[Therapeutic decisions and treatment with sorafenib in hepatocellular carcinoma: final analysis of GIDEON study in Italy]. / Scelte terapeutiche e trattamento con sorafenib nell'epatocarcinoma: analisi finale dello studio GIDEON in Italia.

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.

Incidence of arterial cardiovascular events in patients with idiopathic venous thromboembolism. A retrospective cohort study.

Recent data have shown a higher incidence of arterial events in patients with venous thromboembolism (VTE) of unknown origin than in those with the secondary form of disease. Whether patients with idiopathic VTE have a higher risk of subsequent arterial events than the general population is unknown. The aim was to evaluate the rates of subsequent arterial events in patients with idiopathic VTE and control subjects. In a retrospective cohort study we compared the rates of subsequent arterial events (i.e. acute myocardial infarction, ischemic stroke and peripheral arterial disease) in 151 consecutive patients with objectively confirmed spontaneous VTE and 151 control subjects randomly selected from the database of two family physicians. We collected information about cardiovascular risk-factors (hypertension, hypercholesterolemia, diabetes, obesity and smoke) at the time of VTE episode, or corresponding date for the controls, and considered the follow-up from this time. Patients and controls who had suffered from arterial events before the index date were excluded. During a mean follow-up of 43.1 (+/- 21.7) months there were 16 arterial events in the VTE patients and six in the control group (HR, 2.84;95% CI,1.11 to 7.27; p = 0.03). The difference remained significant after adjusting for age and other cardiovascular risk factors (HR 2.86;95% CI,1.07 to 7.62). Overall mortality was also higher in the VTE patients (12 vs.4 deaths). In conclusion, arterial events are more common in patients with previous idiopathic VTE than in the general population. These findings may have practical implications.

Importance of troponin T for the risk stratification of normotensive patients with pulmonary embolism. A prospective, cohort study with a three-month follow-up.

To determine the prognostic importance of troponin T in normotensive patients with pulmonary embolism, we investigated the rate of adverse events in patients with normal and elevated troponin values, during the hospital period and at three months of follow-up. We also calculated the proportion of patients with abnormal troponin values and adverse outcomes who could have been treated with more aggressive therapy according to published criteria.

Incidence of post-thrombotic syndrome in patients with previous pulmonary embolism. A retrospective cohort study.

There is little information available about the true incidence of post-thrombotic syndrome (PTS) after pulmonary embolism (PE). The aim of this study was to investigate the incidence of PTS in patients with previous pulmonary embolism without concomitant ultrasonographically-detectable deep vein thrombosis (DVT). A retrospective cohort study was conducted at a single tertiary care centre, Cosenza, Italy. Forty-seven consecutive patients with proved PE without DVT within the previous 2 to 6 years, 45 patients with previous DVT in the same years, and 45 patients with diseases unrelated to venous thromboembolism (VTE) underwent a blind assessment for PTS using a clinical score. Two of 47 (4.2%, 95%CI: 0.01-9.9) patients with PE, 2 of 45 (4.4%, 95%CI: 0.01-10.4) patients with diseases unrelated to VTE, and 23 of 45 (53.3%, 95%CI: 38.7-67.9) patients with DVT showed signs and symptoms of PTS. The difference between the first two groups was not statistically significant (p = 0.7). In conclusion, the incidence of PTS after pulmonary embolism without DVT is low, and no different from that of patients without previous VTE.

The value of four-detector row spiral computed tomography for the diagnosis of pulmonary embolism.

Although spiral computed tomography (CT) is being used increasingly as the first-line imaging procedure in the diagnostic workup of patients with clinically suspected pulmonary embolism (PE), the diagnostic value of negative findings, at least when using the four-detector row scanners, is still controversial. A total of 702 consecutive patients with clinical symptoms suggestive of PE underwent four-slice CT. Patients with negative findings received the determination of D-dimer. Those with positive D-dimer underwent further diagnostic workup to confirm or rule out the diagnosis of PE. Those with negative D-dimer were followed-up to 6 months to detect the development of symptomatic venous thromboembolism (VTE). The CT test was interpreted as negative in 536 patients (76.3%). These patients had the D-dimer determination, which was positive in 279 and negative in the remaining 257 patients. Of the former, PE subsequently was documented in 55 patients (19.7%). Of the latter, symptomatic VTE in the follow-up period developed in three patients (1.17%; 95% confidence interval, 0.24 to 3.38%). In conclusion, when using the four-detector row, the negative predictive value of CT findings in patients with clinically suspected PE and positive D-dimer is low. In contrast, it is safe to withhold anticoagulation from patients with negative findings and negative D-dimer.

Diagnostic utility of echocardiography in patients with suspected pulmonary embolism.

The aim of this study was to investigate the clinical utility of echocardiography in the diagnosis of pulmonary embolism (PE). For this, we enrolled 162 patients with suspected PE in a prospective study. We evaluated the sensitivity and specificity of right ventricular dilatation, the Doppler evidence of pulmonary hypertension, and their possible associations. We also calculated the number of lung-scan angiography procedures avoided and the number of patients unnecessarily treated when echocardiography was included in the diagnostic work-up. The sensitivity and specificity of echocardiography ranged between 29 and 52% and between 96% and 87%, respectively. Adding echocardiography to the diagnostic strategy for PE would avoid about 12 to 28% of lung-scan angiography procedures, but would cause inappropriate treatment of 4 to 14% of all treated patients. The clinical utility of echocardiography in the diagnosis of PE is limited. The reduction in the number of standard diagnostic procedures obtained through its use would be counterbalanced by an excess of patients inappropriately treated.