Resected Esophageal Squamous Cell Carcinoma Research Articles

Benefits of camrelizumab plus carboplatin and albumin paclitaxel as induction therapy for locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma.

To evaluate the safety and efficacy of camrelizumab plus albumin paclitaxel and carboplatin in the neoadjuvant treatment of borderline resectable or unresectable locally advanced esophageal cancer. A retrospective analysis was conducted on 27 patients with borderline resectable or unresectable locally advanced esophageal cancer who received neoadjuvant treatment with camrelizumab plus albumin paclitaxel and carboplatin at Shanxi Cancer Hospital from January 2020 to March 2022. Of these, 20 patients underwent thoracoscopic esophagectomy after neoadjuvant treatment. Overall, 88.9% (24/27) of patients completed neoadjuvant treatment. The objective response rate was 79.2% (19/24) according to the RECIST criteria. Of the 20 patients who underwent surgery, the R0 resection rate was 95%, and 35% (7/20) achieved pathological complete response (pCR). During neoadjuvant treatment, 30% (6/20) of patients experienced grade ≥3 treatment-related adverse events (TRAEs), and 20% (4/20) had grade ≥3 postoperative complications. There were no cases of reoperation or perioperative mortality. Camrelizumab plus albumin paclitaxel and carboplatin were found to be safe and effective in the neoadjuvant treatment of borderline resectable or unresectable locally advanced esophageal cancer. It was observed to improve the rate of curative resection without increasing perioperative complications.

Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma.

Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

Chemotherapy plus camrelizumab versus chemotherapy alone as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (ESCORT-NEO): A multi-center, randomized phase III trial.

LBA244 Background: Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, recurrence post-surgery remains a concern. Recent single-arm studies with neoadjuvant camrelizumab plus chemotherapy showed promising results. This multicenter, randomized, open-label, phase III study aims to evaluate the role of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, versus neoadjuvant chemotherapy alone for resectable LA-ESCC. Methods: Patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified according to clinical stage (I/II, III, or IVa) and randomized (1:1:1) to three groups for two 3-week cycles of neoadjuvant therapy. Group A received camrelizumab, albumin-bound paclitaxel and cisplatin; group B used camrelizumab, paclitaxel and cisplatin; group C received paclitaxel and cisplatin. Surgery was planned 4-6 weeks post-neoadjuvant therapy. Postoperative adjuvant camrelizumab every 3 weeks was given to groups A and B for up to 15 cycles. The co-primary endpoints were pathological complete response (pCR) rate, assessed by an independent blinded pathological committee, and event-free survival, evaluated by investigators per RECIST 1.1. The overall type I error was controlled at a one-sided 0.025 across the primary endpoints using a graphical method. Results: Between April, 2021, and August, 2023, we enrolled 391 patients: group A (n = 132), group B (n = 130), and group C (n = 129). 106 (27.1%), 279 (71.4%), 6 (1.5%) patients were in clinical stage I/II, III, and IVa. Tumors were located in the upper, middle, and lower thoracic esophagus for 41 (10.5%), 201 (51.4%), and 149 (38.1%) patients. 128 (97.0%), 125 (96.2%), and 122 (94.6%) patients from groups A, B, and C completed two cycles of neoadjuvant therapy, and 114 (86.4%), 116 (89.2%), and 103 (79.8%) underwent surgery. In the intention-to-treat population, the pCR rate was significantly higher in groups A (28.0%) and B (15.4%) compared to group C (4.7%) (group A vs. C: difference, 23.5%, 95%CI, 15.1-32.0; OR, 8.11, 95%CI, 3.28-20.06; two-sided P < 0.0001; group B vs. C: difference, 10.9%, 95%CI, 3.7-18.1; OR, 3.81, 95%CI, 1.48-9.80; two-sided P = 0.0034); major pathologic response rates were 59.1%, 36.2%, 20.9% for groups A, B and C. In the surgical set, the R0 resection rate was 99.1%, 95.7% and 92.2% for groups A, B and C, and the incidence of postoperative complications was 34.2%, 38.8% and 32.0%. During neoadjuvant treatment, the incidence of grade ≥3 treatment-related adverse events was 34.1%, 28.5% and 28.8%. Conclusions: In resectable LA-ESCC patients, neoadjuvant camrelizumab with chemotherapy showed superior pCR and a tolerable safety profile compared to neoadjuvant chemotherapy alone. Clinical trial information: ChiCTR2000040034 .

Absence of Hypercoagulation Status after Neoadjuvant Treatment is Associated with Favorable Prognosis in Patients Undergoing Subtotal Esophagectomy for Esophageal Squamous Cell Carcinoma.

Abnormal activation of the coagulation system is associated with malignant tumor progression. Although neoadjuvant treatment (NAT) for resectable esophageal squamous cell carcinoma (ESCC) is the standard of care, the correlation between coagulation status and prognosis of patients undergoing preoperative treatment is insufficiently understood. Patients (n = 200) who underwent radical subtotal esophagectomy after preoperative treatment for ESCC between January 2012 and December 2021were included in the analysis. Plasma D-dimer and fibrinogen levels and their combined indices (non-hypercoagulation; D-dimer and fibrinogen levels within the upper normal limit, or hypercoagulation; D-dimer or fibrinogen levels above the upper normal limit) were determined before and after NAT and correlated to clinicopathological factors and prognosis. The nonhypercoagulation group achieved superior overall survival (OS) than the hypercoagulation group (5-year OS rates = 89% vs. 55%; hazard ratio 3.62, P = 0.0008) when determined according to coagulation status after NAT. Multivariate analysis showed that hypercoagulation after NAT served as an independent factor for poor postoperative OS (hazard ratio 3.20; P = 0.0028). The nonhypercoagulation group achieved significantly better disease-free survival (76% vs. 54%; P = 0.0065) than the hypercoagulation group that experienced a significantly higher rate of hematogenous metastasis as an initial recurrence (P = 0.0337). Hypercoagulation state after NAT served as a valid indicator correlating with postoperative outcomes of patients with ESCC who underwent NAT followed by radical subtotal esophagectomy.

Recurrence-free survival as a surrogate for overall survival in esophageal squamous cell carcinoma: Nationwide real-world data from Japan.

269 Background: One of the limitations of the established gold standard, overall survival (OS), is that it requires an extended follow-up period. Addressing this challenge involves investigating appropriate statistically and clinically relevant surrogate endpoints. However, there is a paucity of studies using real-world data (RWD) to explore surrogacy in patients with esophageal squamous cell carcinoma (ESCC). Our study aims to investigate whether recurrence-free survival (RFS) is a valid surrogate endpoint for OS in surgically resectable advanced ESCC patients, utilizing a comprehensive nationwide database in Japan. Methods: The ESCC patients who received neoadjuvant CF (cisplatin and 5-fluorouracil) or DCF (docetaxel, cisplatin and 5-fluorouracil) at 58 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. Kendall's tau between RFS and OS was used at the individual level, and the coefficient of determination was used at the institutional level to assess surrogacy. Additionally, surrogacy between each short-term postoperative endpoint (pathological complete response [pCR] or pathological grade) and OS was investigated using novel statistical methods. Results: Our study encompassed 3154 ESCC patients who underwent subtotal esophagectomy from 2010 to 2015. The cStage I/II/III/IVA/IVB (due to supraclavicular lymph node metastasis) was 224 (7.1%), 1008 (32.0%), 1664 (52.8%), 117 (3.7%), and 140 (4.4%), respectively. The 5-year OS and RFS rate for the entire cohort was 56.6% and 47.7%, respectively. In the primary analysis, a strong correlation between RFS and OS was found (Kendall's tau = 0.797, 95% confidence interval [CI]: 0.782 to 0.812) at the individual level. Subgroup analysis revealed that the better the pathological response, the higher the tau value. An adjusted R2 of 100.0% (95% CI: 40.2 to 100.0) was obtained with the meta-regression model at the institutional level. The surrogate threshold effect was 0.703. Tau between pCR or pathological grade and OS were -0.025 (95% CI: -0.335 to 0.285) and 0.062 (95% CI: -0.086 to 0.209), respectively. Conclusions: The present study was the first nationwide RWD investigation to demonstrate a strong correlation between RFS and OS in surgically resectable ESCC patients who underwent neoadjuvant chemotherapy (NAC). Notably, this correlation was more pronounced in patients who had a more effective response to NAC. These findings hold promise for expediting the development of novel neoadjuvant treatment by shortening the duration of clinical trials.

Larynx-preserving treatment strategy for patients with resectable cervical esophageal squamous cell carcinoma.

311 Background: Preservation of the larynx is an important treatment strategy for cervical esophageal squamous cell carcinoma (CESCC), because surgery for CESCC often involves laryngectomy. At our hospital, we actively perform dCRT (cisplatin + 5-fluorouarcil + radiation 60Gy) to preserve laryngeal function. In this study, we compared the treatment results of esophagectomy and definitive chemoradiation (dCRT) for resectable CESCC and examined larynx-preserving treatment strategies. Methods: Patients who were treated for resectable CESCC at our hospital from January 2003 to March 2019 were divided into surgery group and dCRT group for the initial treatment. All patients were eligible for both treatments. The treatment results were compared retrospectively. Results: Of all 61 patients, 23 patients received surgery and 38 received dCRT. There was no significant difference in patients’ characteristics between 2 groups. In surgery group, 19 cases lost their laryngeal function by surgery (82.6%). Recurrence was observed in 7 cases, of which only 3 case was local. In CRT group, 33 cases (86.8%) achieved complete response, of which 16 cases relapsed. 8 cases (21.1%) lost their laryngeal function by additional surgery after dCRT. There was no significant difference in 5-year survival rate between two groups (surgery, 60.8%; dCRT, 70.1%; p = 0.750). In dCRT group, 5-year laryngeal-preserving survival rate was 64.8%, and esophageal stenosis before treatment was the independent risk factor for non-larynx preservation. 5-year laryngeal-preserving survival rate was 78.5%, and 5-year survival rate was 85.4% for non-stenotic cases in dCRT group, which were significantly higher than those for stenotic cases. 5-year laryngeal-preserving survival rate was also high in the patients with Ce localized tumor (72.6%). In those patients, non-stenotic patients and cT1-T3 patients had significantly high 5-year laryngeal-preserving survival rate (87.5% and 92.3%). Conclusions: dCRT for CESCC was comparable to surgery in terms of long-term prognosis, and the rate of larynx preservation was high. Among the cases where the tumor was localized to Ce, the laryngeal preservation rate was particularly high in non-stenotic cases and cases with cT1-T3, and dCRT should be actively indicated for these cases.

Anlotinib plus TQB2450 as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II study (ALTER-E005).

347 Background: There is currently a limited range of therapeutic options available for postoperative patients (pts) with esophageal squamous cell carcinoma (ESCC), emphasizing the urgent requirement to investigate more efficient and safer postoperative treatment regimens for resectable ESCC. TQB2450, a novel PD-L1 blockade, has shown promising activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors, including advanced ESCC,1 and biliary tract cancer.2 The ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with TQB2450 as adjuvant therapy in pts with ESCC. Methods: This was a single-arm, multi-center phase II clinical trial. 30 pts (≥18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and ECOG PS ≤ 1 would been rolled. Enrolled pts received oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1200 mg on day 1every 3 weeks for up to 16 cycles, until disease recurrence. The primary endpoint was disease recurrence free (DFS). The secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Results: Between August 18, 2022, and August 25, 2023, a total of 12 patients were enrolled. Out of the 12 surgically resected cases of ESCC, 11 (91.7%) had an ECOG score of 1, 10 (83.3%) were male, and 6 (50%) were under the age of 65. According to the eighth edition of the AJCC Cancer Staging Manual, 7 (58.3%) were classified as stage II, and 5 (41.7%) were classified as stage III. As of the data cut-off date (August 25, 2023), the median follow-up time was 5.1 months (95% CI: 3.4-6.8). 2 pts experienced disease recurrence, and the median duration of DFS has not yet been reached. Currently, 9 pts are still undergoing therapy, with treatment durations ranging from 0.3 months to 9.6 months. 2 pts discontinued therapy due to adverse events (AE), which subsequently improved after treatment. One patient experienced immune-related myocarditis, while the other patient had mouth ulcers and hand-foot syndrome. Additionally, one patient voluntarily withdrew from the study. Out of the total 12 patients, 3 (25%) experienced grade 3 treatment-emergent adverse events (TEAEs). There was no grade 4 or higher TEAEs reported. The grade 3 TEAEs included hand-foot syndrome (16.7%), abnormal liver function (8.3%), and immune-related hepatitis (8.3%). Conclusions: The study demonstrated the preliminary efficacy and safety of combining anlotinib with TQB2450 as adjuvant therapy in patients with ESCC who had undergone radical (R0) resection and showed no recurrence 6 to 12 weeks after surgery. 1. Zhi-Ye Zhang, et al. poster 4041: ASCO 2023. 2. Zhou J, et al. Hepatology 2022. Clinical trial information: NCT05252078 .

