Sentinel Node Mapping With Robotic Assisted Near Infra-red Fluorescent Imaging in Women With Cervical and Endometrial Cancer
Phase: NA
Conditions: Uterine Cervical Neoplasms, Uterine Neoplasms
Sponsor: University of Southern Denmark

 
Sentinel Node Mapping with Robotic Assisted Near Infra-Red Fluorescent Imaging in Women with Cervical and 
Endometrial Cancer (SENTIREC). Protocol high risk studies– 05.08.2018.  Inclusive statistical amendment 04.12.2020 
 
 
 
SENTIREC 
                    
Sentinel Node Mapping  
with Robotic Assisted Near Infra-Red Fluorescent Imaging 
in Women with Cervical and Endometrial Cancer 
 
 
- Project Description -  
 
 
 
 
Ph.D. applicants:  
 
                                     SENTIREC CERIVX:  MD Sara Elisabeth Sponholtz  
                                     SENTIREC ENDO:      MD Sarah Marie Bjørnholt  
 
 
 
Principal supervisor: Professor, Senior Consultant Pernille Tine Jensen 
 
 
 
 
Co-supervisors:  
Professor, Chief Consultant, DMSc Ole Mogensen 
Senior Hospital Physician, Ph.D., Associate Professor Malene Hildebrandt 
Senior Hospital Physician, Ph.D., Associate Professor Kirsten Bauchelauche 
Senior Hospital Physician Doris Schledermann 
Associate Professor, Ph.D. Thiusius Rajeeth Savarimuthu 
 
 
 
 
 
Aarhus University Hospital, Department of Gynaecology and Obstetrics   & 
Odense University Hospital, Department of Gynaecology and Obstetrics 
Denmark 
 
 
 
 
 

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Endometrial Cancer (SENTIREC). Protocol high risk studies– 05.08.2018. Statistical amendment  04.12.2020 
 
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Table of contents  
Introduction ................................................................................................................................................................ 3 
Background ................................................................................................................................................................. 3 
Aims of the study .................................................................................................................................................. 5 
Study population .................................................................................................................................................. 6 
Study design ................................................................................................................................................................ 6 
Surgical Procedure: ............................................................................................................................................. 7 
Pathology: ................................................................................................................................................................ 7 
Patient reported outcome measures ........................................................................................................... 8 
Special considerations ....................................................................................................................................... 8 
Primary outcome measurements ................................................................................................................. 9 
Secondary outcome measurements ............................................................................................................. 9 
Statistical analysis .................................................................................................................................................... 9 
Study IIA cervix cancer: ..................................................................................................................................... 9 
Study IIB endometrial cancer: ...................................................................................................................... 10 
Biological material ............................................................................................................................................. 10 
Recruitment of patients ....................................................................................................................................... 10 
Publications ............................................................................................................................................................... 11 
Potential risks, side effects and complications .......................................................................................... 11 
Ethical considerations .......................................................................................................................................... 11 
Approvals ................................................................................................................................................................... 12 
Quality assurance .................................................................................................................................................... 12 
Economy ..................................................................................................................................................................... 12 
References: ................................................................................................................................................................ 14 
Appendix I. Predefined anatomical locations, for registration of lymph nodes. ......................... 17 
Appendix II. English version of all included PROMS ............................................................................... 18 
EORTC IL76 .......................................................................................................................................................... 18 
LYMFQOL ............................................................................................................................................................... 19 
EORTC QLQ-C30 ................................................................................................................................................. 21 
 
 
 
 
 
 
 

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Introduction 
Lymph node metastasis is the most significant negative prognostic factor in women with cervical- 
and endometrial cancer. Surgical staging serves to allocate women with lymph node metastases to 
adjuvant therapy. For women with cervical cancer with tumours of >2 cm the standard surgical 
staging includes pelvic lymph node dissection (PLD) and additional paraaortic lymph node 
dissection (PALD) is recommended for women with high-risk histology endometrial cancer.  PLD 
and PALD is associated with morbidity including blood loss, nerve injury, and lymphoedema.   
 
Sentinel lymph node (SLN) mapping is a highly specialized surgical procedure, which may replace 
radical lymphadenectomy in many cancer diseases without compromising diagnostic safety. The 
technique has been described previously and has proved safe for detecting lymph node metastasis in 
early-stage cervical cancer (tumour < 2 cm) and in low-risk endometrial cancer, but has so far not 
been implemented in the daily clinical treatment of women with cervical and endometrial cancer in 
Denmark. The diagnostic safety of SLN mapping for identifying lymph node metastases in women 
with cervical cancer with tumours of >2cm and for women with endometrial cancer with high-risk 
histology is unclear. The risk of late effects e.g., leg and groin lymphoedema and its impact on 
quality of life after radical PLD and PALD has not been evaluated. In these studies, we will 
investigate if SLN mapping is a diagnostically safe staging modality for women with cervical 
cancer with tumours >2cm and for women with endometrial cancer with high-risk histology. 
Further, we will assess the patient experienced incidence of lymphedema and its impact on the 
quality of life after PLD and PALD.  
 
Background 
The systematic staging with PLD and PALD offers diagnostic information to allocate women to 
follow-up or adjuvant treatment. Two randomized controlled trials found no survival benefit of 
PLD (1,2). Lymph node involvement is observed in 12-22% of women with early-stage cervical 
cancer and in 20-30% with early-stage high-risk endometrial cancer (3–5). As a consequence, 
approximately 80% of the women undergoing PLD do not benefit from the procedure. There are 
several intra- and postoperative complications related to PLD including lymphedema, lymphocysts, 
neurovascular damage, ureteral injury, and blood loss (6–8). Following radical PLD, it is estimated 
that about 11-28% of women develop lower limb lymphedema that may give rise to heaviness, 
tingling, aching, numbness, and pain (9). These symptoms may be associated with decreased quality 
of life that is likely to impact on the woman’s physical functioning and psychosocial- and sexual 
well-being (9–11).  
 
Sentinel lymph node (SLN) mapping has proved diagnostically safe and is implemented in the 
treatment of breast, melanoma, and vulva cancer (12,13). The SLN mapping concept is based on 
two principles; lymphatic drainage follows an orderly and predictable pattern to a regional lymph 
node basin and the first lymph node in this pattern functions as an effective filter for tumour cells. 
Hence, the SLN is the first lymph node(s) to which the primary tumour metastasizes. If the sentinel 
node is without metastatic disease, theory is that all lymph nodes in that region are free of cancer 

Sentinel Node Mapping with Robotic Assisted Near Infra-Red Fluorescent Imaging in Women with Cervical and 
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and complete lymph node removal is unnecessary (6,13). The technique has proved diagnostically 
safe in early stage cervical cancer (tumour < 2 cm) and in low-risk endometrial cancer (14).  
The uterus is a midline structure with bilateral lymphatic drainage. The detection of SLNs per 
hemipelvis is therefore important to ensure complete removal of possible metastases (6). SLN 
mapping in cervical and endometrial cancer may have several advantages compared to radical PLD. 
The intra- and postoperative complications may decrease and the surgical procedure is shorter. 
Further, the SLN may be identified in areas (e.g. the paraaortic and presacral areas) that would have 
been ignored with standard PLD (15). In addition, the SLN technique allows the use of the ultra -
staging technique that enables identifying micrometastases (16).  
 
One of the main challenges of the SLN procedure is the rate of false negative procedures. However, 
studies in early stage cervical tumours have shown this rate to decrease significantly if SLN 
mapping is supplemented by removal of enlarged nodes, PLD in cases of failed SLN mapping, 
paraaortic evaluation, and ultra-staging (6,17) (Figure 1). Following this algorithm, one study 
showed a decrease in false negative procedures from 14.9% to 1.9% in women with endometrial 
cancer (17).  Whether this algorithm will have equal safety in women with cervical cancer with 
tumours >2cm and women with high-risk endometrial cancer is unknown.  
 
 
Figure 1: SLN algorithm for lowering the rate of false negative procedures (17). 
 
The size of the primary cervical tumour has been suggested to influence on the diagnostic safety of 
SLN mapping. Hence, one study showed a significantly higher detection rate (94.0% vs. 83.6%) in 
tumours <=2 cm in size as opposed to larger tumours (18). However, additional studies are needed 
to further evaluate SLN mapping in cervical tumours > 2 cm.  
 
For women with high-risk endometrial cancer most studies on the safety of SLN mapping has been 
based on mixed populations of high-risk and low-risk endometrial cancer patients (17,19,20). 
Despite this the only three false negative SLN cases in the SENTIENDO study, were found among 
high-risk patients. Further the sensitivity and NPV of SLN mapping in previous studies were 
calculated on women were the majority had PLD and not both PLD and PALD as a reference, with 
the risk of  overseeing isolated para-aortic nodal metastasis (17,19,21).  In the study by Barlin et al. 
the only false negative SLN case had an isolated paraaortic metastasis (17).  
 
Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is the 
most accurate imaging modality to detect lymph node-  and peritoneal metastases in gynaecological 

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cancers (22). Previous studies have shown a comparatively high sensitivity and specificity of FDG-
PET/CT to detect lymph node metastases in women with cervical cancer compared to other imaging 
modalities (23). For smaller cervical tumours and low volume metastasis several studies have 
shown a high false positive and false negative rate whereas FDG-PET/CT performed significantly 
better with higher tumour stage (22,23). In the group of women with cervical cancer and tumour 
size > 2 cm, FDG-PET/CT imaging may assist SLN mapping in detecting lymph node metastasis.   
 
The accuracy of FDG-PET/CT is challenged for small-volume disease but may have a high 
sensitivity in detecting larger metastasis >10mm for both high-risk endometrial cancer and cervical 
cancers (24). By adding FDG-PET/CT to the SLN mapping the sensitivity for paraaortic 
macrometastasis might improve and thus minimising the risk of overseeing at least macroscopic 
paraaortic isolated metastasis. However, the role of FDG-PET/CT as an integrated part of an SLN 
algorithm for women with cervical cancer with tumours of >2cm and women with high-risk 
endometrial cancer and is still unsettled.   
 
Even though SLN mapping with indocyanine green (ICG) shows a consistently high overall 
detection rate (78-100%) and a high bilateral detection rate (57-97%)in women with cervical cancer 
<2cm  and low-risk endometrial cancer (3,18,25–28), the use of SLN mapping in larger cervical and 
endometrial cancer with high-risk histology is more doubtful. The present study will investigate if 
the combination of SLN mapping and a preoperative diagnostic FDG-PET/CT improves the 
detection of metastases in women with large cervical tumours (>2cm) and in women with high risk 
histology endometrial cancer.   
 
Aims of the study 
I. 
To evaluate the diagnostic safety of SLN mapping in combination with FDG-PET/CT 
imaging in women with cervical cancer with tumour size > 2 cm and in women with high-
risk histology endometrial cancer  
II. 
To evaluate the course of lymphedema in women with early-stage cervical (tumour>2 cm) 
following SLN mapping and PLD.  
III. 
To evaluate the course of lymphedema following SLN mapping, PLD and PALD in women 
with high-risk endometrial cancer.  
 
 
It is hypothesized that SLN mapping in combination with FDG-PET/CT imaging is a diagnostically 
safe technique in women with high risk cervical cancer (tumour >2cm) and in women with high-
risk endometrial  
It is further hypothesized that PLD- for cervical cancer and PLD+ PALD for high-risk endometrial 
cancer in combination with SLN mapping will lead to an incidence of chronic lymphedema (as 
measured 12 months postoperatively) of around 30%, leading to a significantly impaired quality of 
life.  

Sentinel Node Mapping with Robotic Assisted Near Infra-Red Fluorescent Imaging in Women with Cervical and 
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Study population 
- 
Study IIA: Women with cervical cancer (FIGO stage IB1, IB2 and IIA1) and a tumour size > 2 
cm with planned robotic assisted laparoscopic radical surgery including radical hysterectomy 
and PLD are eligible.  
- 
Study IIB: Women with presumed stage I high-risk endometrial cancer (Endometriorid 
adenocarcinoma grade 3 or Type 2 histology; serous adenocarcinoma, clearcell adenocarcinoma 
and carcinosarcoma) (32-33) planned for robotic assisted laparoscopic radical surgery including 
total hysterectomy, PLD and PALD are eligible.  
 
*The size of the cervical tumour will be determined by clinical evaluation in the diagnostic gynaecologic examination 
as customary. 
 
Both studies will be commenced at Odense University Hospital. Copenhagen University Hospital 
from March 2017 and at Aarhus University Hospital from June 2018. International collaboration 
will be sought to assist in inclusion due to the low number of eligible patients in Denmark. Patients 
will be included over a three-year period from February 2017 to February 2020. A total of 100 
patients in Study IIA and 150 patients in Study IIB (please see the power calculation) will be 
included in this two-year inclusion period. The study period may be extended until the expected 
number of patients are included 
 
Study design  
Both studies are prospective observational diagnostic studies with the purpose of investigating the 
diagnostic safety of SLN mapping and FDG-PET/CT to detect lymph node metastases. All patients 
will receive SLN mapping and removal of FDG-PET/CT positive lymph nodes followed by 
conventional radical PLD and for endometrial cancer also PALD.  
Please see appendix 3-4 for flowcharts of the procedure. 
 
FDG-PET/CT scans will be performed in all patients prior to surgery. An experienced specialist in 
nuclear medicine will systematically describe the FDG-PET/CT for each patient prior to surgery. 
Inclusion criteria: 
- 
Women 18 years or older 
- 
Study IIA: patients with early stage cervical cancer with tumour size >2 cm*, 
FIGO stage IB1, IB2 or IIA1 
- 
Study IIB: patients with high risk endometrial cancer, type 1 histology grade 3 
Endometrioid adenocarcinoma or type 2 histology (serous-, clearcel-, 
carcinosarcoma or undifferentiated adenocarcinoma. 
- 
Capable of filling out questionnaire in Danish 
- 
Booked for robotic assisted operation 
Exclusion criteria: 
- 
Prior PLD 
- 
Known allergy towards ICG and/or iodine (ICG contains 5% sodium iodine) 
- 
Women included in other studies affecting outcome-measures of the present study 
- 
Women where pelvic lymphadenectomy is  discarded or previously performed 
been deselected due to reasons related to the patients health status 
- 
Women in active treatment for a secondary cancer diagnosis within the past 5 years 
(excl. basal cell carcinoma) 
- 
Women with dementia 

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FDG-PET/CT positive lesions are described with exact anatomic localizations (appendix I), size 
and amount. All lesions will be evaluated on an ordinal scale ranging from 0 to 3. A score of 0 or 1 
carry the meaning of ‘no’ or ‘probably no’ signs of metastasis, and a score of 2 or 3 carry the 
meaning of ‘probable’ or ‘definite’ signs of metastasis, respectively. For overall accuracy analyses, 
these values will be dichotomized into test negative (0 and 1) and test positive results (2 and 3). 
Furthermore, in all FDG avid lesions, the standard uptake value (SUV) will be registered for 
quantification purposes. Blood sugar levels will be taken on patients in order to calculate the SUV.  
 
Surgical Procedure: 
Shortly prior to surgery a vial of 25 mg ICG is diluted with 20 ml of sterile water to produce a 1.25 
mg/ml concentration. For each patient, a new vial of ICG is used due to degradation of the 
fluorescence signal of ICG after dissolving. The same vial of ICG may however be used for several 
patients if the patients are operated the same day, since degradation of the fluorescence signal of 
ICG after dissolving is very low within the first 24 hours. When the woman has been anesthetized 
and immediately prior to surgery, 4 ml of the 1.25mg/ml ICG solution is injected into the cervix.. 
An injection of 2 ml will be made on each side of the cervix at positions 3 and 9 o’clock, with 1 ml 
deep in the cervical stroma (>10 mm) and 1 ml submucosally (< 5 mm). 
The surgical robot is routinely docked and the NIR fluorescence system is initiated. All standard 
locations of a PLD are examined for fluorescence using the NIR fluorescence imaging system. 
Fluorescent hotspots are denominated as SLNs and the amount and localization are described and 
drawn into an anatomical illustration (Appendix I). All denominated SLNs are then removed 
surgically and sent for ultra-staging.  The FDG-PET/CT positive lymph nodes will be localized 
following the SLN mapping. If the FDG-PET/CT positive lymph node has already been nominated 
as a SLN, the lymph node- will be labeled SLN and FDG-PET positive. Any enlarged lymph nodes 
suspicious of metastatic disease will be removed and marked as such with the predefined 
anatomical location (Appendix I). Finally radical PLD is performed in all women. Women with 
endometrial cancer will further undergo PALD to the level of the renal vein.   
 
