Although surgical resection is still the optimal treatmentoption for early-stage hepatocellular carcinoma（HCC） in patients with well compensated cirrhosis,thermal ablation techniques provide a valid ...nonsurgicaltreatment alternative, thanks to their minimalinvasiveness, excellent tolerability and safety profile,proven efficacy in local disease control, virtuallyunlimited repeatability and cost-effectiveness. Differentenergy sources are currently employed in clinics asphysical agents for percutaneous or intra-surgicalthermal ablation of HCC nodules. Among them, radiofrequency（RF） currents are the most used, whilemicrowave ablations （MWA） are becoming increasinglypopular. Starting from the 90s＇, RF ablation （RFA） rapidlybecame the standard of care in ablation, especially inthe treatment of small HCC nodules; however, RFAexhibits substantial performance limitations in thetreatment of large lesions and/or tumors located nearmajor heat sinks. MWA, first introduced in the FarEastern clinical practice in the 80s＇, showing promisingresults but also severe limitations in the controllabilityof the emitted field and in the high amount of poweremployed for the ablation of large tumors, resultingin a poor coagulative performance and a relativelyhigh complication rate, nowadays shows better resultsboth in terms of treatment controllability and of overallcoagulative performance, thanks to the improvementof technology. In this review we provide an extensiveand detailed overview of the key physical and technicalaspects of MWA and of the currently available systems,and we want to discuss the most relevant published dataon MWA treatments of HCC nodules in regard to clinicalresults and to the type and rate of complications, both inabsolute terms and in comparison with RFA.
Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer.
Patients were stratified and randomly assigned to receive sunitinib 37.5 mg ...once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS).
Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median OS was 7.9 versus 10.2 months (hazard ratio HR, 1.30; one-sided P = .9990; two-sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR, 1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1 v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one-sided P = .9829) and hepatitis B-infected patients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infected patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was associated with more frequent and severe adverse events (AEs) than sorafenib. Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%).
OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib. OS was comparable in Asian and hepatitis B-infected patients. OS was superior in hepatitis C-infected patients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.
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.
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
ases 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,
< 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.
Drug Eluting Microsphere-Transarterial Chemoembolization (DEM-TACE) is a new delivery system to administrate drugs in a controlled manner useful for application in the chemoembolization of colorectal ...cancer metastases to the liver. DEM-TACE is focused to obtain higher concentrations of the drug to the tumor with lower systemic concentrations than traditional cancer chemotherapy. Therefore a specific, precise and sensitive LC–ESI-MS/MS assay procedure was properly designed to detect and quantify epirubicin at the concentrations expected from a transarterial chemoembolization with microspheres. Serum samples were kept acidic (pH approximately of 3.5) and sample preparation consisted of a solid phase extraction (SPE) procedure with HLB OASIS
® cartridges using a methylene chloride/2-propanol/methanol mixture solution to recover epirubicin. The analyses consisted of reversed-phase high-performance liquid chromatography (rp-HPLC) coupled with tandem mass spectrometry (MS/MS). Accuracy, precision and matrix effect of this procedure were carried out by analyzing four quality control samples (QCs) on five separate days. The validation parameters were assessed by recovery studies of spiked serum samples. Recoveries were found to vary between 92 and 98% at the QC levels (5, 40, 80 and 150
μg/L) with relative standard deviation (RSD) always less than 3.7%. The limit of detection (LOD) was set at 1
μg/L. The developed procedure has been also applied to investigate the different capability of two types of commercially available microspheres to release epirubicin into the human circulatory system.
Intrahepatic cholangiocarcinoma (ICC) is a rare life-threatening disease, whose only treatment with potential for cure is surgical resection. However, only 27% of patients at most are suitable for ...surgery when first diagnosed. For patients with unresectable disease, therapeutic options are chemotherapy or chemoradiation. We evaluated the feasibilty and safety of oxaliplatin-eluting microspheres transarterial chemoembolization (OEM-TACE) associated with chemotherapy (ChT) in patients affected by unresectable ICC. Between December 2005 and May 2008 we treated nine patients (six female and three male) with unresectable ICC. All patients had undergone OEM-TACE associated with chemotherapy with oxaliplatin and gemcitabine. A retrospective comparison was carried out with a historical group of 11 patients treated with ChT only, estimating the prevalence of adverse effects and the median survival of the two groups. A total of 30 TACEs were performed during the observational time (ranging from one to seven procedures per patient). OEM-TACEs were followed by few adverse effects (AEs), without G4 AEs, according to CTACAE 3.0. According to RECIST criteria, 44% (4/9) of patients achieved partial responses and 56% (5/9) stabililization of disease. Overall survival analysis in the two groups showed a significantly increased survival in patients treated with ChT and OEM-TACE, with respect to those treated with ChT (30 vs. 12.7 months;
p
= 0.004). In conclusion, in our experience OEM-TACE associated with ChT in the treatment of advanced unresectable ICC is a safe and feasible treatment causing no major adverse events. Although RECIST criteria can underestimate the rate of responses in patients treated with locoregional therapies, we achieved very encouraging results. A randomized multicentric trial is warranted to assess the actual superiority of OEM-TACE associated with ChT compared to conventional chemotherapy.
Background: 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. Patients and Methods: 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. Results: 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. Conclusion: TACE with oxaliplatin-loaded microspheres
is a safe and feasible treatment without major adverse events and with a favorable pharmacokinetic profile.
Hepatocellular carcinoma is one of the most common malignancies in the world, with the liver being the second most frequently
involved organ in metastatic disease. Although the gold standard ...treatment for malignant liver disease is surgical resection,
only few patients can undergo such an intervention. This explains the current great interest in various loco-regional therapies,
of which radiofrequency thermal ablation (RFA) is the most common. To date, only a few studies have evaluated the complications
associated with this treatment. The aim of this study was to determine the rate of complications, divided into major and minor,
in patients treated with RFA. A total of 373 hepatic lesions in 250 patients were treated with 292 sessions of percutaneous
ultrasound-guided RFA. According to our data, ten patients (4%) had major complications, twelve patients (4.8%) had minor
complications, no deaths occurred. Around 30% of patients had a body temperature increase of up to 38ÃC. All complications,
except one, were treated with non-surgical therapies. One patient with massive hemoperitoneum required surgery. In conclusion,
percutaneous RFA is a loco-regional therapy associated with a low incidence of side-effects and a negligible risk of death.
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