Resected Esophageal Squamous Cell Carcinoma Research Articles

Clinical outcomes of conversion surgery after induction immunochemotherapy for borderline resectable T4 esophageal squamous cell carcinoma

BackgroundThe current treatment strategies for borderline resectable esophageal squamous cell carcinoma remain controversial. This study aimed to evaluate the efficacy and safety of programmed cell death 1 inhibitors combined with chemotherapy, followed by conversion surgery, for borderline resectable esophageal squamous cell carcinoma.MethodsPatients with borderline resectable esophageal squamous cell carcinoma treated with induction immunochemotherapy from January 1, 2020 to July 1, 2023 at our hospital were retrospectively analyzed. The primary study outcome was the R0 resection rate. Secondary study outcomes included progression-free survival (PFS), overall survival (OS), pathological complete remission (pCR) rate, and safety.ResultsForty patients with borderline resectable esophageal squamous cell carcinoma were included in the analysis. The R0 resection rate was 23/40 (57.5%); the conversion success rate was 27/40 (67.5%), and the pCR rate was 11/40 (27.5%). The median follow-up was 23.6 months (95% CI, 19.1–28.2). One-year OS and PFS rates were 77.7% and 71.8%, respectively. The incidence rate of Grade 3–4 adverse events was 10%. There was a significant difference in PFS between patients who underwent surgery and those who did not (P = 0.008, HR: 0.144 95%CI: 0.034–0.606). However, the difference in OS was not significant (P = 0.128, HR: 0.299 95%CI: 0.063–1.416). Patients who achieved clinical downstaging after induction therapy had significantly better OS (P = 0.004 h: 0.110 95%CI: 0.025–0.495) and PFS (P = 0.0016, HR: 0.106 95%CI: 0.026–0.426) compared to those who did not.ConclusionsConversion surgery after induction immunochemotherapy is a promising new strategy with a high conversion rate, inspiring R0 resection rate, significant pathological remission rate, and mild toxicity for borderline resectable esophageal squamous cell carcinoma.

Radiomics nomogram combined with clinical factors for predicting pathological complete response in resectable esophageal squamous cell carcinoma

IntroductionPredicting the efficacy of neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESSC) prior to surgery can minimize unnecessary surgical interventions and facilitate personalized treatment strategies. Our goal is to develop and validate an image-based radiomic model using preoperative computed tomography (CT) scans and clinical data to predict pathological complete response (pCR) in resectable ESSC following neoadjuvant immunotherapy.MethodsWe retrospectively collected data from patients diagnosed with ESCC at the First Affiliated Hospital of Soochow University between January 2018 and May 2023, who received preoperative neoadjuvant immunochemotherapy. Eligible patients were randomly divided into training and validation sets. Radiomic features extracted from preprocessed CT images were used to develop a radiomic model, incorporating Radiomic score (Rad-score) and clinical factors through multivariate logistic regression analysis. The model’s performance was assessed for calibration, discrimination, and clinical utility in an independent validation cohort.ResultsWe enrolled a total of 105 eligible participants who were randomly divided into two groups: a training set (N=74) and a validation set (N=31). After data dimension reduction and feature selection, we identified 11 radiomic features, which collectively formed the Rad-score. Rad-score had an area under the curve (AUC) of 0.83 (95% CI 0.72-0.93) in the training set and 0.78 (95% CI 0.60-0.95) in the validation set. Multivariate analysis revealed that radiological response and Neutrophil–Lymphocyte Ratio (NLR) were independent predictors of pCR, with p-values of 0.0026 and 0.0414, respectively. We developed and validated a nomogram combining Rad-score and clinical features, achieving AUCs of 0.90 (95% CI 0.82-0.98) in the training set and 0.85 (95% CI 0.70-0.99) in the validation set. The Delong test confirmed the nomogram’s superiority over pure radiomic and clinical models. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) assessment supported the clinical value and superiority of the combined model.ConclusionThe nomogram, which integrates Rad-score and clinical features, offers a precise and reliable method for predicting pCR status in ESCC patients who have undergone neoadjuvant immunochemotherapy. This tool aids in tailoring treatment strategies to individual patients.

