Indocyanine green lymphangiography is superior to clinical staging in breast cancer-related lymphedema

Mads Gustaf Jørgensen, Anne Pernille Hermann, Anette Riis Madsen, Steffanie Christensen, Jens Ahm Sørensen, Mads Gustaf Jørgensen, Anne Pernille Hermann, Anette Riis Madsen, Steffanie Christensen, Jens Ahm Sørensen

Abstract

Precise staging of breast cancer-related lymphedema (BCRL) is important to guide treatment-decision making. Recent studies have suggested staging of BCRL using indocyanine green lymphangiography (ICG-L) based on the extent of lymphatic injury and dermal backflow patterns. Currently, the benefits of ICG-L compared to conventional clinical staging are unknown. For this study, we included 200 patients with unilateral BCRL. All BCRL patients were staged using ICG-L and clinical exam. The amounts of excess arm volume, fat mass and lean mass were compared between stages using Dual Energy X-Ray Absorptiometry. Multivariate regression models were used to adjust for confounders. For each increase in the patient's ICG-L stage, the excess arm volume, fat mass and lean mass was increased by 8, 12 and 6.5 percentage points respectively (P < 0.001). For each increase in the patient's clinical ISL stage, the volume was increased by 3.5 percentage points (P < 0.05), however no statistically significant difference in the lean and fat mass content of the arm was observed for ascending stages. However, the residual plots showed a high degree of variance for both ICG-L and clinical staging. This study found that ICG-L staging of BCRL was superior to clinical staging in forecasting BCRL excess arm volume, fat mass, and lean mass. However, there was a high degree of variance in excess arm volume, fat mass, and lean mass within each staging system, and neither the ICG-L nor clinical staging forecasted perfectly.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Figure 1
Figure 1
This figure shows the flowchart of the include patients.
Figure 2
Figure 2
This figure shows the distribution of excess arm volume, fat and lean mass in lymphedema patients stratified by clinical ISL and lymphangiography staging. (A) Excess volume and ISL stage. (B) Excess volume and ICG stages. (C) Excess fat mass and ISL stage (D) Excess fat ass and ICG stages. (E) Excess lean mass and ISL stage (F) Excess lean mass and ICG stages. Black horizontal dotted lines denote 25%, 50%, and 75%. The red striped line denotes the mean excess volume, fat and lean mass for the study. *P-value < 0.05. **P-value < 0.001.
Figure 3
Figure 3
This figure shows the residuals of predicted minus observed excess volume, fat, and lean mass by (A) ISL stage and (B) ICG stage.

