Carbon Nanoparticles and Indocyanine Green for Sentinel Lymph Node Biopsy in Early Stage Cervical Cancer

The metastasis rate of pelvic lymph node in early cervical cancer is low. Systemic lymph node resection is traumatic and has many complications. Sentinel lymph node (SLN) biopsy can effectively avoid unnecessary lymph node dissection, which has been recommended in clinical guidelines. Indocyanine green(ICG) fluorescence imaging as the method of SLN mapping is recommended in international guidelines. However, the imaging equipment is very expensive which limits the popularization of ICG in different medical centers of various surgical volumes. Carbon nanoparticle is an innovative tracer without any special imaging equipment for SLN mapping in China. Some retrospective researches have proved that carbon nanoparticle is effective, simple, economic and suitable for popularization in different medical centers. In this study, a prospective randomized controlled trial will be conducted to analyze the non-inferiority of carbon nanoparticles compared to ICG, and to verify the application value of carbon nanoparticles. 144 cervical cancer patients with stage IB1 (FIGO2018) will be prospectively enrolled and randomly divided into two groups (R = 1:1). 72 patients will undergo SLN biopsy with carbon nanoparticles and 72 patients will be mapped by ICG. The primary endpoint is overall SLN detection rate. The secondary endpoints include bilateral SLN detection rate, the number of SLN detected, sensitivity, false negative rate and negative predictive value of SLN biopsy. Diagnostic accuracy will be evaluated at both pelvis and patient levels. What's more, SLN pathological ultrastaging will be conducted to increase the diagnostic accuracy. The hypothesis of this study is that the overall SLN detection rate by carbon nanoparticles is not inferior to that using ICG. And the differences of bilateral SLN detection rate, sensitivity, false negative rate and negative predictive value between two groups are not significant.

Sex

Female

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

* Cervical squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma diagnosed by pathological biopsy;
* Tumor stage is IB1 (FIGO 2018);
* No distant metastasis (chest, abdominal and pelvic enhanced CT or positron emission tomography (PET) -CT);
* 18-70 years old;
* Eastern Cooperative Oncology Group (ECOG) score ≤ 2 and tolerable for radical hysterectomy and systemic lymph node resection;
* No obvious dysfunction or chronic disease of heart, liver and kidney, and no history of other malignant tumors;
* Volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

* Residual cervical cancer;
* Small cell carcinoma, neuroendocrine carcinoma and other special histological types;
* Patients who have received radiotherapy or chemotherapy before enrollment;
* Allergic constitution, allergic to iodine;
* ICG skin test is positive;
* Patients considered unsuitable for inclusion by the researchers.

• BACKGROUNDCibula D, Dusek J, Jarkovsky J, Dundr P, Querleu D, van der Zee A, Kucukmetin A, Kocian R. A prospective multicenter trial on sentinel lymph node biopsy in patients with early-stage cervical cancer (SENTIX). Int J Gynecol Cancer. 2019 Jan;29(1):212-215. doi: 10.1136/ijgc-2018-000010. PMID 30640706
• BACKGROUNDCibula D, McCluggage WG. Sentinel lymph node (SLN) concept in cervical cancer: Current limitations and unanswered questions. Gynecol Oncol. 2019 Jan;152(1):202-207. doi: 10.1016/j.ygyno.2018.10.007. Epub 2018 Oct 11. PMID 30318103
• BACKGROUNDFrumovitz M, Plante M, Lee PS, Sandadi S, Lilja JF, Escobar PF, Gien LT, Urbauer DL, Abu-Rustum NR. Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial. Lancet Oncol. 2018 Oct;19(10):1394-1403. doi: 10.1016/S1470-2045(18)30448-0. Epub 2018 Aug 22. PMID 30143441
• BACKGROUNDSalvo G, Ramirez PT, Levenback CF, Munsell MF, Euscher ED, Soliman PT, Frumovitz M. Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer. Gynecol Oncol. 2017 Apr;145(1):96-101. doi: 10.1016/j.ygyno.2017.02.005. Epub 2017 Feb 8. PMID 28188015
• BACKGROUNDBuda A, Crivellaro C, Elisei F, Di Martino G, Guerra L, De Ponti E, Cuzzocrea M, Giuliani D, Sina F, Magni S, Landoni C, Milani R. Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye. Ann Surg Oncol. 2016 Jul;23(7):2183-91. doi: 10.1245/s10434-015-5022-1. Epub 2015 Dec 29. PMID 26714944
• BACKGROUNDBats AS, Frati A, Mathevet P, Orliaguet I, Querleu D, Zerdoud S, Leblanc E, Gauthier H, Uzan C, Deandreis D, Darai E, Kerrou K, Marret H, Lenain E, Froissart M, Lecuru F. Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort. Gynecol Oncol. 2015 May;137(2):264-9. doi: 10.1016/j.ygyno.2015.02.018. Epub 2015 Feb 26.