Overexpression of Fibroblast Growth Factor 8 Is a Predictor of Impaired Survival in Esophageal Squamous Cell Carcinoma and Correlates with ALK/EML4 Alteration

FGF8, ALK, and EML4 have been identified as promising biomarkers in a number of malignancies. The aim of this study was to examine the prognostic role of FGF8, ALK, and EML4 in esophageal squamous cell carcinoma (ESCC). Methods: Consecutive patients with ESCC who underwent upfront resection were included in this study. ALK and EML4 gene status was evaluated by fluorescence in situ hybridization (FISH) using a triple-color break-apart single-fusion probe and a probe against 2p11. FGF8, ALK, and EML4 protein expression was determined by immunohistochemistry. Results: A total of 122 patients were included in this study. Multivariate analysis revealed that FGF8 overexpression is an independent negative prognostic factor for patients’ overall survival (OS) (p = 0.04). Furthermore, a significant correlation between the expression of FGF8, and ALK (p = 0.04) and EML4 (p = 0.01) alteration was found. Conclusions: FGF8 overexpression is an adverse independent prognostic factor in patients with upfront resected ESCC. Furthermore, FGF8 expression significantly correlates with ALK and EML4 amplification and may therefore qualify as a future therapeutic target.

Comparison of neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma: a retrospective study with 3-year survival analysis

BackgroundNeoadjuvant chemoimmunotherapy (nCIT) for locally advanced esophageal squamous cell cancer (ESCC) has shown short-term benefits, but long-term survival outcomes are unclear. This study compares nCIT and neoadjuvant chemotherapy (nCT) in resectable ESCC.Patients and methodsA retrospective analysis was conducted on ESCC patients who underwent nCT or nCIT followed by esophagectomy. Propensity score matching (PSM) with a caliper of 0.02 was employed to minimize bias. The primary endpoints included disease-free survival (DFS) and overall survival (OS).ResultsA total of 131 comparable pairs of ESCC patients receiving nCT and nCIT were selected for the final analysis. The nCIT had higher rates of pathological complete response (pCR) and major pathological response (mPR) compared to nCT. Additionally, nCIT led to significant tumor down-staging, higher rates of R0 resection, and increased lymph node clearance during surgery. Patients who received nCIT exhibited improved disease-free survival (DFS) and overall survival (OS) at the 3-year follow-up. The incidence of distant and mixed relapses was lower in the nCIT group compared to the nCT group. However, the risk of locoregional relapse was comparable between the two groups. Subgroup analyses showed that the benefits of nCIT were generally observed across most patient subgroups. Interestingly, in patients without pCR or mPR, nCIT still demonstrated better survival benefits than nCT.ConclusionnCIT demonstrated superior pathological response rates and improved 3-year DFS and OS compared to nCT alone in locally advanced ESCC, but long-term survival validation is needed.

Prognostic Impact of Thoracic Duct Resection in Patients Who Underwent Transthoracic Esophagectomy Following Neoadjuvant Therapy for Esophageal Squamous Cell Carcinoma: Exploratory Analysis of JCOG1109.

Although several studies have investigated whether thoracic duct (TD) resection improves prognosis, the conclusion remains controversial. JCOG1109 is a three-arm randomized phase III trial to confirm the survival advantage of docetaxel, cisplatin, 5-fluorouracil (DCF), and cisplatin plus 5-fluorouracil (CF) combined with radiotherapy (CF-RT) over CF as neoadjuvant treatment. The study aimed to evaluate the survival impact of TD resection and its association with neoadjuvant treatment and pathological response in patients enrolled in JCOG1109. Clinicopathological factors, surgical results, and prognosis were compared between TD preserved and resected groups. The survival impact of TD resection was also evaluated in the subgroups on the basis of combinations of preoperative therapy and pathological response. Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200) in JCOG1109. Of them, 541 patients underwent esophagectomy (183/181/177), and TD was resected in 265 patients (93/91/81). For the entire cohort, TD resection was not a significant prognostic factor for overall survival in the multivariable analysis (HR 1.20, 95% CI 0.91-1.57). In the subgroup analyses by combinations of neoadjuvant treatment and pathological response, TD resected group had a significantly better overall survival compared with TD preserved group in patients who received DCF and achieved pathological response (HR 0.20, 95% CI 0.07-0.61). The survival benefit of TD resection was not demonstrated in patients with surgically resectable esophageal squamous cell carcinoma enrolled in JCOG1109. The residual tumor burden after neoadjuvant treatment might be linked to the survival impact of TD resection.

