Prospective Validation of Indocyanine Green Lymphangiography Staging of Breast Cancer-Related Lymphedema

Mads Gustaf Jørgensen, Navid Mohamadpour Toyserkani, Frederik Christopher Gulmark Hansen, Jørn Bo Thomsen, Jens Ahm Sørensen, Mads Gustaf Jørgensen, Navid Mohamadpour Toyserkani, Frederik Christopher Gulmark Hansen, Jørn Bo Thomsen, Jens Ahm Sørensen

Abstract

Indocyanine green lymphangiography (ICG-L) allows real-time investigation of lymphatics. Plastic surgeons performing lymphatic reconstruction use the ICG-L for patient selection and stratification using the MD Anderson (MDA) and the Arm Dermal Backflow (ADB) grading systems. However, the applicability of ICG-L in evaluating breast cancer-related lymphedema (BCRL) is sparse and not well established. This study comprehensively examines the usability of ICG-L in the assessment of BCRL. We prospectively performed ICG-L in 237 BCRL patients between January 2019 and February 2020. The aim of this study was to assess the interrater and intrarater agreement and interscale consensus of ratings made using the MDA and ADB scales. Three independent raters performed a total of 2607 ICG-L assessments. The ICG-L stage for each grading system was correlated to the lymphedema volume to assess the agreement between the ICG-L stage and clinical severity. The interrater agreement was near perfect for the MDA scale (kappa 0.82-0.90) and the ADB scale (kappa 0.80-0.91). Similarly, we found a near-perfect intrarater agreement for the MDA scale (kappa 0.84-0.94) and the ADB scale (kappa 0.88-0.89). The agreement between the MDA and the ADB scales was substantial (kappa 0.65-0.68); however, the ADB scale systematically overestimated lower ICG-L stages compared to the MDA scale. The volume of lymphedema correlated slightly with MDA stage (Spearmans rho = 0.44, p < 0.001) and ADB stage (rs = 0.35, p < 0.001). No serious adverse events occurred. The staging of BCRL with ICG-L is reliable, safe, and provides unique disease information unobtainable with clinical measurements alone. The MDA scale seems to provide better disease stratification compared to the ADB scale.

Keywords: breast cancer; indocyanine green; lymphangiography; lymphedema; observer.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
This figure shows the flowchart of included patients.
Figure 2
Figure 2
This figure shows Bland–Altman plots for interrater agreements in MDA and ADB scales. The x-axis represents the mean interrater stage (range: 0–5). The y-axis shows the difference in interrater staging (range: −5–5). R1= rater 1, R2 = rater 2, R3 = rater 3. The horizontal dotted lines denote the 95% confidence intervals for the limits of agreement.
Figure 3
Figure 3
This figure shows Bland–Altman plots for intrarater agreements in MDA and ADB scales. The x-axis represents the mean intrarater stage (range: 0–5). The y-axis shows the difference in intrarater staging (range: −5–5). The horizontal dotted lines denote the 95% confidence intervals for the limits of agreement. R2 = rater 2, R3 = rater 3. a = second assessment.
Figure 4
Figure 4
This figure shows Bland–Altman plots for interscale agreements between the MD Anderson and the Arm Dermal Backflow stages. The x-axis represents the mean interscale stage (range: 0–5). The y-axis shows the difference in interscale staging (range: −5–5). The horizontal dotted lines denote the 95% confidence intervals for the limits of agreement. R1 = rater 1, R2 = rater 2, R3 = rater 3. a = second assessment.
Figure 5
Figure 5
This figure shows the correlation between the MDA and ADB stages and clinical examination. (A) This figure shows the distribution of patients by MD Anderson stage. (B) This figure shows the distribution of patients by Arm Dermal Backflow stage. (C) This figure shows a violin plot of lymphedema volume stratified by MD Anderson stage. The thick dashed line denotes the median, and thin dashed lines denote the interquartile range. Plot thickness denotes the probability density of volumes at different values. (D) This figure shows a violin plot of lymphedema volume stratified by Arm Dermal Backflow stages. (E) This figure shows a violin plot of ICG velocity stratified by MD Anderson stage. (F) This figure shows a violin plot of ICG velocity stratified by the Arm Dermal Backflow stage. n = number of patients, p = p-value, n.s = not significant.

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Source: PubMed

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