Lucinda Orsini

Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study

Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. The global HCC BRIDGE study was a multiregional, large‐scale, longitudinal cohort study undertaken to improve understanding of real‐life management of patients with HCC, from diagnosis to death.

Factors That Affect Risk for Hepatocellular Carcinoma and Effects of Surveillance

BACKGROUND & AIMS The incidence of hepatocellular carcinoma (HCC) in the United States is increasing. Surveillance may affect the stage at diagnosis and consequently the treatment options available for HCC. We evaluated risk factors for HCC, the proportion of cases detected via surveillance, tumor characteristics, treatment approaches, and overall patient survival in a referral center cohort. METHODS The study included all patients diagnosed with HCC at the Mayo Clinic, Rochester, Minnesota, from 2007 to 2009 (n = 460). Clinical information was retrospectively abstracted from the medical record. RESULTS Hepatitis C virus (HCV, 36%), alcohol use (29%), and nonalcoholic fatty liver disease (NAFLD, 13%) were the most common risk factors for HCC. HCV was present in 56% of patients younger than 60. NAFLD was present in 19% of patients older than 60. HCC was detected during surveillance in 31% of patients. Patients with worse liver function were more likely to be on surveillance. Transarterial chemoembolization, surgical resection, and liver transplantation were the most common treatment approaches for HCC. Patients diagnosed with HCC during surveillance had less advanced disease, were more likely to be eligible for potentially curative treatments, and had increased survival times (P < .001). CONCLUSIONS At a major US referral center, the predominant HCC etiologies were HCV, alcohol use, and NAFLD. HCCs were detected during surveillance in the minority of patients. HCCs detected during surveillance were of less advanced stage, and patients were more likely to receive treatment that prolonged their survival.

Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes

Abstract Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional

Q‐TWiST analysis of ixabepilone in combination with capecitabine on quality of life in patients with metastatic breast cancer

151,560 and

Design and rationale of the HCC BRIDGE study in China: a longitudinal, multicenter cohort trial in hepatocellular carcinoma

140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar (

Value-based assessment of pharmacodiagnostic testing from early stage development to real-world use.

152,229 and

Impact of Nivolumab versus Docetaxel on Health-Related Quality of Life and Symptoms in Patients with Advanced Squamous Non–Small Cell Lung Cancer: Results from the CheckMate 017 Study

141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.

Partitioned Survival Versus State Transition Modeling in Oncology: a Case Study with Nivolumab in Advanced Melanoma

Combination therapy with ixabepilone and capecitabine (cape) is approved for use in patients with locally advanced/metastatic breast cancer that is resistant to treatment with anthracyclines or taxanes. The current study evaluated the trade‐off between quality and quantity of life using quality‐adjusted time without symptoms or toxicity (Q‐TWiST) outcomes.

Quality of Survival: A New Concept Framework to Assess the Quality of Prolonged Life in Cancer

BackgroundMore than 50% of the worldwide cases of hepatocellular carcinoma occur in China, and this malignancy currently represents the countrys second leading cause of cancer death in cities and the leading cause in rural areas. Despite recent advances in the control and management of hepatocellular carcinoma within China, this disease remains a major health care issue. The global HCC BRIDGE study, designed to assess patterns of hepatocellular carcinoma therapy use and associated outcomes across real-world clinical practice, has recently been expanded as a national study in China, allowing a detailed analysis of hepatocellular carcinoma in this important country.Methods/DesignThe global HCC BRIDGE study is a multiregional longitudinal cohort trial including patients newly diagnosed with hepatocellular carcinoma between January 1, 2005, and June 30, 2011, who are receiving treatment for hepatocellular carcinoma via sites in the Asia-Pacific, European, and North American regions. The HCC BRIDGE China national study comprises the portion of the global HCC BRIDGE study conducted within mainland China. Patients will be followed from time of diagnosis of hepatocellular carcinoma (post-January 1, 2005) to time of death or December 31, 2011, whichever comes first. Data will be collected on demographic/clinical characteristics, relevant laboratory values, hepatocellular carcinoma/underlying liver disease treatment, tumor response, adverse events, hospitalizations, and overall survival. The primary study end point is overall survival; secondary end points are disease progression, treatment-limiting adverse events, and treatment failure.ResultsAt the time of writing, 15 sites have selected for participation across all 7 traditional regions of China (North, North-East, East, South, South-West, North-West, and Central). The anticipated study population from the China national study is approximately 9000 patients.DiscussionFindings from the HCC BRIDGE China national study, the first geographically representative study of hepatocellular carcinoma in China, will contribute to the understanding of patterns of therapy use and related clinical outcomes and will provide further information on continuing unmet needs for hepatocellular carcinoma throughout this important country.

Overall Survival (Os), Quality Of Life (Qol), And Neurocognitive Function (Nf) In Recurrent Glioblastoma Multiforme (Gbm): A Systematic Literature Review.

Disease etiology may be regarded as a consequence of both genotypic and biochemical phenomena, which impact individual patients in different ways. Disease prognosis, beneficial treatment response, and susceptibility to adverse drug effects are often intimately tied to individual biology. Clinical and genetic biomarkers applied individually or in concert are increasingly used to stratify patient populations in terms of prognosis, therapeutic benefit, or safety. As a result, clinical trialists are challenged to design studies that reflect these determinants of outcome, to optimize the patients eventual clinical course both in the trial and in actual practice. These designs are informed both by preclinical studies and by real-world research that can establish proof of concept for a novel biomarker and provide a basic understanding of the relationship between biomarker and clinical outcome. As clinical and real-world studies unfold, a deeper understanding of the nature of the biomarker and its potential uses in drug development is gained. Specifically, one can eventually define the biomarker as prognostic (i.e., predicts disease progression), predictive (predicts treatment response or adverse outcome(s)), or exhibiting both prognostic and predictive properties. One must further validate the performance of these emerging biomarkers, again in both the trial and real-world environments. The eventual adoption of the biomarker as a useful pharmacodiagnostic test is premised upon this early translational research. In this article, the development and validation of predictive and prognostic biomarkers is discussed by using selected examples that highlight factors contributing to the valuation of biomarkers and their application to personalized medicine in the real world.