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Summary. Introduction. Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients. Methods. Patients with unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Patients demographics disease characteristics and treatment history were recorded at baseline visit. Sorafenib dose, concomitant medications, performance status, liver function, adverse events and efficacy (survival and response rate) were collected throughout the study. Results. In the Italian cohort of the GIDEON study 278 patients were included in 36 centers. The global rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of grade 1 and 2, and only 8% were classified as serious. The most common were diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%), hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall survival was 14.4 months and time to progression 6.2 months. Objective responses were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease control rate. Discussion. The safety profile of sorafenib in terms of rate and type of adverse events is similar to that emerged in the global international GIDEON study as well as in the pivotal registration studies.

La chemioembolizzazione intraarteriosa epatica (TACE), è una tecnica ampiamente utilizzata nel trattamento di tumori epatici primitivi e secondari non resecabili. Anche se considerata una procedura relativamente sicura, la TACE è stata associata a varie complicanze. L'obiettivo di questo studio è stato quello di determinare la preva-lenza di complicanze e la correlazione con alcuni fattori di rischio. Tra il 2004 e il 2009 sono stati trattati 155 pazienti (106 uomini e 49 donne) per un totale di 297 procedure. 193 pazienti erano affetti da tumore primitivo epatico, 104 da metastasi epatiche da differenti primitività. I pazienti avevano un'età compresa tra 49 e 86 anni. Le procedure di TACE sono state eseguite sia con microsfere caricate con farmaci chemioterapici (136 sessioni con DCBead®, 124 con Hepasphere®), sia con un mezzo oleoso ioda-to (33 con Lipiodol®). Gli agenti chemioterapici utilizzati sono stati l’Epirubicina in 217 sessioni, l’Irinotecan e l’Oxaliplatino sono stati utilizzati rispettivamente in 30 e in 50 procedure. I nostri dati hanno mostrato che le complicanze gravi si sono verificate nel 16.5% delle procedure. Nello specifi-co abbiamo riscontrato una prevalenza di pancreatiti acute pari al 2.7%, di ascessi epatici pari al 3%, di colecisti-ti del 3.7% e una prevalenza di piastrinopenie del 3.4%. Circa l'80% dei pazienti ha manifestato la comparsa della sindrome post-chemioembolizzazione che non deve essere considerata una complicanza maggiore, ma un effetto collaterale che, nella maggioranza dei casi, tende a risolversi spontaneamente non causando un allunga-mento dell’ospedalizzazione. Complicanze maggiori si sono verificate più frequentemente nei pazienti diabetici rispetto ai non diabetici (26.7% vs 13.1%, p=0.006). Al contrario non abbiamo trovato alcuna differenza statisti-camente significativa riguardo gli agenti di embolizzazione utilizzati (Lipiodol® vs microsfere), gli agenti che-mioterapici (Epirubicina vs Oxaliplatino vs Irinotecan), l'età dei pazienti e l'istologia (tumori primitivi vs tumori metastatici). Tutti i pazienti hanno ricevuto antibioticoterapia prima e dopo la TACE e differenze statisticamente significative sono state riscontrate in relazione alla varie classi di antibiotici utilizzati. Non è stato evidenziato un’aumento della prevalenza di complicanze nei pazienti trattati con approccio bimodale (TACE + RFTA) ri-spetto a quelli trattati con sola chemioembolizzazione intrarteriosa epatica (TACE)., Bollettino della Società Medico Chirurgica di Pavia, Vol 123, N° 1 (2010)

The currently recommended treatment for patients infected with hepatitis C virus (HCV) is pegilated interferon α (IFN α) plus ribavirin. Despite the numerous benefits of this therapy, there is an increasing concern regarding his tolerance. Among the most common side effects, interferon may trigger the onset or exacerbation of autoimmune diseases. When chronic hepatitis C coexists with an autoimmune disorder, it is not clear whether using interferon is better than avoiding it. We evaluated the disease state of a 55-year old female affected by sistemic sclerosis (SSc), during and after therapy with IFNα pegilated plus ribavirin for chronic HCV infection. We were worried about the potential worsening of the autoimmune disease during the therapy, but we were confident that we would give our patient a short course of peginterferon and ribavirin. A mild, asymptomatic worsening of lung SSc was observed during IFN administration, without life threatening symptoms. After 24 months follow up we observed the maintenance of the virological response and a good control of the rheumatological disease. Thus, in liver disease at high risk of progression and concomitant SSc, the antiviral therapy with IFNα is a feasible approach.

While conventional transhepatic arterial chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC), its use in other hepatic tumors is not supported by randomized studies. Preliminary results have shown that new drug-eluting microspheres (DEM) seem to optimize TACE procedures. The aim of this study was to evaluate the capability of HepaSphere to load oxaliplatin and their pharmacokinetic outcome. The feasibility and safety of treatment with oxaliplatin-eluting microspheres (OEM-TACE) was also evaluated in patients with unresectable liver metastasis of colorectal cancer and unresectable intrahepatic cholangiocarcinoma.An inductively coupled plasma mass spectrometer (ICP-MS) was used to quantify the oxaliplatin bound to microspheres and the oxaliplatin in liver biopsies. Fifteen patients (8 with colorectal carcinoma liver metastases, 7 with intrahepatic cholangiocarcinoma) were treated with 27 sessions of OEM-TACE.The data suggested that the microspheres can bind oxaliplatin entirely. The pharmacokinetic parameters were significantly different between the OEM-TACE patients and a control group of patients treated with oxaliplatin chemotherapy. The mean oxaliplatin concentration within the tumor was twenty-times higher than the extratumoral liver concentration in the OEM-TACE patients. According to response evaluating criteria in solid tumors (RECIST), stable disease was observed in 8 out of the 15 patients (53.3%), a partial response in 2 (13.3%) and intrahepatic or extrahepatic tumor progression in 5 out of the 15 patients (33.3%). No major adverse event (AE G3/4) occurred.TACE with oxaliplatin-loaded microspheres is a safe and feasible treatment without major adverse events and with a favorable pharmacokinetic profile.

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years, 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12–218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32–2.15), however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11–0.51, p &lt, 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

Background & Aims The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC). Methods We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of β-catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by immunostaining. Stains were scored semiquantitatively and compared with a reference group of 56 untreated HCCs. Results Overall, the expression of antigens was comparable between treated and untreated patients. Shorter progression-free survival (PFS) and overall survival (OS) were associated with increased pERK staining (≥ 2+ scores) (PFS: 75th percentile 4.4 vs 8.4 months; P = 0.01; OS: 75th percentile 7.0 vs 15.0 months; P = 0.005) and VEGFR-2 staining (≥ 2+ scores) (PFS: 75th percentile 3.8 vs 7.0 months; P = 0.039; OS: 75th percentile 6.3 vs 15.0 months; P = 0.004). At multivariate analysis, both pERK and VEGFR-2 staining maintained an independent effect on OS (HR 2.09; 95% CI, 1.13–3.86, P = 0.019 and HR 2.28; 95% CI, 1.13–4.61, P = 0.021 respectively). No effect was observed for the other tested biomarkers. Conclusions Elevated tissue expression of pERK and VEGFR-2 was predictive of poor outcome in advanced HCC treated with sorafenib.