Perspectives on immunotherapy utilization for hepatobiliary cancers in the United States.
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ABSTRACT:
SUBMITTER: Uson Junior PLS
PROVIDER: S-EPMC7423557 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Perspectives on immunotherapy utilization for hepatobiliary cancers in the United States.
Usón Junior Pedro Luiz Serrano PLS Ahn Daniel D Sonbol Mohamad Bassam MB Bekaii-Saab Tanios T Borad Mitesh J MJ
Hepatobiliary surgery and nutrition 20200801 4
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Project description:Cancer of the hepatobiliary system can be divided into primary liver cancer and biliary tract cancer (BTC), which includes hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder cancer (GBC). These aggressive cancers often present at an advanced stage or among patients with poorly preserved liver function. The primary treatment for HCC and BTC when diagnosed early is surgical resection, but given the high rate of recurrence and often advanced stage at diagnosis, many patients will require systemic therapy. Unfortunately, even with systemic therapy, long-term survival is poor. The immune system plays an important role in preventing cancer progression. The unique immune environment of the liver and subsequent alterations to the immune microenvironment by tumor cells to create a favorable microenvironment plays a key role in the progression of HCC and BTC. Due to the paucity of effective systemic therapies and distinctive immune environment of the liver, research and clinical trials are investigating the use of immunotherapy in HCC and BTC. This review will focus on current immunotherapies and emerging data for the treatment of HCC and BTC.
| S-EPMC9698563 | biostudies-literature
Project description:Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials. In advanced CCA and GBC, PD-1 ICIs have resulted in antitumor responses, but only in a minority of select patients. Other ICIs are being investigated for patients with CCA and GBC. Adoptive transfer may hold promise, with reports of complete durable regression in metastatic CCA, yet this therapeutic approach may not be generalizable. Alternative approaches have been developed and promising results have been observed, but clinical trials are needed to validate their utility. While the treatment of hepatobiliary cancers involves unique challenges that these cancers present, the progress seen with ICIs and adoptive transfer has solidified immunotherapy as an important approach in these challenging patients with few other effective treatment options.
| S-EPMC8393650 | biostudies-literature
Project description:BackgroundIdentifying the projected incidence of hepatobiliary cancers and recognizing patient cohorts at increased risk can help develop targeted interventions and resource allocation. The expected incidence of subtypes of hepatobiliary cancers in different age groups, races, and genders remains unknown.MethodsHistorical epidemiological data from the Surveillance, Epidemiology, and End Results (SEER) database was used to project future incidence of hepatobiliary malignancies in the United States and identify trends by age, race, and gender. Patients ≥18 years of age diagnosed with a hepatobiliary malignancy between 2001 and 2017 were included. US Census Bureau 2017 National Population projects provided the projected population from 2017 to 2029. Age-Period-Cohort forecasting model was used to estimate future births cohort-specific incidence. All analyses were completed using R Statistical Software.ResultsWe included 110381 historical patients diagnosed with a hepatobiliary malignancy between 2001 and 2017 with the following subtypes: hepatocellular cancer (HCC) (68%), intrahepatic cholangiocarcinoma (iCCA) (11.5%), gallbladder cancer (GC) (8%), extrahepatic cholangiocarcinoma (eCCA) (7.6%), and ampullary cancer (AC) (4%). Our models predict the incidence of HCC to double (2001 to 2029) from 4.5 to 9.03 per 100,000, with the most significant increase anticipated in patients 70-79 years of age. In contrast, incidence is expected to continue to decline among the Asian population. Incidence of iCCA is projected to increase, especially in the white population, with rates in 2029 double those in 2001 (2.13 vs. 0.88 per 100,000, respectively; p < 0.001). The incidence of GC among the black population is expected to increase. The incidence of eCCA is expected to significantly increase, especially among the Hispanic population, while that of AC will remain stable.DiscussionThe overall incidence of hepatobiliary malignancies is expected to increase in the coming years, with certain groups at increased risk. These findings may help with resource allocation when considering screening, treatment, and research in the coming years.
