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.
調査の概要
状態
詳細な説明
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Bin Zheng, M.D.
- 電話番号：15959002753
- メール：lacustrian@163.com
研究連絡先のバックアップ
- 名前：Jianting Du, M.D., Ph.D
- 電話番号：13023806690
- メール：dujt1220@fjmu.edu.cn
研究場所
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Fujian
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Fuzhou、Fujian、中国、350000
- Fujian Medical University Union Hospital
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コンタクト：
- Bin Zheng
- 電話番号：15959002753
- メール：lacustrian@163.com
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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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アクティブコンパレータ：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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3-year Disease free survival rate
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Postoperative complications
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
協力者
捜査官
- 主任研究者：Bin Zheng、Fujian Medical University Union Hospital
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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