Pathology:  
Removed SLNs are fixed in formalin after excision. A national ultra-staging protocol is 
implemented in all three participating centres. At the Department of Clinical Pathology the SLNs 
will be serially sectioned at 2-mm intervals in cross-section and entirely embedded in paraffin. The 
SLNs will be examined by the ultra-staging protocol consisting of four consecutive sections 5 µm 
thick, each obtained at 350 µm intervals according to the Danish guideline for SLN analysis in 
breast cancer. The first section at each level is stained with routine hematoxylin and eosin staining, 
the second section will be used for immunohistochemical staining for cytokeratin AE1/AE3 and the 
third section is available for additional analysis. Non SLNs will be examined conventionally 
through microscopy and routine hematoxylin and eosin staining of each block. 
Histopathological features that will be recorded include tumor size, presence or absence of 
lymphovascular space invasion, the number of SLNs per case, the number of nonSLNs per case, the 
presence of metastases in SLNs and non-SLNs and the size and location of the metastasis in the 
SLNs.  
 

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Patients with histologically verified metastatic disease (including micro metastases) will be 
allocated to postoperative therapy according to national guidelines. Postoperative clinical follow up 
will be performed according to national guidelines.  
 
Patient reported outcome measures 
A combination of validated questionnaires are completed to assess the incidence of lymphedema 
and its impact on quality of life:  
 
 Ten questions on lymphedema selected from the European Organization for Research and 
Treatment of Cancer (EORTC) Vulva Cancer Questionnaire Module (VU34) and included in 
the EORTC item bank: IL76. The questions will be used to screen for lymphedema, if the 
patient answers yes to any of the questions, they will be asked to complete the LYMPQOL 
questionnaire (please see below). Two items in the IL76 constitute a validated scale of leg 
lymphedema in women with cervical and endometrial cancer as entailed in the questionnaires 
EORTC CX24 and EN24.  
 Lymphedema Quality of Life Questionnaire (LYMQOL) (29). A validated condition-specific 
quality of life assessment tool (Lymphedema Clinic, Derby Hospital NHS Foundation Trust, 
England). 
 The generic questionnaire, EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) 
(30) and the disease specific instruments for cervical (CX-24) and endometrial (EN-24) cancer  
 
The LYMQOL questionnaire will be translated to Danish using independent forward-backward 
translation and pilot tested before administration.  
The questionnaires are completed as paper/pen version or electronically at the patient’s individual 
preference at 3, 12, 24, and 36 months after surgery. The incidence of early lymphedema will be 
evaluated at 3 months postoperatively as a difference score between 3 months and the baseline 
score. The course of chronic lymphedema will be evaluated over time. Written reminders will be 
sent once after three weeks at each questionnaire interval if the patient has not responded. 
Sociodemographic variables will be collected using a questionnaire designed for the purpose and 
included in the first questionnaire package. The sociodemographic variables include Danish social 
security number, age, hospital, date of inclusion, BMI, smoking status and contact information. 
Other data recorded from patient medical files include comorbidity, prior abdominal surgery, type 
of cancer, presumed preoperative FIGO stage, final FIGO stage postoperatively and whether or not 
the patient undergoes postoperative oncological therapy. This information will be used for 
stratification and adjustment in the analyses of lymphedema and quality of life. 
 
Special considerations 
In Study IIA radiologically and/or clinically suspected lymph nodes may be sent for frozen section 
to rule out the metastatic disease. Alternatively, a two-step procedure: removal of suspected lymph 
nodes for histology as a first step operation followed by completion surgery as a second step, if no 
metastatic disease in the removed lymph nodes is revealed. If metastatic lymph node involvement is 
histologically confirmed intra-operatively, the surgical procedure of women with cervical cancer 
will be terminated and the patient will be referred for chemo-radiotherapy.  

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In study IIB In case of clinically highly suspicious lymph nodes a frozen section evaluation is 
recommended, and if metastatic disease is identified, systematic PLD and PALD should be 
abandoned and replaced by removal of all clinically and by imaging suspicious lymph nodes in the 
pelvic and paraaortic area. All women with serous adenocarcinomas and with carcinosarcomas 
should further undergo infracolic omentectomy (31).   
 
Primary outcome measurements 
Study IIA: The overall sensitivity of SLN mapping combined with removal of FDG-PET/CT 
positive lymph nodes in the detection of lymph node metastases. Due to the low prevalence of the 
disease this study is primarily explorative. 
Study IIB: The NPV of SLN mapping combined with FDG-PET/CT. Please see below for a power 
calculation. 
 
Secondary outcome measurements 
Study IIA:  
- 
Prevalence of lymph node metastasis.  
- 
The detection rate of SLNs. The positive- and negative predictive values of SLN mapping per 
patient and per hemi-pelvis. 
- 
The positive- and negative predictive value, sensitivity and specificity analyses of FDG-
PET/CT.  
- 
The specific size of the cervical tumour determined by a combination of MR imaging, 
pathology and clinical evaluation will be described for comparison.  
- 
Incidence and severity of lymphedema and quality of life assessment of all patients. 
 
