Clinical trial NCT05191212: The Role of Real-time Appearance of Lymphatic Flow in Lymphatic Mapping in Endometrial Cancer
Official title: The Role of Real-time Appearance of Lymphatic Flow in the Detection of Bilateral Sentinel Lymph Node With Fluorescence Imaging Technique in Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sentinel Lymph Node
Keywords: Endometrial cancer
Sentinel lymph node
İndocyanine green
Robotic surgery
Lymphatic channel
Real-time appearance of lymphatic flowing
Lead sponsor: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
Sponsor class: OTHER_GOV
First posted: 2022-01-13
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Purpose of the study Primary treatment of clinical early stage endometrial cancer is total hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection for staging. It was stated in the National Comprehensive Cancer Network (NCCN) guideline that sentinel lymph node biopsy can be performed as an alternative to systematic lymphadenectomy, including high-risk endometrial cancer histologies (2).

In a study, the rate of bilateral sentinel lymph node detection in sentinel lymph node mapping using the cervical injection technique of indocyanine green was found to be 73.3%. After re-injection of cervical indocyanine green in patients whose sentinel lymph node could not be detected, the rate of detection of bilateral sentinel lymph nodes increased to 94.5% (4). However, repeated cervical injection causes a waste of time.

In our clinic, sentinel lymph node mapping method is applied using indocyanine green for lymph node dissection for staging purposes, since the robotic system has a fluorescent imaging system in patients operated with robotic surgery for endometrial cancer. In accordance with the literature, our bilateral sentinel lymph node detection rate was 75%. During cervical indocyanine green injection in our last 6 patients, the lymphatic channels in the pelvic region were followed simultaneously with the injection and indocyanine injection was performed until the channels were seen transperitoneally. Bilateral lymphatic channels were seen in all of these patients, and sentinel lymph nodes were found bilaterally in all of them.

The aim of the planned study is to compare the traditional cervical indocyanine green injection and indocyanine injection until the lymphatic channels are visualized for bilateral detection of sentinel lymph nodes in patients with clinical early stage endometrial cancer.

Material-Method The number of patients planned to be included in the study was calculated as 24 patients in both groups, with an alpha error value of 5% and a statistical power above 80% when the bilateral sentinel lymph node detection rate was 75% in the traditional method and 99% in the study group (SPH analytics 2021).

Detailed description: Purpose of the study Endometrial cancer is the most common cancer of the female genital tract. In the USA, 65,620 new cases were detected in 2020, and 12,590 deaths occurred.

Primary treatment of clinical early stage endometrial cancer is total hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection for staging. It was stated in the National Comprehensive Cancer Network (NCCN) guideline that sentinel lymph node biopsy can be performed as an alternative to systematic lymphadenectomy, including high-risk endometrial cancer histologies.

Although dyes such as methylene blue or isosulfan blue and radioactive substances such as technetium-99 can be used in sentinel lymph node biopsy, fluorescent imaging systems using indocyanine green have recently been widely used due to high detection rates. Side-specific pelvic lymphadenectomy should be performed in the region where no sentinel lymph node can be detected. This increases the duration and difficulty of the operation and may cause morbidities such as leg edema and lymphocele.

In a study, the rate of bilateral sentinel lymph node detection in sentinel lymph node mapping using the cervical injection technique of indocyanine green was found to be 73.3%. After re-injection of cervical indocyanine green in patients whose sentinel lymph node could not be detected, the rate of detection of bilateral sentinel lymph nodes increased to 94.5%. However, repeated cervical injection causes a waste of time.

In investigator's clinic, sentinel lymph node mapping method is applied using indocyanine green for lymph node dissection for staging purposes, since the robotic system has a fluorescent imaging system in patients operated with robotic surgery for endometrial cancer. In accordance with the literature, the investigator's bilateral sentinel lymph node detection rate was 75%. During cervical indocyanine green injection in the last 6 patients of the investigators, the lymphatic channels in the pelvic region were followed simultaneously with the injection and indocyanine injection was performed until the channels were seen transperitoneally. Bilateral lymphatic channels were seen in all of these patients, and sentinel lymph nodes were found bilaterally in all of them.

The aim of the planned study is to compare the traditional cervical indocyanine green injection and indocyanine green injection until the lymphatic channels are visualized for bilateral detection of sentinel lymph nodes in patients with clinical early stage endometrial cancer.

