Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China, with most patients presenting with locally advanced disease. Neoadjuvant chemoradiotherapy (nCRT) is the current standard of care, while neoadjuvant immunochemotherapy (nICT) has emerged as a promising alternative. However, no large-scale randomized controlled trial has directly compared nICT versus nCRT for long-term overall survival (OS) in this population. This study aims to compare the causal effects of nICT versus nCRT on OS and other key outcomes in patients with resectable locally advanced ESCC using target trial emulation (TTE) methodology. This is a single-center, retrospective, observational cohort study using TTE. Data are derived from electronic health records (EHR) of esophageal cancer patients hospitalized at Henan Cancer Hospital between January 2013 and December 2025. Patients meeting eligibility criteria (age ≥18 years; histologically confirmed ESCC; clinical stage cT3-4a N0-2 M0 or cT2N+ M0; ECOG PS 0-1; no prior antitumor therapy) are assigned to nICT or nCRT groups based on actual treatment initiation. Propensity score overlap weighting is used to balance baseline covariates. The primary outcome is overall survival (OS). Secondary outcomes include event-free survival (EFS), pathological complete response (pCR) rate, tumor regression grade (TRG), R0 resection rate, and safety. This study will provide real-world causal evidence on the comparative effectiveness of nICT versus nCRT in the Chinese ESCC population.

In this prospective paired diagnostic study and single-center, randomized controlled trial, patients with early esophageal squamous neoplasia or high-grade intraepithelial neoplasia meeting the inclusion and exclusion criteria will be enrolled in a paired diagnostic cohort (60 patients) and subsequently randomly assigned (1:1) to receive endoscopic submucosal dissection (ESD) with AI-based Dissection Trajectory Prediction System (ADTPS) guidance or conventional ESD (without AI). Clinical data and operator workload scores (NASA-TLX) are collected during the procedure, and postoperative follow-up assessments are performed at days 1, 3, 7, and 14. The study aims to analyze the impact of ADTPS on the mean single-dissection time and operator workload in patients undergoing ESD by comparing the efficacy differences between the experimental and control groups. Additionally, the study investigates the effects of ADTPS on other postoperative complications including R0 resection rate, muscularis propria injury, intraoperative bleeding, perforation (acute and delayed), and total procedure time; conducts a comparative analysis of the safety and efficiency of AI-assisted versus conventional ESD; and develops effective clinical strategies for optimizing dissection trajectory and reducing complications in endoscopic submucosal dissection.

This is a prospective, single-arm phase II clinical trial intended to investigate the efficacy of neoadjuvant CTLA-4 monoclonal antibody combined with PD-1 monoclonal antibody plus preoperative chemoradiotherapy for locally advanced esophageal cancer. A total of 44 patients with resectable esophageal squamous cell carcinoma (ESCC) will be enrolled.All enrolled subjects will receive induction therapy with the combination of a CTLA-4 inhibitor and a PD-1 inhibitor. Three weeks afterwards, patients will transition to concurrent chemoradiotherapy combined with PD-1 inhibitor. Intensity-modulated radiotherapy (IMRT) will be delivered at a total dose of 40 Gy in 20 fractions. Radical esophagectomy with two-field thoracic and abdominal lymph node dissection will be performed 6-8 weeks after completion of chemoradiotherapy.The primary objective of this trial is to evaluate the efficacy and safety of the triplet regimen consisting of CTLA-4 inhibitor plus PD-1 inhibitor combined with preoperative chemoradiotherapy in locally advanced esophageal cancer, so as to further optimize the multimodal therapeutic strategy for esophageal cancer.

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy with poor prognosis, particularly in patients with locally advanced disease. Neoadjuvant chemoimmunotherapy has shown promising antitumor activity and may improve pathological response; however, a proportion of patients achieve only stable disease (SD) or progressive disease (PD) after initial treatment and may have limited benefit from proceeding directly to surgery. This prospective, single-center, phase II clinical study aims to evaluate an early response-guided sequential selective radiotherapy strategy after neoadjuvant chemoimmunotherapy in patients with locally advanced, resectable ESCC. Patients will initially receive neoadjuvant chemotherapy combined with PD-1 inhibitor therapy. Based on radiological response assessment, patients with major response (complete response or partial response) will proceed directly to radical surgery, whereas patients with insufficient response (stable disease or progressive disease but still considered resectable) will receive sequential chemoradiotherapy followed by surgery. The study aims to assess the safety and efficacy of this individualized treatment strategy, with primary evaluation focusing on pathological response, surgical outcomes, and treatment-related adverse events. Exploratory analyses will investigate potential biomarkers associated with treatment response and prognosis.