Study IIB:  
- 
Prevalence of lymph node metastasis.  
- 
The detection rate of SLNs in high risk endometrial cancer.  
- 
The sensitivity of SLN mapping per patient. 
- 
Incidence and severity of lymphedema and affection of quality of life after SLN mapping, PLD 
and PALD. 
- 
Intra- and postoperative complications after surgery with SLN mapping, PLD and PALD.  
 
Statistical analysis 
 
Study IIA cervix cancer: 
The exact prevalence of lymph node metastases in cervical cancers of > 2cm is not known from the 
literature. In studies including low risk cervical cancer patients (tumors < 20 mm) it has been 
estimated to be < 10%. The present study is explorative and will include 100 patients in Study IIA 
(cervical cancer) who have undergone PLD after SLN mapping. 
Further, the rate of true positive (TP), false positive (FP), false negative (FN) and true negative 
(TN) findings of PET/CT and SN mapping will be identified to assess the positive predictive value, 

Sentinel Node Mapping with Robotic Assisted Near Infra-Red Fluorescent Imaging in Women with Cervical and 
Endometrial Cancer (SENTIREC). Protocol high risk studies– 05.08.2018. Statistical amendment  04.12.2020 
 
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the negative predictive value, the sensitivity of PET/CT and SN mapping, respectively. Explorative 
comparisons will be made for each of the intervention tests (PET/CT and SN mapping).  
 
Study IIB endometrial cancer:  
Amendment 04.12.2020 
The prevalence of lymph node metastasis in high-risk endometrial cancer has been reported to be 
around 18-25% in women with high- risk histology endometrial cancer. The known prevalence 
enables a power calculation for the negative predictive value (NPV). For a possible implementation 
of SLN mapping, an NPV of 94% is considered acceptable, and a confidence interval below 90% is 
deemed unacceptable for implementation of SLN mapping in clinical practice. The power 
calculation is based on women who undergo SLN mapping, followed by PLD and paraaortic lymph 
node dissection. Assuming the true incidence of metastasis is 20%, and the sensitivity of the SLN 
mapping algorithm is 96%, 150 women with PLD and PALD are needed to conclude that NPV is 
larger than 94% using a 95% one-sided exact Clopper–Pearson confidence interval.  
 
Biological material 
Lymph nodes in all studies will be removed as described and sent for analyses at the Department of 
Clinical Pathology. Biological material will not be stored in a biobank for further research in the 
present project. Biological material is stored in the Department of Clinical Pathology as customary 
with all histological specimens and may be retrieved for other purposes. This will demand a new 
ethical application and informed consent from the patients.  
The lymph nodes will be fixed in formalin on the day of removal. Lymph nodes will be examined 
macroscopically and tissue will be excised for microscopy. The residual tissue will be stored for 4 
weeks, in case there is a need for additional examination. On day 3 or 4 the tissue from the lymph 
nodes will be ready for HE and immunohistochemical examination. On day 5 or 6 results will be 
ready.  
Microscopy glasses will be scanned and saved digitally in the pathology system. Only personnel in 
the Department of Clinical Pathology will have access to these images. The images will be saved 
for at least 5 years. Excised tissue will be saved as paraffin blocs eternally, as is standard with 
histological specimens in Denmark. The blocs will be safely locked away and patients can only be 
identified via the pathology system of which only personnel have access to.  
 
Recruitment of patients 
Patients will be recruited at their first visit to the outpatient clinic at the hospital during the 
diagnostic process and planning of treatment. The written patient information given to the patient 
during this visit. A doctor from the gynaecologic oncology team provides oral information on 
relevant study. The doctors work with treatment of patients with gynaecological cancer on a daily 
basis and are very competent in informing the patient thoroughly about the disease and treatment 
besides potential project participation. The doctor have sufficient time for the appointment and will 
not be disturbed by telephone calls in order to ensure that the conversation can proceed undisturbed. 
The participant will be made aware of the possibility of bringing a family member or other relation 
to the appointment besides the patient’s right to have time to consider the information before 
entering the study. 

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If the patient requests further oral information, the patient will be asked if she is willing to be 
contacted by phone for further oral information by a doctor after a couple of days. Final consent to 
participate in the study is obtained in connection with one of the patient’s visits to the hospital prior 
to surgery. 
Patients are free to accept or decline participation and will receive a minimum of 24 hours to 
consider before entering the study. Each patient will have a contact person delegated and will 
receive contact information to this person in case of a need for further information about the study. 
Each patient must give informed consent before they can be included in the study and is free to 
withdraw consent at any time. Patients who withdraw consent will instead receive the best available 
conventional treatment according to the guidelines from the Danish Gynaecologic Cancer Group. 
Please see attachments regarding written and oral participant information for further information. 
 
Publications 
Positive as well as negative results and inconclusive results will be presented at relevant national 
and international scientific congresses and published in scientific journals. This project is expected 
to result in at least six publications related to two PhD studies on cervical cancer and endometrial 
cancer. Further, two-three publications are expected on each study. All patient information will be 
anonymous prior to publication. 
 
Potential risks, side effects and complications 
The risk of allergic reaction is 1 per 42000 (32). Approximately 30 minutes extra duration of 
surgery is estimated in patients who are allocated to receive SLN mapping followed by 
conventional PLD. 
  
We expect no other side effects, risks or other disadvantages.  
 
Ethical considerations    
A potential advantage for the participants in the study is the possible detection of a SLN and 
thereby potential metastases in an area outside the standard area of PLD. Further, patients may 
benefit from the diagnosis of micro-metastases by the ultrastaging technique, both allowing correct 
allocation for adjuvant treatment and potential improvement in survival. 
 
