Cost-Effectiveness of Cabozantinib in the Second-Line Treatment of Advanced Hepatocellular Carcinoma.

BACKGROUND: Treatment options are limited for patients with advanced hepatocellular carcinoma (HCC) that progresses after treatment with sorafenib. Cabozantinib, an oral small molecule inhibitor of multiple tyrosine kinase receptors, recently showed improved overall survival (OS) compared with placebo in sorafenib-pretreated patients with advanced HCC in the CELESTIAL trial. This study assessed the cost-effectiveness of cabozantinib for second-line treatment of patients with advanced HCC from a US healthcare system perspective. PATIENTS AND METHODS: Cost and utility data were extracted from the CELESTIAL trial and used to determine the cost-effectiveness of cabozantinib compared with placebo plus best supportive care. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained by using cabozantinib compared with placebo plus best supportive care in sorafenib-pretreated HCC. RESULTS: In the base-case analysis using data from the CELESTIAL trial, the incremental QALY and ICER were 0.067 and $1,040,675 for cabozantinib compared with placebo and best supportive care. OS reported in the CELESTIAL trial (hazard ratio, 0.76; 95% CI, 0.63-0.92) had the strongest association with the ICER. In one-way sensitivity analyses, there were no scenarios in which cabozantinib was cost-effective. In a cost-threshold analysis, cabozantinib would have to be priced at least $50 per pill to be cost-effective considering a willingness to pay of $100,000 per QALY. Although the CELESTIAL trial demonstrated that cabozantinib improves OS compared with placebo in patients with HCC that progresses after treatment with sorafenib, our analysis shows that cabozantinib is not a cost-effective therapy in this scenario. CONCLUSIONS: At current costs, cabozantinib is not cost-effective for second-line therapy of HCC in the United States.

Insurance status impacts treatment for hepatocellular carcinoma.

INTRODUCTION AND AIM: Previous studies have identified treatment disparities in the treatment of hepatocellular carcinoma (HCC) based on insurance status and provider. Recent studies have shown more Americans have healthcare insurance; therefore we aim to determine if treatment disparities based on insurance providers continue to exist. MATERIALS AND METHODS: A retrospective database analysis using the NIS was performed between 2010 and 2013 including adult patients with a primary diagnosis of HCC determined by ICD-9 codes. Multivariable logistic regressions were performed to analyze differences in treatment, mortality, features of decompensation, and metastatic disease based on the patient's primary payer. RESULTS: This study included 62,368 patients. Medicare represented 44% of the total patients followed by private insurance (27%), Medicaid (19%), and other payers (10%). Patients with Medicare, Medicaid, and other payer were less likely to undergo liver transplantation [(OR 0.63, 95% CI 0.47-0.84), (OR 0.23, 95% CI 0.15-0.33), (OR 0.26, 95% CI 0.15-0.45)] and surgical resection [(OR 0.74, 95% CI 0.63-0.87), (OR 0.40, 95% CI 0.32-0.51), (OR 0.42, 95% CI 0.32-0.54)] than patients with private insurance. Medicaid patients were less likely to undergo ablation then patients with private insurance (OR 0.52, 95% CI 0.40-0.68). Patients with other forms of insurance were less likely to undergo transarterial chemoembolization (TACE) compared to private insurance (OR 0.64, 95% CI 0.43-0.96). CONCLUSION: Insurance status impacts treatment for HCC. Patients with private insurance are more likely to undergo curative therapies of liver transplantation and surgical resection compared to patients with government funded insurance.

Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.

Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the United States, where they are a growing cause of cirrhosis and hepatocellular carcinoma (HCC) and increasingly an indicator for liver transplantation. A Markov model was used to forecast NAFLD disease progression. Incidence of NAFLD was based on historical and projected changes in adult prevalence of obesity and type 2 diabetes mellitus (DM). Assumptions were derived from published literature where available and validated using national surveillance data for incidence of NAFLD-related HCC. Projected changes in NAFLD-related cirrhosis, advanced liver disease, and liver-related mortality were quantified through 2030. Prevalent NAFLD cases are forecasted to increase 21%, from 83.1 million (2015) to 100.9 million (2030), while prevalent NASH cases will increase 63% from 16.52 million to 27.00 million cases. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 to 55 years during 2015-2030. In 2015, approximately 20% of NAFLD cases were classified as NASH, increasing to 27% by 2030, a reflection of both disease progression and an aging population. Incidence of decompensated cirrhosis will increase 168% to 105,430 cases by 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths will increase 178% to an estimated 78,300 deaths in 2030. During 2015-2030, there are projected to be nearly 800,000 excess liver deaths. CONCLUSION: With continued high rates of adult obesity and DM along with an aging population, NAFLD-related liver disease and mortality will increase in the United States. Strategies to slow the growth of NAFLD cases and therapeutic options are necessary to mitigate disease burden. (Hepatology 2018;67:123-133).

