Comparison of Two-Position and Four-Position Cervical Injection Techniques for Sentinel Lymph Node Mapping in Endometrial Cancer Using Methylene Blue

NCT07040657 | Recruiting

• 1 other identifier: 693-SBKAEK
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

This clinical trial evaluates lymph node mapping in newly diagnosed endometrial cancer patients undergoing surgery. The standard technique uses a 2-point methylene blue cervical injection. The study aims to determine if increasing injection points improves mapping success.

Conditions

Endometrial Neoplasms; Endometrial Cancer Stage I; Sentinel Lymph Node; Metastasis

Keywords

endometrial neoplasm; methylene blue; metastasis; cervix

Outcome Measures

Primary Outcomes (4)

• Sentinel Lymph Node (SLN) Detection Rate

  The detection rate will be measured as the number of sentinel lymph nodes identified using methylene blue divided by the total number of lymph nodes excised during surgery. Comparison will be made between the two-point and four-point cervical injection techniques. (Unit of Measure: Proportion (%))

  1 day

• Sensitivity of SLN Biopsy for Detecting Lymph Node Metastases

  Sensitivity will be calculated as the proportion of true positive SLNs (confirmed by histopathology) over the total number of lymph nodes with metastases. (Unit of Measure: Percentage (%))

  1 day

• Specificity of SLN Biopsy for Detecting Lymph Node Metastases

  Description: Specificity will be calculated as the proportion of true negative SLNs over all lymph nodes without metastasis. (Unit of Measure: Percentage (%))

  1 day

• Rate of Positive SLNs Detected

  Proportion of SLNs identified as positive for metastasis in each injection technique group. (Unit of Measure: Proportion (%))

  1 day

Secondary Outcomes (4)

• Procedure Duration

  1 day

• Complications and Side Effects - Injection-Related Side Effects

  1 month

• SLN Anatomical Distribution

  1 day

• Surgical Complications

  1 month

Study Arms (2)

2- Point Methylene Blue Injection

EXPERIMENTAL

In the 2-point injection arm, participants will receive the standard sentinel lymph node (SLN) mapping technique using methylene blue. The procedure involves injecting methylene blue dye into two specific locations on the cervix: At the 3 o'clock position At the 9 o'clock position

Procedure: Sentinel Lymph Node Detection/Cervical Methylene Blue Injection

4- Point Methylene Blue Injection

ACTIVE COMPARATOR

In the 4-point injection arm, participants will receive the standard sentinel lymph node (SLN) mapping technique using methylene blue. The procedure involves injecting methylene blue dye into two specific locations on the cervix: At the 2 o'clock position At the 4 o'clock position At the 8 o'clock position At the 10 o'clock position

Procedure: Sentinel Lymph Node Detection/Cervical Methylene Blue Injection

Interventions

Sentinel Lymph Node Detection/Cervical Methylene Blue Injection PROCEDURE

Sentinel Lymph Node (SLN) detection using cervical methylene blue injection is a surgical technique designed to identify the primary lymph nodes responsible for draining the uterus in patients with endometrial cancer. The procedure involves injecting methylene blue dye into specific locations within the cervical stroma to enable lymphatic uptake. The dye subsequently travels through the lymphatic channels, allowing for intraoperative visual identification of the sentinel nodes. This targeted approach facilitates selective SLN excision for pathological evaluation, providing critical information about lymphatic involvement while minimizing the extent of surgical dissection. The effectiveness of SLN mapping is contingent upon the accuracy of the injection technique and the anatomical distribution of lymphatic drainage.

2- Point Methylene Blue Injection; 4- Point Methylene Blue Injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: This study is limited to female participants, as it focuses on sentinel lymph node (SLN) mapping in patients with endometrial cancer, a disease that exclusively affects individuals with a uterus. Male participants are not eligible for inclusion in this study.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals diagnosed with stage I endometrial cancer based on CT and PET-CT imaging.
• Individuals with a pathologically confirmed diagnosis of stage I endometrial cancer.

