Combination treatment of trans-arterial chemo-embolisation, radiotherapy and hyperthermia (CERT) for hepatocellular carcinoma with portal vein tumour thrombosis: Interim analysis of prospective phase II trial

Figures & data

Figure 1. CONSORT diagram. RT, radiotherapy; TACE, trans-arterial chemo-embolisation; FU, follow-up.

Table 1. Baseline characteristics of 46 enrolled patients.

Variables	No. of patients (%)
Age in years
Median	54
Range	35–79
Sex
Male	38 (82.6)
Female	8 (17.4)
ECOG performance status
0	31 (67.4)
1	12 (26.1)
2	3 (6.5)
Cause of hepatitis
HBV	38 (82.6)
HCV	5 (10.9)
Alcohol	3 (6.5)
Liver cirrhosis
Yes	37 (80.4)
No	9 (19.6)
HCC diagnosis
Pathologic	9 (19.6)
Clinical	37 (80.4)
Child-Pugh class
A	41 (89.1)
B	5 (10.9)
No. of viable tumours
Solitary	20 (43.5)
Multiple	26 (56.5)
mUICC T stage
T3	20 (43.5)
T4	26 (56.5)
mUICC N stage
N0	45 (97.8)
N1	1 (2.2)
mUICC M stage
M0	45 (97.8)
M1	1 (2.2)
Tumour size (cm)
Median	7.4
Range	1.7–15.6
α-fetoprotein (ng/mL)
Median	272.9
Range	1.6–200 000
Location of PVTT
Main	12 (26.1)
First-order branch	21 (45.7)
Second-order branch	13 (28.3)
Fraction size
3.0 Gy	18 (39.1)
3.5 Gy	17 (37.0)
4.0 Gy	7 (15.2)
4.5 Gy	3 (6.5)
Previous treatment (repeated measure)
Surgery	4 (85)
RFA	6 (12.8)
TACE	9 (19.1)
Sorafenib	1 (2.1)
Naïve	28 (61.7)

ECOG, Eastern Cooperative Oncology Group; HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; mUICC, modified International Union Against Cancer; PVTT, portal vein tumour thrombosis; RFA, radiofrequency ablation; TACE, trans-arterial chemo-embolisation.

Table 2. Objective response according to mRECIST after CERT at 1 and 3 months.

	CR (%)	PR (%)	SD (%)	PD (%)	Not evaluable
Follow-up at 1 month
PVTT	16 (34.0)	19 (41.3)	9 (19.6)	0	2 (4.3)
In-field	11 (23.9)	26 (56.5)	7 (15.2)	0	2 (4.3)
Overall	10 (21.7)	22 (47.8)	5 (10.9)	7 (15.2)	2 (4.3)
Follow-up at 3 months
PVTT	20 (43.5)	14 (30.4)	5 (10.9)	3 (6.5)	4 (8.7)
In-field	14 (30.4)	19 (41.3)	5 (10.9)	4 (8.7)	4 (8.7)
Overall	13 (28.3)	10 (21.7)	1 (2.2)	19 (41.3)	4 (8.7)

CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; PVTT, portal vein tumour thrombosis.

Table 3. Toxicity profile during or after CERT.

Grade	I (%)	II (%)	III (%)	IV (%)	V (%)
During RT with hyperthermia (n = 46)
Fatigue	4 (8.7)	1 (2.2)	–	–	–
Anorexia	5 (10.9)	3 (6.5)	–	–	–
Nausea	7 (15.2)	2 (4.3)	–	–	–
Vomiting	2 (4.3)	–	–	–	–
Diarrhoea	–	–	–	–	–
Dysphagia	4 (8.7)	1 (2.2)	–	–	–
Coughing	1 (2.2)	2 (4.3)	–	–	–
Acute toxicity during 3 months follow-up (n = 44)
Anaemia	3 (6.8)	2 (4.5)	–	–	–
Neutropenia	2 (4.5)	–	2 (4.5)
Thrombocytopenia	7 (15.6)	–	–	–	–
AST	3 (6.8)	–	–	–	–
ALT	2 (4.5)	–	–	–	–
ALP	2 (4.5)	–	–	–	–
GGT	3 (6.8)	–	–	–	–
Anorexia	1 (2.3)	3 (6.8)	–	–	–
Nausea	1 (2.3)	–	1 (2.3)	–	–
Vomiting	–	–	1 (2.3)	–	–
Diarrhoea	1 (2.3)	–	1 (2.3)	–	–
Abdominal pain	2 (4.5)	1 (2.3)	2 (4.5)	–	–

RT, radiotherapy; AST, aspartate aminotransperase; ALT, alanine aminotransperase; ALP, akaline phosphatase; GGT, gamma-glutamyl transferase.

Figure 2. Changes in laboratory and clinical findings before and after CERT. MELD scores (A) and Child-Pugh scores (B) were restored without significant differences in contrast to AFP (C) even more decreased at 1-month follow-up after completion of treatments.

Figure 3. Kaplan–Meier survival curves of all enrolled patients. Local progression-free survival (LPFS) was 75.1%, progression-free survival (PFS) was 29.8% and overall survival (OS) was 78.9% at 1 year.