Material-Method Among the patients who applied to the Health Sciences University, Bakırköy Dr Sadi Konuk Training and Research Hospital, Gynecological Oncology clinic due to endometrial cancer and were found to be in the clinical early stage as a result of imaging, those suitable for robotic surgery will be included in the study.

An informed consent form will be signed by the patients who agree to participate in the study.

Procedure:

In this technic, 25 mg of indocyanine green powder dissolved in 10 cc of sterile water. A 10 mL sterile syringe is filled with 2 cc of ICG and diluted with 8 cc of sterile water, obtaining a total of 10 cc solution with a ICG final concentration of a 0,5 mg/mL.

After docking of the Da Vinci Xi Surgical System (Intuitive Surgical, Sunnyvale, CA, USA), firstly, each 1 cc volume of the ICG is injected to the deep stroma (1 cm of depth) and submucosa (1 mm depth) at 9 o'clock position into the cervix by using 22-gauge spinal needle. While the injection is performing, the surgeon watches real-time appearance of ICG in the lymphatic channel transperitoneally from the console using fire-fly mode of the robotic system. If the appearance of ICG can not been observed, additional 1 cc volume of ICG is injected to the near side of first injection site of deep stroma and submucosa respectively until visualization of real-time appearance of ICG in lymphatic channel.

The same procedure is performed contralateral site, at 3 o'clock position of the cervix. Then retroperitoneum is opened. Fire-fly mode of the robot is activated and sentinel nodes are removed gently All these procedures were performed by two collaborating surgeons.

Demographic data of the patients such as age, parity, body-mass index, systemic diseases, tumor histology, presence of lymphovascular invasion, disease data such as tumor diameter, operation time, amount of bleeding, bilateral or unilateral detection rates of sentinel lymph nodes, if any, intraoperative and operative results such as postoperative complications, whether blood product replacement is performed, length of stay in hospital, and whether there is a need for postoperative intensive care unit will be recorded.

Statistical View The number of patients planned to be included in the study was calculated as 24 patients in both groups, with an alpha error value of 5% and a statistical power above 80% when the bilateral sentinel lymph node detection rate was 75% in the traditional method and 99% in the study group (SPH analytics 2021).

For continuous variables, the Mann-Whitney U test will be compared if appropriate, and for categorical variables, the frequency distribution will be compared with Chi-square or Fisher's exact test. Univariate and multivariate Cox proportional hazard ratio (HR) analyzes will be performed to identify independent prognostic factors. For all cases, a p value \< 0.05 would be considered statistically significant. SPSS version 25.0 (IBM, Armonk, NY, USA) will be used for statistical analysis.

Inclusion criteria

Patients with clinical stage 1-2 endometrial cancer ASA 1-3 patients

Exclusion criteria from the study Patients with clinical stage 3-4 endometrial cancer Patients who are not suitable for robotic surgery due to their comorbidities (such as glaucoma, COPD, asthma) ASA 4-5 patients

Eligibility criteria: Inclusion Criteria: Patients with clinical stage 1-2 endometrial cancer ASA 1-3 patients

Exclusion Criteria: Patients with clinical stage 3-4 endometrial cancer Patients who are not suitable for robotic surgery due to their comorbidities (such as glaucoma, COPD, asthma) ASA 4-5 patients

Primary outcomes:
measure: Bilateral sentinel lymph node detection rate
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Gökhan Demirayak
Study officials:
References:
citation: Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
citation: 2- NCCN Clinical Practice Guidelines in Oncology. Uterine Neoplasms Version 4.2021 -September 3, 2021 https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf
citation: Yost KJ, Cheville AL, Al-Hilli MM, Mariani A, Barrette BA, McGree ME, Weaver AL, Dowdy SC. Lymphedema after surgery for endometrial cancer: prevalence, risk factors, and quality of life. Obstet Gynecol. 2014 Aug;124(2 Pt 1):307-315. doi: 10.1097/AOG.0000000000000372.
citation: Maramai M, Achilarre MT, Aloisi A, Betella I, Bogliolo S, Garbi A, Maruccio M, Quatrale C, Aletti GD, Mariani A, Colombo N, Maggioni A, Multinu F, Zanagnolo V. Cervical re-injection of indocyanine green to improve sentinel lymph node detection in endometrial cancer. Gynecol Oncol. 2021 Jul;162(1):38-42. doi: 10.1016/j.ygyno.2021.04.026. Epub 2021 Apr 24.