Effectiveness and Safety of the PD-1 Inhibitor Lenvatinib Plus Radiotherapy in Patients with HCC with Main PVTT: Real-World Data from a Tertiary Centre

Figures & data

Figure 1 Protocol of this study.

Abbreviations: OS, overall survival; PFS, progression-free survival; ORR, objective response rate; PVTT, portal vein tumour thrombus; AE, adverse event.

Table 1 Patient Demographics and Clinical Characteristics

Characteristics	Patients (n=39)
Gender
Male	37 (94.9%)
Female	2 (05.1%)
Age
Median	56 (32–73)
ECOG score
0	7 (17.9%)
1	28 (71.8%)
2	4 (10.3%)
Child-Pugh grade
A	29 (74.4%)
B	10 (25.6%)
PVTT position
PVTT trunk combined with left and right branch	16 (41.1%)
PVTT trunk combined with left or right branch	23 (58.9%)
Extrahepatic spread
No	29 (74.4%)
Yes	10 (25.6%)
AFP (ng/mL)
≤400	17 (43.6%)
>400	22 (56.4%)
Hepatitis
HBV	36 (92.3%)
HCV	1 (02.6%)
Alcoholic	2 (05.1%)
Previously treated
No	10 (25.6%)
Yes	29 (74.4%)

Table 2 Radiological Response of PVTT According to mRECIST

CR	2 (5.1%)
PR	22 (56.4%)
SD	6 (15.4%)
PD	9 (23.1%)
ORR (CR+PR)	24 (61.5%)
DCR (CR+PR+SD)	30 (76.9%)

Abbreviations: CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease; DCR, disease control rate; ORR, objective response rate; mRECIST, modified Response Evaluation Criteria in Solid Tumors.

Figure 2 OS and PFS.

Figure 3 Patients survival information.

Abbreviations: PFS, progression-free survival; OS, overall survival.

Figure 4 Typical case demonstration. A 69-year-old male HCC patient with main PVTT achieved complete response (mRECIST) after receiving Lenvatinib plus Pembrolizumab combined with Radiotherapy. Sub-figure A B C show the pre-treatment images and sub-figure D E F show the post-treatment images. Sub-figure G H show the radiotherapy target area. The red arrows in the sub-figure A and C indicate the range of PVTT before treatment. The red arrow in the sub-figure B indicate the range of liver tumor before treatment. The red arrows in the sub-figure D and F indicate the range of PVTT after treatment. The red arrow in the sub-figure E indicate the range of liver tumor after treatment. After treatment, the liver tumor and PVTT had shrunk and there was no enhancement on the enhanced image.

Abbreviations: HCC, hepatocellular carcinoma; PVTT, portal vein tumor thrombus; mRECIST, modified response evaluation criteria in solid tumors.

Table 3 Treatment Related Adverse Events

Adverse Event	Any Grade(%)	Grade 1	Grade 2	Grade 3
Lymphopenia	33(84.6%)	16(41.0%)	13(33.3%)	4(10.3%)
Fatigue	21(53.8%)	20(51.3%)	1(2.5%)	0
Nausea/Anorexia	17(43.6%)	17(43.6%)	0	0
Elevated aminotransferases	15(38.5%)	11(28.2%)	3(7.7%)	1(2.5%)
Leukopenia	14(35.9%)	12(30.8%)	2(5.1%)	0
Elevated bilirubin	12(30.8%)	12(30.8%)	0	0
Thrombocytopenia	11(28.2%)	10(25.6%)	1(2.5%)	0
Proteinuria	10(25.6%)	8(20.5%)	2(5.1%)	0
Hypertension	10(25.6%)	10(25.6%)	0	0
Hypoproteinemia	7(17.9%)	5(12.8%)	2(5.1%)	0
Hand and foot skin reactions	7(17.9%)	6(15.4%)	1(2.5%)	0
Diarrhoea	6(15.4%)	6(15.4%)	0	0
Rash	5(12.8%)	4(10.3%)	0	1(2.5%)
Gastric ulcer	1(2.5%)	0	0	1(2.5%)
Immune-related adverse event	12(30.8%)
Immune-related Adrenal hypofunction		3(7.7%)	0	0
Immune-related myocarditis		2(5.1%)	1(2.5%)	0
Immune-related hypothyroidism		2(5.1%)	3(7.7%)	0
Immune-related pneumonitis		1(2.5%)	0	0

Notes: Listed are adverse events, as defined by the National Cancer Institute Common Terminology Criteria (version 4.01).

Table 4 Univariate and Multivariate Analyses of Prognostic Factors Affecting OS

Variable	Univariate Cox Analysis			Multivariate Cox Analysis
	HR	95% CI	P-value	HR	95% CI	P-value
Sex (male vs female)	2.528	0.589–10.854	0.196
Age(<55 vs ≥55)	0.875	0.441–1.736	0.703
ECOG PS (0 vs.1/2)	2.331	0.107–4.907	0.720
Extrahepatic metastasis (yes vs no)	0.705	0.305–1.631	0.364
BED (<50Gy vs ≥50Gy)	0.792	0.399–1.567	0.502
GTV (<544mL vs ≥544mL)	1.370	0.678–2.768	0.358
Child-Pugh (Grade A vs Grade B)	0.736	0.322–1.686	0.430
AFP (<400ng/mL vs ≥400ng/mL)	1.104	0.557–2.189	0.776
*AFP dropped to normal (yes vs no)	0.141	0.068–0.295	0.0009	0.145	0.032–0.648	0.011
#AFP reduced by half (yes vs no)	2.468	1.201–5.071	0.011	0.629	0.303–1.303	0.212
Previously treated with TACE (yes vs no)	0.888	0.448–1.762	0.731

Notes: *AFP dropped to normal 3 months after radiotherapy. #AFP reduced by half 1 month after radiotherapy. Statistically significant data has been highlighted in red according to multivariate cox analysis.

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group Performance Status; BED, Equivalent Biological Dose; GTV, Gross Tumor Volume; AFP, a-fetoprotein; TACE, Transcatheter arterial chemoembolization/.

Figure 5 Independent risk factor for OS.

Abbreviations: AFP, α-fetoprotein; HR, Hazard Ratio; CI, Confidence Interval.