Phase II Trial of Adjuvant S-1 Following Neoadjuvant Chemotherapy and Surgery in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: The PIECE Trial.

Neoadjuvant chemotherapy followed by surgery (NAC-S) is the standard therapy for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan. The aim of this phase II trial was to assess the efficacy and safety of the addition of adjuvant S-1 after R0 resection in ESCC patients who received NAC-S. Key eligibility criteria included clinical stage IB-III (without T4 disease) ESCC, age 20-75years, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received adjuvant therapy with four cycles of S-1 (80mg/m2/day) administered orally for 4 weeks of 6-week cycles. The primary endpoint was 3year relapse-free survival (RFS). If the lower confidence limit for 3year RFS was >50%, we judged that the primary endpoint of this study was met. A total of 52 patients were enrolled between January 2016 and January 2019. Two patients were excluded from analysis; five patients were determined to have R1 or R2 resection, and seven patients did not receive adjuvant S-1. The 3-year RFS and overall survival rates in the intention-to-treat population were 72.3% (90% confidence interval [CI] 59.9-81.5) and 85.0% (90% CI 73.9-91.6), indicating that the primary endpoint was met. Grade ≥3 adverse events with an incidence ≥10% included neutropenia (13.2%), anorexia (13.2%), and diarrhea (10.5%). There were no treatment-related deaths. Adjuvant S-1 after NAC-S showed promising efficacy with a manageable safety profile for patients with resectable ESCC and warrants further evaluation in larger studies.

Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

442. POSTOPERATIVE ADJUVANT RADIOTHERAPY REDUCES LOCOREGIONAL RECURRENCE IN PATIENTS WITH BORDERLINE RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background borderline resectable esophageal squamous cell carcinoma (Br-ESCC) patients who underwent R0 resection had a significantly improved prognosis. However, local recurrence cannot be ignored. We sought to investigate the efficacy of postoperative adjuvant radiotherapy in reducing locoregional recurrence in patients with Br-ESCC. Methods we established a new resection status, Rbr+, which was defined as no clear boundary between the mass/scar and the outer aortic/tracheal membrane, no visible cancer remaining on the outer aortic/tracheal membrane, and a pathologically negative circumferential margin. patients with Br-ESCC who underwent curative esophagectomy at our center from January 2018 to December 2021 were eligible for this study. Patient characteristics, and perioperative variables were included in this study. univariable and multivariable analyses were performed to compare locoregional recurrence based on the logistic regression model. The Kaplan-Meier method and Cox proportional hazard model were used to compare overall and cause-specific survival. Results A total of 99 patients were included, among whom 27 (27.3%) had a locoregional recurrence. 71.7% (71/99) were classified as Rbr+ resection, and 28.3% (28/99) were classified as Rbr- resection. With a median postoperative follow-up of 55.3 months (range, 24.3-70.8 months), 25 patients out of 71 with Rbr+ resection suffered from local recurrence. However, 2 patients out of 28 with Rbr- resection suffered from locally recurrence. The locoregional recurrence was 25%(7/28) and 41.9%(18/43) in Rbr+ resection with and without postoperative adjuvant radiotherapy. While, the locoregional recurrence was 8.33%(1/12) and 6.25%(1/16) in Rbr- resection patients with and without postoperative adjuvant radiotherapy. Conclusion Rbr+ resection was independently associated with locoregional recurrence in patients with Br-ESCC. postoperative adjuvant radiotherapy was independently associated with overall and cause-specific survival in patients with Br-ESCC.

