A Non-inferiority Study of Indocyanine Green-guided Sentinel Lymph Node Mapping Versus Conventional Lymph Node Dissection in Esophageal Cancer (SIGN)
Indocyanine Green-guided Sentinel Lymph Node Dissection Versus Systematic Lymph Node Dissection in cN0 Esophageal Squamous Cell Carcinoma: a Multicenter, Prospective, Non-inferiority Randomized Controlled Trial
In the comprehensive treatment system for esophageal cancer, surgical resection combined with regional lymph node dissection remains the core component for achieving cure in patients with resectable esophageal squamous cell carcinoma (ESCC). The traditional surgical concept holds that the more thorough the lymph node dissection, the better. However, increasing basic and clinical evidence indicates that lymph nodes without metastasis-particularly tumor-draining lymph nodes-play an irreplaceable role in maintaining the host's anti-tumor immune response. Preclinical studies have found that radiation exposure to tumor-draining lymph nodes can impair the efficacy of radiotherapy combined with immunotherapy. In the surgical field, this shift in understanding has given rise to an important clinical question: in radical esophagectomy for esophageal cancer, is it possible to maximally preserve non-metastatic normal lymph nodes while ensuring complete removal of metastatic lymph nodes? If achievable, patients may not only benefit from reduced postoperative complications (such as chylothorax and recurrent laryngeal nerve injury) but also retain important immune organ function, providing a stronger basis for subsequent immunotherapy responses. Therefore, this study intends to conduct a multicenter, prospective, randomized controlled, non-inferiority trial in patients with cT1-3N0M0 esophageal squamous cell carcinoma who have not received neoadjuvant therapy, to evaluate the oncological safety of sentinel lymph node dissection based on the ICG near-infrared fluorescence imaging system in radical esophagectomy for esophageal cancer.
During the study, ICG will be injected around the tumor under intraoperative gastroscopy guidance, followed by tracking of fluorescent lymph nodes using a thoracoscopic near-infrared camera. Professional thoracic surgeons will group and mark these lymph nodes for intraoperative frozen pathology. If intraoperative frozen section shows negative sentinel lymph nodes, patients will be randomized 1:1 into two groups: one group will undergo esophagectomy alone without further lymph node dissection, while the other group will undergo conventional lymph node dissection plus esophagectomy. The primary objective of this study is to evaluate the non-inferiority of ICG-guided sentinel lymph node dissection compared with conventional systematic lymph node dissection in terms of 3-year disease-free survival in patients with cT1-3N0M0 esophageal squamous cell carcinoma who have not received neoadjuvant therapy, thereby validating the oncological safety of the sentinel lymph node dissection strategy.
Participants will:
- Undergo minimally invasive ESCC surgery within 2 weeks of enrollment, including the 14th day.
- Receive ICG injection around the tumor under intraoperative gastroscopy guidance during surgery.
- Have perioperative, postoperative pathology, and complication information recorded.
- Undergo standardized follow-up after surgery.
Visão geral do estudo
Status
Condições
Descrição detalhada
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
- Nome: Bin Zheng, M.D.
- Número de telefone: 15959002753
- E-mail: lacustrian@163.com
Estude backup de contato
- Nome: Jianting Du, M.D., Ph.D
- Número de telefone: 13023806690
- E-mail: dujt1220@fjmu.edu.cn
Locais de estudo
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Fujian
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Fuzhou, Fujian, China, 350000
- Fujian Medical University Union Hospital
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Contato:
- Bin Zheng
- Número de telefone: 15959002753
- E-mail: lacustrian@163.com
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria
- Aged 18 to 75 years, regardless of gender;
- Histopathologically confirmed esophageal squamous cell carcinoma or adenocarcinoma by endoscopic biopsy (including esophagogastric junction carcinoma, Siewert type I/II);
- Preoperative clinical stage cT1-3N0M0 (based on contrast-enhanced CT ± PET-CT ± endoscopic ultrasound evaluation);
- No prior neoadjuvant therapy of any form (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, targeted therapy, etc.);
- Scheduled for minimally invasive radical esophagectomy (combined thoracoscopic and laparoscopic McKeown or Ivor-Lewis procedure);
- No surgical contraindications, with cardiac, pulmonary, hepatic, and renal functions sufficient to tolerate surgery;
- ECOG performance status score of 0 to 1;
- Written informed consent signed by the patient or legal representative.
Exclusion Criteria
- Preoperative imaging clearly indicating lymph node metastasis (cN+) or distant metastasis (cM1);
- Prior systemic or local treatment for esophageal cancer of any kind (including chemotherapy, radiotherapy, chemoradiotherapy, immunotherapy, etc.);
- Previous history of esophageal or gastric surgery (except endoscopic mucosal resection/submucosal dissection);
- History of allergy to iodine contrast agents or indocyanine green;
- Severe hepatic or renal insufficiency (Child-Pugh class B or C; serum creatinine ≥ 1.5 times the upper limit of normal);
- Uncontrolled hyperthyroidism;
- Concomitant other malignancies requiring simultaneous treatment;
- Pregnant or lactating women;
- Other conditions deemed unsuitable for enrollment by the investigator.
Withdrawal Criteria
- Intraoperative exploration revealing inability to achieve radical resection (R2 resection) or extensive thoracic and abdominal metastasis;
- Intraoperative exploration revealing definite lymph node metastasis (cN+) inconsistent with preoperative staging;
- Severe allergic reaction after ICG injection requiring discontinuation of the study;
- Intraoperative change of surgical plan due to severe complications;
- Withdrawal of informed consent by the patient.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: ICG-guided sentinel lymph node dissection only plus esophagectomy
The experimental group will undergo sentinel lymph node dissection only plus esophagectomy
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In the experimental group, the investigators will perform only sentinel lymph node dissection and esophagectomy, without further lymph node resection.
This intervention is distinguished by its de-escalated surgical approach: unlike conventional radical esophagectomy with systematic lymph node dissection, no additional lymph node stations will be removed beyond the identified sentinel lymph nodes.
By preserving non-sentinel regional lymph nodes, this strategy aims to reduce surgical trauma and postoperative complications-such as chylothorax and recurrent laryngeal nerve injury-while maintaining oncological safety in patients with cT1-3N0M0 esophageal squamous cell carcinoma.
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Comparador Ativo: ICG-guided systematic lymph node dissection plus esophagectomy
The control group will undergo conventional lymph node dissection plus esophagectomy
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In the control group, in addition to dissecting the sentinel lymph nodes, the investigators will proceed with standard two-field or three-field lymph node dissection for esophageal cancer.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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3-year Disease free survival rate
Prazo: The time from randomization to the first occurrence of any of the following events (local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause), assessed up to 36 months.
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3-year disease-free survival rate: defined as the time from randomization to the first occurrence of any of the following events: local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause
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The time from randomization to the first occurrence of any of the following events (local recurrence, regional lymph node recurrence, distant metastasis, or death from any cause), assessed up to 36 months.
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Postoperative complications
Prazo: 30 days after surgery
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The incidence of severe complications with Clavien-Dindo grade ≥ III within 30 days after surgery; the incidence of specific complications such as chylothorax, recurrent laryngeal nerve injury, anastomotic leakage, and pulmonary infection.
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30 days after surgery
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Immune status indicators
Prazo: Baseline (day -1), post-operative day 1, day 7, and month 1.
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Immune status indicators: changes in peripheral blood lymphocyte subsets (CD4+, CD8+, NK cells) counts before and after surgery.
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Baseline (day -1), post-operative day 1, day 7, and month 1.
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lmmune status indicators
Prazo: Baseline (day -1), post-operative day 1, day 7, and month 1.
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lmmune status indicators: changes in peripheral blood lymphocyte subsets (CD4+CD8+, NK cells) rates before and after surgery.
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Baseline (day -1), post-operative day 1, day 7, and month 1.
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3-year Overall Survival rate
Prazo: 3-year after surgery
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3-year Overall Survival rate
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3-year after surgery
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Diagnostic performance of ICG
Prazo: 7-day after surgery
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Diagnostic performance of ICG (using postoperative routine pathology as the gold standard): sensitivity, specificity, positive predictive value, negative predictive value, and false negative rate of ICG in identifying sentinel lymph nodes.
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7-day after surgery
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Bin Zheng, Fujian Medical University Union Hospital
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- SIGN study
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