Survival benefit of higher fraction dose delivered by three-dimensional conformal radiotherapy in hepatocellular carcinoma smaller than 10 cm in size

Figures & data

Table 1 Clinicopathological data of patients with HCC who underwent different fraction doses of hypofractionated 3DCRT

Variables	Before propensity matching		P-value	After propensity matching		P-value
	Group A	Group B		Group A	Group B
Median age in years (range)	50(28–77)	49(27–82)	0.857	49(30–77)	49 (27–82)	0.594
Gender, Male/Female (%) KPS 70 80 90 100	96(86.5)/15(13.5) 2 52 54 3	76(87.4)/11(12.6) 1 29 52 5	0.857 0.018	72(88.9)/9(11.1) 1 32 46 2	70(86.4)/11(13.6) 1 28 49 3	0.633 0.248
Tumor size in cm, n (%)			0.413			0.872
≤5cm	35	32		31	32
5–9.7cm	76	55		50	49
No. (%) of patients with PVTT	50	25	0.007	23	25	0.731
No. (%) of patients ± for hepatitis B surface antigen	92(82.9)/19(17.1)	71(81.6)/16(18.4)	0.816	67(82.7)/14(17.3)	65(80.2)/16(19.8)	0.686
No. (%) of patients CP class A/B	104(93.7)/7(6.3)	82(94.3)/5(5.7)	0.870	76(93.8)5(6.2)	77(95.1)/4(4.9)	0.732
Serum AFP, n (%)			0.931			0.753
≥400 ng/mL	58	46		38	40
<400 ng/mL	53	41		43	41
Median prothrombin time, s (range)	12.6(10.3–20)	12(9.5–17)	0.017	12.8(10.3–20)	12(9.5–16.9)	0.192
Median albumin, g/dL (range)	3.9(2.6–4.7)	3.9(2.9–5.1)	0.654	3.9(2.6–4.7)	3.9(2.9–5.1)	0.934
Median ALT, U/L (range)	65 (24–266)	48 (18–183)	0.002	66(28–210)	58 (25–180)	0.794
Median total bilirubin, umol/L (range)	15.2(4–325)	13.5(4–113)	0.008	15.2(4–325)	13.2(4–80)	0.104
AJCC tumor stage			0.008			0.183
T1	55	48		49	45
T2	3	10		2	7
T3	48	29		28	29
T4	5	0		2	0
TACE			0.433			0.868
Yes	43	29		27	28
No Tumor number Solitary Multiple	68 78 33	58 67 20	0.004	54 64 19	53 63 18	0.813
Median survival time in months (range)	14.4(1–136)	24.8(1.0–186.0)	0.003	14.7(1–136)	21.6(1.0–186.0)	0.032

Abbreviations: HCC, hepatocellular carcinoma; 3DCRT, three-dimensional conformal radiotherapy; KPS, Karnofsky performance scale; PVTT, portal vein tumor thrombus; CP, Child–Pugh; AFP, Alpha-fetoprotein; ALT, alanine aminotransferase; AJCC, American Joint Committee on Cancer; TACE, transcatheter arterial chemoembolization.

Table 2 Mean values of dosimetric parameters in patients

Variables	Group A	Group B	P-values
Median dose (Gy) (range)	53 (40–72)	52 (40–63)	<0.001
Median BED 10 (Gy) (range)	73.80(56.00.-87.5)	79.04(61.40–91.35)	<0.001
Median radiation fraction (range)	13(8–28)	9(7–14)	<0.001
Dose of normal liver (Mean ± SD)
Mean	21.76±6.07	22.55±5.85	0.087
V5	71.32±12.34	83.58±9.87	0.002
V10	61.56±14.76	66.31±13.23	0.132
V15	48.65±13.99	52.36±13.19	0.352
V20	44.21±12.56	45.08±12.47	0.730
V30	30.55±9.94	30.08±10.79	0.875

Abbreviations: BED, bio¬logically equivalent dose; V5, percentage of whole liver covered by at least 5 Gy; V10, V15, V20, and V30, same as V5 for 10 Gy, 15 Gy, 20 Gy, and 30 Gy, respectively.

Figure 1 Overall survival curves of the entire patient population who underwent different fraction doses of hypofractionated three-dimensional conformal radiotherapy (P=0.009).

Table 3 Characteristics for hepatocellular carcinoma recurrence

Variable		Group A	Group B	P-value
Number of recurrence		50	38	0.446
Site of recurrence	Extrahepatic	14	7	0.699
	Intrahepatic	30	27
	Both	8	5

Table 4 Multivariate analysis of clinicopathological factors predictive of poor overall survival

Variables	Before propensity matching			After propensity matching
	Hazard ratio	95% confidence interval	P-value	Hazard ratio	95% confidence interval	P-value
AFP≥400 ng/mL	0.926	0.676–1.269	0.634	1.011	0.714–1.433	0.949
ALT >80 U/L	1.258	1.171–1.491	0.032	0.897	0.696–1.165	0.586
Tumor size>5cm	1.162	1.013–1.337	0.036	1.083	1.003–1.312	0.012
CP class B	1.240	1.084–1.485	<0.001	1.304	1.165–1.536	0.001
PVTT	1.301	1.014–1.569	<0.001	1.263	1.006–1.489	0.002
fractions of 2.5−4.9 Gy/fx	1.502	1.093–2.064	0.012	0.604	0.425–0.859	0.005

Abbreviations: AFP, alpha-fetoprotein; ALT, alanine aminotransferase; CP, Child–Pugh; PVTT, portal vein tumor thrombus.

Figure 2 Overall survival curves of the propensity score-matched patient population who underwent different fraction doses of hypofractionated three-dimensional conformal radiotherapy (P=0.041).

Table 5 Complications after treatment

Complication	Group A(n=111)		Group B(n=87)		P-value
	No.	%	No.	%
Nausea	64	57.7	56	64.4	0.809
Grade 1	50	45.0	43	49.4
Grade 2	13	11.7	12	13.8
Grade 3	1	0.9	1	1.1
Platelets	37	33.3	30	34.5	0.988
Grade 1	25	22.5	21	24.1
Grade 2	9	8.1	6	6.9
Grade 3	2	1.8	2	2.3
Grade 4	1	0.9	1	1.1
Leukopenia	31	27.9	24	27.6	0.863
Grade 1	22	19.8	15	17.2
Grade 2	8	7.2	7	8.0
Grade 3	1	0.9	2	2.3
Liver enzyme	21	18.9	20	23.0	0.867
Grade 1	10	9.0	12	13.8
Grade 2	8	7.2	6	6.9
Grade 3	2	1.8	1	1.1
Grade 4	1	0.9	1	1.1
Bilirubin	29	26.1	19	21.8	0.591
Grade 1	18	16.2	9	10.3
Grade 2	10	9.0	8	9.2
Grade 3	1	0.9	2	2.3
Albumin	28	25.2	23	26.4	0.989
Grade 1	17	15.3	15	17.2
Grade 2	9	8.1	7	8.0
Grade 3	2	1.8	1	1.1
Gastrointestinal bleeding	2	1.8	2	2.3	0.589
Grade 3	2	1.8	2	2.3