SENtinel lymph node mapping with GAllium-68-tilmanocept PET/CT in high/high-intermediate risk endometrial cancer: a proof-of-concept study

Endometrial cancer is the most prevalent gynaecological cancer in the
Netherlands, affecting more than 2000 women per year (IKNL). When metastasized
to the lymph nodes, it impacts stage, prognosis and adjuvant therapy,
highlighting the importance of accurate nodal assessment. Lymphatic mapping to
identify SLNs, i.e. the first nodes along the drainage route of a tumour, is a
frequently studied practice in managing endometrial cancer. Currently,
indocyanine green (ICG) with near-infrared fluorescence imaging is the widely
accepted sentinel lymph node (SLN) mapping technique in endometrial cancer. Use
of ICG is limited by a tissue penetration of <1cm, especially in patients with
high BMI. Another limitation is its rapid spreading towards higher echelon
nodes, leading to a higher number of lymph nodes removed compared to more
conventional techniques with a radiotracer and blue dye. Improving the SLN
mapping technique, with more accurate identification of SLNs, may increase
bilateral detection and decrease tissue damage. We propose that preoperative
imaging, which can guide the surgeon towards the true SLN intraoperatively,
could improve SLN mapping in patients with endometrial cancer. The use of
radiotracer Gallium-68-tilmanocept (68Ga-tilmanocept) enables preoperative
PET/CT. Tilmanocept has sustained retention at the SLNs which provides low
second echelon node accumulation compared to ICG. Use of 68Ga-tilmanocept could
result in increased bilateral detection of SLNs and better differentiation
between SLN(s) and second echelon nodes.

This study has been transitioned to CTIS with ID 2024-516708-40-00 check the CTIS register for the current data.

The primary objective of this proof-of-concept study is to evaluate feasibility
of 68Ga-tilmanocept PET/CT for SLN mapping in patients with stage I-II
high/high-intermediate risk endometrial cancer. Secondary objectives are: - To
investigate the correlation between SLN detection rate and anatomical location
of SLNs with preoperative 68Ga-tilmanocept PET/CT versus intraoperative ICG
with NIR fluorescence; - To assess pathological status of the SLNs: tumour
negative, macrometastasis (diameter >2.0 mm), micrometastasis (diameter between
0.2 and 2.0 mm) or isolated tumour cells (diameter <0.2 mm or individual tumour
cells); - To investigate adverse events related to SLN mapping with
68Ga-tilmanocept PET/CT up to one hour post-PET/CT (graded by Common
Terminology Criteria for Adverse Events (CTCAE) v5.0).

The proposed study is a non-randomised, single-arm proof-of-concept study
conducted in the UMC Utrecht. All included subjects will undergo preoperative
68Ga-tilmanocept PET/CT (PET + contrast enhanced CT-abdomen) for the purpose of
SLN detection, in adjunct to intraoperative SLN detection with ICG (considered
standard-of-care).

Extra burden for subjects concerns one additional site visit for the cervical
injection of a radiotracer followed by PET/CT imaging, with a total duration of
two hours (including one hour waiting time). The preoperative injection with
68Ga-tilmanocept could be accompanied by pain or irritation at the point of
injection, but this is rare. The additional site visit does not delay the
scheduled surgerical treatment.

The extra administration of 10 MBq 68Ga-tilmanocept followed by PET/CT exposes
subjects to a radiation of 6.3 mSv, which is considered an acceptable radiation
burden to the patient. We advise patients not to enroll in another trial with
exposure to radiation in the near future.

Subjects may benefit from this study since the SLN detection rate may be
increased by adding 68Ga-tilmanocept PET/CT to the diagnostic procedure.