Clinical trial NCT05184140: Mapping Sentinel Lymph Node in Initial Stages of Ovarian Cancer
Official title: MELISA Trial: Mapping sEntinel Lymph Node in Initial StAges of Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ovarian Cancer
Sentinel Lymph Node
Keywords: Ovarian Cancer
Sentinel Lymph Node
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: Berta Diaz-Feijoo
name: Aureli Torné
name: Pilar Paredes
name: Sergi Vidal-Sicart
name: Ariel Glickman
name: Pere Fusté
name: Tiermes Marina
name: Francisco Campos
First posted: 2022-01-11
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Controlled, prospective, descriptive
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Detection rate of sentinel node technique
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Tracer specific detection rate
timeFrame: 2 years
measure: Tracer-related adverse events
timeFrame: 1 month
measure: False negative rate and negative predictive value
timeFrame: 2 years
measure: Anatomical location of the sentinel lymph node
timeFrame: 2 years
measure: Detection rate of gamma-camera, gamma-probe and Infrared fluorescence camera
timeFrame: 2 years
measure: Surgical time extension performing SLN technique
timeFrame: 2 years
measure: Anatomopathological ultrastaging examination of the sentinel lymph node
timeFrame: 2 years
Other outcomes:
measure: Evaluation of sentinel lymph node technique
timeFrame: Through study completion, an average of 2 years
Locations:
city: Barcelona
country: Spain
facility: Núria Agustí Garcia
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Aureli Torné, PhD
role: STUDY_DIRECTOR
affiliation: Hospital Clinic of Barcelona
name: Berta Díaz-Feijóo, PhD
role: STUDY_DIRECTOR
References: