challenges of advanced hepatocellular carcinoma Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami ...
World journal of gastroenterology,
09/2016, Volume:
22, Issue:
34
Journal Article
Open access
Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any ...underlying liver disease must be considered conjointly. Although surveillance by imaging,clinical and biochemical parameters is routinely performed,a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice,several phase Ⅲ clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Locoregional therapies have also been tested as first line treatment,but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally,robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.
AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established cirrhosis.METHODS:From October 2009 to July ...2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled.According to the Barcelona Clinic Liver Cancer(BCLC)classification,patients were in the advanced stage(BCLC-C)or in the intermediate stage(BCLC-B)but unfit or unresponsive to other therapeutic strategies.Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response Evaluation Criteria in Solid Tumors.Sorafenib was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(AEs).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.RESULTS:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of B7.AEs caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,P<0.001)and in the BCLC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years.After 16 wk of treatment,18 patients(41%)had stable disease or partial response.Patients with viral infection or BCLC-C were at higher risk of disease progression.ECOG,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.CONCLUSION:In patients with cirrhosis and HCC treated with sorafenib,AEs are a common cause of early treatment withdrawal.Vascular invasion and extrahepatic spread condition early response to treatment and survival.Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.
Background & Aims
Determining risk for recurrence or survival after curative resection or ablation in patients with hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) is important for ...stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct‐acting antivirals (DAAs). The aims of this meta‐analysis were to estimate the recurrence and survival probabilities of HCV‐related early HCC following complete response after potentially curative treatment and to identify predictors of recurrence and survival.
Methods
Studies reporting time‐dependent outcomes (HCC recurrence or death) after potentially curative treatment of HCV‐related early HCC were identified in MEDLINE through May 2016. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution‐free summary survival curve. Primary outcomes were actuarial probabilities of recurrence and survival.
Results
Eleven studies met the inclusion criteria. Pooled estimates of actuarial recurrence rates were 7.4% at 6 months and 47.0% at 2 years. Pooled estimates of actuarial survival rates were 79.8% at 3 years and 58.6% at 5 years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta‐regression analyses, lower serum albumin, randomized controlled trial study design and follow‐up were independently associated with higher recurrence risk, whereas tumour size and alpha‐foetoprotein levels were associated with higher mortality.
Conclusions
This meta‐analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV‐related HCC, providing a useful benchmark for indirect comparisons of the benefits of DAAs and for a correct design of randomized controlled trials in the adjuvant setting.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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