NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Role of Adjuvant Chemotherapy in Pulmonary Carcinoids: An NCDB Analysis.

BACKGROUND/AIM: Typical carcinoids (TC) and atypical carcinoids (AC) are rare diseases. A paucity of randomized studies and disagreements among various guidelines makes the management challenging. PATIENTS AND METHODS: Using codes for TC (8240) and AC (8249) in the National Cancer Database (NCDB), all surgically resected cases from 2004-2014 were included to evaluate the need for adjuvant chemotherapy. RESULTS: A total of 6,673 cases were included, 88% were TCs and 12% were ACs. From 2004 to 2014, the proportion of TCs went up from 1.3% to 1.8% and ACs from 0.1% to 0.3% of all lung malignancies. TC patients did well with surgery alone in all stages. AC patients with stage I [5-year overall survival (OS) - 84% vs. 52%; S vs. S+CT] and stage II disease (5-year OS - 81% vs. 55%; S vs. S+CT) showed better OS trend with surgery alone, while stage III patients showed some benefit with the use of adjuvant chemotherapy (5-year OS - 46% vs. 54%; S vs. S+CT). These results supported the National Comprehensive Cancer Network (NCCN) guidelines. CONCLUSION: No benefit was seen from adjuvant chemotherapy in TCs. While the adjuvant therapy may add benefit in stage III AC, the numbers are small and did not reach statistical significance.

Augmentation of IFN-γ+ CD8+ T cell responses correlates with survival of HCC patients on sorafenib therapy.

BACKGROUNDSorafenib has been shown to reduce the extent of immunosuppression in patients with hepatocellular carcinoma (HCC). The rationale of this investigation was to identify biomarkers that can predict treatment efficacy of sorafenib in HCC patients and to unravel the mechanism by which sorafenib impedes immune suppression mediated by distinct immunosuppressive cell subsets.METHODSWith informed consent, blood samples were collected from 30 patients with advanced HCC, at baseline and 2 time points after initiation of sorafenib treatment. The frequency of PD-1+ T cells, ERK2 phosphorylation on flt-3+ Tregs and MDSCs, and T effector cell function were quantified by using flow cytometry.RESULTSElevated levels of CD8+Ki67+ T cells producing IFN-γ were associated with improved progression-free survival and overall survival (OS). High frequencies of these T cells were correlated with significantly reduced risk of death over time. Patients with an increased pretreatment T effector/Treg ratio showed significant improvement in OS. ERK+flt-3+ Tregs and MDSCs were significantly decreased after sorafenib therapy. Increased numbers of baseline flt-3+p-ERK+ MDSCs were associated with survival benefit of patients.CONCLUSIONA high baseline CD4+ T effector/Treg ratio is a potential biomarker of prognostic significance in HCC. CD8+Ki67+ T cells producing IFN-γ are a key biomarker of response to sorafenib therapy resulting in survival benefit. The immune modulation resulted from sorafenib-mediated blockade of signaling through the VEGF/VEGFR/flt-3 pathway, affecting ERK phosphorylation. These insights may help identify patients who likely would benefit from VEGFR antagonism and inform efforts to improve the efficacy of sorafenib in combination with immunotherapy.TRIAL REGISTRATIONNCT02072486.FUNDINGNational Comprehensive Cancer Network Oncology Research Program from general research support provided by Bayer US LLC (NCCNSORA0002), National Cancer Institute grant P30CA016056, and pilot funds from Roswell Park Alliance Foundation.

Multidisciplinary Management of Patients with Unresectable Hepatocellular Carcinoma: A Critical Appraisal of Current Evidence.

