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Lecchini et al. HCC vascular invasion in sorafenib treatment

problem of cirrhosis developing in the setting of non- Diseases and Hepatology, Azienda Ospedaliero-
alcoholic fatty liver disease in patients with obesity, Universitaria di Parma. Data were obtained from the
type 2 diabetes, dyslipidemia and hypertension [5-8] . analysis of medical charts and a dedicated database.
Programs of surveillance with upper abdomen Inclusion criteria were: radiological or histological
ultrasound examination and characterization of focal diagnosis of HCC not amenable to surgical resection
liver lesions with computed tomography (CT) scan or locoregional treatment, BCLC stage C, PS < 2
or magnetic resonance imaging (MRI) increase according to the Eastern Cooperative Oncology Group
the rate of early diagnosis and curative treatments system, measurable lesions in CT or MRI scans.
such as surgical resection, liver transplantation and Patients with an impaired liver function and a Child-
locoregional ablative treatments [9-13] with improved Pugh score ≥ 10 were excluded. Eighty-four patients
survival. In the advanced stage, Barcelona Clinic were considered, 63 males (75%) and 21 females
Liver Cancer (BCLC) stage C, systemic therapy with (25%), with a median age of 73 years (range 32-81)
sorafenib [14] represents the first line treatment for these [Table 1]. Of these patients, 45% had comorbidities:
patients, while regorafenib is available for second line the most frequent was hypertension (29 subjects),
as well as anti-PD-1 that has been recently approved followed by diabetes mellitus (16 subjects), previous
by the Food and Drug Administration for HCC. ischemic vascular events like heart attacks and stroke
(11 subjects) and chronic obstructive pulmonary
Sorafenib is an oral multi-kinase inhibitor that disease (COPD, 9 subjects). Eight subjects had a
acts both on tumor cells by inhibiting cytoplasmic history of tumors other than HCC [Table 1]. The
cascades RAS-RAF and MEK-ERK, involved in etiology of chronic liver disease underlying HCC was
cells proliferation, and also on endothelial cells by HCV infection in 46 patients (54.5%), nonalcoholic
blocking plasmatic receptors implicated mainly in neo- steatohepatitis or alcohol in 21 patients (25%), HBV
angiogenesis (VEGFR and PDGFR) [15-19] . A correct infection in 7 patients (8.5%), HBV-HCV confection in
patient management can increase drug tolerability 3 patients, while in 7 patients (8.5%) the cause of liver
and seems to improve significantly quality of life and disease was unknown [Table 1]. Most of subjects (91.5%)
survival [20-24] . The opportunity to continue treatment was on a Child-Pugh score A, seven were scored B7
also in patients with radiological progressive disease [Table 1]. Majority of patients (82%) was previously
or when tolerance is poor despite dose adaptation treated: 72.5% underwent loco-regional therapies, 33%
remains controversial [25,26] . However, in clinical practice, surgical resection and 18% both [Table 1]. Regarding
progression is not always a clear indication to stop the anatomical characteristics of HCC, it appeared
sorafenib, especially if there isn’t a second-line trial multifocal in 96.5% of cases and was interested in
available and in patients with a good Performance only one lobe of the liver in 77.5% of cases, most
Status (PS) with a reasonable life expectancy, an frequently the right [Table 2]. In 47 patients (56%) HCC
excellent drug tolerance and slow tumor progression. showed signs of neoplastic vascular invasion and 20
Sorafenib, compared to other target therapies, shows subjects (24%) presented both vascular invasion and
low frequency of radiological responses, but stable extrahepatic spread [Table 2]. Treatment was stopped
disease can be achieved frequently as shown in at radiological evaluation at 8 weeks of treatment in
registration trials [27] . case of disease progression.

The aim of the present study was to evaluate The study was approved by the local ethical committee
prognostic relevance of clinical, epidemiological and [Comitato Etico Indipendente (IRB/IEC) of the Azienda
tumor characteristics on survival. Reported results Ospedaliero-Universitaria of Parma, Italy].
confirmed that dose reduction is associated with longer
survival underlining relevance of drug management Treatment with sorafenib and evaluation of
to increase tolerability. On the other hand, neoplastic response rate
portal vein thrombosis, a condition associated with fast Sorafenib was administered at a dose of 400 mg bid
liver decompensation and disease progression, was continuously, equivalent to a total daily dose of 800 mg,
independently associated with poor clinical outcome. without food or with a low or moderate fatty meal.
Therapy was continuous, but by convention was
METHODS codified in cycles of 28 days. Patients had to measure
their blood pressure at least twice daily and use skin
Patient characteristics lotions to prevent or reduce any hand-foot syndrome
This is an observational monocentric retrospective manifestation. Every 4 weeks a revaluation of treatment
study conducted on 84 consecutive subjects was planned through a detailed physical examination
starting sorafenib treatment at the Unit of Infectious of patients, the correction of possible adverse effects

Hepatoma Research ¦ Volume 3 ¦ November 16, 2017 261