HIF-1α and VEGF as prognostic biomarkers in hepatocellular carcinoma patients treated with transarterial chemoembolization.

BACKGROUND: Neoangiogenesis plays a crucial role in the progression of hepatocellular carcinoma (HCC), and concerns have been raised about the role of neoangiogenesis on the effectiveness of transarterial chemoembolization (TACE). AIM: In this study, we aimed to evaluate Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Inducible Factor-1α (HIF-1α) as circulating prognostic biomarkers in HCC patients treated with TACE. METHODS: Blood samples were collected from 163 patients before (t0) and four weeks after TACE (t1). RESULTS: Higher levels of VEGF after TACE were demonstrated (264.0 [78.7-450.8] vs. 278.6 [95.0-576.6] pg/mL; p < 0.0001). Responders to TACE had lower levels of VEGF than non-responders both at t0 (200.0 [58.9-415.8] vs. 406.6 [181.4-558.6] pg/mL; p = 0.006) and at t1 (257.3 [68.5-528.6] vs. 425.9 [245.2-808.3] pg/mL; p = 0.003), and in both groups there was an increase in VEGF compared to measurements before treatment (p = 0.001 and p = 0.005, respectively). VEGF was not associated with overall survival (OS), while patients with HIF-1α ≤ 0.49 ng/mL showed better prognosis (median OS 28.0 months [95% CI 19.7-36.3] vs. 17.0 months [95% CI 11.1-22.9]; p = 0.01). Moreover, HIF-1α was identified as an independent prognostic parameter. CONCLUSIONS: VEGF and HIF-1α can be considered useful prognostic biomarkers in HCC patients treated with TACE.

Applications of Artificial Intelligence in the Automatic Diagnosis of Focal Liver Lesions: A Systematic Review.

BACKGROUND AND AIMS: Focal liver lesions (FLLs) are defined as abnormal solid or liquid masses differentiated from normal liver, frequently being clinically asymptomatic. The aim of this systematic review is to provide a comprehensive overview of current artificial intelligence (AI) applications, deep learning systems and convolutional neural networks, capable of performing a completely automated diagnosis of FLLs. METHODS: We searched PubMed, Cochrane Library, EMBASE, and WILEY databases using predefined keywords. Articles were screened for relevant publications about AI applications capable of automated diagnosis of FLLs. The search terms included: (focal liver lesions OR FLLs OR hepatic focal lesions OR liver focal lesions OR liver tumor OR hepatic tumor) AND (artificial intelligence OR machine learning OR neural networks OR deep learning OR automated diagnosis OR ultrasound OR US OR computer scan OR CT OR magnetic resonance imaging OR MRI OR computer-aided diagnosis OR automated computer tomography OR automated magnetic imaging). RESULTS: Our search identified a total of 32 articles analyzing complete automated imagistic diagnosis of FLLs, out of which 14 studies analyzing liver ultrasound images, 8 studies analyzing computer tomography images and 10 studies analyzing images obtained from magnetic resonance imaging. CONCLUSIONS: We found significant evidence demonstrating that implementing a complete automated system for FLLs diagnosis using AI-based applications is currently feasible. Various automated AI-based applications have been analyzed. However, there is no clear evidence about the superiority of any of the systems.

Impact of Microscopic Confirmation on Therapeutic Management of Pancreatic Cancer Patients: Lessons from an Italian Regional Tumor Registry.

Background: Incidence of pancreatic cancer (PC) is increasing worldwide and is set to become the second leading cause of cancer-related death in 2040 with a poor 5-year overall survival (OS). The aim of this study was to analyze the impact of microscopic diagnosis of PC (MiDPC) on diagnostic−therapeutic management and outcome. Methods: The Veneto region (north-eastern Italy) has been covered by a cancer registry (CR) since 1987. Clinical and oncological data about all cases of PC in the Veneto region from 1987 were extracted from the Veneto CR database. Results: In 2018, 1340 incident cases of PC in the Veneto population were registered (4.1% of all malignant tumors), with an increasing trend in females and stable incidence in males. Five-year OS in patients with PC was 8%. The percentage of MiDPC increased from 44% in 2010 to 60% in 2018 (p = 0.001). MiDPC was higher among patients aged < 75 years old (84.4%) compared to those aged ≥75 years old (38.9%), p = 0.001. Between 2010 and 2018, a significant increase in biopsy on the primary neoplasm (24.9% vs. 13%, p < 0.001) was reported. Patients with MiDPC had higher 5-year survival than patients with no MiDPC (12.9% vs. 1.2%, p < 0.001). Conclusions: The implementation of MiDPC was essential to improve diagnostic−therapeutic pathways and consequently the survival of PC patients.

Surveillance for hepatocellular carcinoma with a 3-months interval in "extremely high-risk" patients does not further improve survival.

BACKGROUND: An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). AIMS: We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. METHODS: Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. RESULTS: The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9-64.0]) was not significantly different from the observed (47.0 months [35.0-58.9]; p = 0.43) and adjusted (44.9 months [33.4-56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. CONCLUSIONS: A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.

Monofocal hepatocellular carcinoma: How much does size matter?

BACKGROUND & AIMS: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). METHODS: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2-5 cm; SEM-HCC), 163 patients with larger tumours (>5 cm; LEM-HCC) and 1048 intermediate stage patients (BCLC B). RESULTS: LEM-HCC patients had a worse overall survival (OS) than SEM-HCC (31.0 vs 49.0 months; P < .0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29-2.05; P < .0001). The small difference in OS between LEM-HCC and BCLC B patients (31.0 vs 27.0 months; P = .03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77-1.25; P = .89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM-HCC was significantly shorter than that of SEM-HCC (44.0 vs 78.0 months; P = .002), but liver resection provided the highest survival benefit in both groups compared to other treatments. CONCLUSIONS: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients.

Capecitabine in advanced hepatocellular carcinoma: A multicenter experience.

BACKGROUND: Recent data suggest a potential activity and a good tolerability of capecitabine in advanced hepatocellular carcinoma (HCC). AIMS: To evaluate capecitabine activity and safety in a wide cohort of advanced HCC patients. METHODS: Retrospective analysis of 143 capecitabine-treated patients (January 2010 to December 2017) in three centers of the Veneto Oncology Network. RESULTS: Capecitabine was administered in second and third line, but also in first line instead of sorafenib in Child-Pugh B patients (70%), compromised clinical conditions (14%) or contraindications to antiangiogenetics (16%). Median overall survival (OS) and time to progression (TTP) were 6.9 and 2.8 months, respectively. There were no differences in OS and TTP between the 32 patients treated with non-metronomic scheme (2000 mg/day for 14 days) and the 111 patients treated with metronomic scheme (1000 mg/day) after correction for prognostic factors at baseline with a propensity score analysis. Capecitabine was more active in patients intolerant to sorafenib than in those progressing during treatment (p = 0.024). At least one adverse event (mainly hematological) was experienced by 73% of patients but discontinuation was necessary only in 11 (8%). CONCLUSIONS: Capecitabine can be considered an active and safe option in advanced HCC, especially for patients unfit for other treatments.