Mapping Sentinel Lymph Node in Initial Stages of Ovarian Cancer (MELISA)

MELISA Trial: Mapping sEntinel Lymph Node in Initial StAges of Ovarian Cancer

Epithelial ovarian cancer (EOC) diagnosed in the initial stage (stage I-II) require complete staging surgery to histologically assess the possible existence of peritoneal or lymph node disease.

Systematic pelvic and paraaortic lymphadenectomy in stage I-II EOC is essential since confirming the presence of lymph node metastases means re-staging the disease as stage III. This change of stage has important prognostic and therapeutic implications. However, the lymph node involvement rate is around 10-30% (average of 15%). Systematic pelvic and para-aortic lymphadenectomy carries a risk of intraoperative complications, as well as longer operative time, postoperative complications and longer hospital stay. Moreover, by now there is no evidence suggesting a possible therapeutic value.

The sentinel lymph node (SLN) detects the first level of lymph node drainage. The absence of metastases in the SLN predicts the absence of tumor infiltration of the rest of lymph nodes of the same anatomical region and allows to safely avoid lymphadenectomy and its associated morbidity. In addition, the exhaustive evaluation of the SLN by ultrastaging and immunohistochemical study allows to increase the detection of microscopic disease.

Sentinel lymph node (SLN) biopsy, implemented in clinical practice in other gynecological tumors (breast, vulva, cervix or endometrium), has been studied very little in the initial ovarian epithelial cancer. Unlike other gynecological tumors, there are multiple anatomical and technical aspects that largely explain this lack of information. The double ovarian vascularization that accompanies lymphatic drainage explains this higher complexity. Therefore, at the present time, the detection of SLN in the initial EOC remains an experimental area without applicability in clinical practice. There are multiple doubts and issues to be resolved regarding the different tracers, the site and time injection and the actual accuracy of the SLN versus the lymphadenectomy.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer; Sentinel Lymph Node
• Intervention / Treatment: Procedure: Sentinel node detection

Detailed Description

The objective of this study is to know the lymphatic drainage and, if the lesion is malignant, remove the sentinel lymph nodes to know if it can predict the involvement of the remaining lymph nodes to assess the possible applicability of SLN in clinical practice.

Study design:

1. Evaluation of the ovarian lymphatic map: injection of radiotracer (99mTc-nanocolloid albumin) in patients with a diagnosis of adnexal mass with high suspicion of malignancy. Intraoperative lymphogammagraphy will be performed using a portable gammacamera. Patients with a delayed diagnosis of ovarian cancer who are candidates to undergo a re-staging surgery will be included.
2. After the adnexectomy a frozen section will be performed to confirm the diagnosis of malignancy and then the ICG (Indocyanine green) tracer will be injected. Since the spread and persistence of the ICG in the lymph nodes is rapid, this tracer will be injected only after confirmation of EOC. Simultaneous screening with a gammadetector probe and NIR (near-infrared spectrum) camera will be used to proceed to the detection of SLN according to the lymphatic map previously.
3. Ultrastaging of the SLN by applying hematoxylin and eosin staining (H&E) and, in the absence of metastatic disease, evaluation by immunohistochemistry with cytokeratin AE1: AE3.

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Núria Agustí, MD; Phone Number: 5334 +34 932 27 54 00; Email: nagusti@clinic.cat
• Study Contact Backup: Name: Pilar Paredes, PhD; Email: pparedes@clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08014
    • Recruiting
    • Núria Agustí Garcia
    • Contact: Núria Agustí Garcia, MD; Phone Number: +34627654987; Email: nagusti@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients with a diagnosis of adnexal mass with high suspicion of malignancy and frozen section examination will undergo the lymphatic map with a radiotracer.
• Patients with intraoperative diagnosis of epithelial ovarian cancer will undergo the SLN exeresis with two tracers.
• Patients with a delayed diagnosis of epithelial ovarian cancer who are candidates to undergo a re-staging surgery will undergo the SLN exeresis with two tracers.

