Binaural auditory beats vs music of choice as audio distraction behaviour guidance technique among children: A randomized controlled trial.

Background: Binaural beat is created by presenting two different pure-tone sine waves with less than a 30Hz difference dichotically. In dental settings, children listening to familiar music during treatments gain control over the anxiety caused by tools like the airotor or syringe, creating a comforting, familiar environment.

Aim: To evaluate and compare anxiety level during restorative treatment using No Music, Music of choice and Binaural Auditory Beats as Audio distraction behaviour guidance technique in children aged 6-12 years.

IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies.

Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations in cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with the ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As a result, pharmacologic inhibition of mIDH has become an attractive therapeutic strategy in CCAs harboring this mutation.

Olaparib and Radiotherapy Induce Type I Interferon- and CD8+ T Cell-Dependent Sensitization to Immunotherapy in Pancreatic Cancer.

PARP inhibitors sensitize pancreatic ductal adenocarcinoma (PDAC) to radiation by inducing DNA damage and replication stress. These mechanisms also have the potential to enhance radiation-induced type I interferon (T1IFN)-mediated antitumoral immune responses. We hypothesized that the PARP inhibitor olaparib would also potentiate radiation-induced T1IFN to promote antitumor immune responses and sensitization of otherwise resistant PDAC to immunotherapy.

Antigen-independent single-cell circulating tumor cell detection using deep-learning-assisted biolasers.

Circulating tumor cells (CTCs) in the bloodstream are important biomarkers for clinical prognosis of cancers. Current CTC identification methods are based on immuno-labeling, which depends on the differential expression of specific antigens between the cancer cells and white blood cells. Here we present an antigen-independent CTC detection method utilizing a deep-learning-assisted single-cell biolaser.

Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study.

Purpose: Metastatic pancreatic adenocarcinoma (mPC) remains a difficult-to-treat disease. Fluorouarcil, oxaliplatin, irinotecan, and leucovorin (FFX) is a standard first-line therapy for mPC for patients with a favorable performance status and good organ function. In a phase I study, devimistat (CPI-613) in combination with modified FFX (mFFX) was deemed safe and exhibited promising efficacy in mPC.

PARP inhibitor therapy in patients with IDH1 mutated cholangiocarcinoma.

Background: Isocitrate dehydrogenase 1 (IDH1) missense mutations occur at a frequency of 10%-15% in intrahepatic cholangiocarcinoma (iCCA). IDH1 mutations result in accumulation of (R)-2-hydroxyglutarate, an oncometabolite that leads to DNA hypermethylation and impairment of homologous recombination (HR). Impairment of HR results in a "BRCAness" phenotype which may confer sensitivity to poly(ADP ribose) polymerase (PARP) inhibition.

An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202.

Background: Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period.

Regorafenib in Patients With Solid Tumors With Alterations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Purpose: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with alterations treated with regorafenib are reported.

Methods: Eligible patients had measurable disease (RECIST v.

Targeting PIKfyve-driven lipid homeostasis as a metabolic vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) subsists in a nutrient-deregulated microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism. For example, PDAC utilizes and is dependent on high levels of autophagy and other lysosomal processes. Although targeting these pathways has shown potential in preclinical studies, progress has been hampered by the challenge of identifying and characterizing favorable targets for drug development.

A Comparison of Spatial and Phenotypic Immune Profiles of Pancreatic Ductal Adenocarcinoma and Its Precursor Lesions.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of 12.5%. PDAC predominantly arises from non-cystic pancreatic intraepithelial neoplasia (PanIN) and cystic intraductal papillary mucinous neoplasm (IPMN).

A multicenter, randomized phase 2 study to establish combinations of CBP501, cisplatin and nivolumab for ≥3rd-line treatment of patients with advanced pancreatic adenocarcinoma.

Background: There is no standard of care for ≥ 3rd-line treatment of metastatic pancreatic adenocarcinoma (PDAC). CBP501 is a novel calmodulin-binding peptide that has been shown to enhance the influx of platinum agents into tumor cells and tumor immunogenicity. This study aimed to (1) confirm efficacy of CBP501/cisplatin/nivolumab for metastatic PDAC observed in a previous phase 1 study, (2) identify combinations that yield 35% 3-month progression-free survival rate (3MPFS) and (3) define the contribution of CBP501 to the effects of combination therapy.

Are We There Yet? - Alternating Chemotherapy Regimens in Pancreatic Cancer.

In the randomized phase 2 SEQUENCE trial in patients with metastatic pancreatic cancer, reported in this issue of , the authors compared therapy with alternating FOLFOX and nab-paclitaxel/gemcitabine chemotherapy versus standard-of-care, single-regimen nab-paclitaxel/gemcitabine therapy. They were testing the idea that because most tumor cells express both basal and classic markers, alternating treatment would target both cell populations and thus confer a survival benefit. The trial, which enrolled 157 patients, met the primary end point of an overall survival rate at 12 months of 55.

In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum.

Extracellular vesicle (EV) secretion has been observed in many types of both normal and tumor cells. EVs contain a variety of distinctive cargoes, allowing tumor-derived serum proteins in EVs to act as a minimally invasive method for clinical monitoring. We have undertaken a comprehensive study of the protein content of the EVs from several cancer cell lines using direct data-independent analysis.

Risk of Toxicity From Topical 5-Fluorouracil Treatment in Patients Carrying DPYD Variant Alleles.

Patients carrying DPYD variant alleles have increased risk of severe toxicity from systemic fluoropyrimidine chemotherapy. There is a paucity of data regarding risk of toxicity from topical 5-fluorouracil (5-FU) treatment in these patients, leading to inconsistent guideline recommendations for pretreatment testing and topical 5-FU dosing. The objective of this retrospective cohort study was to investigate whether DPYD variant allele carriers have increased risk of toxicity from topical 5-FU.

Predictors of Acute and Late Toxicity in Patients Receiving Chemoradiation for Unresectable Pancreatic Cancer.

Purpose: Patients with pancreatic cancer undergoing chemoradiation therapy may experience acute and chronic side effects. We conducted an exploratory analysis of patients with locally advanced pancreatic cancer (LAPC) undergoing definitive chemoradiation to identify factors influencing the occurrence of gastrointestinal (GI) bleeding, short-term radiation side effects, patterns of failure, and survival.

Methods And Materials: Under an institutional review board-approved protocol, we retrospectively studied patients with LAPC treated with chemoradiation.

Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies.

Purpose: The safety, pharmacokinetics, and efficacy of elraglusib, a glycogen synthase kinase-3β (GSK-3β) small-molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied.

Patients And Methods: Elraglusib (intravenously twice weekly in 3-week cycles) monotherapy dose escalation was followed by dose escalation with eight chemotherapy regimens (gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin, and pemetrexed/carboplatin) in patients previously exposed to the same chemotherapy.

Results: Patients received monotherapy (n = 67) or combination therapy (n = 171) elraglusib doses 1 to 15 mg/kg twice weekly.

KRT17high/CXCL8+ Tumor Cells Display Both Classical and Basal Features and Regulate Myeloid Infiltration in the Pancreatic Cancer Microenvironment.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single-cell RNA sequencing has uncovered the coexistence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach.

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.