Although immunotherapy combined with chemotherapy has become the first-line standard regimen for advanced esophageal squamous cell carcinoma (ESCC) and improved clinical outcomes in advanced patients, the prognosis of patients with esophageal cancer remains unsatisfactory, with a 5-year overall survival rate below 20%. As an effective modality for local disease control, local radiotherapy has no established optimal sequencing schedule when combined with systemic therapy. The timing of radiotherapy intervention may directly affect treatment efficacy, treatment tolerance and quality of life of patients. Several studies have explored the impact of radiotherapy timing in oligometastatic ESCC, yet substantial limitations persist in current evidence, resulting in a lack of unified guideline recommendations and wide heterogeneity in clinical practice. Most existing investigations are retrospective or small-sample prospective studies with high heterogeneity in study design, patient population selection and treatment regimens, yielding inconsistent conclusions that cannot support consistent clinical consensus. To clarify the impact of radiotherapy timing on clinical efficacy in oligometastatic esophageal cancer, the investigator designed the present clinical trial. This study aims to compare the efficacy and safety of concurrent radiotherapy versus sequential radiotherapy on the basis of immunochemotherapy among patients with oligometastatic ESCC, so as to fill the evidence gap in existing research.

This is a single-arm, multi-center phase II study to evaluate the efficacy and safety of sacituzumab tirumotecan (Sac-TMT/SKB264) combined with tagitanlimab (KL-A167) as 2nd line therapy for recurrent or metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction adenocarcinoma (G/GEJA). A total of 75 participants are planned to be enrolled with 10 in the safety lead-in phase and 33 ESCC and 42 G/GEJA in expansion phase, seperately.

This is a prospective, multicenter, observational cohort study of patients with esophageal squamous cell carcinoma who have received neoadjuvant immunochemotherapy and are scheduled to undergo curative esophagectomy with standard systematic lymphadenectomy. The study will not alter the current standard surgical approach. All patients will receive curative esophagectomy and systematic lymph node dissection according to institutional practice. Lymph nodes will be separated and recorded by anatomical station during surgery, followed by station-level pathological assessment. Imaging findings, pathological response, perioperative outcomes, recurrence patterns, disease-free survival, overall survival, and selected immune microenvironment features will be collected and analyzed. The purpose of this study is to characterize station-level residual lymph node metastasis risk and immune activity after neoadjuvant immunochemotherapy. The findings may help identify candidate lymph node stations for future research on individualized or lymph node-preserving surgical strategies in esophageal squamous cell carcinoma.

Gastrointestinal (GI) cancers remain a major global health burden, largely due to the lack of effective and accessible early screening strategies. Current diagnostic approaches-including endoscopy, computed tomography (CT), and magnetic resonance imaging (MRI)-are either invasive, resource-intensive, or insufficiently sensitive for detecting early-stage disease, and are therefore not suitable for population-wide screening or for simultaneously identifying multiple GI tumor types. As a result, many patients are diagnosed at advanced stages, when therapeutic options are limited and prognosis is poor. Circulating microRNAs (miRNAs) offer a promising alternative, as they are stable in peripheral blood and reflect tumor-related molecular alterations. In this study, the investigators aim to develop and validate a robust, noninvasive miRNA-based signature capable of distinguishing GI cancers from non-malignant controls. By integrating multi-cohort datasets and applying machine learning-based feature selection and predictive modeling, the investigators will construct a screening panel optimized for reproducibility, scalability, and early-stage detection. This noninvasive miRNA signature has the potential to support accessible, cost-effective, and clinically practical population-level screening for GI cancers, ultimately facilitating earlier diagnosis and improving outcomes for participants.