We believe that the results of the present study have advantages to the patients in the studies as well 
as to future patients with cervical and endometrial cancer. We believe that potential disadvantages 
outweigh the potential risks and complications related to the SLN mapping procedure. Intra- and 
postoperative complications will be closely monitored as part of the study. 
We expect that the present project will have substantial significance in changing the national 
treatment strategy of early stage cervical and endometrial cancer patients. A significant part of these 
patients undergo a systematic radical surgical lymph node staging procedure (PLD +/- PALD) that 
has never shown any survival benefit and which is considered to carry a substantial risk of chronic 
lymphedema. For women with cervical tumours >2 cm and endometrial cancer with high-risk 
histology, the sentinel node technique has not been established as a diagnostically safe procedure. 
With the present study, we will assess the diagnostic safety of the SLN procedure in itself and in 

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combination with a systematic use of FDG-PET/CT. Establishing the evidence of diagnostic safety 
as described may save future patients from systematic lymph node dissection procedures and hence 
likely decrease the risk of early and chronic lymphedema.   
 
Approvals  
 
A permit for the use of ICG has been obtained and authorized for this project by the Danish Health 
Authority (Journal nr. 2015053824). Approval has been authorized from the Regional Committee 
on Health Research Ethics (Project-ID S-20150207 SRJ/csf) and the Danish Data Protection 
Agency (Journal nr. 15/52037). The study is in conformity with the principles of the Helsinki 
Declaration II. Patients will be under protection of the Danish Legislation of Treatment of Personal 
Data and the Danish Health Legislation.  
Copenhagen University Hospital and Arhus University Hospital will participate with inclusion for 
study IIA and study IIB. A permit for the use of ICG has been obtained and authorized for this 
project for use at Copenhagen University Hospital and Aarhus University Hospital by the Danish 
Health Authority.  
Quality assurance  
Before inclusion in study IIA and study IIB all centres will go through the national SENTIREC 
pilot study to ensure a structured surgical training and surgeon proficiency in accurate SLN 
mapping at the participating cancer centres. All centres will performe at least 30 successful SLN 
mappings, with a total (uni- and bilateral) SLN detection of > 80%.   
Before entering study IIA and IIB, all centres will be thoroughly introduced to the protocol at site 
visits. The protocol along with local instructions for procedures including written and video 
material will be introduced before the study start. Each centre will have a senior consultant as local 
responsible co-investigator for the project. Only named, experienced surgeons who perform robotic 
surgery and are allocated to the gynaecological oncological team at one of the centres will perform 
the surgical procedure in the study. Before and during inclusion national investigator meetings will 
be held annually to ensure change of experiences, procedure adherence, and continued proficiency.  
Economy 
Professor Ole Mogensen and Chief Physician, Ph.D. Pernille Tine Jensen at the Department of 
Gynaecology and Obstetrics at Odense University Hospital (OUH), Denmark have taken the initiative 
to begin this project in cooperation with Ph.D. student, MD Sara Elisabeth Sponholtz.  
This PhD is work package two of the ROSOR project (Research On Surgical Robotics), a large 
multicentre project examining different aspects of robotic surgery in collaboration with The Maersk 
McKinney Moeller Institute, Denmark. The current project examines techniques in robotic surgery, 
while the other work packages will be examining robotic surgery from an economical point of view, 
general quality of life after robotic surgery, muscular skeletal influences on the surgeon and 
development of the robotic function. 
The Ph.D. student Sara Elisabeth Sponholtz salary is financed by a one-year faculty scholarship of 
500.000 DKK from The Faculty of Health Science, Southern University of Denmark (SDU). The 
second year’s salary is financed by a 500.000 DKK grant from OUH’s Ph.D. Fund (account number 
OL 10212036). The third year is financed by a 500.000 DKK grant from the ROSOR project (account 

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number OL 6109), which is financed through OUH’s Frontliniepulje and The Danish Cancer Society. 
Extra salary expenses for year two and three are covered by Eva and Henry Fraenkels Fond (45.410 
DKK) and Danish Cancer Research Fund (106.286 DKK). Sara Elizabeth Sponholtz is employed at 
the Clinical Institute, SDU, who will manage payment of salary. The Ph.D. student Sarah Marie 
Bjørnholts is employed at Aarhus University the faculty of health, her salary is fully financed by a 
PhD scholarship from Aarhus University.  
 
All included centres cover expenses and running costs related to SLN mapping. At Odense 
University hospital external funding has been achieved for the ultrastaging procedures and the 
purchase of ICG tracer, the Danish Cancer Research Fund has partly funded Study IIB. At Aarhus 
University hospital external funding has been achieved for running costs in study IIB by the Vissing 
Fund. Patients will not receive compensation for participating in this project. 
 
