Evaluation of a radioactive and fluorescent hybrid tracer for sentinel lymph node biopsy in head and neck malignancies: prospective randomized clinical trial to compare ICG-99mTc-nanocolloid hybrid tracer versus 99mTc-nanocolloid
- 759 Downloads
There is some controversy about the value of sentinel lymph node excision (SLNE) in patients with head and neck malignancies. The gold standard for detection and targeted extirpation of the SLN is lymphoscintigraphy with 99mTc-nanocolloid. The purpose of this prospective randomized study was to analyse the feasibility and clinical benefit of a hybrid tracer comprising the near-infrared (NIR) fluorescent indocyanine green (ICG) and 99mTc-nanocolloid (ICG-99mTc-nanocolloid) in direct comparison with standard 99mTc-nanocolloid for guiding SLNE in patients with head and neck cutaneous malignancies.
We analysed the data from 40 clinically lymph node-negative patients with melanoma, high-risk cutaneous squamous cell carcinoma, Merkel cell carcinoma or sweat gland carcinoma who underwent SLNE with ICG-99mTc-nanocolloid (cohort A) or with the standard 99mTc-nanocolloid (cohort B).
Overall SLNs were identified preoperatively in all 20 patients (100 %) in cohort A and in 18 of 20 patients (90 %) in cohort B. The SLN basin was detected preoperatively in 18 patients (90 %) in cohort A and also in 18 patients (90 %) in cohort B. SLNs were identified intraoperatively in all 20 patients (100 %) in cohort A and in 19 patients (95 %) in cohort B (p = 0.487). Metastatic SLNs were detected in 9 patients (22.5 %), 3 (15.0 %) in cohort A and 6 (30.0 %) in cohort B (p = 0.228).
The hybrid tracer ICG-99mTc-nanocolloid is an innovative imaging tracer, reliably and readily providing additional information for the detection and excision of SLN in the head and neck region. Therefore, SLNE with combined radioactive and NIR fluorescence guidance is an attractive option for improving the SLN detection rate in patients with cutaneous head and neck malignancies.
KeywordsMalignant melanoma Head and neck cancer Sentinel lymph node Hybrid tracer Indocyanine green
Compliance with ethical standards
Conflicts of interest
Dr. Schadendorf reported receiving consultancy fees, having board membership, and receiving lecture fees from GlaxoSmithKline, Novartis, Amgen, Bristol-Myers Squibb, Roche, Genentech, Boehringer Ingelheim and MSD. The other authors declare that they have no conflicts of interest.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Statement on the welfare of animals
This article does not describe any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
- 7.Fisher SR, O’Brien CJ. Head and neck melanomas. In: Balch CM, Houghton Jr A, Sober A, Soong SJ, editors. Cutaneous melanoma. St. Louis: Quality Medical Publishing; 2003. p. 275–96.Google Scholar
- 9.Leiter U, Buettner PG, Bohnenberger K, Eigentler T, Meier F, Moehrle M, et al. Sentinel lymph node dissection in primary melanoma reduces subsequent regional lymph node metastasis as well as distant metastasis after nodal involvement. Ann Surg Oncol. 2010;17:129–37. doi: 10.1245/s10434-009-0780-2.CrossRefPubMedGoogle Scholar
- 11.Stoffels I, Boy C, Poppel T, Kuhn J, Klotgen K, Dissemond J, et al. Association between sentinel lymph node excision with or without preoperative SPECT/CT and metastatic node detection and disease-free survival in melanoma. JAMA. 2012;308:1007–14. doi: 10.1001/2012.jama.11030.CrossRefPubMedGoogle Scholar
- 14.Stoffels I, Dissemond J, Pöppel T, Schadendorf D, Klode J. Intraoperative fluorescence imaging for sentinel lymph node detection: prospective clinical trial to compare the usefulness of indocyanine green vs technetium Tc 99m for identification of sentinel lymph nodes. JAMA Surg. 2015. doi: 10.1001/jamasurg.2014.3502 PubMedGoogle Scholar
- 20.Klode J, Poeppel T, Boy C, Mueller S, Schadendorf D, Korber A, et al. Advantages of preoperative hybrid SPECT/CT in detection of sentinel lymph nodes in cutaneous head and neck malignancies. J Eur Acad Dermatol Venereol. 2011;25:1213–21. doi: 10.1111/j.1468-3083.2010.03954.x.CrossRefPubMedGoogle Scholar
