Treatment Outcomes in Patients with Advanced Fibrolamellar Hepatocellular Carcinoma Under Systemic Treatment: Analysis of Clinical Characteristics, Management, and Radiomics

Figures & data

Table 1 Baseline Characteristics of the Patients Included in the Analysis

Characteristics	N= 23 (100%)
Median age, years (IQR)	23.6 (21.8–28.6)
Female/Male n(%)	11 (41.8%)/12 (52.2%)
Performance status, n(%)
0	20 (86.9%)
1	3 (13.1%)
Cirrhosis, n(%)	1 (4.3%)
No comorbidities	18 (78.3%)
Family history of cancer	4 (17.4%)
Disease extent
Intrahepatic unresectable	4 (17.4%)
Metastatic	19 (82.6%)
Liver affection
Single lesion	12 (52.2%)
Multinodular	11 (47.8%)
Macrovascular invasion	7 (30.7%)
Lung metastasis	9 (39.1%)
Lymph node metastasis	9 (39.1%)
Peritoneal metastasis	5 (21.7%)
Bone metastasis	1 (4.3%)
Previous local treatment
Hepatic surgery	15 (65.2%)
Ablation	2 (8.7%)
SBRT	1 (4.3%)
Palliative radiotherapy	4 (17.4%)
Median size of the largest liver tumor, cm (IQR)	8.8 cm (3.1–13.3)

Abbreviations: IQR, interquartile range; SBRT, Stereotactic Body Radiotherapy.

Table 2 Response Assessment and Time to Treatment Failure in the First, Second, and Third Lines

	n	n - SD / PR / PD / NE	Time to Failure, Median (95% CI)
First-line	23	7 / 2 /10 /4	3.8 mo (3.2–8.7)
Sorafenib	9	1 / 0 / 4 / 4	7.8 mo (1.2-NA)
Capecitabine	7	2 / 1 / 4 / 0	3.2 mo (0.4-NA)
IFN plus capecitabine	3	2 / 1 / 0 / 0	4.0 mo (3.5-NA)
GemOX	1	1 / 0 / 0 / 0	NA
Cisplatin plus capecitabin	1	0 / 0 / 1 /0	NA
Cisplatin plus doxorubicin	1	1 / 0 / 0 / 0	NA
Cisplatin	1	0 /0 /1 / 0	NA
Second-line	19	5 /5 / 8 /1	3.5mo (1.5–11.6)
IFN plus capecitabine	8	1 /1 / 5 / 1	3.5 mo (2.7-NA)
mFLOX	3	0 / 2/ 1 / 0	NA
GemOX	3	1 /1 /1 /0	6.8 mo (3.6-NA)
GemCis	2	1 /1 / 0 / 0	8.7 mo (NR-NA)
Doxorubicin	2	1 / 0 / 1 /0	1.4 mo (NR-NA)
Cisplatin plus capecitabine	1	1 / 0 / 0 /0	NA
Third-line	12	3 / 1 / 6 / 2	2.4 mo (1.1–22)
Doxorubicin	3	1 /0 /2 / 0	1.7 mo (1.4-NA)
GemOx	3	1 /1 /1 / 0	5.1 mo (2.4-NA)
mFLOX	1	0 / 0 / 1 / 0	2.7 mo (NA-NA)
Gemcitabine	2	1 / 0 / 1 / 0	1.4 mo (NA-NA)
Others	3	0 / 0 / 1 / 2	NA

Abbreviations: SD, stable disease; PR, partial response; PD, progressive disease; NE, non-evaluable; NA, not-achieved; CI, confidence interval.

Figure 1 Plot illustration representing the duration of each line of systemic treatment and systemic treatment free interval individually.

Table 3 Median Survival and Univariate Analysis

Characteristics	n	Median Survival (95% CI)	P value Univariate
Female	11	26.7 mo (10–39)	0.07
Male	12	22.7 mo (12.7-NA)
No comorbidities	18	39.1 mo (15.1–58.5)	0.56
Any comorbidity	5	17.9 mo (2.1-NA)
Family history	4	40.4 mo (15.1-NA)	0.20
No family history	19	22.7 mo (13.5–39.1)
Liver only disease	4	20.8 mo (2.1-NA)	0.83
Metastatic spread	19	26.7 mo (15.1–40.4)
Node metastasis	9	29.6 mo (12.7-NA)	0.35
No node metastasis	14	22.7 mo (10–40.4)
Lung metastasis	9	39.1 mo (10-NA)	0.09
No lung metastasis	14	19.8 mo (12.7–58.5)
Peritoneal metastasis	5	19.8 mo (4.0-NA)	0.07
No peritoneal metastasis	18	39.1 mo (15.1–40.4)
Multinodular	11	22.7 mo (10.0–64.8)	0.47
Uninodular	12	29.6 mo (12.7–39.1)
Macrovascular invasion	7	26.7 mo (12.7–39.1)	0.84
No macrovascular invasion	16	40.4 mo (15.1-NA)
NLR high*	7	22.7 mo (2.1-NA)	0.02 (HR: 1.8; 95% CI 1.1–4.3).
NLR low	6	39.1 mo (29.6-NA)

Notes: Multivariate analysis was not performed because NLR was the only significant variable. *10 patients did not have baseline blood cell count available.

Abbreviations: CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio; NA, not achieved; HR, Hazard ratio.

Figure 2 Survival curves (A) Total cohort; (B) Neutrophil-to-lymphocyte ratio (NLR) high versus low (p=0.02); (C) Peritoneal metastasis (Peritoneal mets) yes versus no (p=0.07); (D) Lung metastasis (Lung mets) yes vs no (p=0.09).