Determining the time to cholangiocarcinoma in pediatric-onset PSC-IBD.

Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. When a child is diagnosed with both PSC and inflammatory bowel disease (IBD), evidence-based information on counseling families and risk management of developing cholangiocarcinoma is limited. In this case series (PubMed/collaborators), we included patients with PSC-IBD who developed cholangiocarcinoma and contacted authors to determine an event curve specifying the time between the second diagnosis (IBD or PSC) and a diagnosis of cholangiocarcinoma.

Changes in alpha-fetoprotein across the systemic therapy continuum in advanced hepatocellular carcinoma-a real-world, multicenter study.

Background: Early changes in alpha-fetoprotein (AFP) are a promising surrogate endpoint for systemic treatment outcomes in hepatocellular carcinoma (HCC).

Objectives: We sought to investigate the utility of AFP response across first-line sorafenib (1L SOR) and later-line checkpoint inhibitor (CPI) therapies.

Design: We conducted a multicenter, retrospective cohort study of patients with advanced HCC who received 1L SOR and any subsequent CPI.

Plain language summary: an analysis of the safety of futibatinib treatment in people with different types of cancer.

What Is This Summary About?: Researchers combined information from three separate phase 1 and 2 clinical trials, including over 400 people who had one of 33 different cancer types and who all received futibatinib in their clinical trial. This type of study is called a pooled analysis. Futibatinib is taken orally (by mouth) as a tablet and works by reducing the activity of a group of proteins called fibroblast growth factor receptors (FGFRs).

Plain language summary of the FOENIX-CCA2 study: futibatinib for people with advanced bile duct cancer.

What Is This Summary About?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions.

COMPANION-002 A clinical trial of investigational drug CTX-009 plus paclitaxel vs paclitaxel in second line advanced BTC.

Treatment options for patients with biliary tract cancer are limited, and the prognosis is poor. CTX-009, a novel bispecific antibody targeting both DLL4 and VEGF-A, has demonstrated antitumor activity in patients with advanced cancers as both a monotherapy and in combination with chemotherapy. In a phase II study of patients with advanced biliary tract cancer who had received one or two prior therapies, CTX-009 with paclitaxel demonstrated a 37.

Hypofractionated Radiotherapy-Related Lymphopenia Is Associated With Worse Survival in Unresectable Intrahepatic Cholangiocarcinoma.

Objective: The aim of this study was to evaluate the incidence of radiotherapy (RT)-related lymphopenia, its predictors, and association with survival in unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated-RT (HF-RT).

Methods: Retrospective analysis of 96 patients with unresectable ICC who underwent HF-RT (median 58.05 Gy in 15 fractions) between 2009 and 2022 was performed.

Pemigatinib in previously treated solid tumors with activating FGFR1-FGFR3 alterations: phase 2 FIGHT-207 basket trial.

Fibroblast growth factor receptor (FGFR) alterations drive oncogenesis in multiple tumor types. Here we studied pemigatinib, a selective, potent, oral FGFR1-FGFR3 inhibitor, in the phase 2 FIGHT-207 basket study of FGFR-altered advanced solid tumors. Primary end points were objective response rate (ORR) in cohorts A (fusions/rearrangements, n = 49) and B (activating non-kinase domain mutations, n = 32).

Are FGFR Fusions and Mutations the Next Tumor-Agnostic Targets in Oncology?

Gong et al present two NCI-MATCH tumor-agnostic trials evaluating erdafitinib for FGFR-altered cancers, marking steppingstones in precision oncology.

Safety Profile and Adverse Event Management for Futibatinib, An Irreversible FGFR1-4 Inhibitor: Pooled Safety Analysis of 469 Patients.

Purpose: Futibatinib, a covalently-binding inhibitor of fibroblast growth factor receptor (FGFR)1-4 gained approval for the treatment of refractory, advanced intrahepatic cholangiocarcinoma (iCCA) harboring an FGFR2 fusion/other rearrangement. An integrated analysis was performed to evaluate safety and provide guidance on the management of futibatinib-associated adverse events (AEs) in patients with unresectable/metastatic tumors, including iCCA.

Patients And Methods: Data from three global phase I or II studies of futibatinib (NCT02052778; JapicCTI-142552) were pooled.

Brightline-2: a phase IIa/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors.

Mouse double minute 2 homolog (MDM2) is a key negative regulator of the tumor suppressor p53. Blocking the MDM2-p53 interaction, and restoring p53 function, is therefore a potential therapeutic strategy in -amplified, wild-type tumors. is amplified in several tumor types, including biliary tract cancer (BTC), pancreatic ductal adenocarcinoma (PDAC), lung adenocarcinoma and bladder cancer, all of which have limited treatment options and poor patient outcomes.

Patient-Reported Outcomes, Tumor Markers, and Survival Outcomes in Advanced GI Cancer.

Importance: Patient-reported outcomes (PROs), such as quality of life (QOL) and symptoms, are often associated with clinical outcomes in patients with cancer. In practice, oncologists use serum tumor markers (TMs) (ie, carcinoembryonic antigen [CEA] and carbohydrate antigen 19-9 [CA 19-9]) and imaging to monitor clinical outcomes in patients with gastrointestinal cancer.

Objective: To examine associations of 1-month changes in PROs and TMs with treatment response and survival among patients with gastrointestinal cancer.

The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

Purpose: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer.

Gastrointestinal (GI) cancers, including esophageal, gastroesophageal junction, gastric, duodenal and distal small bowel, biliary tract, pancreatic, colon, rectal, and anal cancer, comprise a heterogeneous group of malignancies that impose a significant global burden. Immunotherapy has transformed the treatment landscape for several GI cancers, offering some patients durable responses and prolonged survival. Specifically, immune checkpoint inhibitors (ICIs) directed against programmed cell death protein 1 (PD-1), either as monotherapies or in combination regimens, have gained tissue site-specific regulatory approvals for the treatment of metastatic disease and in the resectable setting.

Tumor biology and immune infiltration define primary liver cancer subsets linked to overall survival after immunotherapy.

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field.

Cholangiocarcinoma - novel biological insights and therapeutic strategies.

In the past 5 years, important advances have been made in the scientific understanding and clinical management of cholangiocarcinoma (CCA). The cellular immune landscape of CCA has been characterized and tumour subsets with distinct immune microenvironments have been defined using molecular approaches. Among these subsets, the identification of 'immune-desert' tumours that are relatively devoid of immune cells emphasizes the need to consider the tumour immune microenvironment in the development of immunotherapy approaches.

Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma.

Background: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.

Methods: This multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions.