PET/CT and Lymph Node Mapping in Finding Lymph Node Metastasis in Patients With High-Risk Endometrial Cancer

Study Overview
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Brief Summary
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This clinical trial studies positron emission tomography (PET)/computed tomography (CT) and lymph node mapping in finding lymph node metastasis in patients with endometrial cancer that is at high risk of spreading. A PET/CT scan is a procedure that combines the pictures from a PET scan and a CT scan, which are taken at the same time from the same machine. The combined scans give more detailed pictures of areas inside the body than either scan gives by itself. Lymph node mapping uses a radioactive dye, called indocyanine green solution, to identify lymph nodes that may contain cancer cells. PET/CT and sentinel lymph node mapping may be better ways than surgery to identify cancer in the lymph nodes.

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate the false negative rate of PET/CT and/or sentinel lymph node mapping in the detection of positive lymph nodes in women with high risk endometrial cancers. SECONDARY OBJECTIVES: I. To estimate the sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT and/or sentinel lymph node mapping in the detection of positive lymph nodes in women with high risk endometrial cancer. II. To determine if a molecular panel of estrogen-induced genes that we have previously identified from retrospective studies correlate with extra-uterine spread including lymph node metastasis at the time of surgical staging for endometrial cancer. III. To prospectively identify patterns of lymphatic spread of endometrial cancer. IV. To correlate cancer antigen 125 (CA-125) and WAP four-disulfide core domain 2 (HE4) levels with disease metastasis at the time of surgical staging and to explore the use of other serum biomarkers to predict recurrence. V. To prospectively collect morbidity and mortality data related to performing lymph node dissection including intra-operative and postoperative complications. VI. To determine whether metabolic parameters of the primary endometrial tumor on PET including tumor intensity (maximum standard uptake value [SUV] and peak SUV), metabolic tumor volume (obtained at a threshold of 40% of maximum and at a threshold of SUV=3), and total lesion glycolysis (expressed average SUV over the metabolic tumor volume) are predictive of locoregional or metastatic spread, and whether these parameters correlate with CA-125 and HE4 levels. OUTLINE: Patients undergo PET/CT prior to surgery. Patients then undergo intraoperative lymph node mapping with indocyanine green solution, given via superficial and deep cervical injection during full lymphadenectomy.

Official Title
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Prospective Evaluation of Lymph Node Metastasis at the Time of Surgical Staging for High Risk Endometrial Cancer

Conditions
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Endometrial Clear Cell Adenocarcinoma, Endometrial Mixed Adenocarcinoma, Endometrial Serous Adenocarcinoma, Grade 3 Endometrial Endometrioid Adenocarcinoma, Malignant Mixed Mesodermal (Mullerian) Tumor

