A Novel Nomogram to Predict Prognosis of Advanced Hepatocellular Carcinoma Treated with Intensity-Modulated Radiotherapy Plus Anti-PD1

Figures & data

Figure 1 Research technology roadmap.

Abbreviations: Anti-PD1, monoclonal antibody against programmed cell death 1; AUROC, the area under the subject received operating characteristic curve; BCLC, barcelona clinic liver cancer; HCC, hepatocellular carcinoma; IMRT, intensity-modulated radiotherapy.

Table 1 Baseline Characteristics of the Patients

Variables	Total, n=102 (%)
Age, >60years	22 (21.57)
Gender, Male	96 (94.12)
HBV infection, present	90 (88.24)
ECOG-PS
0	33 (32.35)
1	68 (66.67)
Child Pugh class
A	76 (74.51)
B	26 (25.49)
TBIL, >21umol/L	30(29.41)
Alb, ≤35g/L	50 (49.02)
AFP, >400ng/mL	53 (51.96)
Liver cirrhosis, present	71 (69.61)
Ascites, present	30 (29.41)
MVI, present	68 (66.67)
Largest tumor size, >86mm	46 (45.10)
Number of tumors, ≥2	77 (75.49)
Extrahepatic metastases, present	49 (48.04)
Prior treatment
Surgery	39 (38.24)
TACE	73 (71.57)
Targeted therapy	47 (46.08)
Immunotherapy	56 (54.90)
Concurrent targeted therapy	38 (37.25)

Abbreviations: IMRT, intensity-modulated radiotherapy; ECOG-PS, eastern cooperative oncology group performance status; TBIL, total bilirubin; Alb, albumin; AFP, alpha-fetoprotein; HBV, hepatitis B virus; MVI, macrovascular invasion; TACE, transcatheter arterial chemoembolization;

Table 2 Summary of Efficacy Outcomes (N=93)

Outcomes	RECIST1.1
Objective response	53(56.99)
Disease control	73(78.49)
Best overall response
CR	5(5.38)
PR	48(51.61)
SD	20(21.51)
PD	20(21.51)
Progression-free survival, median months (95% CI)	9.9 (5.20–14.54)
Overall survival, %
6-month, (95% CI)	86.2 (79.54–89.46)
9-month, (95% CI)	74.2 (73.42–83.02)
12-month, (95% CI)	61.5 (50.92–72.08)
Median overall survival time, months (95% CI)	14.3 (9.36–19.18)
Duration of response, median months (quartile)	4.1(2.28–9.20)
Time to response, median months (quartile)	1.8(1.47–2.65)

Note: Data are N (%, or 95% CI), unless indicated.

Abbreviations: CR, Complete response; PD, Progressive disease; PR, Partial response; SD, Stable disease.

Figure 2 Kaplan–Meier analysis of overall and progression free survival.

Figure 3 Best percentage change from baseline in sums of diameters of target lesions.

Abbreviations: CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.

Table 3 Univariate and Multivariate Cox Regression Analyses for Overall Survival and Progression-Free Survival

Characteristics	Overall Survival				Progression Free Survival
	Univariable Analysis		Multivariable Analysis		Univariable Analysis		Multivariable Analysis
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
ECOG-PS	0.63(0.35–1.12)	0.116			0.58(0.35–0.98)	0.041	0.61 (0.36-1.05)	0.076
Alb g/L (>35 vs ≤35)	0.40(0.22–0.73)	0.003	0.47 (0.22-0.99)	0.047	0.57(0.34–0.95)	0.031	0.76 (0.43-1.33)	0.332
AFP ng/mL (>400 vs ≤400)	1.79(0.99–3.22)	0.054	2.33 (1.19- 4.58)	0.014	1.95(1.15–3.28)	0.013	1.80 (1.04-3.11)	0.036
Number of tumors (>1 vs ≤1)	2.55(1.14–5.70)	0.023	1.55 (0.65-3.66)	0.323	2.04(1.06–3.93)	0.033	1.32 (0.65-2.68)	0.442
Largest tumor size mm (>86 vs ≤86)	1.88(1.05–3.34)	0.033	0.81 (0.39-1.70)	0.578	1.44(0.87–2.39)	0.159
Concurrent targeted therapy (yes vs no)	0.48(0.21–1.08)	0.076			0.50(0.27–0.93)	0.029	0.59 (0.31-1.13)	0.110
ANC3-4w (>6.75 vs ≤6.75)	4.28(1.93–9.47)	0.000	5.23 (1.78- 15.33)	0.003	2.28(1.07–4.85)	0.032	1.76 (0.79-3.89)	0.164
PLR3-4w (>337.5 vs ≤337.5)	2.06(1.12–3.76)	0.019	2.94 (1.22-7.08)	0.017	1.19(0.71–2.00)	0.508
NLR3-4w (>13.5 vs ≤13.5)	1.91(1.06–3.45)	0.031	0.78 (0.35-1.74)	0.541	1.11(0.65–1.89)	0.703
SII3-4w (>1122.477 vs ≤1122.477)	1.82(1.02–3.24)	0.042	1.23 (0.53-2.85)	0.637	1.32(0.80–2.20)	0.279
Change NLR1m (>-0.803 vs ≤-0.803)	3.67(1.27–10.60)	0.016	2.48 (0.79-7.75)	0.119	1.67(0.60–4.64)	0.324

