Low-dose Radiation Combined With Neoadjuvant Immunochemotherapy for Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title: Efficacy and Safety of Low-dose Radiation Combined With Neoadjuvant Chemotherapy and Immunotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma

Status Not yet recruiting

Clinical Trial Summary

This study aims to investigate the efficacy and safety of low-dose radiation combined with neoadjuvant chemotherapy and immunotherapy in the treatment of locally advanced thoracic esophageal squamous cell carcinoma. By reducing the radiation dose from 40 Gy in 20 fractions to 4 Gy in 2 fractions, the goal is to lessen the adverse reactions caused by radiotherapy. Additionally, the study explores whether low-dose radiation therapy can promote the cross-presentation of tumor-specific antigens and increase lymphocyte infiltration into the tumor site. Study also examines whether this approach can enhance tumor-specific immune responses, thereby potentially improving the efficacy of immune checkpoint inhibitors.

Clinical Trial Description

According to 2020 GLOBOCAN data, esophageal cancer ranks fifth in incidence among all malignant tumors in China, with new cases reaching 324,000 and annual deaths at 301,000. These figures indicate a significant burden of esophageal cancer in China, accounting for 55% of esophageal cancer cases globally. Unlike in Western countries, most esophageal cancer patients in China have squamous cell carcinoma, and 40% are diagnosed at an advanced stage. Surgery is a key treatment for locally advanced esophageal cancer, but patients may achieve better clinical outcomes if they receive neoadjuvant therapy before surgery. However, the prognosis for these patients remains relatively poor. From 2009 to 2015, the overall 5-year relative survival rate for esophageal cancer was 21.4%, with local tumors at 46.7%, regional metastasis at 25.1%, and distant metastasis at only 4.8%.

In recent years, immunotherapy has shown significant survival benefits in patients with advanced esophageal cancer. Immuno-chemotherapy has now become the standard first-line treatment for advanced esophageal cancer. Currently, the introduction of immunotherapy as neoadjuvant treatment in locally advanced esophageal cancer is a highly regarded research area. Many studies are underway involving the combined application of neoadjuvant chemotherapy and immunotherapy, as well as neoadjuvant chemoradiotherapy and immunotherapy. Regarding safety, tislelizumab is similar to foreign similar drugs, mostly causing grade 1-2 adverse reactions, and is within a controllable range. Our center's previous research results have shown that tislelizumab can be used as a neoadjuvant immunotherapy drug for esophageal squamous cell carcinoma, with good perioperative safety.

It is worth noting that recent study reports indicate that the pathological complete response (PCR) rate of neoadjuvant chemotherapy combined with immunotherapy in small sample studies ranges from 17% to 22%, showing significant heterogeneity. Recently, Chinese scholars published a study in the international authoritative academic journal "Nature Medicine," indicating that using a PD-L1 antibody for immunotherapy combined with surgery, although the PCR rate was only 8%, the long-term survival effect was comparable to traditional chemoradiotherapy. This further proves that compared to traditional neoadjuvant chemoradiotherapy, neoadjuvant immunotherapy has broad development potential. However, the local control effects of immunotherapy alone or combined with chemotherapy are still unsatisfactory, which may affect the radical outcome of surgery and the long-term survival of patients. Therefore, combining more effective local treatment methods with immunotherapy is undoubtedly a more promising treatment option.

Low-dose radiotherapy (LDRT) is generally defined as a treatment not exceeding 2 Gy per session, totaling no more than 10 Gy, and is considered a non-ablative treatment [13]. The low toxicity of low-dose radiotherapy makes it a treatment option for those not suitable for body-targeted radiation therapy. Furthermore, although low-dose radiotherapy does not directly kill cancer cells, it can promote tumor regression by readjusting the tumor immune microenvironment.

Low-dose radiotherapy damages cell DNA, causing previously hidden or difficult-to-recognize tumor antigens to be exposed on the cell surface. This change promotes the cross-presentation of tumor-specific antigens, increases lymphocyte infiltration into the tumor site, enhances tumor-specific immune responses, and further improves the efficacy of immune checkpoint inhibitors. Preoperative immunotherapy can activate the patient's immune system, enabling it to recognize tumor antigens and establish immune memory. This allows the immune system to continue to function in immune surveillance after the surgical removal of the tumor. Currently, the main focus of clinical research is on how to maximize the synergistic effects between different treatment modalities to achieve the best survival outcomes for patients with locally advanced esophageal cancer while minimizing treatment side effects.

This study is a Phase IIA clinical trial, a preliminary study of efficacy and safety. This study envisions a comprehensive treatment of neoadjuvant low-dose radiotherapy combined with chemotherapy and immunotherapy (chemo-immuno), which, by reducing the radiotherapy dose, can enhance local control efficacy and reduce adverse reactions caused by the combined treatment mode. Therefore, it is proposed to perform neoadjuvant low-dose radiotherapy combined with chemo-immuno treatment in patients with locally advanced esophageal squamous cell carcinoma, adjust the preoperative radiotherapy dose from 40 Gy/20f to 4 Gy/2f, evaluate the efficacy and safety of this treatment mode, and provide more evidence for the neoadjuvant treatment model for locally advanced esophageal cancer patients. Additionally, exploratory analyses of preoperative and postoperative tissue and blood samples will be conducted to understand the impact of preoperative low-dose radiotherapy combined with immunotherapy on the esophageal cancer immune microenvironment; suitable biological markers will be selected to identify the optimal beneficiary group. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

• NCT number: NCT06446726
• Study type: Interventional
• Source: Sichuan University
• Contact: Yong Yuan, Professor
• Phone: +86 18980606739
• Email: yongyuan@scu.edu.cn
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 30, 2024
• Completion date: December 30, 2026