Neoadjuvant Short-Course Radiotherapy Followed by Tislelizumab Plus Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma This is a prospective, randomized, two-arm, parallel-group, multicenter, exploratory Phase II clinical trial. It aims to evaluate the efficacy and safety of neoadjuvant short-course radiotherapy followed by tislelizumab combined with chemotherapy in participants with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Eligible participants will be randomized in a 1:1 ratio to receive either low-dose or high-dose short-course radiotherapy, followed by tislelizumab, nab-paclitaxel, and carboplatin for 3 cycles. Surgery will be performed 4-6 weeks after the last neoadjuvant treatment. Primary endpoint: Pathological Complete Response (pCR) rate. Secondary endpoints: Major Pathological Response (MPR) rate, Objective Response Rate (ORR), R0 resection rate, downstaging rate, 3-year Event-Free Survival (EFS), 3-year Overall Survival (OS), safety profile, and quality of life. Approximately 50 participants will be enrolled. Randomization will be stratified by tumor location, clinical T stage, and clinical N stage using a stratified block design via an EDC/IWRS system.

Esophageal cancer (EC) ranks among the leading malignant gastrointestinal tumors globally in terms of both incidence and mortality. Cases of EC in China account for over 50% of the global total, with squamous cell carcinoma being the primary pathological type. Locally advanced EC (LAEC), particularly cases where radical surgical resection is not feasible, exhibits high recurrence rates and low 5-year survival rates. However, studies have shown that patients with LAEC who undergo comprehensive treatment followed by surgery experience significantly prolonged survival and improved quality of life compared to those who do not receive surgical intervention. Current conversion treatment regimens under investigation include: chemotherapy alone, chemoradiotherapy, immunotherapy combined with chemotherapy, and immunotherapy combined with chemoradiotherapy-each of these approaches has distinct advantages and limitations. Immunochemotherapy has emerged as a current research focus: it not only demonstrates significantly superior efficacy compared to chemotherapy alone but also exhibits lower cumulative toxicity than radiotherapy-combined conversion regimens, resulting in a more favorable overall benefit-risk ratio. As such, it represents the most promising conversion treatment strategy. Retrospective and prospective clinical studies have shown that low-dose radiotherapy targeting the small intestine can enhance the anti-tumor response of immune checkpoint inhibitors (ICIs) in patients with advanced solid tumor, prolong their overall survival, and increase the incidence of the abscopal effect. Further mechanistic investigations have revealed that intestinal low-dose radiotherapy (ILDR) may augment the immune cancerous lethality by modulating the gut microbiota and their metabolic profiles. Based on the findings from these preliminary studies, the current research plans to conduct a prospective phase II single-arm clinical trial to investigate the efficacy and safety of ILDR combined with immunochemotherapy as conversion therapy in patients with borderline resectable or unresectable esophageal squamous cell carcinoma (BR/UR ESCC). This research plans to enroll at least 39 evaluable cases or a total of 43 cases in two seperated stages, focusing on patients with thoracic BR/UR ESCC. Patients will receive a single fraction of ILDR with a mean dose of 1 Gy, concurrently with 3 cycles of albumin-bound paclitaxel (260 mg/m² on day 1), cisplatin (75 mg/m² on day 1), and tislelizumab (200 mg on day 1). The efficacy and safety of the treatment will be evaluated throughout the study.

This clinical trial aims to preliminarily evaluate the efficacy and safety of adebrelimab combined with albumin-bound paclitaxel and carboplatin as neoadjuvant therapy for borderline resectable locally advanced esophageal squamous cell carcinoma (ESCC). The primary research objectives are to increase the R0 resection rate in such patients, thereby reducing the recurrence rate and improving overall survival (OS), as well as avoiding adverse reactions associated with radiotherapy.

This is a multicenter, randomized, open-label, controlled phase III clinical study to evaluate the efficacy and safety of HS-20093- injection versus investigator's choice of chemotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma after progress of first-line standard therapy.

The goal of this clinical trial is to assess the percentage of patients alive at 6 months in elderly patients, not eligible to an platinum-based chemotherapy, but who can received the Tislelizumab treatment alone as first-line treatment for an advanced esophageal squamous-cell carcinoma (ESCC). Tislelizumab is a monoclonal antibody administred by intravenous infusion This study aims to anwer too at the questions: * the Safety of the drug * Overall survival (OS) at 6 months according the diagnostic of PD-L1 expression (PD-L1 is a protein present on the surface of immune cells) * Overall response rate (ORR) according to imagery criteria * Progression-free survival (PFS) at 3 and 6 months according to imagery criteria and depending on PDL1 expression * Patients' health-related quality of life * OS and PFS according to geriatric parameters * Prognostic value of immune biomarkers

This study aims to systematically evaluate the safety and efficacy of adalimumab combined with paclitaxel, carboplatin, and short-course radiotherapy in the neoadjuvant treatment of esophageal squamous cell carcinoma.