780. NEOADJUVANT IMMUNOTHERAPY COMBINED WITH CHEMORADIOTHERAPY VS NEOADJUVANT CHEMORADIOTHERAPY FOR LOCALLY ADVANCED ESOPHAGEAL CARCINOMA (CSTAGEII-III): A MULTI-CENTER PROSPECTIVE RANDOMIZED CLINICAL TRIAL (ICROSS)

Abstract Background The role of neoadjuvant immunotherapy combined with chemoradiation in the treatment of esophageal cancer is not yet fully understood. This study aims to compare the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiation versus traditional neoadjuvant chemoradiation in treating locally advanced esophageal squamous cell carcinoma (stages cII-III). Methods This prospective randomized controlled trial included histologically confirmed patients with potentially resectable esophageal squamous cell carcinoma (stages cII-cIII). Patients were randomly assigned to two groups: the treatment group (Arm A) received BGB-A317 (200mg IV) combined with the CROSS regimen of chemotherapy and radiation, while the control group (Arm B) received only the CROSS chemotherapy and radiation regimen. All patients underwent surgery followed by a five-year follow-up. The primary endpoints included pathological complete response rate (pCR), tumor regression grades, and lymph node clearance. Results The study enrolled 67 patients (52 males, 15 females) aged between 18-75 years. Tumor locations were as follows: upper segment in 16 cases, middle segment in 45 cases, and lower segment in 6 cases. A total of 64 patients were included in the analysis. There were no significant differences between the two groups in terms of pCR rates (Arm A 41.4% vs. Arm B 30.8%, p=0.414), tumor regression grades, Surgical time (221.09 ± 37.54 minutes vs. 227.05 ± 50.28 minutes, p=0.593), Estimated blood loss (182.73 ± 337.41 ml vs. 90.47 ± 66.36 ml, p=0.109), and postoperative hospital stay (9.31 ± 4.12 days vs. 8.42 ± 1.16 days, p=0.555). However, the treatment group had significantly more lymph nodes retrieved during surgery compared to the control group (26.86 ± 7.96 vs. 20.85 ± 9.68, p=0.020). The safety profiles were similar between the groups with no significant adverse events observed. Conclusion For patients with locally advanced esophageal squamous cell carcinoma, neoadjuvant immunotherapy combined with chemoradiation is comparable in efficacy and safety to neoadjuvant chemoradiation alone and may facilitate more effective lymph node clearance. Although these preliminary results are encouraging, further long-term follow-up and larger-scale studies are needed to validate these clinical findings once the study is complete.

Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis of randomized clinical trials

BackgroundThe comparison of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) for locally advanced esophageal squamous cell carcinoma (ESCC) remains inconclusive, and the optimal regimen is still under investigation. MethodsProspective randomized clinical trials were systematically searched in electronic databases from inception to Oct 2023. A graphical reconstructive algorithm was employed to extract time-to-event outcomes from Kaplan-Meier curves presented in the original studies. Using reconstructed individual patient data, summary overall survival (OS) and disease progression-free survival (DFS) for nCRT versus nCT, primarily doublet chemotherapy were recalculated. Hazard Ratios (HRs) of OS and DFS reported were also pooled by the fixed-effects model. ResultsA total of 6 randomized clinical trials comprising 1162 patients were included in our analysis. In the individual patient data (IPD) pooled analysis, a significant OS benefit was found for nCRT in ESCC (HR=0.81, 95 %CI:0.67–0.98, p=0.029), compared with the treatment of nCT. The median overall survival time were 53 months (95 %CI:41.9–67.7 m) and 66 months(95 %CI:57.2-NA) respectively in the nCT and nCRT groups. Additionally, a significant improvement in PFS for nCRT compared to nCT in the IPD pooled analysis (HR=0.79,95 %CI:0.64–0.98; p=0.027). Consistent with above results, the pooled HRs of OS and DFS for nCRT versus nCT were 0.78 (95 % CI 0.65–0.92, p=0.004) and 0.79 (95 % CI: 0.65–0.97, p=0.02), respectively. Notably, no substantial heterogeneity across studies was observed. ConclusionsOur findings indicate that nCRT offers better survival outcomes for ESCC, at least when compared to neoadjuvant doublet chemotherapy.This evidence continues to support the clinical practice of employing nCRT in locally advanced resectable ESCC.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial

BackgroundNeoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC.MethodsIn this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT.ResultsTotally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses.ConclusionsNeoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

Conversion chemoradiotherapy combined with nab-paclitaxel plus cisplatin in patients with locally advanced borderline-resectable or unresectable esophageal squamous cell carcinoma: a phasei/ii prospective cohort study.

