Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Endometrial Neoplasms

Lymphatic Metastasis

Neoplastic Processes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Patients with high risk endometrial cancer will undergo Sentinel Node Mapping followed by Systematic Pelvic and Para-Aortic Lymphadenectomy

Patients with high risk endometrial cancer will undergo Sentinel Node Mapping per NCCN algorithm

At least one sentinel node should be retrieved in both hemipelvis. If no sentinel node is found in one hemipelvis, a side specific lymphadenectomy will be performed.

Sentinel Node Mapping

Systematic Pelvic and Para-Aortic Lymphadenectomy

Lymphadenectomy

Bruna Goncalves, RN, MSc

Reitan Ribeiro, MD

Carlos Andrade, MD, PhD

Glauco Baiocchi, MD, PhD

Renato Moretti-Marques, MD, PhD

Andre Lopes, MD, PhD

This study will evaluate the role of systematic lymphadenectomy after sentinel node (SLN) mapping in high risk endometrial cancer (high grade histologies or deep myometrial invasion). The participants will be randomized in a non-inferiority controlled trial in 2 groups: SLN mapping or SLN mapping followed by systematic lymphadenectomy.

Although most patients with endometrial cancer present with early-stage disease, the standard treatment still includes systematic lymph node dissection for staging. Recently, SLN mapping has emerged as an acceptable surgical strategy when deciding between complete lymphadenectomy and no node dissection. This approach can help avoid the morbidity that is associated with a complete lymphadenectomy, such as neurovascular injury, lymphocyst formation, and lymphedema. A recent meta-analysis that included 55 studies and 4915 patients reported an overall SLN detection rate of 81% versus 50% for bilateral SLNs. Moreover, the use of indocyanine green increased the bilateral SLN detection rate compared with blue dye (74.6% vs. 50.5%). Yet, the studies noted an overall sensitivity of 96% and false negative rates of less than 5% when analyzed per hemipelvis. Since 2014, the National Comprehensive Cancer Network (NCCN) guidelines have recommended SLN mapping as an alternative option for node staging in endometrial cancer. However, most studies on SLN mapping have included patients who are at low risk for lymph node involvement and thus might underestimate the false negative rate. Recently, Soliman et al. reported a series of only high-grade and deep invasive endometrial cancers for which patients underwent SLN mapping, followed by pelvic and para-aortic lymph node dissection. An 89% detection rate was reported, suggesting that SLN mapping accurately identifies node metastases, with an negative predictive value (NPV) of 98% and an false negative predictive value (FNPV) of 2% when analyzed by hemipelvises. Positive nodes were found in 22.8% of patients (43% of isolated tumor cells and micrometastases), and in 40% of cases, the SLN was the only positive node. Data from the investigators corroborate these findings-26.7% of high-risk cases had positive nodes (50% of isolated tumor cells and micrometastases), and when analyzed by hemipelvis, the NPV was 97.9% and the FNPV was 2.1%. In 14 (70%) patients, the SLN was the only positive node. Moreover, there are few publications that have compared the results of the addition of SLN mapping to lymphadenectomy alone. Raimond et al. compared 156 patients that had SLN mapping with 95 who had pelvic node dissection. In their study, SLN mapping and imuno-histochemistry (IHC) were performed in low- and intermediate-risk patients, and the former detected metastatic node 3 times more often than complete pelvic lymphadenectomy alone (16.2% vs. 5.1%, p=0.03). They had no false negatives, and the IHC findings modified the adjuvant therapy in half of all cases. Holloway et al. compared a series of 661 patients who had undergone pelvic and para-aortic lymphadenectomy with 119 who were subjected to SLN mapping plus node dissection, including 68 high-intermediate- and high-risk patients in the SLN mapping group (GOG99 stratification). Despite the similarity in demographics and pathological risk factors, the SLN group had more LN metastases that were detected (30.3% vs. 16.3%; p\<0.001) and received more adjuvant therapy (28.6% vs. 16.3%; p=0.003). The SLN was the only positive node in 18 (50%) of mapped cases, and the false negative rate was 2.8%.The investigators recently published a series on high risk endometrial cancer and also recorded a higher pelvic node metastasis rate for the SLN mapping group (26.7% vs. 14.3%, p=0.02) but no significant difference in para-aortic node metastases (13.5% vs. 5.6%, p=0.12). Notably, if considered only patients in whom SLNs were mapped, 31.3% had pelvic positive nodes. Despite the differences in uterine risk factors between groups, 10.6% (8/75) of patients in the SLN group had node metastasis that was diagnosed only after IHC. Excluding these patients, the SLN group would have had a node positivity rate of 17.3%, similar to the N-SLN group (17.4%), reinforcing the impact of IHC in the detection of node metastases. Moreover, the SLN group received more adjuvant chemotherapy (33.5% vs. 48%). The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60%. The investigators noted an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false negative predictive value of 4.3%. Recently, Touhami et al. showed that the risk of non-SLN metastasis is 61% when the SLN metastasis size is ≥2mm, and 5% for SLN metastasis of \<2mm. However, one of the remaining uncertainties is the role of systematic lymphadenectomy after a positive SLN. In other words, is there any benefit in favor of systematic lymphadenectomy in a patient that already undergo adjuvant chemotherapy? The investigators hypothesized that there is no disease free survival benefit in adding systematic lymphadenectomy to only sentinel node mapping and proposed a prospective randomized controlled non-inferiority trial comparing SLN mapping to SLN mapping with systematic lymphadenectomy in high risk endometrial cancer.