References

    1. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14(6):500–515. doi: 10.1016/S1470-2045(13)70076-7.
    1. Jørgensen MG, Toyserkani NM, Hansen CR, et al. Quantification of chronic lymphedema in a revised mouse model. Ann. Plast. Surg. 2018;81(5):594–603. doi: 10.1097/SAP.0000000000001537.
    1. The diagnosis and treatment of peripheral lymphedema: 2020 consensus document of the international society of lymphology. Lymphology. 2020.
    1. Sierla R, Dylke ES, Shaw T, Poon S, Kilbreath SL. Clinician assessment of upper limb lymphedema: an observational study. Lymphat. Res. Biol. 2021;19(2):159–164. doi: 10.1089/lrb.2020.0005.
    1. Abbaci M, Conversano A, De Leeuw F, Laplace-Builhé C, Mazouni C. Near-infrared fluorescence imaging for the prevention and management of breast cancer-related lymphedema: a systematic review. Eur. J. Surg. Oncol. 2019;45(10):1778–1786. doi: 10.1016/j.ejso.2019.06.009.
    1. Chang DW, Suami H, Skoracki R. A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema. Plast Reconstr. Surg. 2013;132(5):1305–1314. doi: 10.1097/PRS.0b013e3182a4d626.
    1. Jørgensen MG, Toyserkani NM, Hansen FCG, Thomsen JB, Sørensen JA. Prospective validation of indocyanine green lymphangiography staging of breast cancer-related lymphedema. Cancers (Basel). 2021;13(7):19.
    1. Christiansen P, Ejlertsen B, Jensen MB, Mouridsen H. Danish breast cancer cooperative group. Clin. Epidemiol. 2016;8:445–449. doi: 10.2147/CLEP.S99457.
    1. Davidsson L, Ellis K, Heymsfield S, et al. IAEA human health series number 15:-dual energy X-ray absorptiometry for bone mineral density and body composition assessment. Int. Energy Agent. 2010;2:13000.
    1. Gjorup CA, Hendel HW, Klausen TW, Zerahn B, Hölmich LR. Reference values for assessment of unilateral limb lymphedema with dual-energy X-Ray absorptiometry. Lymphat. Res. Biol. 2018;16(1):75–84. doi: 10.1089/lrb.2016.0064.
    1. Nguyen AT, Suami H, Hanasono MM, Womack VA, Wong FC, Chang EI. Long-term outcomes of the minimally invasive free vascularized omental lymphatic flap for the treatment of lymphedema. J. Surg. Oncol. 2017;115(1):84–89. doi: 10.1002/jso.24379.
    1. Dylke ES, Ward LC, Meerkin JD, Nery L, Kilbreath SL. Tissue composition changes and secondary lymphedema. Lymphat. Res. Biol. 2013;11(4):211–218. doi: 10.1089/lrb.2013.0018.
    1. Abdelfattah U, Jaimez PM, Clavero JA, Bellantonio V, Pons G, Masia J. Correlation between superficial and deep lymphatic systems using magnetic resonance lymphangiography in breast cancer-related lymphedema: clinical implications. J. Plast Reconstr. Aesthetic. Surg. 2020;73(6):1018–1024. doi: 10.1016/j.bjps.2019.11.053.
    1. Al-Jindan FK, Lin C-Y, Cheng M-H. Comparison of outcomes between side-to-end and end-to-end lymphovenous anastomoses for early-grade extremity lymphedema. Plast. Reconstr. Surg. 2019;5:19.
    1. Yamamoto T, Yamamoto N, Ishiura R. Time to re-consider a gold standard of lymph flow imaging: importance of reliability to detect abnormal lymphodynamics in lymphedema screening after cancer treatments. Plast. Reconstr. Surg. 2016;2:16.
    1. Pons G, Clavero JA, Alomar X, Rodríguez-Bauza E, Tom LK, Masia J. Preoperative planning of lymphaticovenous anastomosis: the use of magnetic resonance lymphangiography as a complement to indocyanine green lymphography. J. Plast Reconstr. Aesthetic. Surg. 2019;72(6):884–891. doi: 10.1016/j.bjps.2019.02.024.
    1. Kajita H, Oh A, Urano M, et al. Photoacoustic lymphangiography. J. Surg. Oncol. 2019;9:25575. doi: 10.1002/jso.25575.
    1. Jørgensen MG, Toyserkani NM, Hansen FG, Bygum A, Sørensen JA. The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment. NPJ Breast Cancer. 2021;7(1):70. doi: 10.1038/s41523-021-00276-y.
    1. Thomis S, Dams L, Fourneau I, et al. Correlation between clinical assessment and lymphofluoroscopy in patients with breast cancer-related lymphedema: a study of concurrent validity. Lymphat. Res. Biol. 2020;18(6):539–548. doi: 10.1089/lrb.2019.0090.
    1. Garza RM, Ooi ASH, Falk J, Chang DW. The relationship between clinical and indocyanine green staging in lymphedema. Lymphat. Res. Biol. 2019;17(3):329–333. doi: 10.1089/lrb.2018.0014.
    1. Pigott A, Doig E, McCann A, Trevethan M. It was just mind blowing to be honest: a qualitative phenomenological study exploring cancer survivor’s experiences of indocyanine green lymphography used to inform lymphedema therapy management. Support Care Cancer. 2021;9:637.
    1. Suami H, Heydon-White A, Mackie H, Czerniec S, Koelmeyer L, Boyages J. A new indocyanine green fluorescence lymphography protocol for identification of the lymphatic drainage pathway for patients with breast cancer-related lymphoedema. BMC Cancer. 2019;19(1):1000. doi: 10.1186/s12885-019-6192-1.
    1. Koelmeyer LA, Thompson BM, Mackie H, et al. Personalizing conservative lymphedema management using indocyanine green-guided manual lymphatic drainage. Lymphat. Res. Biol. 2021;19(1):56–65. doi: 10.1089/lrb.2020.0090.
    1. Committee E. The diagnosis and treatment of peripheral lymphedema: 2016 consensus document of the international society of lymphology. Lymphology. 2016;49(4):170–184.
    1. Markkula SP, Leung N, Allen VB, Furniss D. Surgical interventions for the prevention or treatment of lymphoedema after breast cancer treatment. Cochrane Database Syst. Rev. 2019;7:1736.
    1. Ezzo J, Manheimer E, McNeely ML, et al. Manual lymphatic drainage for lymphedema following breast cancer treatment. Cochrane Database Syst. Rev. 2015;5:CD003475.
    1. Rosian K, Stanak M. Efficacy and safety assessment of lymphovenous anastomosis in patients with primary and secondary lymphoedema: a systematic review of prospective evidence. Microsurgery. 2019;39(8):763–772. doi: 10.1002/micr.30514.
    1. Rj D, Hg V, van Wd S, et al. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res. Treat. 2009;113(2):199–206. doi: 10.1007/s10549-008-9932-5.
    1. Qiu SS, Pruimboom T, Cornelissen AJM, Schols RM, van Kuijk SMJ, van der Hulst RRWJ. Outcomes following lymphaticovenous anastomosis (LVA) for 100 cases of lymphedema: results over 24-months follow-up. Breast Cancer Res. Treat. 2020;184(1):173–183. doi: 10.1007/s10549-020-05839-4.
    1. Jørgensen MG, Toyserkani NM, Jensen CH, Andersen DC, Sheikh SP, Sørensen JA. Adipose-derived regenerative cells and lipotransfer in alleviating breast cancer-related lymphedema: An open-label phase I trial with 4 years of follow-up. Stem Cells Transl. Med. 2021;7:1073.
    1. Beederman M, Garza RM, Agarwal S, Chang DW. Outcomes for physiologic microsurgical treatment of secondary lymphedema involving the extremity. Ann. Surg. 2020;6:11109.

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