Endometrial Cancer
Conditions
Keywords
Sentinel lymph nodes, da Vinci, Firefly, Sentinel lymph node mapping, Fluorescence Imaging, SLN, SLN mapping
Brief summary
The investigators hypothesis is that if sensitivity and specificity are found to be significantly higher than the current reports with Technesium-99 and ISB colorimetric dye, SLN biopsies might allow omission of full lymphadenectomy in lower-risk cases, thereby limiting peri-operative morbidity. SLN biopsies might also improve the detection of metastatic disease, essentially lowering the recognized false-negative rate of standard lymphadenectomy analyzed by routine H&E pathologic analysis.
Detailed description
The study objective is to compare two sentinel lymph node detection technologies \[fluorescence imaging and Indocyanine Green (ICG) dye verses standard laparoscopic colorimetric analysis using Isosulfan Blue (ISB) dye\] for sensitivity and specificity of detecting metastatic disease in pelvic lymph nodes of women with endometrial cancer undergoing robotic-assisted laparoscopic hysterectomy and lymphadenectomy. The following three specific aims would be addressed in this research proposal: Specific Aim 1: To determine the ability of mapping bilaterally pelvic SLN in women with endometrial cancer undergoing robotic-assisted laparoscopic staging comparing two different methods (i.e., comparing the combination of colorimetric analysis-ISB dye + fluorescence imaging-ICG dye vs. colorimetric analysis-ISB dye alone). Specific Aim 2: To estimate the negative predictive value (NPV) of pelvic SLN in endometrial cancer with respect to predicting nodal metastasis. Specific Aim 3: To evaluate the ability of sentinel lymph nodes to increase the detection of metastatic disease through ultra-sectioning and immuno-histochemical (IHC) staining by comparing IHC results and standard hematoxylin and eosin (H&E) results.
Interventions
DEVICEISB dye and standard white light imaging
Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging.
DEVICEICG dye and FireFly fluorescence imaging
Sentinel lymph node mapping utilizing the da Vinci surgical system with ICG dye and FireFly fluorescence imaging.
Sponsors
AdventHealth
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. The patient must be ≥18 and ≤85 years of age. 2. The patient must be female. 3. The patient must be willing and able to provide informed consent. 4. The patient is willing and able to comply with the study protocol. 5. The patient has endometrial cancer and is scheduled for robotic hysterectomy and lymphadenectomy. 6. The patient agrees to follow-up examinations out to 6-weeks post-treatment
Exclusion criteria
1. The patient is not a candidate for robotic assisted hysterectomy and lymphadenectomy. 2. The patient has known or suspected allergies to iodine, ICG or ISB. 3. The patient has hepatic dysfunction confirmed by elevated liver function studies (i.e., hepatic enzyme SGOT, SGPT or Bilirubin \> 2 x normal (based on reference values from the laboratory used by the patient)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes. | through 6 weeks post-operative |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis. | through 6 weeks post-operative | The standard definition for negative predictive value was used to calculate NPV. There was one false negative SLN in this study, 39 true positive sentinel lymph nodes, and 140 negative pelvic metastatic patients. NPV = 140/141=99.3% |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | through 6 weeks post-operative | Of the 127 positive nodes with pathology information, the percentage of each type of node will be summarized by the staining method. Statistical testing of the individual staining methods compared to both will be computed using Chi-square test of independence. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ISB Dye, Standard White Light SLN mapping utilizing da Vinci surgical system with Isosulfan Blue (ISB) dye and standard white light imaging.
ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging. | 20 |
| ICG Dye, FireFly Fluorescence Imaging SLN mapping utilizing da Vinci surgical system with ISB dye and standard white light first, and then additionally, Indocyanine Green (ICG) dye and FireFly fluorescence imaging.
ISB dye and standard white light imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system and ISB dye with standard white light imaging.
ICG dye and FireFly fluorescence imaging: Sentinel lymph node mapping utilizing the da Vinci surgical system with ICG dye and FireFly fluorescence imaging. | 180 |
| Total | 200 |
Baseline characteristics
| Characteristic | Total | ICG Dye, FireFly Fluorescence Imaging | ISB Dye, Standard White Light |
|---|---|---|---|
| Age | 64.5 years STANDARD_DEVIATION 8.4 | 64.4 years STANDARD_DEVIATION 8.6 | 66.0 years STANDARD_DEVIATION 6.7 |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 114 Participants | 101 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 86 Participants | 79 Participants | 7 Participants |
| Region of Enrollment United States | 200 Participants | 180 Participants | 20 Participants |
| Sex: Female, Male Female | 200 Participants | 180 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 20 | 29 / 180 |
| serious Total, serious adverse events | 0 / 20 | 0 / 180 |
Outcome results
Primary
Number of Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes.
Time frame: through 6 weeks post-operative
Population: The ISB dye alone group (n=20) and the ICG group (n=180) are combined, because both groups received the ISB dye.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ISB Dye, Standard White Light | Number of Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes. | 1.25 nodes | Standard Deviation 0.901 |
| ICG Dye, FireFly Fluorescence Imaging | Number of Pelvic Sentinel Lymph Nodes (SLN) in Endometrial Cancer Patients Detected by Either ICG and/or ISB Dyes. | 2.03 nodes | Standard Deviation 0.72 |
Secondary
Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis.
The standard definition for negative predictive value was used to calculate NPV. There was one false negative SLN in this study, 39 true positive sentinel lymph nodes, and 140 negative pelvic metastatic patients. NPV = 140/141=99.3%
Time frame: through 6 weeks post-operative
Population: Comparison of metastatic disease (yes or no) with ICG dye node detection (yes or no)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ISB Dye, Standard White Light | Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis. | Metastatic Disease | 1 Participants |
| ISB Dye, Standard White Light | Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis. | Non Metastatic Disease | 140 Participants |
| ICG Dye, FireFly Fluorescence Imaging | Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis. | Metastatic Disease | 39 Participants |
| ICG Dye, FireFly Fluorescence Imaging | Negative Predictive Value (NPV) of Pelvic SLN in Endometrial Cancer in Relation to the Number of Nodes With Metastasis. | Non Metastatic Disease | 0 Participants |
Other Pre-specified
Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E).
Of the 127 positive nodes with pathology information, the percentage of each type of node will be summarized by the staining method. Statistical testing of the individual staining methods compared to both will be computed using Chi-square test of independence.
Time frame: through 6 weeks post-operative
Population: These are positive sentinel lymph nodes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ISB Dye, Standard White Light | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Sentinel Nodes | 16 nodes |
| ISB Dye, Standard White Light | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Pelvic Nodes Only | 1 nodes |
| ISB Dye, Standard White Light | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Aortic | 1 nodes |
| ISB Dye, Standard White Light | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Infrarenal | 0 nodes |
| ICG Dye, FireFly Fluorescence Imaging | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Infrarenal | 10 nodes |
| ICG Dye, FireFly Fluorescence Imaging | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Sentinel Nodes | 31 nodes |
| ICG Dye, FireFly Fluorescence Imaging | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Aortic | 14 nodes |
| ICG Dye, FireFly Fluorescence Imaging | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Pelvic Nodes Only | 36 nodes |
| Both IHC and H&E | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Infrarenal | 0 nodes |
| Both IHC and H&E | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Pelvic Nodes Only | 2 nodes |
| Both IHC and H&E | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Aortic | 0 nodes |
| Both IHC and H&E | Number of Pelvic Sentinal Lymph Nodal Metastasis in Regard to Staining by Immunohistochemical (IHC) Staining in Comparison to Standard Hematoxylin and Eosin (H&E). | Sentinel Nodes | 16 nodes |