Molecular pathways and targeted therapy in cholangiocarcinoma.

Cholangiocarcinoma (CCA) encompasses a rare group of malignancies arising from epithelial cells lining the biliary tree that connects the liver and gallbladder to the small intestine. Most patients present with advanced incurable disease that has a poor prognosis, and standard treatment options remain limited. Effective nontoxic treatment options for advanced CCA are needed. Fibroblast growth factors (FGFs) and their fibroblast growth factor receptor (FGFR) pathways are crucial to cellular proliferation, cellular survival, and differentiation of many malignancies, but are especially relevant in CCA. The targeting of FGF/FGFR has become the most promising approach to treating patients with advanced/metastatic CCA. Here we review CCA, and discuss the promise of FGFR-directed therapy in advanced CCA.

Stereotactic body radiation therapy and immunotherapy.

Immunotherapy has revolutionized the treatment of various types of cancers in recent years. Since the US Food and Drug Administration approval of the anti-cytotoxic T-lymphocyte-associated antigen 4 agent ipilimumab for late-stage melanoma in 2011, results from multiple clinical trials have proven the benefit of immunotherapy in the treatment of other cancers. However, therapeutic resistance to immunotherapy often develops. This has led investigators to combine immunotherapy with stereotactic body radiation therapy (SBRT) in an attempt to improve outcomes. The benefit of the combination is believed to stem from stimulating and suppressing various immune pathways and is further aided by the abscopal effect, in which tumors respond to radiation therapy even in nonradiated metastatic sites. When combined with immunotherapy, radiation causes the tumor to act much like a vaccine by exposing the tumor antigens to activate the immune response. This article reviews the association between the immune system and cancer, as well as the additional systemic benefit that SBRT can have in patients with advanced-stage malignancies being treated with immunotherapy.

Initial Diagnostic Work-Up of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists and American Society of Hematology Guideline.

PURPOSE: The College of American Pathologists (CAP) and the American Society of Hematology (ASH) developed an evidence-based guideline on the initial diagnostic work-up of acute leukemia (AL). Because of the relevance of this topic to the ASCO membership, ASCO reviewed the guideline and applied a set of procedures and policies for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS: The CAP-ASH guideline on initial diagnostic work-up of AL was reviewed for developmental rigor by methodologists. Then, an ASCO Endorsement Expert Panel updated the literature search and reviewed the content and recommendations. RESULTS: The ASCO Expert Panel determined that the recommendations from the guideline, published in 2016, are clear, thorough, and based on the most relevant scientific evidence. ASCO fully endorsed the CAP-ASH guideline on initial diagnostic work-up of AL and included some discussion points according to clinical practice and updated literature. CONCLUSION: Twenty-seven guideline statements were reviewed. Some discussion points were included to better assess CNS involvement in leukemia and to provide novel insights into molecular diagnosis and potential markers for risk stratification and target therapy. These discussions are categorized into four sections: (1) initial diagnosis focusing on basic diagnostics and determination of risk parameters, (2) molecular markers and minimal residual disease detection, (3) context of referral to another institution with expertise in the management of AL, and (4) reporting and record keeping for better outlining and follow-up discussion. Additional information is available at: www.asco.org/hematologic-malignancies-guidelines .