Randomized Controlled Non-Inferiority Trial

Sentinel Node Mapping in High Risk Endometrial Cancer

Sentinel Node Mapping Versus Sentinel Node Mapping With Systematic Lymphadenectomy in High Risk Endometrial Cancer: a Open Label, Non-inferiority, Randomized Trial.

AC Camargo Cancer Center

Director, Department of Gynecologic Oncology

Skin and Connective Tissue Diseases

Breast Neoplasms

Patients will undergo preoperative lymphoscintigraphy in the nuclear medicine department to access axillary and extra-axillary sites of localization. Intraoperatively, patients will also be injected with approximately 4 to 5 mL of 1% isosulfan blue dye (by intradermal, intraparenchymal, or subareolar route). Patients will undergo intraoperative identification and biopsy of all SLN candidates. A confirmatory axillary lymph node dissection will then be performed on all patients.

Sentinel node mapping

Stephen P Povoski, MD

The purpose of the present proposed clinical trial will be to assess the utility of SLN mapping and biopsy for predicting the final axillary status after completion of preoperative neoadjuvant systemic chemotherapy in patients who had biopsy-proven positive axillary lymph nodes at initial presentation

Multiple retrospective reports have verified the overall utility of post-treatment sentinel lymph node (SLN) mapping and biopsy for assessing the final axillary lymph node status in breast cancer patients who have undergone preoperative neoadjuvant systemic chemotherapy. However, to date, only one report, in abstract form, currently exists within the literature which specifically assesses the utility of post-treatment SLN mapping and biopsy after completion of preoperative neoadjuvant systemic chemotherapy in patients with biopsy-proven positive axillary lymph nodes at initial presentation.

The purpose of the present proposed clinical trial will be to assess the utility of SLN mapping and biopsy for predicting the final axillary status after completion of preoperative neoadjuvant systemic chemotherapy in patients who had biopsy-proven positive axillary lymph nodes at initial presentation.

All eligible patients must have biopsy-proven invasive breast cancer and must also have biopsy-proven involvement of the axillary lymph nodes at initial presentation. Biopsy-proven involvement of the axillary lymph nodes at initial presentation will be based on fine needle aspiration (FNA) cytology, core/Tru-cut biopsy, or pre-treatment SLN biopsy. All eligible patients will have undergone preoperative neoadjuvant systemic chemotherapy.

After completion of preoperative neoadjuvant systemic chemotherapy and on the day of definitive breast cancer surgery, patients will be injected intradermally with approximately 400 microcuries of Tc-99m sulfur colloid. Patients will undergo preoperative lymphoscintigraphy in the nuclear medicine department to access axillary and extra-axillary sites of localization. Intraoperatively, patients will also be injected with approximately 4 to 5 mL of 1% isosulfan blue dye (by intradermal, intraparenchymal, or subareolar route). Patients will undergo intraoperative identification and biopsy of all SLN candidates. A confirmatory axillary lymph node dissection will then be performed on all patients.

The SLN mapping and biopsy procedure that we are proposing to perform on these breast cancer patients with known positive axillary lymph nodes at initial presentation will be done in an identical fashion to the SLN mapping and biopsy procedure that is currently performed as a routine and acceptable standard of care on every breast cancer patient with a clinically negative axilla at presentation.

The primary endpoints of this study would be address the success of identification of the SLN and the accuracy of the SLN mapping and biopsy procedure in women having undergone preoperative neoadjuvant systemic chemotherapy who had biopsy-proven involvement of their axillary lymph nodes at initial presentation. We would like to show that the proportion of women with false negative SLN biopsy results is less than 10%.

The study will require a minimum of 49 women with newly diagnosed breast cancer with biopsy-proven involvement of their axillary lymph nodes at initial presentation that have undergone preoperative neoadjuvant systemic chemotherapy. The study accrual time may take in the range of approximately 24 to 36 months to complete.

Axillary Lymph Node Status After Completion of Preoperative Neoadjuvant Systemic Chemotherapy in Patients

Sentinel Lymph Node Mapping and Biopsy For Predicting the Axillary Lymph Node Status After Completion of Preoperative Neoadjuvant Systemic Chemotherapy in Patients Who Had Biopsy-Proven Axillary Lymph Node Involvement at Initial Presentation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sentinel Node Mapping in High Risk Endometrial Cancer	NCT03366051	Endometrial Can... Lymph Node Meta...	Sentinel Node M... Lymphadenectomy	18 Years - 75 Years	AC Camargo Cancer Center
Axillary Lymph Node Status After Completion of Preoperative Neoadjuvant Systemic Chemotherapy in Patients	NCT00507611	Invasive Breast...	Sentinel node m...	18 Years -	Ohio State University Comprehensive Cancer Center

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