You may not qualify if:

• Medical Conditions
• Individuals diagnosed with dementia.
• Individuals with allergies to methylene blue or iodine.
• Individuals who have received active treatment for another malignancy within the past five years.
• Inability to successfully perform PLD (pelvic lymphadenectomy) or history of prior PLD.
• Women with multiple and confluent lymph nodes identified as positive on FDG-PET/CT (such cases are not considered stage I).
• Cancer-Related Conditions
• Individuals with clinically or radiologically identified positive lymph nodes or metastatic disease.
• Individuals with a history of pelvic dissection and/or radiation therapy.
• Individuals with advanced cervical or uterine cancer.
• Individuals with T3/T4 lesions.
• Individuals with cervical tumors larger than 2 cm.
• Organ Dysfunction
• Individuals with hepatic dysfunction and a MELD score ≥ 10 and creatinine ≥ 2·0 mg/dl patients.

Sponsors & Collaborators

• Dokuz Eylul University: lead

Study Sites (2)

Ankara University

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Dokuz Eylul University

Izmir, Turkey (Türkiye)

RECRUITING

Related Publications (14)

• Sehnal B, Waldauf P, Matej R, Hruda M, Robova H, Drozenova J, Pichlik T, Zapletal J, Rob L, Halaska MJ. Comparison of tracer application methods for sentinel lymph node detection in open surgery patients with endometrial cancer: a retrospective cohort study. BMC Cancer. 2025 Apr 8;25(1):638. doi: 10.1186/s12885-025-14037-8.

  PMID: 40200256 BACKGROUND

• Holloway RW, Abu-Rustum NR, Backes FJ, Boggess JF, Gotlieb WH, Jeffrey Lowery W, Rossi EC, Tanner EJ, Wolsky RJ. Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol Oncol. 2017 Aug;146(2):405-415. doi: 10.1016/j.ygyno.2017.05.027. Epub 2017 May 28.

  PMID: 28566221 BACKGROUND

• Salman L, Cusimano MC, Marchocki Z, Ferguson SE. Sentinel lymph node mapping in endometrial cancer: Current evidence and practice. J Surg Oncol. 2024 Jan;129(1):117-119. doi: 10.1002/jso.27550. Epub 2023 Dec 7.

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• Leitao MM Jr, Zhou QC, Gomez-Hidalgo NR, Iasonos A, Baser R, Mezzancello M, Chang K, Ward J, Chi DS, Long Roche K, Sonoda Y, Brown CL, Mueller JJ, Gardner GJ, Jewell EL, Broach V, Zivanovic O, Dowdy SC, Mariani A, Abu-Rustum NR. Patient-reported outcomes after surgery for endometrial carcinoma: Prevalence of lower-extremity lymphedema after sentinel lymph node mapping versus lymphadenectomy. Gynecol Oncol. 2020 Jan;156(1):147-153. doi: 10.1016/j.ygyno.2019.11.003. Epub 2019 Nov 25.

  PMID: 31780238 BACKGROUND

• Terada S, Tanaka T, Murakami H, Tsuchihashi H, Toji A, Daimon A, Miyamoto S, Nishie R, Ueda S, Hashida S, Morita N, Maruoka H, Konishi H, Kogata Y, Taniguchi K, Komura K, Ohmichi M. Lymphatic Complications Following Sentinel Node Biopsy or Pelvic Lymphadenectomy for Endometrial Cancer. J Clin Med. 2023 Jul 7;12(13):4540. doi: 10.3390/jcm12134540.

  PMID: 37445574 BACKGROUND

• Altin D, Taskin S, Ortac F, Tokgozoglu N, Vatansever D, Guler AH, Gungor M, Tasci T, Bese T, Turan H, Kahramanoglu I, Yalcin I, Celik C, Demirkiran F, Kose F, Arvas M, Ayhan A, Taskiran C. Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006). Gynecol Oncol. 2022 Mar;164(3):492-497. doi: 10.1016/j.ygyno.2022.01.009. Epub 2022 Jan 13.

