Technetium Tc 99m tilmanocept fails to detect sentinel lymph nodes in endometrial cancer

Ravali A Reddy, Ashley S Moon, Stephanie Chow, Lucas Heilbroner, Brooke Howitt, Elisabeth Diver, Oliver Dorigo, Babak Litkouhi, Malte Renz, Amer Karam, Ravali A Reddy, Ashley S Moon, Stephanie Chow, Lucas Heilbroner, Brooke Howitt, Elisabeth Diver, Oliver Dorigo, Babak Litkouhi, Malte Renz, Amer Karam

Abstract

Background: Technetium Tc 99m tilmanocept is a synthetic radiotracer specifically designed for sentinel lymph node (SLN) mapping that has been FDA-approved in breast cancer, melanoma, and head and neck cancer. No published studies exist for the use of this radiotracer in endometrial cancer.

Objective: The primary objective was to determine the detection rate of bilateral SLNs in endometrial cancer with the concurrent use of technetium Tc 99m tilmanocept and ICG.

Methods: An open-label, single cohort, prospective feasibility study was conducted with participants receiving preoperative cervical injections of technetium Tc 99m tilmanocept followed by subsequent imaging and SPECT/CT. Intraoperative ICG injections were administered for all patients with near-infrared imaging used to visualize lymphatic vessels and nodes. A laparoscopic gamma counter was used to detect radioactive SLN intraoperatively.

Results: All six evaluated patients had FIGO grade 1 or 2 endometrioid histology. Stage IA/IB were in 33% and 66% of patients, respectively. Tilmanocept did not map any SLN in the first six patients but instead showed retention of the tracer in the cervical stroma, leading to study discontinuation for futility. ICG mapped bilateral SLN in all patients with the most common location being the external iliac region, followed by the obturator and common iliac areas. All patients had CD206 positive staining throughout the full wall thickness of ectocervix, transformation zone, endocervix, and lymphatic vessels. No patients experienced adverse events.

Conclusion: Technetium Tc 99m tilmanocept did not detect SLN in early stage endometrial cancers and is unlikely to improve bilateral detection rate compared to ICG alone. ICG remains a standard technique for SLN detection in low stage, low grade endometrial cancer.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2022 The Authors. Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Representative SPECT/CT Imaging. Technetium Tc 99m tilmanocept was found in high concentration in the cervix on preoperative imaging for all six patients.
Fig. 2
Fig. 2
Immunohistochemical staining for CD206 in cervical tissue from patients included in the study. CD206 stained primarily tissue macrophages, which were present throughout the full wall thickness of the cervix in the ectocervix (A), transformation zone (B), and endocervix (C). In some instances, focal staining of endothelial cells lining lymphatic channels was noted (D).

