Construction of Artificial Intelligence Model for Esophageal Cancer Digital Twin Patients and Drug Efficacy Simulation Verification Based on Supercomputing Platform and Multi-Omics Data
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 400
- 主要终点
- Event-Free Survival (EFS)
研究概览
简要总结
This study aims to integrate multi-omics data (genomics, transcriptomics, proteomics) from esophageal cancer patients with artificial intelligence and digital twin technology to construct personalized virtual patient models that precisely simulate individual responses to targeted therapies. Through a drug simulation platform, this study will rapidly screen potential effective drug combinations and optimize dosage and treatment regimens. The project attempts to replace portions of traditional clinical trials with virtual clinical trial technology, substantially shortening the R&D cycle, reducing costs, and effectively addressing the complexity of individualized treatment. Specifically, this study will conduct a head-to-head virtual clinical trial parallel to a real-world investigator-initiated trial (IIT) in patients with locally advanced esophageal squamous cell carcinoma, comparing the efficacy predictions from the virtual model with actual clinical outcomes. The ultimate goal is to explore the application of large-scale AI models in esophageal cancer targeted therapy, provide personalized treatment recommendations, and advance the implementation of precision medicine in esophageal cancer.
详细描述
This is a prospective, single-center, observational cohort study integrating virtual clinical trial technology. The study is designed to validate the feasibility and accuracy of AI-driven digital twin models for predicting treatment responses in esophageal cancer patients.
Background and Rationale:
China accounts for approximately half of the global esophageal cancer cases, with the highest incidence rates concentrated in the Taihang Mountain region, particularly Henan Province. Despite advances in early diagnosis and treatment, tumor heterogeneity and individual patient variability continue to limit therapeutic efficacy, especially in advanced-stage patients. Virtual clinical trial technology, which uses supercomputing to simulate drug efficacy and safety across virtual patient populations, offers a promising approach to accelerate drug screening while reducing costs and ethical constraints associated with conventional trials.
Study Population:
The study will enroll 400 patients with locally advanced (T1N1-3M0 or T2-3N0-3M0) thoracic esophageal squamous cell carcinoma (8th UICC-TNM staging), aged 18 to 75 years, with ECOG performance status 0-1 and adequate organ function. All patients must have received no prior antitumor therapy for esophageal cancer and be candidates for R0 resection.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Treatment-naïve patients with clinical stage locally advanced (T1N1-3M0 or T2-3N0-3M0) thoracic esophageal squamous cell carcinoma, according to the 8th UICC-TNM staging system.
- •Cervical color Doppler ultrasound shows no suspicious metastatic lymph nodes, or patients with suspected lymph node metastasis on ultrasound who are eligible for three-field lymphadenectomy.
- •No prior antitumor therapy for esophageal cancer (including chemotherapy, radiotherapy, or immunotherapy).
- •Preoperative evaluation of organ function indicates no surgical contraindications.
- •Adequate bone marrow, liver, and renal function, confirmed by the following laboratory tests performed within 7 days prior to enrollment:
- •Hemoglobin ≥ 90 g/L;
- •White blood cell count ≥ 4.0 × 10^9/L;
- •Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
- •Platelet count ≥ 100 × 10^9/L;
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN);
- •ALT and AST ≤ 2.5 × ULN;
- •International normalized ratio (INR) of prothrombin time ≤ 1.5 × ULN, with activated partial thromboplastin time (APTT) within normal range;
- •Serum creatinine ≤ 1.5 × ULN.
- •No prior chemotherapy, radiotherapy, or hormone therapy for malignant tumors; no history of other malignancies, except for prostate cancer patients who received hormone therapy and have achieved disease-free survival (DFS) > 5 years.
- •Expected to achieve R0 resection.
- •Eastern Cooperative Oncology Group (ECOG) performance status score 0 to
- •Life expectancy ≥ 3 months.
- •Women of childbearing potential must agree to use effective contraceptive measures (e.g., intrauterine device, oral contraceptives, or condoms) during the study and for 6 months after study completion. Serum or urine pregnancy test must be negative within 7 days prior to enrollment, and patients must not be breastfeeding. Male patients must agree to use contraceptive measures during the study and for 6 months after study completion.
- •Patients must voluntarily participate in the study, provide written informed consent, demonstrate good compliance, and agree to follow-up.
排除标准
- •Patients not meeting the inclusion criteria.
- •Presence of multiple primary malignancies (synchronous or metachronous).
- •Active infections requiring systemic treatment.
- •Requirement for continuous systemic corticosteroid therapy (>10 mg/day prednisone or equivalent) for comorbid conditions.
- •Unstable angina within 3 months or myocardial infarction within 6 months prior to enrollment.
- •Psychiatric disorders that may affect study compliance.
- •Known or concurrent hemorrhagic disorders.
- •Female patients who are pregnant or breastfeeding.
- •Patients with pre-existing or concurrent pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, or other severe pulmonary impairment.
- •Autoimmune diseases, immunodeficiency states, or history of organ transplantation.
- •Known hypersensitivity to the study drugs (toripalimab, paclitaxel, cisplatin) or their excipients.
- •Abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s, Fib < 1.5 g/L), bleeding tendency, or patients receiving thrombolytic or anticoagulant therapy.
- •Bronchial asthma requiring intermittent use of bronchodilators or medical intervention.
