metastases to a zone and the 5-year survival rate (%) of patients with metastases to that zone, and then dividing by 100. RESULTS: The EI was high in the supraclavicular and mediastinal zones in patients with upper esophageal tumors, and the EI of 101R was 17.39, which was the highest among the lymph node stations. In patients with middle esophageal tumors, the EI was highest in the mediastinal zone, followed by the celiac and supraclavicular zones. Furthermore, the EI was highest in the celiac zone, followed by the mediastinal zones in patients with lower esophageal tumors. CONCLUSIONS: The EI of resected lymph nodes was found to vary between stations and was related to the primary location of the tumor.

Resected lymph nodes and survival of patients with esophageal squamous cell carcinoma: an observational study.

BACKGROUND: The incidence and mortality of esophageal cancer are high. Therefore, the authors aimed to investigate how the number of dissected lymph nodes (LNs) during esophagectomy for esophageal squamous cell carcinoma impacts overall survival (OS), particularly that of patients with positive LNs. MATERIALS AND METHODS: Data from 2010 to 2017 were obtained from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database. Participants were divided into two groups: patients with negative lymph nodes (N0) and patients with positive lymph nodes (N+). The median number of resected LNs during surgery was 24; therefore, patients with 15-23 and those with 24 or more resected LNs were assigned to subgroups A and B, respectively. RESULTS: After a median follow-up of 60.33 months, 1624 patients who underwent esophagectomy were evaluated; 60.53 and 39.47% had a pathological diagnosis of N+ or N0, respectively. The median OS was 33.9 months for the N+ group; however, the N0 group did not achieve the median OS. The mean OS was 84.9 months. In the N+ group, the median OS times of subgroups A and B were 31.2 and 37.1 months, respectively. The OS rates at 1, 3, and 5 years were 82, 43, and 34%, respectively, for subgroup A of the N+ group; they were 86, 51, and 38%, respectively, for subgroup B of the N+ group. Subgroups A and B of the N0 group exhibited no statistically significant differences. CONCLUSION: Increasing the number of LNs harvested during surgery to 24 or more could improve the OS of patients with positive LNs but not that of patients with negative LNs.

Impact of two­field or three­field lymphadenectomy on overall survival in middle and lower thoracic esophageal squamous cell carcinoma: A single­center retrospective analysis.

Squamous cell carcinoma is the main subtype of esophageal cancer in East Asia. The effect of the number of lymph nodes (LNs) removed to treat middle and lower thoracic esophageal squamous cell carcinoma (ESCC) in China remains controversial. Therefore, the present study aimed to investigate the impact of the number of LNs removed during lymphadenectomy on the survival of patients with middle and lower thoracic ESCC. Data were obtained from the Sichuan Cancer Hospital and Institute Esophageal Cancer Case Management Database from January 2010 to April 2020. Either three-field systematic lymphadenectomy (3F group) or two-field systematic lymphadenectomy (2F group) was performed for ESCC cases with or without suspicious tumor-positive cervical LNs, respectively. Subgroups were designed for further analysis based on the quartile number of resected LNs. After 50.7 months of median follow-up, 1,659 patients who underwent esophagectomy were enrolled. The median overall survival (OS) of the 2F and 3F groups was 50.0 months and 58.5 months, respectively. The OS rates at 1, 3 and 5 years were 86, 57 and 47%, respectively, in the 2F group, and 83, 52 and 47%, respectively, in the 3F group (P=0.732). The average OS of the 3F B and D groups was 57.7 months and 30.2 months, respectively (P=0.006). In the 2F group, the OS between subgroups was not significantly different. In conclusion, resection of >15 LNs during two-field dissection in patients with ESCC undergoing esophagectomy did not affect their survival outcomes. In three-field lymphadenectomy, the extent of LNs removed could lead to different survival outcomes.

The efficacy and safety of neoadjuvant immunotherapy in resectable locally advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Background: Several studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking. Methods: Studies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0. Results: Thirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26-0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31-0.65; nICT: 0.29, 95% CI: 0.26-0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1-2 and 3-4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56-0.84) and 0.16 (95% CI: 0.09-0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3-4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17-0.77; nICT: 0.14, 95% CI: 0.07-0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15-0.53; cisplatin: 0.04, 95% CI: 0.01-0.09; p<0.01). Conclusion: Neoadjuvant immunotherapy has good efficacy and safety profiles in patients with locally advanced ESCC. Additional RCTs with long-term survival data are warranted.