Contrast-enhanced CT radiomics features to preoperatively identify differences between tumor and proximal tumor-adjacent and tumor-distant tissues of resectable esophageal squamous cell carcinoma

BackgroundEsophagectomy is the main treatment for esophageal squamous cell carcinoma (ESCC), and patients with histopathologically negative margins still have a relatively higher recurrence rate. Contrast-enhanced CT (CECT) radiomics might noninvasively obtain potential information about the internal heterogeneity of ESCC and its adjacent tissues. This study aimed to develop CECT radiomics models to preoperatively identify the differences between tumor and proximal tumor-adjacent and tumor-distant tissues in ESCC to potentially reduce tumor recurrence.MethodsA total of 529 consecutive patients with ESCC from Centers A (n = 447) and B (n = 82) undergoing preoperative CECT were retrospectively enrolled in this study. Radiomics features of the tumor, proximal tumor-adjacent (PTA) and proximal tumor-distant (PTD) tissues were individually extracted by delineating the corresponding region of interest (ROI) on CECT and applying the 3D-Slicer radiomics module. Patients with pairwise tissues (ESCC vs. PTA, ESCC vs. PTD, and PTA vs. PTD) from Center A were randomly assigned to the training cohort (TC, n = 313) and internal validation cohort (IVC, n = 134). Univariate analysis and the least absolute shrinkage and selection operator were used to select the core radiomics features, and logistic regression was performed to develop radiomics models to differentiate individual pairwise tissues in TC, validated in IVC and the external validation cohort (EVC) from Center B. Diagnostic performance was assessed using area under the receiver operating characteristics curve (AUC) and accuracy.ResultsWith the chosen 20, 19 and 5 core radiomics features in TC, 3 individual radiomics models were developed, which exhibited excellent ability to differentiate the tumor from PTA tissue (AUC: 0.965; accuracy: 0.965), the tumor from PTD tissue (AUC: 0.991; accuracy: 0.958), and PTA from PTD tissue (AUC: 0.870; accuracy: 0.848), respectively. In IVC and EVC, the models also showed good performance in differentiating the tumor from PTA tissue (AUCs: 0.956 and 0.962; accuracy: 0.956 and 0.937), the tumor from PTD tissue (AUCs: 0.990 and 0.974; accuracy: 0.952 and 0.970), and PTA from PTD tissue (AUCs: 0.806 and 0.786; accuracy: 0.760 and 0.786), respectively.ConclusionCECT radiomics models could differentiate the tumor from PTA tissue, the tumor from PTD tissue, and PTA from PTD tissue in ESCC.

ASO Visual Abstract: Completely Resectable (cT1-2) Esophageal Squamous Cell Carcinoma with Minimal Lymph Node Involvement (cN1): Is Neoadjuvant Chemoradiation Therapy the Only Viable Treatment Option?

ASO Visual Abstract: Completely Resectable (cT1-2) Esophageal Squamous Cell Carcinoma with Minimal Lymph Node Involvement (cN1): Is Neoadjuvant Chemoradiation Therapy the Only Viable Treatment Option?

A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma.

Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.

Completely Resectable (cT1-2) Esophageal Squamous Cell Carcinoma with Minimal Lymph Node Involvement (cN1): Is Neoadjuvant Chemoradiation Therapy the Only Viable Treatment Option?

