Top

Published in:

Open Access 04-07-2023 | Breast Cancer | Breast Oncology

Novel Dual Tracer Indocyanine Green and Radioisotope Versus Gold Standard Sentinel Lymph Node Biopsy in Breast Cancer: The GREENORBLUE Trial

Authors: Chu Luan Nguyen, MBBS, MMed, MPhil, Michael Zhou, BCom, Neshanth Easwaralingam, MBBS, MS, FRACS, Jue Li Seah, MBBS, MS, FRACS, Farhad Azimi, MBBS, MS, FRACS, Cindy Mak, MBBS, FRACS, Carlo Pulitano, MD, PhD, FRACS, Sanjay Warrier, MBBS, MS, FRACS

Published in: Annals of Surgical Oncology | Issue 11/2023

Abstract

Background

The methods for sentinel lymph node (SLN) biopsy in breast cancer have been variable in type and number of tracers. Some units have abandoned the use of blue dye (BD) due to adverse reactions. Fluorescence-guided biopsy with indocyanine green (ICG) is a relatively novel technique. This study compared the clinical efficacy and costs between novel dual tracer ICG and radioisotope (ICG-RI) with “gold standard” BD and radioisotope (BD-RI).

Methods

Single-surgeon study of 150 prospective patients with early breast cancer undergoing SLN biopsy (2021-2022) using ICG-RI compared with a retrospective cohort of 150 consecutive previous patients using BD-RI. Number of SLNs identified, rate of failed mapping, identification of metastatic SLNs, and adverse reactions were compared between techniques. Cost-minimisation analysis performed by using Medicare item numbers and micro-costing analysis.

Results

Total number of SLNs identified with ICG-RI and BD-RI was 351 and 315, respectively. Mean number of SLNs identified with ICG-RI and BD-RI was 2.3 (standard deviation [SD] 1.4) and 2.1 (SD 1.1), respectively (p = 0.156). There were no cases of failed mapping with either dual technique. Metastatic SLNs were identified in 38 (25.3%) ICG-RI patients compared with 30 (20%) BD-RI patients (p = 0.641). There were no adverse reactions to ICG, whereas four cases of skin tattooing and anaphylaxis were associated with BD (p = 0.131). ICG-RI cost an additional AU$197.38 per case in addition to the initial cost for the imaging system. Clinical trial registration: ACTRN12621001033831.

Conclusions

Novel tracer combination, ICG-RI, provided an effective and safe alternative to “gold standard” dual tracer. The caveat was the significantly greater costs associated with ICG.

Available only for authorised users

Cody HS, Fey J, Akhurst T. Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures. Ann Surg Oncol. 2001;8:12–9. https://doi.org/10.1007/s10434-001-0013-9.CrossRef

Lyman GH, Giuliano AE, Somerfield MR. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early stage breast cancer. J Clin Oncol. 2005;23:7703–20.CrossRefPubMed

Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391–8.CrossRefPubMedPubMedCentral

Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993;2:335–9.CrossRefPubMed

Lyman GH, Guiliano AE, Somerfield MR. The American Society of Clinical Oncology Guideline recommendations for sentinel lymph node biopsy in early stage breast cancer. J Clin Oncol. 2005;23:7703–20.CrossRefPubMed

Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11(10):927–33. https://doi.org/10.1016/s1470-2045(10)70207-2.CrossRefPubMedPubMedCentral

Efron PKE, Hirshorn S, Copeland EM. Anaphylactic reaction to isosulfan blue used for sentinel node biopsy: case report and literature review. Breast J. 2002;8:396–9.CrossRefPubMed

Cykowska A, Marano L, D’Ignazio A, et al. New technologies in breast cancer sentinel lymph node biopsy; from the current gold standard to artificial intelligence. Surg Oncol. 2020;34:324–35. https://doi.org/10.1016/j.suronc.2020.06.005.CrossRefPubMed

Montgomery LLTA, Van Zee KJ, Fey J, Heerdt AS, Gemignani M. Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer. Anesth Analg. 2002;95(2):385–8. https://doi.org/10.1213/01.ANE.0000018522.99158.FF.CrossRefPubMed

10.

Peek MC, Kovacs T, Baker R, Hamed H, Kothari A, Douek M. Is blue dye still required during sentinel lymph node biopsy for breast cancer? Ecancermedicalscience. 2016;10:674. https://doi.org/10.3332/ecancer.2016.674.CrossRefPubMedPubMedCentral

11.

Kusano M, Tajima Y, Yamazaki K, Kato M, Watanabe M, Miwa M. Sentinel node mapping guided by indocyanine green fluorescence imaging: a new method for sentinel node navigation surgery in gastrointestinal cancer. Dig Surg. 2008;25(2):103–8.CrossRefPubMed

12.