To evaluate the efficacy and safety of nab-paclitaxel plus cisplatin as the regimen of conversional chemoradiotherapy (cCRT) in locally advanced borderline resectable or unresectable esophageal squamous cell carcinoma (ESCC). Patients with locally advanced ESCC (cT3‑4, Nany, M0‑1, M1 was limited to lymph node metastasis in the supraclavicular area) were enrolled. All the patients received the cCRT of nab-paclitaxel plus cisplatin. After the cCRT, those resectable patients received esophagectomy; those unresectable patients continued to receive the definitive chemoradiotherapy (dCRT). The locoregional control (LRC), overall survival (OS), event-free survival (EFS), distant metastasis free survival (DMFS), pathological complete response (pCR), R0resection rate, adverse events (AEs) and postoperative complications were calculated. 45patients with ESCC treated from October 2019 to May 2021 were finally included. The median follow-up time was 30.3 months. The LRC, OS, EFS, DMFS at 1and 2years were 81.5%, 86.6%, 64.3%, 73.2 and 72.4%, 68.8%, 44.8%, 52.7% respectively. 21patients (46.7%) received conversional chemoradiotherapy plus surgery (cCRT+S). The pCR rate and R0resection rate were 47.6 and 84.0%. The LRC rate at 1and 2years were 95.0%, 87.1% in cCRT+Spatitents and 69.3%, 58.7% in dCRT patients respectively (HR, 5.14; 95%CI, 1.10-23.94; P = 0.021). The toxicities during chemoradiotherapy were tolerated, and the most common grade3-4 toxicitiy was radiation esophagitis (15.6%). The most common postoperative complication was pleural effusion (38.1%) and no grade ≥ IIIb complications were observed. nab-paclitaxel plus cisplatin are safe as the regimen of conversional chemoradiotherapy of ESCC.

Preoperative camrelizumab combined with chemotherapy for borderline resectable ESCC: A single-arm, prospective, phase 2 study.

We investigated the safety and efficacy of preoperative camrelizumab combined with chemotherapy for treating thoracic borderline resectable esophageal squamous cell carcinoma (Br-ESCC) (ChiCTR2200056728). Patients with thoracic Br-ESCC received intravenous camrelizumab plus chemotherapy and underwent esophagectomy. The primary endpoint was the pathologic complete response (pCR) rate. We introduced computed tomography and endoscopic examination into the diagnostic criteria to increase its reproducibility. Additionally, we defined a new resection status, Rbr+/-, for Br-ESCC. Thirty-one patients with Br-ESCC were ultimately enrolled in this study. Overall, 71.0% (22/31) of the patients underwent esophagectomy. R0 resection was achieved in 81.8% of patients (18/22). pCR and major pathological response were observed in 40.9% (9/22) and 63.6% (14/22) of the resected patients, respectively. Eighteen R0 resection patients were redefined according to our Rbr definition; 61.1% (11/18) were classified as Rbr+ resection, and 38.9% (7/18) were classified as Rbr- resection. With a median postoperative follow-up of 17.9months, 4 patients out of 11 who underwent Rbr+ resection experienced local recurrence (2 of whom achieved pCR). However, no patients (0/7) who underwent Rbr- resection experienced local recurrence. Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for Br-ESCC. R0 resection was achieved in 81.8% of patients, and a pCR was observed in 40.9% of resected patients. Even after complete excision, Rbr+ resection leads to a higher rate of local recurrence in patients with Br-ESCC. This study was supported by the Key Scientific Research Projects of the Institutions of Higher Learning in Henan Province (no. 21A320032).

