Outcomes of Radiation Segmentectomy for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease versus Chronic Viral Hepatitis

Figures & data

Table 1 Baseline Patient and Tumor Characteristics

Parameter	NAFLD (n=61)	HCV (n=81)	p-value
Age (years)*	70 (65, 74)	66 (62, 69)	< 0.001
Sex			0.85
Female	17 (28%)	21 (26%)
Male	44 (72%)	60 (74%)
BMI (kg/m^2)*	34.2 (28.5, 37.6)	28.2 (24.5, 31.6)	< 0.001
BCLC			0.44
0	6 (10%)	14 (17%)
A	45 (74%)	55 (68%)
C^†	10 (16%)	12 (15%)
ECOG			0.80
0	51 (84%)	69 (85%)
1	10 (16%)	12 (15%)
Tumor size (cm)*	2.3 (2.0, 3.1)	2.5 (2.1, 3.7)	0.27
Tumor focality			0.15
Solitary ≤ 8 cm	47 (77%)	70 (86%)
2 to 3 nodules ≤ 3 cm	15 (22%)	11 (14%)
Child-Pugh class
A	46 (75%)	71 (89%)	0.037
B	15 (25%)	9 (11%)
Albumin (g/dL)*	3.9 (3.5, 4.2)	4.1 (3.7, 4.4)	0.006
Total bilirubin (mg/dL)*	0.9 (0.6, 1.5)	0.7 (0.5, 1.2)	0.023
ALBI score*	−2.53 (−2.88, −2.16)	−2.82 (−3.07, −2.43)	0.003
ALBI grade
1	28 (46%)	56 (69%)	0.008
2	31 (51%)	24 (30%)
3	2 (3%)	0
AST (U/L)*	41 (32, 55)	37 (29, 62)	0.66
ALT (U/L)*	34 (27, 46)	36 (26, 59)	0.63
Platelet count (x10^9/L)*	92 (72, 128)	105 (74, 173)	0.15
INR	1.2 (1.1, 1.3)	1.2 (1.1, 1.3)	0.24
AFP (ng/mL)*	5.2 (3.4, 10.1)	8.6 (3.3, 34)	0.034
Fibrosis stage			0.86
0	2 (3%)	2 (3%)
1	0	1 (1%)
2	2 (3%)	2 (3%)
3	4 (7%)	6 (7%)
4	53 (87%)	70 (86%)
FIB-4 score	5.27 (3.60, 8.07)	4.61 (2.35, 7.95)	0.09

Notes: Bold p-values are statistically significant. Unless otherwise specified, data are frequency (percentage). *Data are median (IQR 25, 75). ^†BCLC-C Patients were allocated to this category due to an ECOG performance status of 1.

Abbreviations: NAFLD, non-alcoholic fatty liver disease; HCV, hepatitis C virus; BMI, body mass index; BCLC, Barcelona Clinic Liver Cancer; ECOG, Eastern Cooperative Oncology Group; ALBI, albumin-bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, International Normalized Ratio; AFP, Alpha-fetoprotein; FIB-4, Fibrosis-4.

Table 2 Radiation Segmentectomy Treatment Parameters

Parameter	NAFLD (n=61)	HCV (n=81)	p-value
Total angiosome volume (mL)	243 (131, 435)	202 (110, 307)	0.13
Total dose (Gy)	508 (355, 593)	452 (339, 607)	0.35
Treatment activity (GBq)	2.57 (1.37, 3.65)	1.68 (0.94, 3.40)	0.06
Lung shunt fraction (%)	2.0 (1.1, 3.0)	1.6 (0.8, 2.9)	0.34
Lung dose (Gy)	2.20 (1.13, 4.08)	1.35 (0.70, 3.27)	0.04
Total microsphere number (million)	4.0 (2.4, 6.2)	3.2 (2.0, 4.8)	0.15
Specific activity* (Bq)	700 (321, 905)	698 (321, 805)	0.19
Microspheres per cc (thousands)	16 (12, 22)	16 (11, 24)	0.77

Notes: Data are median (IQR 25, 75). Bold p-values are statistically significant. *Specific activity assumes 2,500 Bq at calibration.

Abbreviations: NAFLD, non-alcoholic fatty liver disease; HCV, hepatitis C virus; mL, milliliters; Gy, Gray; GBq, Gigabecquerel; Bq, Becquerel.

Table 3 Best Imaging Response at 3 and/or 6-Month Follow-Up After Radiation Segmentectomy

mRECIST	NAFLD (n=61)	HCV (n=81)
Complete response	57 (93%)	66 (81%)
Partial response	4 (7%)	13 (16%)
Stable disease	0	1 (1%)
Target tumor progression	0	1 (1%)

Note: Data are frequency (percentage).

Abbreviations: NAFLD, non-alcoholic fatty liver disease; HCV, hepatitis C virus; mRECIST, modified Response Evaluation Criteria in Solid Tumors.

Figure 1 Pathologic response of target tumors treated with radiation segmentectomy prior to liver transplantation. (A) Complete pathologic necrosis (CPN) was not different between NAFLD vs viral-related HCC (p=0.46). (B) CPN was significantly increased with doses ≥500 Gy and specific activity consistent with ≤ 8 days of decay after calibration vs doses ≥500 Gy and second-week specific activity* (p=0.03). *Specific activity assumed 2,500 Bq at calibration.

Table 4 Survival and Progression Outcomes After Radiation Segmentectomy

Outcome	NAFLD (n=61)	HCV (n=81)
Median follow-up (months)*
Non-censored	24.1 (12.9, 34.9)	32.6 (17.4, 48.4)
Censored	10.8 (6.1, 23.7)	14.8 (7.3, 32.1)
Mean follow-up(months)^†
Non-censored	26.5 (22.6–30.3)	33.2 (29.5–37.1)
Censored	15.6 (12.4–18.8)	20.5 (16.9–24.0)
Liver transplantation	27 (44%)	33 (41%)
Death
Non-censored	12 (20%)	13 (16%)
Censored	10 (16%)	13 (16%)
Overall survival^†
Non-censored	NR	NR
Censored	NR	53.9 (32.1–75.7)
Target tumor progression	1 (2%)	8 (10%)
Within treatment angiosome	0	4 (5%)
In continuity with margin	1 (2%)	4 (5%)
Out-of-field progression	24 (39%)	36 (44%)
Intrahepatic only	24 (39%)	32 (40%)
Extrahepatic only	0	2 (2%)
Both intra- and extrahepatic	0	2 (2%)
Overall progression	23 (38%)	39 (48%)
Target tumor TTP^†	NR	NR
Overall TTP^†	17.4 (13.5–21.3)	13.5 (0.4–26.6)

Notes: Unless otherwise specified, data are frequency (percentage). Outcomes were censored for liver transplantation. *Data are median (IQR 25, 75). ^†Data are median (95% CI).

Abbreviations: NAFLD, non-alcoholic fatty liver disease; HCV, hepatitis C virus; NR, Not reached; TTP, time-to-progression.

Figure 2 Plots show (A and B) overall survival (OS) and (C and D) time-to-progression (TTP) outcomes after radiation segmentectomy in patients with non-alcoholic fatty liver disease (NAFLD)- and hepatitis C virus (HCV)-related hepatocellular carcinoma. (A) Median OS non-censored was not met for either cohort. (B) Median OS censored for liver transplantation was not met in the NAFLD-related HCC cohort and 53.9 months (95% CI 32.1–75.7) in the HCV-related HCC cohort. (C) Overall TTP was 17.4 months (95% CI 13.5–21.3) in NAFLD-related HCC cohort and 13.5 months (0.4–26.6) in HCV-related HCC cohort. (D) Target tumor TTP was not met for either cohort.