Exclusion Criteria:

• Advanced ovarian cancer (FIGO III/IV)
• Patients <18 years
• Pregnancy or lactation
• Previous vascular surgery (cava, aorta, iliac vessels), lymphadenectomy (pelvic or paraortic) or radiotherapy (pelvic or paraortic field)
• Severe adherent syndrome that prevents tracer injection
• The SLN technique will not be performed in case of benign ovarian tumor in the frozen section or borderline tumor (since in these cases there is no clinical indication of performing a lymphadenectomy)
• Non-operable patient
• Previous adverse events to the radiotracer or ICG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adnexal mass with high suspicion of malignancy; An ovarian lymphatic map will be performed in patients with adnexal masses suspected of malignancy. Sentinel node exeresis and a complete staging surgery (including pelvic and para-aortic lymphadenectomy) will be performed in patients with ovarian cancer confirmation including restaging surgeries.

Procedure: Sentinel node detection; Injection of the radiotracer to infundibulo-pelvic and utero-ovarian ligament in patients with high suspicion of malignancy adnexal mass. Injection of green indocyanine r to infundibulo-pelvic and utero-ovarian stumps only in case of malignancy after the adnexectomy. Sentinel node exeresis and a complete staging surgery (including pelvic and para-aortic lymphadenectomy) will be performed in patients with ovarian cancer diagnosis.; Other Names: Complete staging surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection rate of sentinel node technique	Detection of SLN in initial epithelial ovarian cancer by assessing the concordance of the result between the lymph node metastases and the lymphadenectomy	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tracer specific detection rate	To know the global and specific SLN identification rate, depending on the type of tracer used.	2 years
Tracer-related adverse events	The number of patients with tracer-related adverse events	1 month
False negative rate and negative predictive value	Evaluate the existence of false negatives in metastatic involvement of the SLN and negative predictive value	2 years
Anatomical location of the sentinel lymph node	The aortic and pelvic region will be divided 13 regions	2 years
Detection rate of gamma-camera, gamma-probe and Infrared fluorescence camera	Evaluate the performance of intraoperative lymphoscintigraphy with gamma-camera, gamma-probe and Infrared fluorescence camera in the visualization of the ovarian lymphatic map.	2 years
Surgical time extension performing SLN technique	Evaluate the time it takes to perform the SLN technique	2 years
Anatomopathological ultrastaging examination of the sentinel lymph node	Evaluate if ultrastaging of the SLN improves the detection of micrometastases compared to conventional histology. Ultrastaging protocol will be performed, consisting of two consecutive histological sections (4 μm thick) obtained at regular intervals of 150 μm, performing 4 levels of each paraffin block. The first section will be stained with H&E and the second section will be stained immunohistochemically with an AE1-AE3 anti-keratin antibody (Dako®).	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of sentinel lymph node technique	To check the ovarian lymphatic drainage in patients with suspected malignant adnexal masses	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Collaborators: Berta Diaz-Feijoo; Aureli Torné; Pilar Paredes; Sergi Vidal-Sicart; Ariel Glickman; Pere Fusté; Tiermes Marina; Francisco Campos
• Investigators: Study Director: Aureli Torné, PhD, Hospital Clinic of Barcelona; Study Director: Berta Díaz-Feijóo, PhD, Hospital Clinic of Barcelona

Publications and helpful links

Helpful Links

• 834 Study of the lymphatic map and detection of the sentinel lymph node in ovaric masses with suspected malignancy
• Sentinel lymph node mapping in early-stage ovarian cancer: surgical technique in 10 steps

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: December 4, 2021
• First Submitted That Met QC Criteria: January 5, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 4, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Ovarian Cancer; Sentinel Lymph Node
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: HCB/2021/0130

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The IPD will be shared only with those making official request to the study investigator
• IPD Sharing Time Frame: The data will become available One year after publication, and they will be available for 6 months.
• IPD Sharing Access Criteria: Direct request to the study PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No