Dynamic Lymphocyte Changes Following Transarterial Radioembolization: Association with Normal Liver Dose and Effect on Overall Survival

Figures & data

Table 1 Demographic Data

Variable	N=93 Patients and 102 Treatments
Age (years)	64.6 ± 11.5
Sex
Male	78 (78/93, 83.9%)
Female	15 (15/93, 16.2%)
Product
Glass	74 (74/102, 72.5%)
Resin	28 (28/102, 27.5%)
Activity delivered (mCi)	46.5 ± 22.9
MAA mapping based predicted
Normal liver dose (Gy)	111.7 ± 80.6
Tumoral dose (Gy)	289.6 ± 321
TNR	2.9 ± 2.7
Post delivery based realized
Normal liver dose (Gy)	116.7 ± 79.3
Tumoral dose (Gy)	294.3 ± 249.9
TNR	2.6 ± 1.4
Particle load	8,735,225 ± 8,099,547
MELD	10.4 ± 3.9
Child–Pugh	7 ± 1.5
Creatinine (mg/dL)	1.1 ± 0.8
Total bilirubin (mg/dL)	1.1 ± 0.7
Albumin (g/dL)	3.1 ± 0.5
INR	1.2 ± 0.2
Neutrophils (10^3/µL)	3.8 ± 2
Lymphocytes (10^3/µL)	1.2 ± 0.8
Alpha fetoprotein (ng/mL)	3,127 ± 17,122

Abbreviations: MELD, model for end-stage liver disease; TNR, tumor-to-normal ratio; INR, international normalization ratio.

Table 2 Measures of Dynamic Lymphocyte Changes Following Transarterial Radioembolization

Variable	1 Month PT	3 Months PT	6 Months PT	12 Months PT
Lymphocyte count (10^3/µL)
Mean ± SD	0.71 ± 0.47	0.79 ± 0.77	0.81 ± 0.44	0.92 ± 0.8
Median (IQR)	0.5 (0.5)	0.7 (0.5)	0.8 (0.5)	0.7 (0.53)
Change in lymphocyte count^# (10^3/µL)
Mean ± SD	−0.54 ± 0.65	−0.37 ± 0.72	−0.39 ± 0.68	−0.19 ± 0.7
Median (IQR)	−0.5 (0.75)	−0.3 (0.67)	−0.3 (0.64)	−0.13 (0.46)
Percent lymphocyte* (%)
Mean ± SD	79.5 ± 77.6	77.5 ± 47	101.8 ± 122.6	142.6 ± 351.6
Median (IQR)	57.1 (55.3)	66.7 (51.1)	66.7 (54.3)	81.3 (56.4)

Notes: ^#Change in lymphocyte count was calculated by subtracting the pretreatment lymphocyte count from the post treatment lymphocyte count, *Percent lymphocyte calculated by dividing the post treatment lymphocyte count by the pretreatment lymphocyte count.

Abbreviations: PT, post treatment; IQR, interquartile range; SD, standard deviation.

Table 3 Evaluation of Correlation Between Post Treatment Lymphocyte Count and Treatment-Related Variables

Variable	Spearman Correlation (Rho)	p value
1 Month
Normal liver dose	−0.216	0.03
Tumoral dose	−0.154	0.12
Perfused volume	0.122	0.22
Percent liver treated	0.032	0.75
Particle load	0.097	0.34
NLD × PV	−0.067	0.5
NLD/Percent liver	−0.157	0.12
3 Months
Normal liver dose	−0.342	0.008
Tumoral dose	−0.204	0.12
Perfused volume	0.376	0.003
Percent liver treated	0.280	0.03
Particle load	0.234	0.09
NLD × PV	0.085	0.52
NLD/Percent liver	−0.354	0.006
6 Months
Normal liver dose	−0.191	0.17
Tumoral dose	−0.169	0.23
Perfused volume	0.225	0.11
Percent liver treated	0.187	0.18
Particle load	0.356	0.01
NLD × PV	−0.052	0.71
NLD/Percent liver	−0.269	0.054
12 Months
Normal liver dose	−0.045	0.77
Tumoral dose	0.001	0.99
Perfused volume	0.036	0.81
Percent liver treated	0.023	0.88
Particle load	0.185	0.24
NLD × PV	−0.004	0.98
NLD/Percent liver	−0.046	0.76

Abbreviations: NLD, normal liver dose, PV, perfused volume.

Table 4 Receiver Operating Correlation Curve Analysis of Lymphocytes and Normal Liver Dose

Time Point	AUC	p value
1 month post treatment	0.625	0.024
3 months post treatment	0.676	0.078
6 months post treatment	0.560	0.541
12 months post treatment	0.794	<0.001

Table 5 Comparison of Those Above and Below Normal Liver Dose Cutoffs as Determined by Receiver Operating Correlation Curve Analysis

Variable	Below Cutoff	Above Cutoff	p value
1 Month (62.3 Gy cutoff)
Lymphocyte count (10^3/µL)	1 ± 0.6	0.6 ± 0.4	<0.001
% Lymphocyte	1.1 ± 1.6	0.7 ± 0.6	0.03
Lymphocyte change (10^3/µL)	−0.4 ± 0.7	−0.6 ± 0.6	0.09
Overall survival (months)	19 ± 15.9	15.5 ± 15	0.15
3 Months (70.2 Gy cutoff)
Lymphocyte count (10^3/µL)	1.2 ± 1.2	0.6 ± 0.3	0.5
% Lymphocyte	1 ± 0.5	0.69 ± 0.41	0.02
Lymphocyte change (10^3/µL)	−0.1 ± 0.9	−0.5 ± 0.6	0.049
Overall survival (months)	17.2 ± 15.1	16.2 ± 15.5	0.32
6 Months (62.2 Gy cutoff)
Lymphocyte count (10^3/µL)	1 ± 0.6	0.7 ± 0.4	0.01
% Lymphocyte	1.2 ± 2.0	1 ± 0.83	0.27
Lymphocyte change (10^3/µL)	−0.6 ± 0.7	−0.3 ± 0.7	0.12
Overall survival (months)	19 ± 15.9	15.5 ± 14.9	0.15
12 Months (60.6 Gy cutoff)
Lymphocyte count (10^3/µL)	1.4 ± 1.3	0.7 ± 0.3	0.003
% Lymphocyte	2.7 ± 6.4	0.92 ± 0.81	0.067
Lymphocyte change (10^3/µL)	0 ± 1.1	−0.3 ± 0.4	0.15
Overall survival (months)	17.6 ± 15.3	16.1 ± 15.3	0.33

Figure 1 (A) Kaplan–Meier overall survival curve comparing those with pretreatment absolute lymphocyte counts ≤1 10³/µL or >1 10³/µL (HR: 0.77, 95% CI: 0.47–124, p=0.28). (B) Kaplan–Meier overall survival curve comparing those with absolute lymphocyte counts ≤1 10³/µL or >1 10³/µL at 1 month post treatment (HR: 0.56, 95% CI: 0.33–0.95, p=0.03). (C) Kaplan–Meier overall survival curve comparing those with absolute lymphocyte counts ≤1 10³/µL or >1 10³/µL at 3 months post treatment (HR: 0.41, 95% CI: 0.18–0.94, p=0.035). (D) Kaplan–Meier overall survival curve comparing those with absolute lymphocyte counts ≤1 10³/µL or >1 10³/µL at 6 months post treatment (HR: 0.36, 95% CI: 0.17–0.77, p=0.008). (E) Kaplan–Meier overall survival curve comparing those with absolute lymphocyte counts ≤1 10³/µL or >1 10³/µL at 12 months post treatment (HR: 0.52, 95% CI: 0.21–1.28, p=0.15).

Figure 2 (A) Kaplan–Meier overall survival curve comparing those with normal liver dose of less than or greater than 62.3 Gy (HR: 1.23, 95% CI: 0.74–2.05, p=0.41). (B) Kaplan–Meier overall survival curve comparing those with normal liver dose of less than or greater than 70.2 Gy (HR: 1.03, 95% CI: 0.63–1.69, p=0.90). (C) Kaplan–Meier overall survival curve comparing those with normal liver dose of less than or greater than 62.2 Gy (HR1.23, 95% CI: 0.74–2.05, p=0.42). (D) Kaplan–Meier overall survival curve comparing those with normal liver dose of less than or greater than 60.6 Gy (HR0.98, 95% CI: 0.58–1.68, p=0.95).