Neoadjuvant chemoradiation therapy (nCRT) is recommended when lymph node metastasis is evident or strongly suspected on preoperative imaging studies, even for a completely resectable (cT1-2) tumor with minimal lymph node involvement (cN1). We evaluated the validity of upfront surgical approach in this patient group. We retrospectively reviewed data from 247 patients with cT1-2 esophageal squamous cell carcinoma (ESCC) who underwent upfront radical esophagectomy followed by the pathology-based adjuvant treatment. Oncologic outcomes of cN1 patients were compared with those of cN0 patients. There were 203 cN0 and 44 cN1 patients. The lymph node yield was 62.0 (interquartile range [IQR], 51.0-76.0) in cN0 and 65.5 (IQR, 57.5-85.0) in cN1 patients (p = 0.033). The size of metastatic node was 0.6 cm (IQR, 0.4-0.9 cm) in cN0 and 0.8 cm (IQR, 0.5-1.3 cm) in cN1 patients (p = 0.001). Nodal upstaging was identified in 29.1% of cN0 and 40.9% of cN1 patients, whereas 18.2% of the cN1 had no actual lymph node metastasis (pN0). The 5-year disease-free survival rate was not significantly different between the groups (cN0, 74.4%; cN1, 71.8%; p = 0.529). Survival rates were closely correlated with pN stage, and a multivariate analysis revealed that pN2-3 stage was a risk factor for poor disease-free survival. Upfront radical surgery provided accurate nodal staging information, potentially sparing some cN1 patients from unnecessary nCRT while demonstrating comparable survival rates. It might be a valid option for the treatment of cT1-2N1 ESCC.

Peripheral T lymphocyte and immunocyte subset dynamics: markers of neoadjuvant therapy outcomes in esophageal squamous cell carcinoma.

In patients with resectable esophageal squamous cell carcinoma (ESCC), neoadjuvant therapy increased the curative resection rate, disease-free survival, and overall survival for patients with resectable ESCC. However, the efficacy of neoadjuvant therapy varies among different patients. We aim to compare the differences in the characteristics of peripheral blood T lymphocyte subsets before and after neoadjuvant therapy in patients with different curative efficacy. This study enrolled 266 ESCC patients who received neoadjuvant therapy and esophagectomy from August 2018 to August 2022. The postoperative pathological results divided patients into the major pathological response (MPR) and non-MPR groups. Compare the differences in peripheral blood T lymphocyte subsets and analyze the trend of changes in T lymphocyte subsets at different phases of treatment. Propensity score matching was used to reduce the influence of potential confounding factors. Prior to the neoadjuvant therapy, particularly before the second cycle, the MPR group exhibited significantly higher ratios of CD4/CD8 (P=0.009) and helper T cells (TH ratio, P=0.030) compared to the non-MPR group. In contrast, the suppressor T cell ratio (TS ratio) was lower (P=0.016) in the MPR group. The difference in peripheral blood lymphocyte subsets between the two groups of patients who underwent neoadjuvant chemoradiotherapy is significant. In peripheral blood, T lymphocyte subsets varied significantly based on the effectiveness of neoadjuvant treatment. Prior to the second cycle of neoadjuvant therapy, a higher CD4/CD8 and TH ratio, coupled with a decreased TS ratio, might suggest enhanced treatment outcomes.

Perioperative tislelizumab plus chemotherapy for locally advanced resectable thoracic esophageal squamous cell carcinoma trial: a prospective single-arm, phase II study (PILOT trial)

BackgroundThe promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial).MethodsSeventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival.DiscussionThis protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients.Trial registrationClinicalTrial.gov: NCT0605633.

Camrelizumab in combination with neoadjuvant chemotherapy in resectable locally advanced esophageal squamous carcinoma cancer: Results from a retrospective study.