The relationship between the treatment course and prognosis of oligometastasis after esophageal squamous cell carcinoma resection.

The concept of oligometastasis, which represents limited metastatic disease, has recently gained interest, accompanied by a more detailed classification. This study aims to investigate the relationship between the treatment course and prognosis in patients with a recurrence of esophageal squamous cell carcinoma (ESCC) after curative esophagectomy. 126 patients with ESCC recurrence after curative resection were enrolled in this study. Oligometastasis was defined as fewer than five recurrences in a single organ. Patients were classified as having oligometastatic recurrence (OLR) or polymetastatic recurrence (PLR). Patients were further classified into four subgroups according to lesion progression: persistent oligorecurrence (PER-OLR), converted polyrecurrence (CON-PLR), induced oligorecurrence (IND-OLR), and persistent polyrecurrence (PER-PLR). We analyzed the relationship between the recurrence patterns and prognosis according to the progression of oligometastatic lesions. OLR was identified in 58 (46%) of 126 patients with recurrence. Patients with OLR had a significantly better prognosis than those with PLR (P < 0.0001). A further subgroup analysis revealed that patients who underwent IND-OLR had a similar prognosis to those who underwent PER-OLR. This study suggests that OLR is a prognostic factor after recurrence following resection of ESCC and that PLR can be converted to OLR by therapeutic intervention to achieve a long-term survival.

Real-world retrospective study of anti-PD-1 antibody in combination with chemotherapy as a neoadjuvant treatment strategy for locally advanced resectable esophageal squamous cell carcinoma.

Neoadjuvant therapy has become a mainstay of treatment for locally advanced resectable esophageal cancer. The objective of this research was to investigate the effectiveness and safety of neoadjuvant immunotherapy combined with chemotherapy in treating surgically removable esophageal squamous cell carcinoma (ESCC). From January 1, 2016 to April 1, 2023, we conducted a retrospective analysis of patients diagnosed with resectable esophageal cancer who underwent neoadjuvant immunotherapy combined with chemotherapy at The First Affiliated Hospital of Nanchang University. The primary endpoints of this study were pathologic complete response (pCR), major pathologic response (MPR) and disease-free survival (DFS). The secondary endpoints of this study were overall survival (OS), objective response rate (ORR) and safety. A total of 122 patients with ESCC receiving neoadjuvant immune-chemotherapy (nICT) were included. Fifty-four patients achieved partial response (PR) and two patients achieved complete response (CR), with an ORR of 45.9%. Of the 106 patients who underwent surgery, a total of 28 patients achieved pCR (26.4%) and a total of 37 patients achieved MPR (34.9%). Grade 3 or higher adverse events occurred in 26 patients (21.3%). The most common postoperative complication was pneumonitis (25.5%). Neoadjuvant immunotherapy combined with chemotherapy demonstrates satisfactory efficacy in the treatment of locally advanced ESCC, with manageable treatment-related adverse events and postoperative complications.

A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma.

S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC). This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights. A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity. S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1–32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7–18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034.

Optimizing Organ-Preservation Strategies Through Chemotherapy-Based Selection in Esophageal Squamous Cell Carcinoma: Results From the CROC Multi-Institutional Phase 2 Clinical Trial

PurposeThis study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC). Methods and MaterialsChemotherapy-naïve patients with resectable ESCC (stage IB–III, UICC, International Cancer Control 7th edition) were eligible for the study. All patients received three cycles of DCF therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1–5, repeated every three weeks). A remarkable response was defined as a reduction of the tumor to T1, metastatic lymph nodes smaller than 1 cm on the short axis, and downstaging to stage IA after three cycles of DCF therapy. Remarkable responders then underwent dCRT, which included two courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1–4, repeated every four weeks, along with 50.4 Gy of concurrent radiotherapy. The primary endpoint was 1-year progression-free survival (PFS) in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival (EFS). ResultsOf the 92 patients registered, 90 were analyzed. A remarkable response to three courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range: 1–85 months), the 1-year PFS was 89.8% (95% confidence interval = 77.2%–95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and EFS rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after two courses of DCF therapy was significantly associated with OS (p = 0.0049). ConclusionsIn patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with three courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection.