Independent Predictors of Mortality and Resource Utilization in Viral Hepatitis Related Hepatocellular Carcinoma.

INTRODUCTION: Hepatitis B (HBV) and C viruses (HCV) are important causes of hepatocellular carcinoma (HCC). Our aim was to assess mortality and resource utilization of patients with HCC-related to HBV and HCV. MATERIAL AND METHODS: National Cancer Institute's Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (2001-2009) was used. Medicare claims included patient demographic information, diagnoses, treatment, procedures, ICD-9 codes, service dates, payments, coverage status, survival data, carrier claims, and Medicare Provider Analysis and Review (MEDPAR) data. HCC related to HBV/HCV and non-cancer controls with HBV/HCV were included. Pair-wise comparisons were made by t-tests and chi-square tests. Logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals (CIs) were used. RESULTS: We included 2,711 cases of HCC (518 HBV, 2,193 HCV-related) and 5,130 non-cancer controls (1,321 HBV, 3,809 HCV). Between 2001-2009, HCC cases related to HBV and HCV increased. Compared to controls, HBV and HCV patients with HCC were older, more likely to be male (73.2% vs 48.9% and 57.1% vs. 50.5%), die within one-year (49.3% vs. 20.3% and 52.2% vs. 19.2%), have decompensated cirrhosis (44.8% vs. 6.9% and 53.9% vs. 10.4%) and have higher inpatient ($60.471 vs. $47.223 and $56.033 vs. $41.005) and outpatient charges ($3,840 vs. $3,328 and $3,251 vs. $2,096) (all P < 0.05). In two separate multivariate analyses, independent predictors of one-year mortality were older age, being male and the presence of decompensated cirrhosis. CONCLUSIONS: The rate of viral hepatitis-related HCC is increasing. Mortality and resource utilization related to HBV and HCV-related HCC is substantial.

Cost-effectiveness of cetuximab and panitumumab for chemotherapy-refractory metastatic colorectal cancer.

BACKGROUND: Cetuximab and panitumumab are monoclonal antibodies targeting the epidermal growth factor receptor. Both drugs are active against RAS wild type metastatic colorectal cancer after chemotherapy failure, with similar efficacy and toxicity profiles. However, their cost and limited survival benefits may compromise incorporation in the Brazilian public healthcare system, the Unified Heath System (Sistema Único de Saúde) (SUS). METHODS: A cost-effectiveness analysis was conducted using a Markov model from the Brazilian Public health perspective and a lifetime horizon in patients with RAS -wt mCRC. Transition probabilities and mortality rates were extracted from randomized studies. Treatment costs were obtained from price tables regulated by the Brazilian Health Ministry. The World Health Organization recommendation of three times GDP per capita was used to define the cost-effectiveness threshold. RESULTS: The use of cetuximab or panitumumab for chemotherapy-refractory mCRC patients resulted in 0.22 additional life-years relative to BSC, with incremental cost-effectiveness ratios (ICERs) of $58,240 and $52,772 per LY, respectively. That exceeds the pre-specified threshold for cost-effectiveness. Acquisition of biological agents was the major driver of increased costs. CONCLUSIONS: Our economic evaluation demonstrates that both cetuximab and panitumumab are not a cost-effective approach in RAS-wt mCRC patients. Discussion about drug price should be prioritized to enable incorporation of these monoclonal antibodies in the SUS.

International incidence and mortality trends of liver cancer: a global profile.

We examined the global incidence and mortality rates of liver cancer, and evaluated the association between incidence/mortality and socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP]) using linear regression analysis. The average annual percent change (AAPC) of the trends was evaluated from join-point regression analysis. The global incidence of liver cancer varied widely by nine-fold, and was negatively correlated with HDI (men: r = -0.232, p = 0.003; women: r = -0.369, p < 0.001) and GDP per capita (men: r = -0.164, p = 0.036; women: r = -0.212, p = 0.007). Its mortality showed a similarly negative correlation with both indices. The greatest incidence rise in men was observed in Poland (AAPC = 17.5, 95% C.I. = 5.6, 30.9) and Brazil (AAPC = 13.2, 95% C.I. = 5.9, 21.0), whereas Germany (AAPC = 6.6, 95% C.I = 2.0, 11.5) and Norway (AAPC = 6.5, 95% C.I. = 3.2, 10.0) had the greatest increase in women. The mortality rates paralleled the incidence rates in most countries. For mortality, Malta (AAPC = 11.5, 95% C.I. = 3.9, 19.8), Australia (AAPC = 6.8, 95% C.I. = 2.2, 11.5) and Norway (APCC = 5.6, 95% C.I. = 2.8, 8.5) reported the biggest increase among men; whilst Australia (AAPC = 13.4, 95% C.I. = 7.8, 19.4) and Singapore (AAPC = 7.7, 95% C.I. = 4.1, 11.5) showed the most prominent rise among women. These epidemiological data identified countries with potentially increasing trends of liver cancer for preventive actions.

Economic growth leads to increase of obesity and associated hepatocellular carcinoma in developing countries.

 Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer related death worldwide. In recent years, the prevalence of HCC has increased in both developing and developed countries. Most HCC cases develop in the presence of advanced chronic liver disease related to viral hepatitis. In particular hepatitis B virus and hepatitis C virus infections are considered as major HCC risk factors worldwide. However, current studies provide strong evidence for increasing numbers of HCC in nonalcoholic fatty liver disease (NAFLD). NAFLD represents the hepatic manifestation of metabolic syndrome which is based on obesity and insulin resistance. Epidemiologic data clearly demonstrates that NAFLD and obesity-related disorders are significant risk factors for tumor development in general and HCC in particular. As a consequence of life style changes towards higher calorie intake and less exercise, obesity and metabolic syndrome are spreading all over the world. Due to this increase in obesity and metabolic syndrome NAFLD-related HCC will become a major health care problem in the future. In conclusion, better understanding of the impact of NAFLD and obesity in the development of HCC will improve our treatment strategies of HCC and allow preventive measures.

Cost-effectiveness of whole-body bone scans in the pre-liver transplant assessment of patients with hepatocellular carcinoma in Southern Brazil.

BACKGROUND: Bone metastases (BM) are rare in patients with early-stage hepatocellular carcinoma (HCC). In many centers, liver transplantation (LTx) policies require patients with HCC to undergo bone scans (BSs). METHODS: We retrospectively assessed the benefit of BS for patients with a diagnosis of HCC wait-listed for LTx. RESULTS: BS was performed in 259 of 328 patients (78.9%) and was suggestive of BM in only one (0.4%). At follow-up, 276 patients had received LTx, of whom 207 had undergone BS. Histopathological examination of explants failed to confirm the presence of HCC in 20 patients from the BS group. The survival and recurrence rates of the 187 patients with confirmed HCC in the explant who underwent BS as part of pre-LTx assessment and 69 patients who did not undergo BS were compared. The one- and five-yr post-transplant survival rates were 81% and 69%, respectively, in the BS group vs. 78% and 62%, respectively, in patients who did not undergo BS (p = 0.25). The one- and five-yr post-LTx recurrence rates were 4.8% and 10.7%, respectively, in the BS group vs. 2.9% and 10.1%, respectively, in patients who did not undergo BS (p = 0.46). CONCLUSIONS: BS generated expenditures of US$39 296 and was not cost-effective.