This study aimed to evaluate the safety and efficacy of camrelizumab combined with chemotherapy during preoperative neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) of clinical Stages II and III. The patients received camrelizumab plus chemotherapy regimen on Day 1 for up to three to four cycles (3 weeks per cycle). The probabilities of overall survival (OS) were 55.6% at 12 months and 35.6% at 18 months (45 patients). The disease-free survival (DFS) rates were 70.0% at 12 months and 63.3% at 18 months (30 patients). The median OS and DFS were not reached. The proportion of patients at postneoadjuvant pathological tumor stages ypT0, ypT2, and ypT3 were 10 (33.3%), 14 (46.7%), and 6 (20.0%), respectively, and those at stages ypN0 and ypN1 were 19 (63.3%) and 11 (36.7%), respectively. Additionally, the pathological complete response rate was 33.3% (95% confidence interval [CI]: 0.154-0.512), and the major pathologic response rate was 46.7% (95% CI: 0.277-0.656). Grade ≥3 adverse events (AEs) were reported in five patients (11.1%), with vomiting being the most common AE (three patients; 3.3%). Other common AEs of any grade included decreased lymphocyte count (48.9%), reactive capillary endothelial proliferation (46.7%), decreased white blood cell count (40.0%), anemia (31.1%), and vomiting (31.1%). The combination of camrelizumab and neoadjuvant chemotherapy in patients with locally advanced resectable ESCC demonstrated promising efficacy and acceptable safety.

Neoadjuvant sintilimab plus chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: a prospective, single-arm, phase II clinical trial (CY-NICE).

Adding immune checkpoint inhibitors (ICIs) to the chemotherapy has shown significant clinical benefits in neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma (ESCC). Sintilimab is one such ICI used for treatment. Herein, we designed a trial to evaluate the safety and efficacy of sintilimab combined with paclitaxel and platinum for locally advanced resectable ESCC. Patients with locally advanced resectable (stage II-III) ESCC were enrolled and received at least two cycles of neoadjuvant therapy with sintilimab (200 mg on day 1) plus platinum-based chemotherapy in each 3-week cycle followed by esophagectomy. The primary endpoint of the trial was the pathological complete response (pCR) rate. The secondary endpoints were the major pathological response (MPR) rate, the objective response rate (ORR), the treatment-related adverse events (TRAEs), the immune-related adverse events (irAEs) and quality of life (QOL). Besides, relapse-free survival (RFS), overall survival (OS) were exploratory endpoints. Forty-three cases were needed to be enrolled in this trial. It was assumed the regimen of the neoadjuvant sintilimab plus chemotherapy would achieve a pCR rate of 30.5%. Between March 2021 and January 2023, a total of 43 patients (41 men and 2 women) were enrolled, including 11 cases (25.6%) of clinical stage II and 32 cases (74.4%) of clinical stage III at baseline. All the 43 patients completed two cycles of neoadjuvant therapy, and 32 patients received McKeown radical resection for esophageal cancer. The pCR rate was 28.1% (9/32), which was below the 30.5% reference cutoff value, and the MPR rate was 37.5% (12/32). According to RECIST 1.1, four patients (4/43, 9.3%) had a complete response (CR), 21 patients (21/43, 48.8%) had a partial response (PR), ORR was 58.1% (25/43). The incidence of ≥ grade 3 TRAEs was 23.3% (10/43) and there were no ≥ grade 4 TRAEs. Sintilimab plus platinum-based chemotherapy as neoadjuvant therapy is safe, feasible and effective in locally advanced resectable ESCC, suggesting a supportive rationale for its further evaluation in randomized clinical trials. Chinese Clinical Trial Registry identifier: ChiCTR2200056558.

Increased STX3 transcript and protein levels were associated with poor prognosis in two independent cohorts of esophageal squamous cell carcinoma patients.

Some conventional prognostic biomarkers for esophageal squamous cell carcinoma (ESCC) have the disadvantage that they have only been investigated at the level of either mRNA or protein levels or only in individual cohorts. Associations between Syntaxin 3 (STX3) expression and malignancy have been reported in several tumor types but not in ESCC. Here, we investigated the levels of both STX3 mRNA and protein, and its prognostic potential in two independent cohorts of patients with ESCC. STX3 mRNA levels were examined in surgical specimens by quantitative PCR in a cohort that included 176 ESCC patients. STX3 protein levels were investigated in surgically resected ESCC tissues by immunohistochemistry using tissue microarrays in a different cohort of 177 ESCC patients. Correlations were analyzed between the expression of STX3 mRNA and protein with clinicopathological factors and long-term prognosis. Quantitative PCR indicated a significant association between high level of STX3 mRNA expression and lymph node involvement, pathological stage, and poor overall survival. The multivariate analysis demonstrated that high STX3 mRNA expression was independently associated with poor overall survival outcomes. Immunohistochemistry revealed that STX3 protein expression in ESCC tissues and high STX3 protein expression were also significantly correlated with unfavorable overall survival. Overexpression of STX3 mRNA and protein may serve as potential prognostic biomarkers for ESCC patients.

