Sentinel Node Resection With or Without LECS After Noncurative ESD for EGC

Official title

COmpletion Sentinel Node Resection With or Without Minimally invAsive and Endoscopic Cooperative Surgery Following noncuRative Endoscopic Submucosal Dissection for Early Gastric Cancer

Overview

For patients with non-curative resection after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC), complementary surgery is generally recommended. However, about 2/3 of patients have no remaining tumor in the stomach or regional lymph nodes. In this trial, Indocyanine Green (ICG)-guided lymphadenectomy with or without laparoscopic and endoscopic cooperative surgery (LECS) will be tested as a less invasive alternative in such cases. For patients with a primary radically resected EGC, ICG-guided lymphadenectomy alone will be performed. For patients with deep-margin positive EGC, ICG-guided lymphadenectomy and LECS will be performed, in order to ensure both local tumor control in the stomach and in regional nodes.

Detailed description

Endoscopic submucosal dissection (ESD) is the recommended treatment for early gastric cancer (EGC) who are fullfillling the criteria based on international guidelines. After ESD, some resections are classified as non-curative because of factors such as non radicality (especially when the deep margin is positive for cancer), lymphovascular invasion or deep submucosal invasion Sm\>1. In such cases, guidelines recommend complementary gastrectomy and lymphadenectomy. Gastrectomy is known to carry a risk for severe complications in about 9-22 % of cases. Furthermore, up to 2/3 of patients are found to have no remaining tumor in the stomach or regional nodes after surgery.

In this trial, Indocyanine Green (ICG)-guided lymphadenectomy including sentinel node resection, with or without complementary laparoscopic and endoscopic cooperative surgery (LECS) will be tested as a less invasive treatment option. For patients with radically resected EGC, ICG-guided lymphadenectomy alone will be performed. In patients with deep margin positive EGC, ICG-guided lymphadenectomy and LECS will be performed.

ICG-guided lymphadenectomy is performed by first injecting 100 times diluted ICG in four quadrants in the submucosa around the tumor scar with gastroscopy. After 15 minutes, the draining nodes will be visualized with laparoscopy, and locally resected. LECS is performed by endoscopic marking of the scar followed circumferential mucosal cutting, trimming, and perforation of the stomach followed by full-thickness resection of the scar with laparoscopy. After resection, the resected specimen will be taken out and the stomach defect sutured laparoscopically.

After the procedure, the patient will be presented at a multidisciplinary tumor board. If only clinical follow-up is recommended, the patient will be followed closely with gastroscopy and computer tomography (CT) scan every 3 months for the first year.

Interventions

• Procedure ICG-guided lymphadenectomy
  Submucosal injection of ICG in quadrants around the scar after ESD, followed by laparoscopic resection of positive lymph nodes after 15 minutes
• Procedure Laparoscopic and endoscopic cooperative surgery (LECS)
  Endoscopic marking and submucosal cutting around the scar after ESD, followed by perforation of the gastric wall and laparoscopic full thickness resection of the area under endoscopic guidance.

Primary outcome measures

• Severe complications defined as Clavien-Dindo >/= III [Time frame: Periprocedural]

Secondary outcome measures (12)

• Any complications [Time frame: Periprocedural]
• Postoperative bleeding [Time frame: Periprocedural]
• Leakage [Time frame: Periprocedural]
• Operation time [Time frame: Periprocedural]
• Pathological tumor (T)-stage [Time frame: Up to 2 months post procedure]
• Tumor-free resection margins [Time frame: Up to 2 months post procedure]
• Number of lymph nodes [Time frame: Periprocedural]
• Number of positive lymph nodes [Time frame: Up to 2 months post procedure]
• Hospital-stay [Time frame: From the day of the procedure until patient is discharged from the hospital, assessed up to 12 weeks post procedure]
• Health-related quality of life (HQL) score QLQ-30 [Time frame: Preoperatively, after 30 days and 1 year]
• Health-related quality of life (HQL) score OG25 [Time frame: Preoperatively, after 30 days and 1 year]
• 30-day mortality [Time frame: From procedure to maximum 30 days postoperatively]

Eligibility criteria

Inclusion criteria

• EGC previously treated with ESD according to current guidelines (differentiated adenocarcinoma, not ulcerative, of any size, differentiated adenocarcinoma ulcerative </=3cm, undifferentiated adenocarcinoma not ulcerative </=2cm)
• Non curative resection

• Lymphovascular invasion
• Non-radical resection vertical margin
• deep submucosal invasion
• Signed informed consent

Exclusion criteria

• Location within 2 cm from cardia or pylorus
• Non-curative resection with only non-radicality horizontal margin
• Inoperative because of severe comorbidities
• Previous radiotherapy to the upper abdomen
• Pregnancy
• Allergy to ICG
• Inability to provide informed consent due to cognitive impairment, language barrier, or other reasons impairing understanding and autonomous decision-making.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 1 center

• Karolinska University Hospital Huddinge — Stockholm

Publications

• Belia F, Biondi A, Agnes A, Santocchi P, Laurino A, Lorenzon L, Pezzuto R, Tirelli F, Ferri L, D'Ugo D, Persiani R. The Use of Indocyanine Green (ICG) and Near-Infrared (NIR) Fluorescence-Guided Imaging in Gastric Cancer Surgery: A Narrative Review. Front Surg. 2022 Jun 28;9:880773. doi: 10.3389/fsurg.2022.880773. eCollection 2022. PMID 35836598
• Morais R, Libanio D, Dinis Ribeiro M, Ferreira A, Barreiro P, Bourke MJ, Gupta S, Amaro P, Kuttner Magalhaes R, Cecinato P, Boal Carvalho P, Pinho R, Rodriguez de Santiago E, Sferrazza S, Lemmers A, Figueiredo M, Pioche M, Gallego F, Albeniz E, Ramos Zabala F, Uchima H, Berr F, Wagner A, Marques M, Pimentel-Nunes P, Goncalves M, Mascarenhas A, Soares EG, Xavier S, Faria-Ramos I, Sousa-Pinto B, Gul PMID 37666656
• van den Boorn HG, Stroes CI, Zwinderman AH, Eshuis WJ, Hulshof MCCM, van Etten-Jamaludin FS, Sprangers MAG, van Laarhoven HWM. Health-related quality of life in curatively-treated patients with esophageal or gastric cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2020 Oct;154:103069. doi: 10.1016/j.critrevonc.2020.103069. Epub 2020 Aug 5. PMID 32818901
• Tsekrekos A, Vossen LE, Lundell L, Jeremiasen M, Johnsson E, Hedberg J, Edholm D, Klevebro F, Nilsson M, Rouvelas I. Improved survival after laparoscopic compared to open gastrectomy for advanced gastric cancer: a Swedish population-based cohort study. Gastric Cancer. 2023 May;26(3):467-477. doi: 10.1007/s10120-023-01371-8. Epub 2023 Feb 19. PMID 36808262
• Nevo Y, Goldes Y, Barda L, Nadler R, Gutman M, Nevler A. Risk Factors for Complications of Total/Subtotal Gastrectomy for Gastric Cancer: Prospectively Collected, Based on the Clavien-Dindo Classification System. Isr Med Assoc J. 2018 May;20(5):277-280. PMID 29761671
• Wang WJ, Li HT, Yu JP, Su L, Guo CA, Chen P, Yan L, Li K, Ma YW, Wang L, Hu W, Li YM, Liu HB. Severity and incidence of complications assessed by the Clavien-Dindo classification following robotic and laparoscopic gastrectomy for advanced gastric cancer: a retrospective and propensity score-matched study. Surg Endosc. 2019 Oct;33(10):3341-3354. doi: 10.1007/s00464-018-06624-7. Epub 2018 Dec 17. PMID 30560498
• Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2021 (6th edition). Gastric Cancer. 2023 Jan;26(1):1-25. doi: 10.1007/s10120-022-01331-8. Epub 2022 Nov 7. PMID 36342574
• Pimentel-Nunes P, Libanio D, Bastiaansen BAJ, Bhandari P, Bisschops R, Bourke MJ, Esposito G, Lemmers A, Maselli R, Messmann H, Pech O, Pioche M, Vieth M, Weusten BLAM, van Hooft JE, Deprez PH, Dinis-Ribeiro M. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy. 2022 Jun;54(6):591-622. PMID 35523224

Identifiers

NCT: NCT07295002 · 2025-05956-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