 

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References:  
1.  
ASTEC study group, Kitchener H, Swart AM, Qian Q, Amos C PM, H K, AM S, Q Q, C A, 
MK P. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC 
trial): a randomised study. Lancet [Internet]. 2009 Jan 10 [cited 2020 Jan 
20];373(9658):125–36. Available from: https://pubmed.ncbi.nlm.nih.gov/19070889/ 
2.  
Panici PB, Basile S, Maneschi F, Lissoni AA, Signorelli M, Scambia G, et al. Systematic 
pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: 
randomized clinical trial. J Natl Cancer Inst [Internet]. 2008 Dec [cited 2022 Sep 
9];100(23):1707–16. Available from: https://pubmed.ncbi.nlm.nih.gov/19033573/ 
3.  
Plante M, Touhami O, Trinh XB, Renaud MC, Sebastianelli A, Grondin K, et al. Sentinel 
node mapping with indocyanine green and endoscopic near-infrared fluorescence imaging in 
endometrial cancer. A pilot study and review of the literature. Gynecol Oncol [Internet]. 
2015 Jun 1 [cited 2023 Sep 4];137(3):443–7. Available from: 
https://pubmed.ncbi.nlm.nih.gov/25771495/ 
4.  
Sakuragi N. Up-to-date management of lymph node metastasis and the role of tailored 
lymphadenectomy in cervical cancer [Internet]. Vol. 12, International Journal of Clinical 
Oncology. Int J Clin Oncol; 2007 [cited 2020 Jul 23]. p. 165–75. Available from: 
https://pubmed.ncbi.nlm.nih.gov/17566838/ 
5.  
Holloway RW, Gupta S, Stavitzski NM, Zhu X, Takimoto EL, Gubbi A, et al. Sentinel 
lymph node mapping with staging lymphadenectomy for patients with endometrial cancer 
increases the detection of metastasis. Gynecol Oncol [Internet]. 2016 May 1 [cited 2020 Feb 
11];141(2):206–10. Available from: https://www.gynecologiconcology-
online.net/article/S0090-8258(16)30042-7/fulltext#.XkKCEPrxVWc.mendeley 
6.  
Eiriksson LR, Covens A. Sentinel lymph node mapping in cervical cancer: The future? 
[Internet]. Vol. 119, BJOG: An International Journal of Obstetrics and Gynaecology. BJOG; 
2012 [cited 2020 Nov 21]. p. 129–33. Available from: 
https://pubmed.ncbi.nlm.nih.gov/21917113/ 
7.  
Biglia N, Librino A, Ottino MC, Panuccio E, Daniele A, Chahin A. Lower limb lymphedema 
and neurological complications after lymphadenectomy for gynecological cancer. Int J 
Gynecol Cancer [Internet]. 2015 Mar 10 [cited 2023 Sep 4];25(3):521–5. Available from: 
https://pubmed.ncbi.nlm.nih.gov/25621410/ 
8.  
Achouri A, Huchon C, Bats AS, Bensaid C, Nos C, Lécuru F. Complications of 
lymphadenectomy for gynecologic cancer. Eur J Surg Oncol [Internet]. 2013 Jan [cited 2023 
Sep 4];39(1):81–6. Available from: https://pubmed.ncbi.nlm.nih.gov/23117018/ 
9.  
Rowlands IJ, Beesley VL, Janda M, Hayes SC, Obermair A, Quinn MA, et al. Quality of life 
of women with lower limb swelling or lymphedema 3–5 years following endometrial cancer. 
Gynecol Oncol. 2014 May 1;133(2):314–8.  
10.  
Yost KJ, Cheville AL, Al-Hilli MM, Mariani A, Barrette BA, McGree ME, et al. 
Lymphedema After Surgery for Endometrial Cancer: Prevalence, Risk Factors, and Quality 
of Life. Obs Gynecol [Internet]. 2014 [cited 2022 Jun 16];124(2):307–15. Available from: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf 
11.  
Beesley VL, Rowlands IJ, Hayes SC, Janda M, O’Rourke P, Marquart L, et al. Incidence, 
risk factors and estimates of a woman’s risk of developing secondary lower limb 
lymphedema and lymphedema-specific supportive care needs in women treated for 
endometrial cancer. Gynecol Oncol. 2015 Jan 1;136(1):87–93.  
12.  
Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, et al. Final version of 
the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin 
Oncol. 2001 Aug 15;19(16):3635–48.  
13.  
Tanis PJ, Nieweg OE, Valdés Olmos RA, Rutgers EJT, Kroon BBR. History of sentinel node 
and validation of the technique. Breast Cancer Res [Internet]. 2001 [cited 2023 Sep 

Sentinel Node Mapping with Robotic Assisted Near Infra-Red Fluorescent Imaging in Women with Cervical and 
Endometrial Cancer (SENTIREC). Protocol high risk studies– 05.08.2018. Statistical amendment  04.12.2020 
 