- •Active hepatitis B (HBV) or hepatitis C (HCV) infection. (Patients who are HBsAg positive or HBcAb positive may be eligible if HBV DNA is below the lower limit of detection/quantification; patients who are HCV antibody positive may be eligible if HCV RNA is below the lower limit of detection/quantification.)
- •Human immunodeficiency virus (HIV) positivity.
- •Any other condition that, in the investigator's judgment, may compromise patient safety, interfere with study compliance, or preclude successful completion of the study.
研究组 & 干预措施
Neoadjuvant Immunochemotherapy plus Surgery with Postoperative Toripalimab Maintenance
Patients in this group receive neoadjuvant immunochemotherapy consisting of toripalimab (JS001) 240 mg intravenously on day 3, paclitaxel 175 mg/m² intravenously on day 1, and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days for 2 cycles. Approximately 4-8 weeks after completion of neoadjuvant therapy, patients undergo McKeown minimally invasive or open esophagectomy with two-field lymphadenectomy. Following surgery (within 3 weeks ± 3 days, no later than 2.5 months postoperatively), patients receive postoperative toripalimab maintenance therapy at 240 mg intravenously every 3 weeks for up to 8 cycles (approximately 6 months) or until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Cisplatin (Drug)
Neoadjuvant Chemotherapy plus Surgery
Patients in this group receive neoadjuvant chemotherapy consisting of paclitaxel 175 mg/m² intravenously on day 1 and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days for 2 cycles. Approximately 4-8 weeks after completion of neoadjuvant therapy, patients undergo McKeown minimally invasive or open esophagectomy with two-field lymphadenectomy. No postoperative maintenance therapy is administered. Patients are followed up according to the same schedule as the experimental group.
干预措施: Cisplatin (Drug)
Neoadjuvant Immunochemotherapy plus Surgery with Postoperative Toripalimab Maintenance
Patients in this group receive neoadjuvant immunochemotherapy consisting of toripalimab (JS001) 240 mg intravenously on day 3, paclitaxel 175 mg/m² intravenously on day 1, and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days for 2 cycles. Approximately 4-8 weeks after completion of neoadjuvant therapy, patients undergo McKeown minimally invasive or open esophagectomy with two-field lymphadenectomy. Following surgery (within 3 weeks ± 3 days, no later than 2.5 months postoperatively), patients receive postoperative toripalimab maintenance therapy at 240 mg intravenously every 3 weeks for up to 8 cycles (approximately 6 months) or until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Toripalimab (Drug)
Neoadjuvant Chemotherapy plus Surgery
Patients in this group receive neoadjuvant chemotherapy consisting of paclitaxel 175 mg/m² intravenously on day 1 and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days for 2 cycles. Approximately 4-8 weeks after completion of neoadjuvant therapy, patients undergo McKeown minimally invasive or open esophagectomy with two-field lymphadenectomy. No postoperative maintenance therapy is administered. Patients are followed up according to the same schedule as the experimental group.
干预措施: Paclitaxel (Drug)
Neoadjuvant Immunochemotherapy plus Surgery with Postoperative Toripalimab Maintenance
Patients in this group receive neoadjuvant immunochemotherapy consisting of toripalimab (JS001) 240 mg intravenously on day 3, paclitaxel 175 mg/m² intravenously on day 1, and cisplatin 75 mg/m² intravenously on day 1, repeated every 21 days for 2 cycles. Approximately 4-8 weeks after completion of neoadjuvant therapy, patients undergo McKeown minimally invasive or open esophagectomy with two-field lymphadenectomy. Following surgery (within 3 weeks ± 3 days, no later than 2.5 months postoperatively), patients receive postoperative toripalimab maintenance therapy at 240 mg intravenously every 3 weeks for up to 8 cycles (approximately 6 months) or until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Event-Free Survival (EFS)
时间窗: From randomization up to 36 months
Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of any of the following events: inoperability due to any cause, distant metastasis, local recurrence, or death from any cause, whichever occurs first. Distant metastasis is confirmed by: (1) pathological confirmation of squamous cell carcinoma metastasis in other organs, soft tissues, or skin; (2) PET-CT revealing non-local recurrent hypermetabolic soft tissue lesions; or (3) CT, MRI, or abdominal ultrasound diagnosis of distant metastasis.
次要结局
- Pathological Complete Response (pCR) Rate(At the time of surgery (approximately 4-8 weeks after completion of neoadjuvant therapy))
- Overall Survival (OS)(From randomization up to 36 months)
- Disease-Free Survival (DFS)(From surgery up to 36 months)
- Objective Response Rate (ORR)(Up to 24 months)
- R0 Resection Rate(At the time of surgery (approximately 4-8 weeks after completion of neoadjuvant therapy))
- Major Pathological Response (MPR) Rate(At the time of surgery (approximately 4-8 weeks after completion of neoadjuvant therapy))
- EORTC QLQ-OES18 Quality of Life Score(From randomization up to 36 months)
- EORTC QLQ-C30 Quality of Life Score(From randomization up to 36 months)
- Incidence of Treatment-Emergent Adverse Events(From the signing of informed consent through 30 days after the last dose of study treatment (or 90 days for serious adverse events))
研究者
YanZheng,MD
Director
Henan Cancer Hospital