Korn JM, Tellez-Diaz A, Bartz-Kurycki M, Gastman B. Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous melanoma. Plast Reconstr Surg. 2014;133(4):914–22. https://doi.org/10.1097/PRS.0000000000000006.CrossRefPubMed

13.

Sugie T, Kinoshita T, Masuda N, et al. Evaluation of the clinical utility of the ICG fluorescence method compared with the radioisotope method for sentinel lymph node biopsy in breast cancer. Ann Surg Oncol. 2016;23(1):44–50. https://doi.org/10.1245/s10434-015-4809-4.CrossRefPubMed

14.

Benson RC, Kues HA. Fluorescence properties of indocyanine green as related to angiography. Phys Biol. 1978;23:159–63.CrossRef

15.

Kedrzycki MS, Leiloglou M, Ashrafian H, et al. Meta-analysis comparing fluorescence imaging with radioisotope and blue dye-guided sentinel node identification for breast cancer surgery. Ann Surg Oncol. 2020. https://doi.org/10.1245/s10434-020-09288-7.CrossRefPubMedPubMedCentral

16.

Equator Network. Reporting guidelines for main study types. Accessed 1 Aug 2022. https://www.equator-network.org/reporting-guidelines/

17.

NIH National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Published 2017. Accessed 19 December, 2022. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm

18.

Vissapragada R, Bulamu N, Karnon J, Yazbek R, Watson DI. Cost-effectiveness in surgery: concepts of cost-utility analysis explained. ANZ J Surg. 2021. https://doi.org/10.1111/ans.16586.CrossRefPubMed

19.

Samorani D, Fogacci T, Panzini I, et al. The use of indocyanine green to detect sentinel nodes in breast cancer: a prospective study. Eur J Surg Oncol. 2015;41(1):64–70. https://doi.org/10.1016/j.ejso.2014.10.047.CrossRefPubMed

20.

Bargon CA, Huibers A, Young-Afat DA, et al. Sentinel lymph node mapping in breast cancer patients through fluorescent imaging using indocyanine green: the INFLUENCE trial. Ann Surg. 2022;276(5):913–20. https://doi.org/10.1097/SLA.0000000000005633.CrossRefPubMed

21.

Ngo C, Sharifzadehgan S, Lecurieux-Lafayette C, et al. Indocyanine green for sentinel lymph node detection in early breast cancer: prospective evaluation of detection rate and toxicity—the FLUOBREAST trial. Breast J. 2020;26(12):2357–63. https://doi.org/10.1111/tbj.14100.CrossRefPubMed

22.

Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981–22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303–10. https://doi.org/10.1016/s1470-2045(14)70460-7.CrossRefPubMedPubMedCentral

23.

Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006;98(9):599–609. https://doi.org/10.1093/jnci/djj158.CrossRefPubMed

24.

Mok CW, Tan SM, Zheng Q, Shi L. Network meta-analysis of novel and conventional sentinel lymph node biopsy techniques in breast cancer. BJS Open. 2019;3(4):445–52. https://doi.org/10.1002/bjs5.50157.CrossRefPubMedPubMedCentral

25.

Sugie T, Ikeda T, Kawaguchi A, Shimizu A, Toi M. Sentinel lymph node biopsy using indocyanine green fluorescence in early-stage breast cancer: a meta-analysis. Int J Clin Oncol. 2017;22(1):11–7. https://doi.org/10.1007/s10147-016-1064-z.CrossRefPubMed

26.

Schaafsma BE, Verbeek FP, Rietbergen DD, et al. Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer. Br J Surg. 2013;100(8):1037–44. https://doi.org/10.1002/bjs.9159.CrossRefPubMed

27.

Sugie T, Sawada T, Tagaya N. Comparison of the indocyanine green fluorescence and blue dye methods in detection of sentinel lymph nodes in early-stage breast cancer. Ann Surg Oncol. 2013;20:2213–8. https://doi.org/10.1245/s10434-013-2890-0.CrossRefPubMed

28.

Benson JR. Evaluation of the clinical utility of the ICG fluorescence method in comparison to the radioisotope method for sentinel lymph node biopsy in breast cancer (commentary). Ann Surg Oncol. 2015;23:6–8. https://doi.org/10.1245/s10434-015-4809-4.CrossRefPubMed

29.

Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305(6):569–75. https://doi.org/10.1001/jama.2011.90.CrossRefPubMedPubMedCentral

30.

Ballardini B, Santoro L, Sangalli C, et al. The indocyanine green method is equivalent to the (9)(9)mTc-labeled radiotracer method for identifying the sentinel node in breast cancer: a concordance and validation study. Eur J Surg Oncol. 2013;39(12):1332–6. https://doi.org/10.1016/j.ejso.2013.10.004.CrossRefPubMed

31.

Tagaya N, Yamazaki R, Nakagawa A. A novel approach for sentinel lymph node identification using fluorescence imaging and image overlay navigation surgery in patients with breast cancer. World J Surg. 2011;35:154–8.CrossRefPubMed

32.

Schaafsma BE, Verbeek FP, Riebergen DD. Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer. Br J Surg. 2013;100:1037–44.CrossRefPubMed

33.

Ahmed M, Purushotham A, Douek M. Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review. Lancet Oncology. 2014;15:351–62.CrossRef

34.

Gumus M, Gumus H, Jones SE. How long will I be blue? prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye. Breast Care. 2013;8:199–202.CrossRefPubMedPubMedCentral

35.

Perenyei M, Barber ZE, Gibson J, Hemington-Gorse S, Dobbs TD. Anaphylactic reaction rates to blue dyes used for sentinel lymph node mapping: systematic review and meta-analysis. Ann Surg. 2021;273(6):1087–93. https://doi.org/10.1097/SLA.0000000000004061.CrossRefPubMed

36.

Griffiths M, Chae MP, Rozen WM. Indocyanine green-based fluorescent angiography in breast reconstruction. Gland Surg. 2016;5(2):133–49. https://doi.org/10.3978/j.issn.2227-684X.2016.02.01.CrossRefPubMedPubMedCentral

37.

Benya R, Quintana J, Brundage B. Adverse reactions to indocyanine green: a case report and a review of the literature. Cath Cardiovasc Diagn. 1989;17(4):231–3.CrossRef

38.

Hope-Ross M, Yannuzzi LA, Gragoudas ES, et al. Adverse reactions due to indocyanine green. Ophthalmology. 1994;101(3):529–33. https://doi.org/10.1016/s0161-6420(94)31303-0.CrossRefPubMed

39.

Clarke D, Newcombe RG, Mansel RE. The learning curve in sentinel node biopsy: the ALMANAC experience. Ann Surg Oncol. 2004;11:211S-S215. https://doi.org/10.1007/BF02523631.CrossRefPubMed

40.

Sanidas EE, de Bree E, Tsiftsis DD. How many cases are enough for accreditation in sentinel lymph node biopsy in breast cancer? Am J Surg. 2003;185(3):202–10.CrossRefPubMed

41.

Papathemelis T, Jablonski E, Scharl A, et al. Sentinel lymph node biopsy in breast cancer patients by means of indocyanine green using the Karl Storz VITOM(R) Fluorescence Camera. Biomed Res Int. 2018;2018:6251468. https://doi.org/10.1155/2018/6251468.CrossRefPubMedPubMedCentral

42.

Cattin F, Fogacci T, Frisoni G, et al. Icg versus 99tc in breast surgery—How to match quality health care and costs reduction: a cost-effectiveness study. J Cancer Sci Ther. 2017. https://doi.org/10.4172/1948-5956.1000439.CrossRef

Title: Novel Dual Tracer Indocyanine Green and Radioisotope Versus Gold Standard Sentinel Lymph Node Biopsy in Breast Cancer: The GREENORBLUE Trial
Authors: Chu Luan Nguyen, MBBS, MMed, MPhil
Michael Zhou, BCom
Neshanth Easwaralingam, MBBS, MS, FRACS
Jue Li Seah, MBBS, MS, FRACS
Farhad Azimi, MBBS, MS, FRACS
Cindy Mak, MBBS, FRACS
Carlo Pulitano, MD, PhD, FRACS
Sanjay Warrier, MBBS, MS, FRACS
Publication date: 04-07-2023
Publisher: Springer International Publishing
Keywords: Breast Cancer
Breast Cancer
Anaphylaxis
Anaphylaxis
Published in: Annals of Surgical Oncology / Issue 11/2023
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-023-13824-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Novel Dual Tracer Indocyanine Green and Radioisotope Versus Gold Standard Sentinel Lymph Node Biopsy in Breast Cancer: The GREENORBLUE Trial

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2023

ASO Visual Abstract: Younger Patients with Colon Cancer are More Likely to Experience Financial Toxicity Than Older Patients

Validation of the Absent-Cell Theory for Staging Mucinous Appendiceal Cancer

ASO Author Reflections: Long Term Outcomes of Breast Cancer Patients with Local Recurrence After Mastectomy Undergoing Immediate Breast Reconstruction

Neoadjuvant Chemotherapy in Retroperitoneal Sarcoma: A National Cohort Study

Disparities in Presentation, Treatment, and Survival in Anaplastic Thyroid Cancer

Prognosis of Concurrent Versus Sequential Chemo-Radiotherapy Induction Followed by Surgical Resection in Patients with Advanced Thymic Epithelial Tumors: A Retrospective Study