Abbreviations: Alb, albumin; AFP, alpha-fetoprotein; ANC3-4w, neutrophil count3-4w; ECOG_PS, eastern cooperative oncology group performance status; IMRT, intensity-modulated radiotherapy; NLR3-4w = neutrophil count3-4w / lymphocyte count3-4w; NLR = neutrophil count / lymphocyte count; NLR1m = neutrophil count1m / lymphocyte count1m; change NLR1m = (NLR1m – NLR) / NLR; PLR3-4w = platelet count3-4w / lymphocyte count3-4w; SII3-4w = platelet count3-4w× neutrophil count3-4w / lymphocyte count3-4w.

Figure 4 Survival nomogram (A). The total points of each patient can be used to predict survival outcome. ROC curves and AUROCs for the prediction of death within 1–3year among HCC patients after IMRT and anti-PD1 (B). Calibration curve for the prediction of death within 1 years among HCC patients after IMRT and anti-PD1 (C).

Abbreviations: Alb, albumin; AFP, alpha-fetoprotein; ANC3-4w, neutrophil count3-4w; PLR3-4w, platelet count3-4w / lymphocyte count3-4w.

Table 4 Adverse Events of Laboratory Testing After IMRT+ Anti-PD1 Treatment

n=102	Adverse Event	All Grades	Grades 1–2	Grades 3	Grades 4
	Decreased-WBC	76(74.51)	62(60.78)	13(12.75)	1(0.98)
	Decreased-PLT	55(53.92)	39(38.24)	13(12.75)	3(2.94)
	Decreased-Hb	83(81.37)	73(71.57)	10(9.80)	0
	Increased-TBIL	50(49.02)	46(45.10)	3(2.94)	1(0.98)
	Increased-AST	48(47.06)	47(46.08)	1(0.98)	0
	Increased-ALT	38(37.25)	38(37.25)	0	0
	Decreased-Alb	80(78.43)	78(76.47)	2(1.96)	0
	Increased-ALP	27(26.47)	26(25.49)	1(0.98)	0
	Increased-γ-GGT	30(29.41)	30(29.41)	0	0
90	Increased-T3	2(2.22)	2(2.22)	0	0
90	Increased-T4	3(3.33)	3(3.33)	0	0
101	Increased-Cr	5(4.95)	5(4.95)	0	0
101	Increased-UA	20(19.80)	20(19.80)	0	0
99	Increased-Pro	12(12.12)	12(12.12)
99	Increased-Bld	9(9.09)	9(9.09)
99	Increased-Glu	3(3.03)	3(3.03)
99	Increased-OB	15(15.15)	15(15.15)

Note: Data are N (%).

Abbreviations: WBC, white blood cell; PLT, Platelets; Hb, hemoglobin; TBIL, total bilirubin; AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; Alb, albumin; ALP, alkaline phosphatase; γ - GGT, γ - gamma glutamyl transpeptidase; T3, triiodothyronine; T4, thyronine; Cr, creatinine; UA, uric acid; Pro, urine protein; Bld, urine occult blood; Glu, glucose in urine; OB, stool occult blood.

Data Sharing Statement

The data underlying this article will be shared on reasonable request to the corresponding author.