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Background Gastrointestinal stromal tumours ( GISTs), despite complete surgical cytoreduction, are associated with recurrence rates of up to 50% at 2 years. At recurrence, tyrosine kinase inhibitor ( TKI) therapy is recommended, conferring a survival of up to 55 months. Several studies have shown that patients with TKI-responsive recurrent GIST benefit from surgery. However, no studies have compared upfront surgery versus TKI alone. Methods Data were retrospectively collected from patients with recurrent GIST treated at Singapore General Hospital and National Cancer Centre Singapore over a 12-year period. Our primary end points were disease-free and overall survival ( OS). Results A total of 186 patients underwent curative surgery for GIST between January 2000 and June 2012. Fifty-six (30%) patients experienced recurrence, of which 30 (54%) had resectable recurrent disease. Twenty-four patients underwent upfront surgery for their recurrence while the remaining six patients opted for non-surgical management. The median OS for all patients with recurrent GIST was 5.3 years (95% confidence interval ( CI) 3.2-8.4). It was not reached for patients who underwent curative surgery for their recurrence, and was 3.9 years (95% CI 2.4-7.0) for patients who had palliative TKI and conservative management. There were significant differences in OS and disease-specific survival between patients who underwent curative surgery for recurrence compared with those who had not. Conclusion Our study shows that upfront surgery is a reasonable treatment strategy for selected patients with recurrent GIST. [ABSTRACT FROM AUTHOR]

Background: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients.Methods: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy.Discussion: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients.Trial Registration: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Many kinases have been found to be intimately involved in oncogenesis and the deregulation of kinase function has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. Previously, we have performed gene expression profile analysis on HCC samples and have identified a host of kinases that are remarkably overexpressed in HCC. Among these, the Maternal Embryonic Leucine Zipper Kinase (MELK) is highly overexpressed in HCC and its overexpression strongly correlates with early recurrence and poor patients' survival. Silencing MELK inhibited cell growth, invasion, stemness and tumorigenicity of HCC cells by inducing apoptosis and mitosis. We further showed that the overexpression of MELK in HCC samples strongly correlated with the cell cycle- and mitosis-related genes which are directly regulated as part of the forkhead transcription factor FoxM1-related cell division program. Together, our data establish MELK as an oncogenic kinase involved in the pathogenesis and recurrence of HCC and could provide a promising molecular target to develop therapeutic strategies for patients with advanced HCC. [ABSTRACT FROM AUTHOR]