15 
4];3(2):109–12. Available from: https://pubmed.ncbi.nlm.nih.gov/11250756/ 
14.  
Darin MC, Gómez-Hidalgo NR, Westin SN, Soliman PT, Escobar PF, Frumovitz M, et al. 
Role of Indocyanine Green in Sentinel Node Mapping in Gynecologic Cancer: Is 
Fluorescence Imaging the New Standard? J Minim Invasive Gynecol [Internet]. 2016 Feb 1 
[cited 2023 Sep 4];23(2):186–93. Available from: 
https://pubmed.ncbi.nlm.nih.gov/26518716/ 
15.  
Ouldamer L, Marret H, Acker O, Barillot I, Body G. Unusual localizations of sentinel lymph 
nodes in early stage cervical cancer: a review. Surg Oncol [Internet]. 2012 Sep [cited 2023 
Sep 4];21(3). Available from: https://pubmed.ncbi.nlm.nih.gov/22608843/ 
16.  
Kim CH, Soslow RA, Park KJ, Barber EL, Khoury-Collado F, Barlin JN, et al. Pathologic 
Ultrastaging Improves Micrometastasis Detection in Sentinel Lymph Nodes during 
Endometrial Cancer Staging. Int J Gynecol Cancer. 2013 Jun;23(5):964–70.  
17.  
Barlin JN, Khoury-Collado F, Kim CH, Leitao MM, Chi DS, Sonoda Y, et al. The 
importance of applying a sentinel lymph node mapping algorithm in endometrial cancer 
staging: Beyond removal of blue nodes. Gynecol Oncol [Internet]. 2012 Jun [cited 2020 Jan 
20];125(3):531–5. Available from: http://dx.doi.org/10.1016/j.ygyno.2012.02.021 
18.  
Altgassen C, Hertel H, Brandstädt A, Köhler C, Dürst M, Schneider A. Multicenter 
validation study of the sentinel lymph node concept in cervical cancer: AGO Study Group. J 
Clin Oncol [Internet]. 2008 [cited 2023 Sep 4];26(18):2943–51. Available from: 
https://pubmed.ncbi.nlm.nih.gov/18565880/ 
19.  
Ballester M, Dubernard G, Lécuru F, Heitz D, Mathevet P, Marret H, et al. Detection rate 
and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: A 
prospective multicentre study (SENTI-ENDO). Lancet Oncol. 2011 May 1;12(5):469–76.  
20.  
Rossi EC, Kowalski LD, Scalici J, Cantrell L, Schuler K, Hanna RK, et al. A comparison of 
sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES 
trial): a multicentre, prospective, cohort study. Lancet Oncol [Internet]. 2017 Mar 1 [cited 
2020 Jul 1];18(3):384–92. Available from: https://pubmed.ncbi.nlm.nih.gov/28159465/ 
21.  
Omar TouhamiJean GrégoireMarie-Claude RenaudAlexandra SebastianelliMarie Plante. 
Performance of sentinel lymph node (SLN) mapping in high-riskendometrial cancer. 
Gynecol Oncol. 2017;  
22.  
Antonsen SL, Jensen LN, Loft A, Berthelsen AK, Costa J, Tabor A, et al. MRI, PET/CT and 
ultrasound in the preoperative staging of endometrial cancer — A multicenter prospective 
comparative study. Gynecol Oncol. 2013 Feb 1;128(2):300–8.  
23.  
Viswanathan C, Bhosale PR, Shah SN, Vikram R. Positron emission tomography-computed 
tomography imaging for malignancies in women. Radiol Clin North Am [Internet]. 2013 
Nov [cited 2023 Sep 4];51(6):1111–25. Available from: 
https://pubmed.ncbi.nlm.nih.gov/24210447/ 
24.  
Hildebrandt MG, Kodahl AR, Teilmann-Jørgensen D, Mogensen O, Jensen PT. 
[18F]Fluorodeoxyglucose PET/Computed Tomography in Breast Cancer and Gynecologic 
Cancers: A Literature Review. PET Clin [Internet]. 2015 Jan 1 [cited 2023 May 
12];10(1):89–104. Available from: 
http://www.pet.theclinics.com/article/S1556859814000911/fulltext 
25.  
Cibula D, Oonk MHM, Abu-Rustum NR. Sentinel lymph node biopsy in the management of 
gynecologic cancer. Curr Opin Obstet Gynecol [Internet]. 2015 Feb 13 [cited 2020 Jul 
19];27(1):66–72. Available from: http://journals.lww.com/00001703-201502000-00012 
26.  
Jewell EL, Huang JJ, Abu-Rustum NR, Gardner GJ, Brown CL, Sonoda Y, et al. Detection 
of sentinel lymph nodes in minimally invasive surgery using indocyanine green and near-
infrared fluorescence imaging for uterine and cervical malignancies. Gynecol Oncol. 2014 
May 1;133(2):274–7.  
27.  
Cormier B, Diaz JP, Shih K, Sampson RM, Sonoda Y, Park KJ, et al. Establishing a sentinel 

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lymph node mapping algorithm for the treatment of early cervical cancer. Gynecol Oncol. 
2011 Aug;122(2):275–80.  
28.  
Rossi EC, Jackson A, Ivanova A, Boggess JF. Detection of sentinel nodes for endometrial 
cancer with robotic assisted fluorescence imaging: Cervical versus hysteroscopic injection. 
Int J Gynecol Cancer. 2013;23(9):1704–11.  
29.  
Keeley V, Crooks S, Locke J, Veigas D, Riches K, Hilliam R. A quality of life measure for 
limb lymphoedema (LYMQOL) [Internet]. Vol. 5, Journal of Lymphoedema. 2010 [cited 
2020 Jan 20]. Available from: http://www.lymphormation.org/journal/content/0501limb.pdf 
30.  
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European 
organization for research and treatment of cancer QLQ-C30: A quality-of-life instrument for 
use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365–76.  
31.  
Colombo N, Creutzberg C, Amant F, Bosse T, González-Martín A, Ledermann J, et al. 
ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment 
and follow-up †. Ann Oncol. 2015;27:16–41.  
32.  
Speich R, Saesseli B, Hoffmann U, Neftel KA, Reichen J. Anaphylactoid reactions after 
indocyanine-green administration [Internet]. Vol. 109, Annals of Internal Medicine. Ann 
Intern Med; 1988 [cited 2020 Feb 13]. p. 345–6. Available from: 
https://pubmed.ncbi.nlm.nih.gov/3395048/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix I. Predefined anatomical locations, for registration of lymph nodes.  
 
 
 

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Appendix II. English version of all included PROMS 
 
EORTC IL76 
 
 

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LYMFQOL 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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EORTC QLQ-C30 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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EORTC QLQ-CX24 
 
 
 
 
 
 
 
 

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EORTC QLQ-EN24 
 
 
 
 
 
 

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