Intervention / Treatment
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* Procedure: Computed Tomography
* Drug: Indocyanine Green Solution
* Other: Laboratory Biomarker Analysis
* Procedure: Lymph Node Mapping
* Procedure: Lymphadenectomy
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed high grade endometrial cancer including grade 3 endometroid, serous, clear cell, malignant mixed Mullerian tumor (MMMT) or any mixed tumor containing one of these cell types Patients with a grade 1/2 tumors and evidence of deep myometrial invasion or cervical involvement on preoperative imaging or physical exam Candidate for surgery No evidence of peritoneal disease on preoperative imaging Negative pregnancy test if of child-bearing age No preoperative treatment for endometrial cancer including radiation or chemotherapy Previous hormonal therapy is allowed Exclusion Criteria: Medical co-morbidities making surgery unsafe, as determined by the primary treating physician Any contraindications to PET/CT or lymph node mapping (inability to control serum glucose to a value of =< 200 mg/dl for fludeoxyglucose F-18 [FDG]-PET/CT) Does not meet histologic criteria Evidence of peritoneal or distant metastasis on preoperative imaging Baseline creatinine (necessary for imaging studies)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (PET/CT, lymph node mapping)<br>Patients undergo PET/CT prior to surgery. Patients then undergo intraoperative lymph node mapping with indocyanine green solution, given via superficial and deep cervical injection during full lymphadenectomy. | Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: tomography;Drug: Indocyanine Green Solution<br>* Given via superficial and deep cervical injection<br>* Other names: ICG Solution;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Lymph Node Mapping<br>* Undergo lymph node mapping<br>* Other names: lymphatic mapping;Procedure: Lymphadenectomy<br>* Undergo full lymphadenectomy<br>* Other names: lymph node excision;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| False negative rate of positron emission tomography (PET)/computed tomography (CT) | Compared with pathological findings as the gold standard. The false negative rate for the procedure and for the combination of the 2 procedures will be estimated with 90% credible intervals. The posterior probability that the false negative rate is > 10% for each procedure and for the combination of the 2 procedures will also be reported. | Baseline | 
| False negative rate of sentinel lymph node mapping | Compared with pathological findings as the gold standard. The false negative rate for the procedure and for the combination of the 2 procedures will be estimated with 90% credible intervals. The posterior probability that the false negative rate is > 10% for each procedure and for the combination of the 2 procedures will also be reported. | At time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance for each procedure and for the combination of both procedures | The concordance for each procedure and for the combination of the 2 procedures will be estimated with 95% confidence intervals using pathologic findings as the gold standard. | At time of surgery | 
| Sensitivity of each procedure and for the combination of both procedures | The sensitivity of each procedure and for the combination of the 2 procedures will be estimated with 95% confidence intervals using pathologic findings as the gold standard. | At time of surgery | 
| Specificity of each procedure and for the combination of both procedures | The specificity of each procedure and for the combination of the 2 procedures will be estimated with 95% confidence intervals using pathologic findings as the gold standard. | At time of surgery | 
| Positive predictive value (PPV) of each procedure and for the combination of both procedures | The PPV of each procedure and for the combination of the 2 procedures will be estimated with 95% confidence intervals using pathologic findings as the gold standard. | At time of surgery | 
| Negative predictive value (NPV) of each procedure and for the combination of both procedures | The NPV of each procedure and for the combination of the 2 procedures will be estimated with 95% confidence intervals using pathologic findings as the gold standard. | At time of surgery | 
| CA-125 levels | Logistic regression methods will be used to model the logit of the probability of metastatic disease at the time of surgical staging as a function of CA-125 level, HE4 level, and other metabolic parameters including tumor intensity, metabolic tumor volume, and total lesion glycolysis. The odds ratio of the association between these factors and metastatic disease will be estimated with a 95% confidence interval. The logit of the probability of locoregional spread as a function of these factors will be similarly modeled. The correlations among these factors will also be estimated. | Baseline | 
| HE4 levels | Logistic regression methods will be used to model the logit of the probability of metastatic disease at the time of surgical staging as a function of CA-125 level, HE4 level, and other metabolic parameters including tumor intensity, metabolic tumor volume, and total lesion glycolysis. The odds ratio of the association between these factors and metastatic disease will be estimated with a 95% confidence interval. The logit of the probability of locoregional spread as a function of these factors will be similarly modeled. The correlations among these factors will also be estimated. | Baseline | 
| Metabolic parameters | Logistic regression methods will be used to model the logit of the probability of metastatic disease at the time of surgical staging as a function of CA-125 level, HE4 level, and other metabolic parameters including tumor intensity, metabolic tumor volume, and total lesion glycolysis. The odds ratio of the association between these factors and metastatic disease will be estimated with a 95% confidence interval. The logit of the probability of locoregional spread as a function of these factors will be similarly modeled. The correlations among these factors will also be estimated. | Baseline | 
| Incidence of intra-operative complications | Morbidity and mortality data will be tabulated, including intra-operative complications. | At time of surgery | 
| Incidence of post-operative complications | Morbidity and mortality data will be tabulated, including post-operative complications. | At time of surgery |