Hepatocellular carcinoma (HCC) is a leading cause of new cancer diagnoses in the United States, with an incidence that is expected to rise. The etiology of HCC is varied and can lead to differences between patients in terms of presentation and natural history. Subsequently, physicians treating these patients need to consider a variety of disease and patient characteristics when they select from the many different treatment options that are available for these patients. At the same time, the treatment landscape for patients with HCC, particularly those with unresectable HCC, has been rapidly evolving as new, evidence-based options become available. The treatment plan for patients with HCC can include surgery, transplant, ablation, transarterial chemoembolization, transarterial radioembolization, radiation therapy, and/or systemic therapies. Implementing these different modalities, where the optimal sequence and/or combination has not been defined, requires coordination between physicians with different specialties, including interventional radiologists, hepatologists, and surgical and medical oncologists. As such, the implementation of a multidisciplinary team is necessary to develop a comprehensive care plan for patients, especially those with unresectable HCC.

Cholangiocarcinoma: Treatment, Outcomes, and Nutrition Overview for Oncology Nurses.

BACKGROUND: Cholangiocarcinoma is a cancer that arises from the bile ducts inside or outside of the liver. Although it is a rare cancer, cholangiocarcinoma appears to be rising in incidence in the United States and worldwide. OBJECTIVES: The diagnosis of cholangiocarcinoma frequently presents with biliary emergencies from diagnosis through treatment. The lethality of this cancer stems, in part, from challenges with supportive care during treatment. This article provides an overview of intrahepatic and extrahepatic cholangiocarcinoma, including identification of risk factors, differences in treatment approaches, palliation of symptoms, and insight into commonly asked questions. METHODS: A comprehensive review of the current literature regarding incidence, prevalence, and treatment of cholangiocarcinoma was conducted. FINDINGS: Nursing literature regarding cholangiocarcinoma is scarce. Studies that focus on nursing care, symptom management, and nursing management of patients with biliary obstruction are needed. Nutrition and palliative care management of patients with cholangiocarcinoma are key areas of nursing management.

Octreotide and Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors.

Neuroendocrine tumors are heterogeneous, rare malignancies that arise most commonly in the gastrointestinal tract and pancreas. They often secrete vasoactive substances resulting in carcinoid syndrome and the tumor cells exclusively express somatostatin receptors. Octreotide and lanreotide are the two synthetic somatostatin analogs used for the control of carcinoid symptoms and tumor progression in advanced inoperable disease. Recent pivotal trials (PROMID and CLARINET studies) established their antitumor activity. We discuss the available data to support their use as symptom controlling and antiproliferative agents. This article also reviews the guidelines (National Comprehensive Cancer Network and North American Neuro Endocrine Tumor Society), cost-analysis (suggesting the cost-effectiveness of lanreotide autogel compared to higher doses of octreotide long acting release formulation in refractory patients), and future directions of somatostatin analogs in the management of patients refractory to conventional doses of octreotide and lanreotide.

Sorafenib: a clinical and pharmacologic review.

IMPORTANCE OF THE FIELD: Sorafenib is an oral receptor tyrosine kinase inhibitor that inhibits Raf serine/threonine kinases and receptor tyrosine kinases (vascular endothelial growth factor receptors 1, 2, 3 and platelet-derived growth factor-beta, Flt-3 and c-kit) that are implicated in tumorigenesis and tumor progression. Sorafenib is approved for the treatment of advanced inoperable hepatocellular cancer and advanced renal cell cancer. AREAS COVERED IN THIS REVIEW: The findings from the major Phase III studies that led to FDA approval of this drug for the above indications are reviewed. Key aspects of sorafenib pharmacology, dosing in the presence of organ dysfunction, toxicities and weaknesses of the research done so far are summarized. WHAT WILL THE READER GAIN: The reader will have the knowledge of the major studies that form the basis of the clinical use of sorafenib, information on the upcoming Phase III trials that could lead to changes in clinical practice and some insights on aspects of the drugs' mechanism of action and toxicity that still remain unclear. TAKE HOME MESSAGE: Sorafenib is a well-tolerated oral antiangiogenic agent approved for treatment of two angiogenesis-driven cancers. Studies to broaden the clinical indications and increase understanding of the clinical and laboratory biomarkers of response are needed.