- 24.Ballardini B, Santoro L, Sangalli C, Gentilini O, Renne G, Lissidini G, et al. The indocyanine green method is equivalent to the 99mTc-labeled radiotracer method for identifying the sentinel node in breast cancer: a concordance and validation study. Eur J Surg Oncol. 2013;39:1332–6. doi: 10.1016/j.ejso.2013.10.004.CrossRefPubMedGoogle Scholar
- 25.Hutteman M, Mieog JS, van der Vorst JR, Liefers GJ, Putter H, Lowik CW, et al. Randomized, double-blind comparison of indocyanine green with or without albumin premixing for near-infrared fluorescence imaging of sentinel lymph nodes in breast cancer patients. Breast Cancer Res Treat. 2011;127:163–70. doi: 10.1007/s10549-011-1419-0.PubMedCentralCrossRefPubMedGoogle Scholar
- 26.Schaafsma BE, van der Vorst JR, Gaarenstroom KN, Peters AA, Verbeek FP, de Kroon CD, et al. Randomized comparison of near-infrared fluorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer. Gynecol Oncol. 2012;127:126–30. doi: 10.1016/j.ygyno.2012.07.002.PubMedCentralCrossRefPubMedGoogle Scholar
- 27.van der Vorst JR, Schaafsma BE, Verbeek FP, Hutteman M, Mieog JS, Lowik CW, et al. Randomized comparison of near-infrared fluorescence imaging using indocyanine green and 99(m) technetium with or without patent blue for the sentinel lymph node procedure in breast cancer patients. Ann Surg Oncol. 2012;19:4104–11. doi: 10.1245/s10434-012-2466-4.PubMedCentralCrossRefPubMedGoogle Scholar
- 28.Fujisawa Y, Nakamura Y, Kawachi Y, Otsuka F. Indocyanine green fluorescence-navigated sentinel node biopsy showed higher sensitivity than the radioisotope or blue dye method, which may help to reduce false-negative cases in skin cancer. J Surg Oncol. 2012;106:41–5. doi: 10.1002/jso.23045.CrossRefPubMedGoogle Scholar
- 29.Rodier JF, Velten M, Wilt M, Martel P, Ferron G, Vaini-Elies V, et al. Prospective multicentric randomized study comparing periareolar and peritumoral injection of radiotracer and blue dye for the detection of sentinel lymph node in breast sparing procedures: FRANSENODE trial. J Clin Oncol. 2007;25:3664–9. doi: 10.1200/JCO.2006.08.4228.CrossRefPubMedGoogle Scholar
- 30.Jung SY, Kim SK, Kim SW, Kwon Y, Lee ES, Kang HS, et al. Comparison of sentinel lymph node biopsy guided by the multimodal method of indocyanine green fluorescence, radioisotope, and blue dye versus the radioisotope method in breast cancer: a randomized controlled trial. Ann Surg Oncol. 2014;21:1254–9. doi: 10.1245/s10434-013-3437-0.CrossRefPubMedGoogle Scholar
- 32.Brouwer OR, Buckle T, Vermeeren L, Klop WM, Balm AJ, van der Poel HG, et al. Comparing the hybrid fluorescent-radioactive tracer indocyanine green-99mTc-nanocolloid with 99mTc-nanocolloid for sentinel node identification: a validation study using lymphoscintigraphy and SPECT/CT. J Nucl Med. 2012;53:1034–40. doi: 10.2967/jnumed.112.103127.CrossRefPubMedGoogle Scholar
- 33.van den Berg NS, Brouwer OR, Schaafsma BE, Matheron HM, Klop WM, Balm AJ, et al. Multimodal surgical guidance during sentinel node biopsy for melanoma: combined gamma tracing and fluorescence imaging of the sentinel node through use of the hybrid tracer indocyanine green-(99m)Tc-nanocolloid. Radiology. 2015;275:521–9. doi: 10.1148/radiol.14140322.
- 34.Van Den Berg NS, Buckle T, Kleinjan GI, Klop WM, Horenblas S, Van Der Poel HG, et al. Hybrid tracers for sentinel node biopsy. Q J Nucl Med Mol Imaging. 2014;58:193–206.Google Scholar
- 35.van der Vorst JR, Schaafsma BE, Verbeek FP, Keereweer S, Jansen JC, van der Velden LA, et al. Near-infrared fluorescence sentinel lymph node mapping of the oral cavity in head and neck cancer patients. Oral Oncol. 2013;49:15–9. doi: 10.1016/j.oraloncology.2012.07.017.PubMedCentralCrossRefPubMedGoogle Scholar
- 37.van der Poel HG, Buckle T, Brouwer OR, Valdes Olmos RA, van Leeuwen FW. Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer. Eur Urol. 2011;60:826–33. doi: 10.1016/j.eururo.2011.03.024.CrossRefPubMedGoogle Scholar