A Phase 1, First in Human, Open-Label Multicenter Study to Evaluate ALX2004, an Antibody Drug Conjugate Targeting EGFR in Participants with Advanced or Metastatic Select Solid Tumors

This is a prospective, randomized, phase II clinical study in patients with unresectable stage III-IVA esophageal squamous cell carcinoma (ESCC). Eligible patients will be randomly assigned in a 1:1 ratio to two treatment groups. The experimental group will receive 3 cycles of induction therapy with PD-1 antibody plus chemotherapy, followed by radiotherapy, and then maintenance therapy with PD-1 antibody monotherapy. The control group will receive concurrent chemoradiotherapy, followed by maintenance therapy with PD-1 antibody monotherapy. The primary endpoints are the complete response (CR) rate at 3 months after radiotherapy (assessed by investigators) and the 1-year progression-free survival (PFS) rate. Secondary endpoints include overall survival (OS), progression-free survival (PFS), duration of response, objective response rate (ORR), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), quality of life, and safety profile.

This study is designed to assess the efficacy and safety of QLC5508 in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have experienced disease progression following treatment with a platinum-based systemic therapy and an immune checkpoint inhibitor (ICI) compared with investigator's choice of chemotherapy (ICC).

A Phase 1/2a Dose Escalation and Expansion Study of the Safety, Tolerability, and Preliminary Clinical Activity of 177LuBetaBart, a 177Lu-Labeled Anti-B7-H3 Monoclonal Antibody, in Patients with Relapsed/Refractory, Locally Advanced Inoperable, or Metastatic Solid Tumors

The purpose of this study is to evaluate the efficacy and safety of KC1036 in combination with PD-1 antibody and platinum-based chemotherapy as a first-line treatment for patients with unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).

This is a Phase II, open-label, single-arm, multicenter study evaluating the safety and efficacy of combining Tislelizumab with induction chemoradiotherapy (CRT), followed by conversion surgery, in patients with locally advanced, unresectable esophageal squamous cell carcinoma (ESCC). Patients will receive induction CRT with weekly paclitaxel and cisplatin along with Tislelizumab, followed by two cycles of consolidation Tislelizumab-chemotherapy. If the tumor becomes resectable, patients will undergo surgery. The primary goal is to assess the 2-year overall survival (OS) rate. Secondary outcomes include pathological complete response (pCR), conversion rate, R0 resection rate, disease-free survival (DFS), recurrence-free survival (RFS), and treatment-related adverse events.

This study includes patients with resectable esophageal squamous cell carcinoma who will undergo local radiotherapy (PTV: 1.5Gy Bid, for 5 days), followed by neoadjuvant treatment with Serplulimab combined with cisplatin and paclitaxel for three cycles. Afterward, they will undergo surgery. Postoperatively, researchers will select adjuvant treatment plans based on the patients' conditions.

This study is a randomized, controlled, open-label, multicenter Phase III clinical trial, designed to evaluate the efficacy and safety of neoadjuvant toripalimab in combination with nab-paclitaxel and platinum versus neoadjuvant docetaxel in combination with cisplatin and 5-fluorouracil (DCF) in the treatment of resectable locally advanced esophageal squamous cell carcinoma

Brief Summary Study title: Indocyanine green (ICG)-guided omental shield anastomosis (ICG-OSA) technique for cervical esophagogastric anastomosis in esophageal cancer surgery Purpose: To evaluate whether a novel surgical technique can reduce the risk of anastomotic leakage after minimally invasive esophageal cancer surgery. Eligible participants: Adults aged 18-80 years with histologically confirmed esophageal squamous cell carcinoma (ESCC) in the middle or lower thoracic esophagus who are scheduled for esophagectomy. The technique: All participants will undergo the ICG-OSA procedure, which uses indocyanine green fluorescence imaging to assess gastric perfusion, creates a T-shaped esophagogastric anastomosis, and wraps the anastomosis with a pedicled omental flap. Outcome assessments: The primary outcome is anastomotic leakage rate within 30 days after surgery. Secondary assessments include surgical site infection, anastomotic stricture, and hospitalization costs. Study site: Daping Hospital, Army Medical Center, Chongqing, China Study duration: December 2025 to March 2027 Contact: For more information, please contact the research team at Daping hospital.

This prospective, multi-center, observational registry study (PKU-ESCC-EF) aims to evaluate the safety and effectiveness of a standardized diagnosis and treatment protocol for esophageal fistula (EF) in patients with advanced esophageal squamous cell carcinoma (ESCC). Esophageal fistula is a severe complication that often leads to life-threatening infections and poor nutrition. This study will observe patients receiving a comprehensive management strategy, which includes fistula sealing with esophageal or airway stents, targeted anti-infective therapy, nutritional support, and subsequent systemic anti-tumor therapy. The primary goal is to assess whether this standardized approach can improve overall survival and enable more patients to receive further anti-cancer treatments.

SUMMARY Rationale: Esophageal cancer (EC) is the seventh most frequently diagnosed cancer and the sixth leading cause of cancer-related death worldwide. As a result of the late onset of symptoms, most patients with EC present in an advanced stage with a corresponding poor prognosis. Poor disease outcome after surgery alone (5-yr overall survival between 25-40%) prompted many researchers to explore neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant or perioperative chemotherapy (nCT/pCT) approaches. nCRT has led to pathological complete response (pCR) rate in squamous cell EC of almost 50%. Patients with a pCR have a favorable prognosis with 5-year OS \>50%. In addition, patients who will achieve a pCR might be candidates for an organ preserving treatment strategy. Current standard nCRT consists of a relatively low dose of radiation compared to other tumors in the same area. The investigators hypothesize that increasing the dose of radiation will lead to increased local tumor control and pCR rates. Objective: The main objective of this study is to determine the maximum tolerated dose (MTD) of 2-fraction boost MRI-guided radiotherapy (MRgRT) for patients with SCC following CROSS therapy. The secondary objectives are feasibility, non-dose limiting toxicity, oncological outcomes and to explore variables for early response evaluation. Study design: 6+3 dose-escalation design with 3 radiotherapy dose levels. Study population: Patients with a resectable squamous cell esophageal carcinoma who are eligible for nCRT, surgery and MRgRT. Intervention: 2 sequential, homogenous boost fractions of 4-7 Gy on the gross tumor volume (GTV) in the week following CROSS using MR-guided online adaptive radiotherapy on the MR-linac. Start in dose level 0, of 2 x 5Gy boost per patient, and if safe this is increased step-wise to a maximum dose level 2 of 2 x 7Gy per patient. Main study parameters/endpoints: The primary endpoint is the incidence of a dose limiting toxicity (DLT). Early DLT is defined as radiation induced esophageal fistula/ perforation/ hemorrhage/ necrosis or tracheal, bronchial or bronchopleural fistula/tracheal or bronchopulmonary hemorrhage grade ≥ 3 or any non-hematological grade 4 toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0 occurring within 14 weeks after the start of radiotherapy and before surgery or the postponing of surgery \> 14 weeks after the end of radiotherapy due to any grade of treatment-related toxicity. Subacute DLT is defined as peri- and/or postoperative complications occurring within 30 days after surgery, defined as postoperative anastomotic leakage or pneumonitis ≥ 3b according to Clavien-Dindo. Secondary endpoints are non-DLT toxicity, the technical feasibility of dose delivery, perioperative complications, and oncological outcomes including R0 resection rate, histopathological tumor response, local and regional recurrence and death from any cause. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The benefits for the patients may include higher probability of complete pathological response that initially leads to increased survival and could eventually result in organ-sparing treatment programs. Compared to standard treatment, the CROSS regimen including the sequential boost will take 2 days extra in the final week of CROSS. Possible risks include higher radiation toxicity and surgical complication rates. However, it is expected this increase to be minor, for the investigators will use dose constraints on organs at risk, which are associated with low radiation-induced toxicity, and they will not be exceeded.