Investigating esophageal sarcomatoid carcinoma and its comparison with esophageal squamous cell carcinoma on clinicopathological characteristics, prognosis, and radiomics features: a retrospective study.

Esophageal sarcomatoid carcinoma (ESC) is a rare pathological subtype of esophageal carcinomas, wherein its epithelial component typically demonstrates squamous cell carcinoma (SCC). However, the clinicopathological features and prognosis of ESC remain unclear, alongside its unique aspects compared to esophageal SCC (ESCC). Between January 2008 and December 2018, we retrospectively reviewed 67 ESC patients treated at West China Hospital. Among them, 51 patients with resected ESC were matched with 98 resected ESCC patients over the same period using propensity score matching at 1:2. The survival time and radiomics features of the two groups were compared. A total of 59 patients with resected ESC and eight patients with non-resected ESC were enrolled. Progression-free survival (PFS) and overall survival (OS) were significantly different in patients with different TNM stages (p < 0.001). A multivariate analysis showed that length of tumor was an independent factor for OS in resetable ESC (p = 0.041). Among matched ESC and ESCC patients, OS was significantly longer for patients with ESC than those with ESCC (5-year OS, 61.1% vs. 43.6%; HR 0.59, 95% CI 0.35-0.96; p = 0.032). A Rad-score for discriminating ESC from ESCC containing two CT-derived radiomics features was developed [area under the curve: 0.823 (95% CI 0.732-0.913) in the training cohort and 0.828 (95% CI 0.636-1.000) in the validation cohort, respectively]. ESC has a better prognosis when compared with ESCC. By developing a radiomics prediction model, we provide reliability and convenience for the differential diagnosis of ESC from ESCC.

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy for resectable esophageal cancer: a systematic review and meta-analysis.

Esophageal cancer is often overlooked in its early stages, with approximately 70% of patients being diagnosed at a locally advanced or late stage. Surgical treatment and chemotherapy are the mainstays of esophageal cancer management. However, for locally advanced esophageal cancer, both surgery alone and chemotherapy alone have high rates of recurrence and metastasis. The objective of the research was to investigate the security and therapeutic efficacy of neoadjuvant immunochemotherapy (NICT) in the treatment of resectable, locally advanced esophageal squamous cell carcinoma (ESCC). We conducted a literature search on PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), China Biomedical Literature Database, and Wanfang for studies published before November 2023 that investigated on the clinical effectiveness and safety of neoadjuvant immunotherapy in resectable ESCC. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used for assessment, and Stata 17.0 was utilized for meta-analysis and sensitivity analysis. A total of 13 retrospective cohort studies involving 1,276 patients were included in this analysis. The NICT group showed a higher pathological complete response (pCR) rate [odds ratio (OR) =5.72; 95% confidence interval (CI), 3.40-9.63]. The major pathologic response (MPR) rate, objective response rate (ORR), R0 resection rate, and 1-year overall survival (OS) in the NICT group were better than those in the neoadjuvant chemotherapy (NCT) group (OR =3.70, 95% CI: 2.32-5.91; OR =2.22, 95% CI: 1.44-3.40; OR =2.63, 95% CI: 1.58-4.38; OR =10.08, 95% CI: 4.32-23.56). However, the NICT group also showed a drawback in terms of adverse reactions and postoperative complications. The incidence of rash (OR =4.69, 95% CI: 1.42-15.49) and pleural effusion (OR =3.99, 95% CI: 1.75-9.07) was significantly higher in the NCT group compared to the NICT group. The subgroup analysis indicates that the use of camrelizumab is associated with an increased incidence of rash. Additionally, performing a left thoracic esophagectomy and esophagogastric thoracic procedure significantly improved the R0 resection rate. Neoadjuvant immunotherapy has shown promising efficacy in patients with locally advanced ESCC; however, it is linked to a higher occurrence of adverse events. Therefore, its use in clinical practice should be carefully considered.