Hepatocarcinoma en niños: 15 años de experiencia del grupo oncológico pediátrico EsSalud Rebagliati–Almenara, Lima Perú / Hepatocellular Carcinoma in Children: 15 years’ experience EsSalud Pediatric Oncology Group Almenara - Rebagliati, Lima Peru

Objetivo: describir la epidemiologia, tratamiento, evolución y análisis de costos del Hepatocarcinoma infantil y su implicancia en la salud del niño. Material y Métodos: Estudio descriptivo, retrospectivo, longitudinal, tipo serie de casos: Experiencia de 15 años en el tratamiento del Hepatocarcionoma infantil en pacientes de EsSALUD: hospitales Rebagliati-Almenara, del 1 de Enero de 1999 al 15 de Mayo del 2013. Se recolectaron datos demográficos, de laboratorio, im genes, patología, tratamiento, evolución y sobrevida. Se analizó también los costos. Resultados: De una data de 58 casos con tumor hepético maligno infantil, 20 casos (34.5%) fueron reportados como hepatocarcinoma. Siendo predominante en el sexo masculino (3/1) y de origen costeño. En todos los casos hubo hepatomegalia, vómitos y anemia. S¢lo 7 pacientes hab¡an recibido la vacuna de Hepatitis B. El gasto total para EsSalud fue de $132,265. Conclusiones: Este estudio aporta principalmente al manejo multidisciplinario de esta neoplasia, donde la quimioterapia si produce respuesta tumoral en la mayor¡a de casos donde el estado avanzado del tumor limita ser operados al debut y la terapia antiangiogónica prolonga la sobrevida evitando las recaídas. Un tercio de la población estudiada pudo haber evitado el cáncer al hígado si el paciente hubiese sido inmunizado con la vacuna anti Hepatitis B al nacer y completado a los seis meses sus tres dosis.

Objectives: to describe the epidemiology, treatment, evolution and cost analysis of child Hepatocarcinoma and its implication on their health. Material and Methods: descriptive, retrospective, longitudinal, case series study: 15-year experience in treating children with Hepatocellular Carcinoma in Children in EsSALUD in: hospitals Almenara and Rebagliati, from January 1, 1999 to May 15, 2013. Demographic, laboratory, imaging, pathology, treatment, evolution and survival data were collected and costs were analyzed Results: from a data of 58 cases with infantile malignant liver tumor, 20 cases (34.5 %) were reported as Hepatocellular Carcinoma in Children. Being predominant in males (3/1) and of coastal origin. In all cases there was hepatomegaly, vomiting and anemia. Only 7 patients had received the Hepatitis B vaccine. The total expenditure for EsSalud was $ 132.265. Conclusion: This study provides mainly the multidisciplinary management of this neoplasm, where chemotherapy response occurs in most cases where the advanced stage of the tumor limits surgical possibilities at debut and antiangiogenic therapy prolongs survival avoiding relapse. One third of the study population could have avoided liver cancer if the patient had been immunized with the Hepatitis B vaccine at birth and completed three doses at six months.

In whom, how and how often is surveillance for hepatocellular carcinoma cost-effective?

BACKGROUND: Despite well known worldwide differences in hepatocellular carcinoma incidence, which reflect different risk profiles, current recommendation of surveillance with ultrasound and alpha-fetoprotein twice-a-year has been restricted to cirrhotic patients. To evaluate the generalizability of this recommendation, we reviewed the clinical charts of hepatocellular carcinoma cases in a Mexican scenario. To evaluate efficiency, we performed a literature based cost-effectiveness analysis. METHODS: Charts pertaining to 174 consecutive patients with histologically proven hepatocellular carcinoma, seen at a tertiary health care centre were analysed. A decision tree, based on the surveillance and recall algorithm of the European Association for the Study of the Liver was constructed. Ultrasound and/or alpha-fetoprotein, performed every six or twelve months were the diagnostic alternatives, and accurate diagnoses, direct medical costs and cost-effectiveness ratios were the outcomes of interest. RESULTS: Male:female ratio was 1.2:1, underlying liver disease was secondary to alcohol in 44% and to hepatitis C virus in 26%, documented cirrhosis was present in 42%. Cost-effectiveness ratios for twice-a-year ultrasound and alpha-fetoprotein ranged from $303.09 to $346.22 U.S. dollars per accurate diagnosis, and for annual ultrasound from $115.86 to $116.42 U.S. dollars. CONCLUSIONS: Male gender, hepatitis C and cirrhosis were not predominant characteristics in our series. If a hepatocellular carcinoma surveillance program were to be instituted in our setting, or where patient characteristics are similar to ours, it probably should not be restricted to cirrhotic patients. Recommended performance of ultrasound and alpha-fetoprotein every six months is the least cost-effective surveillance strategy. Instead, annual ultrasound optimises diagnoses and costs.