| S-EPMC10886529 | biostudies-literature
Project description: Not available
| S-EPMC5321609 | biostudies-literature
Project description:Primary liver cancers are a heterogenous collection of diseases with variable natural histories and treatments. This review article will focus on hepatocellular carcinoma (HCC), intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer, and the use of immune checkpoint inhibitors (ICIs) in their treatment. This will include the currently studied, approved uses as well as the potential future roles of ICIs in the treatment of cancers of the hepatobiliary system through recent updates on ongoing studies and discussion of phase III studies underway. Currently, only two ICIs are approved for use in hepatobiliary cancers: nivolumab and pembrolizumab. First, pembrolizumab was approved for either microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) unresectable, or metastatic solid tumors, including HCC and biliary tract cancer (BTC) in May 2017. After CheckMate-040, nivolumab gained approval in late 2017 in the second-line setting for patients with advanced HCC and Child-Pugh A or B7 liver disease. Pembrolizumab was granted FDA approval in 2018 in the second-line setting after publication of KEYNOTE-224 for patients with advanced HCC and Child-Pugh A liver disease. All three approvals were independent of PD-L1 tumor or immune cell expression. Several other ICIs have been studied in various aspects of these diverse diseases including resectable disease and the advanced, unresectable, or metastatic setting from first-line to later line after failed systemic therapies. Some of these agents are also being assessed in combination with currently utilized tyrosine kinase inhibitors (TKIs) and/or chemotherapy. Lastly, we draw attention to phase III clinical trials in ICIs that are currently recruiting and will be approaching completion in the next 5 years, potentially altering the landscape of treatment in hepatobiliary malignancies for generations to come.
| S-EPMC7061229 | biostudies-literature
Project description:Background & aimsStudies of liver cancer risk in recipients of solid organ transplants generally have been small, yielding mixed results, and little is known about biliary tract cancers among transplant recipients.MethodsWe identified incident hepatobiliary cancers among 201,549 US recipients of solid organs, from 1987 through 2008, by linking data from the US transplant registry with 15 cancer registries. We calculated standardized incidence ratios (SIRs), comparing risk relative to the general population. We also calculated incidence rate ratios (RRs), comparing risk for hepatocellular carcinoma (HCC) and total (intrahepatic and extrahepatic) cholangiocarcinoma among subgroups of recipients.ResultsOf transplant recipients, 165 developed hepatobiliary cancers (SIR, 1.2; 95% confidence interval [CI], 1.0-1.4). HCC risk was increased among liver recipients (SIR, 1.5; 95% CI, 1.0-2.2), especially 5 or more years after transplant (SIR, 1.8; 95% CI, 1.0-3.0). Cholangiocarcinoma was increased among liver (SIR, 2.9; 95% CI, 1.6-4.8) and kidney recipients (SIR, 2.1; 95% CI, 1.3-3.1). HCC was associated with hepatitis B virus (RR, 3.2; 95% CI, 1.3-6.9), hepatitis C virus (RR, 10; 95% CI, 5.9-16.9), and non-insulin-dependent diabetes (RR, 2.5; 95% CI, 1.2-4.8). Cholangiocarcinoma was associated with azathioprine maintenance therapy (RR, 2.0; 95% CI, 1.1-3.7). Among liver recipients, primary sclerosing cholangitis was associated with an increased risk of cholangiocarcinoma, compared with the general population (SIR, 21; 95% CI, 8.2-42) and compared with liver recipients without primary sclerosing cholangitis (RR, 12.3; 95% CI, 4.1-36.4).ConclusionsRisks for liver and biliary tract cancer are increased among organ transplant recipients. Risk factors for these cancers include medical conditions and potentially medications taken by recipients.
| S-EPMC4064001 | biostudies-literature
Project description:Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors. These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival. Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of significant importance. Recent Food and Drug Administration approvals of immune checkpoint inhibitors (ICI) for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors. Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease, drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.
| S-EPMC9412936 | biostudies-literature
Project description:Hepatobiliary cancers (HBCs) include hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma, which originate from the liver, bile ducts, and gallbladder, respectively. They are responsible for a substantial burden of cancer-related deaths worldwide. Despite knowledge of risk factors and advancements in therapeutics and surgical interventions, the prognosis for most patients with HBC remains bleak. There is evidence from familial aggregation and case-control studies to suggest a familial risk component in HBC susceptibility. Recent progress in genomics research has led to the identification of germline variants including single nucleotide polymorphisms (SNPs) and pathogenic or likely pathogenic (P/LP) variants in cancer-associated genes associated with HBC risk. These findings emerged from genome-wide association studies and next-generation sequencing techniques such as whole-exome sequencing. Patients with other cancer types, including breast, colon, ovarian, prostate, and pancreatic cancer, are recommended by guidelines to undergo germline genetic testing, but similar recommendations are lagging in HBC. This prompts the question of whether multi-gene panel testing should be integrated into clinical guidelines for HBC management. Here, we review the hereditary genetics of HBC, explore studies investigating SNPs and P/LP variants in HBC patients, discuss the clinical implications and potential for personalized treatments and impact on patient's family members, and conclude that additional studies are needed to examine how genetic testing can be applied clinically.
| S-EPMC10899027 | biostudies-literature
Project description:ObjectiveTo compare health care utilization between Canadian and U.S. residents.Data sourcesNationally representative 2007 surveys from the Medical Expenditure Panel Survey for the United States and the Canadian Community Health Survey for Canada.Study designWe use descriptive and multivariate methods to examine differences in health care utilization rates for visits to medical providers, nurses, chiropractors, specialists, dentists, and overnight hospital stays, usual source of care, Pap smear tests, and mammograms.Principal findingsThe poor and less educated were more likely to utilize health care in Canada than in the United States. The differences were especially pronounced for having a usual source of care and for visits to providers, specialists, and dentists. Health care use for residents with high incomes and higher levels of education were not markedly different between the two countries and often higher for U.S residents. Foreign-born residents were more likely to use health care in Canada than in the United States. The descriptive results were confirmed in multivariate regressions.ConclusionsGiven the magnitude of our results, the health insurance structure in Canada might have played an important role in improving access to care for subpopulations examined in this study.
| S-EPMC3626357 | biostudies-literature
Project description:BackgroundThe Department of Health and Human Services National Blood Collection and Utilization Survey (NBCUS) has been conducted biennially since 1997. Data are used to estimate national blood collection and utilization.Study design and methodsThe 2013 Department of Health and Human Services NBCUS is a cross-sectional survey of all US blood collection centers and hospitals as listed in the 2012 American Hospital Association Annual Survey database that perform at least 100 inpatient surgical procedures annually. The study objective was to estimate, with 95% confidence intervals (CIs), the number of blood and blood components collected and transfused in the United States.ResultsIn 2013, a total of 14,237,000 whole blood and apheresis red blood cell (RBC) units (95% CI, 13,639,000-14,835,000) were collected with 13,395,000 available for transfusion. Of these, 13,180,000 (95% CI, 12,389,000-13,972,000) whole blood and RBC units were transfused. This represented a 4.4% decline in the number of transfused units compared to 2011. Outdated (i.e., expired without being transfused) whole blood and RBC units declined by 17.3%. Apheresis (2,318,000; 95% CI, 2,154,000-2,482,000) and whole blood-derived platelet (PLT; 130,000; 95% CI, 23,000-237,000) distribution declined in 2013. Total PLT transfusions increased in 2013 (2,281,000) in comparison to 2011 (2,169,000). Total plasma units distributed (4,338,000) and transfused (3,624,000) declined.ConclusionBoth blood collection and utilization have declined, but the gap between collection and utilization is narrowing. As collections decline further and hospitals decrease transfusions and manage products more efficiently, the decline in surplus inventory may be a concern for disaster preparedness or other unexpected utilization needs.
| S-EPMC5928513 | biostudies-literature