References

    1. Abu-Rustum N.R., Khoury-Collado F., Pandit-Taskar N., Soslow R.A., Dao F., Sonoda Y., Levine D.A., Brown C.L., Chi D.S., Barakat R.R., Gemignani M.L. Sentinel lymph node mapping for grade 1 endometrial cancer: is it the answer to the surgical staging dilemma? Gynecol. Oncol. 2009;113(2):163–169.
    1. Albo D., et al. Anaphylactic reactions to isosulfan blue dye during sentinel lymph node biopsy for breast cancer. Am. J. Surg. 2001;182(4):393–398.
    1. Anderson K.M., et al. Molecular Imaging of endometrial sentinel lymph nodes utilizing fluorescent-labeled Tilmanocept during robotic-assisted surgery in a porcine model. PLoS ONE. 2018;13(7)
    1. Baker J.L., et al. Comparison of [(99m)Tc]tilmanocept and filtered [(99m)Tc]sulfur colloid for identification of SLNs in breast cancer patients. Ann. Surg. Oncol. 2015;22(1):40–45.
    1. Ballester M., 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;12(5):469–476.
    1. Barlin J.N., et al. The importance of applying sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol. Oncol. 2012;125(30):531–535.
    1. Bats A.S., et al. The sentinel node technique detects unexpected drainage pathways and allows nodal ultrastaging in early cervical cancer: insights from the multicenter prospective SENTICOL study. Ann. Surg. Oncol. 2013;20(2):413–422.
    1. Blessing W.D., et al. A comparison of methylene blue and lymphazurin in breast cancer sentinel node mapping. Am. J. Surg. 2002;184(4):341–345.
    1. Cabanas R.M. An approach for the treatment of penile carcinoma. Cancer. 1977;39(2):456–466.
    1. Chow S., et al. Role of sentinel lymph node biopsy for gynecologic cancers. Curr. Opin. Obstet. Gynecol. 2022;34(1):15–19.
    1. Desai P.H., et al. Accuracy of robotic sentinel lymph node detection (RSLND) for patients with endometrial cancer (EC) Gynecol. Oncol. 2014;135(2):196–200.
    1. Emerson D.K., et al. A receptor-targeted fluorescent radiopharmaceutical for multi reported sentinel lymph node imaging. Radiology. 2012;265(1):186–193.
    1. FDA, 2016. Prescribing information on Lymphoseek. 2016.
    1. Holloway R.W., et al. A Prospective Cohort Study Comparing Colorimetric and Fluorescent Imaging for Sentinel Lymph Node Mapping in Endometrial Cancer. Ann. Surg. Oncol. 2017;24(7):1972–1979.
    1. Holloway R.W., et al. Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol. Oncol. 2017;146(2):405–415.
    1. Hope-Ross M., et al. Adverse reaction due to indocyanine green. Ophthalmology. 1994;101:529–533.
    1. International Atomic Energy Agency, 2015. Radiopharmaceuticals for sentinel lymph node detection: status and trends.
    1. Jewell E.L., 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;133(2):274–277.
    1. Kitchener H., et al. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study. Lancet. 2009;373(9658):125–136.
    1. Lee H.J., et al. Fluorescence-based molecular imaging of porcine urinary bladder sentinel lymph nodes. J. Nucl. Med. 2017;58(4):547–553.
    1. Liss M.A., et al. Preclinical evaluation of robotic-assisted sentinel lymph node fluorescence imaging. J. Nucl. Med. 2014;55(9):1552–1556.
    1. Liss, M.A., et al., 2014. Robotic-assisted fluorescence sentinel lymph node mapping using multimodal image guidance in an animal model. Urology 84(4): 982: e9-14.
    1. Marcinow A.M., et al. Use of a novel receptor-targeted (CD206) radiotracer, 99mTc-tilmanocept, and SPECT/CT for sentinel lymph node detection in oral cavity squamous cell carcinoma: initial institutional report in an ongoing phase 3 study. JAMA Otolaryngol Head Neck Surg. 2013;139(9):895–902.
    1. Mikuta J.J. International Federation of Gynecology and Obstetrics staging of endometrial cancer 1988. Cancer. 1993;71(S4):1460–1463.
    1. Nagar H., et al. Sentinel node biopsy for diagnosis of lymph node involvement in endometrial cancer. Cochrane Database Syst. Rev. 2021;6:CD013021.
    1. Panici P.B., Basile S., Maneschi F., Lissoni A.A., Signorelli M., Scambia G., Angioli R., Tateo S., Mangili G., Katsaros D., Garozzo G., Campagnutta E., Donadello N., Greggi S., Melpignano M., Raspagliesi F., Ragni N., Cormio G., Grassi R., Franchi M., Giannarelli D., Fossati R., Torri V., Amoroso M., Croce C., Mangioni C. Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial. J. Natl Cancer Inst. 2008;100(23):1707–1716.
    1. Persson J., et al. Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)-the final step towards a paradigm shift in surgical staging. Eur. J. Cancer. 2019;116:77–85.
    1. Plante M., 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. 2015;137(3):443–447.
    1. Renz M., et al. Immediate intraoperative sentinel lymph node analysis by frozen section is predictive of lymph node metastasis in endometrial cancer. J Robot Surg. 2019
    1. Rossi E.C., et al. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study. Lancet Oncol. 2017;18(3):384–392.
    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA A Cancer J. Clin. 2020;70(1):7–30.
    1. Sinno A.K., et al. A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer. Gynecol. Oncol. 2014;134(2):281–286.
    1. Tanner E.J., et al. Factors associated with successful bilateral sentinel lymph node mapping in endometrial cancer. Gynecol. Oncol. 2015;138(3):542–547.
    1. The Human Protein Atlas - MRC1, Skin: .
    1. The Human Protein Atlas - MRC1, Cervix: .
    1. Touhami O., et al. Predictors of non-sentinel lymph node (non-SLN) metastasis in patients with sentinel lymph node (SLN) metastasis in endometrial cancer. Gynecol. Oncol. 2015;138(1):41–45.
    1. Vera D.R., et al. A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. J. Nucl. Med. 2001;42(6):951–959.
    1. Wallace A.M., et al. Lymphoseek: a molecular radiopharmaceutical for sentinel node detection. Ann. Surg. Oncol. 2003;10(5):531–538.
    1. Wallace A.M., et al. Comparative evaluation of [99m Tc] tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials. Ann Sure Oncol. 2013;20:2590–2599.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa