Does HCC Etiology Impact the Efficacy of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma? An Asian Liver Radiation Therapy Group Study

Figures & data

Table 1 Patient and Tumor Characteristics

Variables		Total (N=415)
Age		67 [59–76]
ECOG PS	0	227 (54.7)
	1–2	188 (45.3)
Sex	Male	312 (75.2)
	Female	103 (24.8)
Etiology	HBV	227 (54.7)
	HCV	125 (30.1)
	Non-viral	63 (15.2)
ALBI score		−2.60 [−2.93 – −2.26]
ALBI grade	1	208 (50.1)
	2	198 (47.7)
	3	9 (2.2)
Previous treatment	Treatment-naïve	70 (16.9)
	Recurrent tumor	345 (83.1)
Number of previous treatments		2 [1–4]
Tumor size, cm		2.5 [1.5–3.9]
	≤3	261 (62.9)
	>3	154 (37.1)
Pre-treatment AFP, ng/mL		14.1 [4.9–102.0]
Gross tumor volume, cm^3		16.6 [3.9–50.2]
Planning target volume, cm^3		52.2 [22.2–101.7]
Total dose, Gy		48.0 [40.0–54.0]
Fractional dose, Gy		10.0 [8.0–12.0]
BED, Gy		100.0 [80.0–116.0]
sBED, Gy		70.0 [46.0–92.5]

Note: Values are presented as patient (%) or median [interquartile range].

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; HBV, hepatitis B virus; HCV, hepatitis C virus; ALBI, albumin–bilirubin score; AFP, alpha-fetoprotein; BED, biologically effective dose (α/β ratio of 10 is used for tumor control); sBED, size-adjusted biologically effective dose (defined as BED minus 10 times the tumor diameter in centimeters).

Table 2 Prognostic Factors for Local Control

		Univariable Analysis			Multivariable Analysis
Variables	(ref. vs)	HR	95% CI	P-value	HR		95% CI	P-value
Age	(continuous)	0.99	0.97–1.01	0.341
ECOG PS	(0 vs 1–2)	1.60	1.01–2.53	0.046	1.53		0.96–2.44	0.076
Sex	(Male vs Female)	1.12	0.67–1.88	0.657
Etiology	(HCV- vs HBV-related)	1.98	1.09–3.59	0.026	1.89		1.03–3.46	0.040
	(HCV-related vs Non-viral)	1.83	0.86–3.90	0.116	1.77		0.82–3.78	0.144
ALBI score	(continuous)	1.49	0.95–2.35	0.086
Previous treatment	(Treatment-naïve vs Recurrent tumor)	1.22	0.64–2.33	0.536
Pre-treatment AFP	(continuous, per doubling)	1.04	0.97–1.12	0.231
Tumor size	(continuous)	1.14	1.04–1.26	0.005
Tumor size	(≤3 vs >3 cm)	1.54	0.97–2.44	0.069
BED	(≥100 vs <100 Gy)	2.22	1.34–3.69	0.002
sBED	(≥70 vs <70 Gy)	2.12	1.30–3.46	0.003	2.23		1.36–3.64	0.001

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; HCV, hepatitis C virus; AFP, alpha-fetoprotein; BED, biologically effective dose (α/β ratio of 10 is used for tumor control); sBED, size-adjusted biologically effective dose (defined as BED minus 10 times the tumor diameter in centimeters).

Table 3 Projected 2-Year Local Control Rates for Common Stereotactic Body Radiation Therapy (SBRT) Schedules and Selected Tumor Diameters, Based on Etiology of Hepatocellular Carcinoma

SBRT Schedule Tumor Diameter	8 Gy × 6 Fractions		10 Gy × 5 Fractions		15 Gy × 4 Fractions
	HCV-Related	Non-HCV-Related	HCV-Related	Non-HCV-Related	HCV-Related	Non-HCV-Related
2 cm	88%	75%	89%	78%	92%	86%
4 cm	85%	71%	87%	73%	91%	84%
6 cm	83%	66%	85%	69%	89%	80%

Abbreviation: HCV, hepatitis C virus.

Figure 1 Kaplan–Meier curves for local tumor control following SBRT stratified by (A) tumor diameter, (B) biologically effective dose (BED), and (C) etiology.

Figure 2 Tumor control probability modelling results for actuarial 2-year local control with size-adjusted biologically effective dose (sBED) for patients with hepatitis C virus (Black) and hepatitis B or non-viral etiology (grey).

Notes: Each circle represents the outcomes of tumors after sorting by sBED. Circle size is proportional to sample size. The solid curve depicts the results of model fitting using all available data. Dotted lines indicate 95% confidence intervals for tumor control probability as a function of sBED.

Abbreviation: sBED, size-adjusted biologically effective dose (calculated from BED minus 10 times the maximal tumor diameter (cm).

Figure 3 Scatter plot of 2-year actuarial local control rate versus percentage of patients with hepatitis C in studies included in the HyTEC analysis as well as in the present study. Marker sizes are proportional to study sample sizes. The dotted line depicts the results of weighted linear regression, excluding the present study.

Abbreviation: LC, local control.