Preoperative CT radiomics of esophageal squamous cell carcinoma and lymph node to predict nodal disease with a high diagnostic capability

PurposeTo develop CT radiomics models of resectable esophageal squamous cell carcinoma (ESCC) and lymph node (LN) to preoperatively identify LN+. Materials and Methods299 consecutive patients with ESCC were enrolled in the study, 140 of whom were LN+ and 159 were LN-. Of the 299 patients, 249 (from the same hospital) were randomly divided into a training cohort (n = 174) and a test cohort (n = 75). The remaining 50 patients, from a second hospital, were assigned to an external validation cohort. In the training cohort, preoperative contrast-enhanced CT radiomics features of ESCC and LN were extracted, then integrated with clinical features to develop three models: ESCC, LN and combined. The performance of these models was assessed using area under receiver operating characteristic curve (AUC), and F-1 score, which were validated in both the test cohort and external validation cohort. ResultsAn ESCC model was developed for the training cohort utilizing the 8 tumor radiomics features, and an LN model was constructed using 9 nodal radiomics features. A combined model was constructed using both ESCC and LN extracted features, in addition to cT stage and LN+ distribution. This combined model had the highest predictive ability among the three models in the training cohort (AUC = 0.948, F1-score = 0.878). The predictive ability was validated in both the test and external validation cohorts (AUC = 0.885 and 0.867, F1-score = 0.816 and 0.773, respectively). ConclusionTo preoperatively determine LN+, the combined model is superior to models of ESCC and LN alone.

Neoadjuvant Chemoradiotherapy Followed by Minimally Invasive Esophagectomy for Borderline Resectable Esophageal Squamous Cell Carcinoma

Neoadjuvant Chemoradiotherapy Followed by Minimally Invasive Esophagectomy for Borderline Resectable Esophageal Squamous Cell Carcinoma

Optimal Treatment Strategies for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Real-World Triple Cohort Analysis Using Propensity Score Matching.

This study aims to identify the most effective treatment approach and compares the survival rates, along with complications, in patients with locally resectable esophageal squamous cell carcinoma (ESCC) who were treated with one of the three treatment patterns: neoadjuvant chemotherapy followed by surgery (NCT+S), neoadjuvant chemoradiotherapy followed by surgery (NCRT+S), or surgery followed by chemoradiotherapy (S+CRT). We conducted a retrospective analysis of the medical records of ESCC patients who received one of these treatments between March 2015 and March 2022. This analysis aimed to identify differences in long-term survival, pathological responses, and complications across the three treatment groups. To address potential confounding factors, propensity score matching (PSM) and Cox proportional hazards models were utilized. This study included a cohort of 715 patients: 197 in the NCT+S group, 188 in the NCRT+S group, and 330 in the S+CRT group, all meeting the selection criteria. After PSM, the median disease-free survival (DFS) time was 38.9 months, 25.6 months, and 15.3 months for NCRT+S, NCT+S, and S+CRT groups, respectively. There were statistically significant differences in the 5-year DFS and 5-year OS among the three groups (P=0.04 and P=0.02, post-matching, respectively). Notably, neoadjuvant therapy showed a correlation with increased postoperative anastomotic leakage rates (17.5% in NCRT+S, 10% in NCT+S, and 5% in S+CRT; P=0.03, post-matching), regardless of the PSM adjustment. The findings indicate that neoadjuvant therapy before surgery offers a significant survival advantage over postoperative adjuvant therapy for patients with locally advanced resectable ESCC. Despite similar safety profiles, neoadjuvant therapy appears to be associated with a higher incidence of anastomotic leakage after surgery.

145P Tislelizumab (TIS) + chemotherapy (Chemo)/chemoradiotherapy (CRT) as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (R-ESCC)

145P Tislelizumab (TIS) + chemotherapy (Chemo)/chemoradiotherapy (CRT) as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (R-ESCC)