  PMID: 35033380 BACKGROUND

• Niikura H, Kaiho-Sakuma M, Tokunaga H, Toyoshima M, Utsunomiya H, Nagase S, Takano T, Watanabe M, Ito K, Yaegashi N. Tracer injection sites and combinations for sentinel lymph node detection in patients with endometrial cancer. Gynecol Oncol. 2013 Nov;131(2):299-303. doi: 10.1016/j.ygyno.2013.08.018. Epub 2013 Aug 27.

  PMID: 23988415 BACKGROUND

• Geppert B, Lonnerfors C, Bollino M, Arechvo A, Persson J. A study on uterine lymphatic anatomy for standardization of pelvic sentinel lymph node detection in endometrial cancer. Gynecol Oncol. 2017 May;145(2):256-261. doi: 10.1016/j.ygyno.2017.02.018. Epub 2017 Feb 10.

  PMID: 28196672 BACKGROUND

• Perrone AM, Casadio P, Formelli G, Levorato M, Ghi T, Costa S, Meriggiola MC, Pelusi G. Cervical and hysteroscopic injection for identification of sentinel lymph node in endometrial cancer. Gynecol Oncol. 2008 Oct;111(1):62-7. doi: 10.1016/j.ygyno.2008.05.032. Epub 2008 Jul 14.

  PMID: 18625518 BACKGROUND

• Dick A, Perri T, Kogan L, Brandt B, Meyer R, Levin G. Sentinel lymph node mapping in endometrial cancer: A comparison of main national and international guidelines. Int J Gynaecol Obstet. 2023 Jan;160(1):220-225. doi: 10.1002/ijgo.14307. Epub 2022 Jul 5.

  PMID: 35700068 BACKGROUND

• Fotopoulou C, Ind T, Baldwin P, Crawford R, Devaja O, Dobbs S, Frost J, Gajjar K, Ganesan R, Kaushik S, Morrison J, Nobbenhuis M, Ratnavelu N, Rolland P, Singh N, Taylor A, Sundar S, Nordin A. Sentinel lymph node consensus document of the British Gynaecological Cancer Society for endometrial, vulvar, and cervical cancers. Int J Gynecol Cancer. 2019 Nov;29(9):1348-1350. doi: 10.1136/ijgc-2019-000798. No abstract available.

  PMID: 31685556 BACKGROUND

• Dioun S, Chen L, Melamed A, Gockley A, St Clair CM, Hou JY, Khoury-Collado F, Hershman DL, Wright JD. Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer. BJOG. 2022 Aug;129(9):1591-1599. doi: 10.1111/1471-0528.17085. Epub 2022 Jan 25.

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• Baiocchi G, Andrade CEMC, Ribeiro R, Moretti-Marques R, Tsunoda AT, Alvarenga-Bezerra V, Lopes A, Costa RLR, Kumagai LY, Badiglian-Filho L, Faloppa CC, Mantoan H, De Brot L, Dos Reis R, Goncalves BT. Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial). Int J Gynecol Cancer. 2022 May 3;32(5):676-679. doi: 10.1136/ijgc-2022-003378.

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  PMID: 32868384 BACKGROUND

MeSH Terms

Conditions

Endometrial Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Ibrahim Yalcin, MD

CONTACT

+90 505 265 60 24; ibrahimyalcin73@gmail.com

Ali Hakan Kula, MD

CONTACT

+905358230685; hkula95@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: To minimize bias and ensure the reliability of study results, both participants and care providers will be blinded to group allocation. The surgeon administering the injection and the pathologist evaluating lymph node samples will not be informed whether the participant received the two-point or four-point cervical injection. This double-masking approach enhances the objectivity of care delivery and outcome assessment, thereby strengthening the validity of the findings.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized Controlled Trial (RCT)

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: June 27, 2025
• Study Start: May 1, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

TU (2)