Ponsegromab for the Treatment of Cancer Cachexia.

Background: Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels.

Keratin 17 is a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma.

Objectives: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

Methods: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

Patterns of Failure in Patients With Borderline Resectable/Locally Advanced Pancreatic Cancer After Preoperative Chemotherapy and Stereotactic Body Radiation Therapy.

Purpose: The role of preoperative stereotactic body radiation therapy (SBRT) in pancreatic cancer is controversial, and questions regarding the optimal dose and radiation treatment field remain. To better inform future investigations of SBRT dose and radiation fields, we evaluated the patterns of failure in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC) after preoperative chemotherapy and SBRT in patients who underwent surgical resection.

Methods And Materials: We performed a single-institution retrospective review of consecutive patients treated from September 2017 to January 2022 with BR/LAPC.

Glutamine Supplementation as an Anticancer Strategy: A Potential Therapeutic Alternative to the Convention.

Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy.

The Disproportionate Rise in Pancreatic Cancer in Younger Women Is Due to a Rise in Adenocarcinoma and Not Neuroendocrine Tumors: A Nationwide Time-Trend Analysis Using 2001-2018 United States Cancer Statistics Databases.

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET).

Cancer-related cells and oncosomes in the liquid biopsy of pancreatic cancer patients undergoing surgery.

Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of less than 10% due to its late diagnosis, rapid metastasis, and chemotherapeutic resistance. For a small proportion (10-20%) of early-stage patients however, surgical resection of the pancreatic tumor offers the best chance for survival but the effect of surgery on disease dissemination is unknown. The primary objective of this study was to characterize cellular and acellular blood-based analytes in portal and peripheral blood before pancreatic manipulation, during tumor dissection and immediately after surgical resection to determine the effects of the surgery.

Socioeconomic disparities in patients with small bowel neuroendocrine tumors.

Background And Objectives: Demographic and socioeconomic disparities affect cancer specific outcomes in numerous malignancies, but the impact of these for patients with small bowel neuroendocrine tumors (SBNETs) is not well understood. The primary objective was to investigate the impact of demographic and socioeconomic factors on overall survival (OS) for patients with SBNETs.

Methods: We performed a retrospective cohort study utilizing the National Cancer Database to assess patients diagnosed with SBNET between 2004 and 2015.

Recent advances in the management of hepatocellular carcinoma.

Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function.

Combination L-Glutamine with Gemcitabine and Nab-Paclitaxel in Treatment-Naïve Advanced Pancreatic Cancer: The Phase I GlutaPanc Study Protocol.

Advanced pancreatic cancer is underscored by progressive therapeutic resistance and a dismal 5-year survival rate of 3%. Preclinical data demonstrated glutamine supplementation, not deprivation, elicited antitumor effects against pancreatic ductal adenocarcinoma (PDAC) alone and in combination with gemcitabine in a dose-dependent manner. The GlutaPanc phase I trial is a single-arm, open-label clinical trial investigating the safety of combination L-glutamine, gemcitabine, and nab-paclitaxel in subjects ( = 16) with untreated, locally advanced unresectable or metastatic pancreatic cancer.

Multitasking dynamic contrast enhanced magnetic resonance imaging can accurately differentiate chronic pancreatitis from pancreatic ductal adenocarcinoma.

Background And Aims: Accurate differentiation of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) is an area of unmet clinical need. In this study, a novel Multitasking dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) technique was used to quantitatively evaluate the microcirculation properties of pancreas in CP and PDAC and differentiate between them.

Methods: The Multitasking DCE technique was able to acquire one 3D image per second during the passage of MRI contrast agent, allowing the quantitative estimation of microcirculation properties of tissue, including blood flow F, plasma volume fraction v, transfer constant K, and extravascular extracellular volume fraction v.

Tumor hyaluronan as a novel biomarker in non-small cell lung cancer: A retrospective study.

Introduction: Hyaluronan (HA) accumulation is associated with tumorigenesis and aggressive tumor behavior.

Aims: We investigated the biomarker potential of HA in non-small cell lung cancer (NSCLC).

Methods: HA levels were scored using affinity histochemistry in 137 NSCLC samples stratified by HA score ≤10, 11-20, 21-30, and >30 with HA-high defined as ≥25% expression in the extracellular matrix (ECM) of the tumor surface area.

Pancreatoblastoma in Elderly Adults: Report of Two Patients.

. Pancreatoblastoma is a rare malignant epithelial neoplasm of the pancreas, which often shows multiple lines of differentiation, but is defined by neoplastic cells with acinar differentiation and characteristic squamoid nests. Pediatric patients are most commonly affected, and although a subset is known to occur in adults, the diagnosis is rarely considered in elderly adults.

A phase II study of sapanisertib (TAK-228) a mTORC1/2 inhibitor in rapalog-resistant advanced pancreatic neuroendocrine tumors (PNET): ECOG-ACRIN EA2161.

This was a two-stage phase II trial of a mTORC1/2 inhibitor (mTORC: mammalian target of rapamycin complex) Sapanisertib (TAK228) in patients with rapalog-resistant pancreatic neuroendocrine tumors (PNETs) (NCT02893930). Approved rapalogs such as everolimus inhibit mTORC1 and have limited clinical activity, possibly due to compensatory feedback loops. Sapanisertib addresses the potential for incomplete inhibition of the mTOR pathway through targeting of both mTORC1 and mTORC2, and thus to reverse resistance to earlier rapamycin analogues.

Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211).

Purpose: Patients with advanced pancreatic neuroendocrine tumors (NETs) have few treatment options that yield objective responses. Retrospective and small prospective studies suggest that capecitabine and temozolomide are associated with high response rates (RRs) and long progression-free survival (PFS).

Patients And Methods: E2211 was a multicenter, randomized, phase II trial comparing temozolomide versus capecitabine/temozolomide in patients with advanced low-grade or intermediate-grade pancreatic NETs.

Exceptional Response to Erdafitinib in FGFR2-Mutated Metastatic Pancreatic Ductal Adenocarcinoma.

Despite advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, with a poor prognosis at time of diagnosis. Research in PDAC has suggested that adaptive signaling in the tumor microenvironment may promote tumor proliferation and survival. Several FGFR fusion genes-specifically FGFR2-are involved with the creation and progression of cancer.

Claudin-18.

Context.—: Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target.

Chemical Exchange Saturation Transfer for Pancreatic Ductal Adenocarcinoma Evaluation.

Objectives: The aims of the study are to evaluate the feasibility of using pH-sensitive magnetic resonance imaging, chemical exchange saturation transfer (CEST) in pancreatic imaging and to differentiate pancreatic ductal adenocarcinoma (PDAC) with the nontumor pancreas (upstream and downstream) and normal control pancreas.

Methods: Sixteen CEST images with PDAC and 12 CEST images with normal volunteers were acquired and magnetization transfer ratio with asymmetric analysis were measured in areas of PDAC, upstream, downstream, and normal control pancreas. One-way analysis of variance and receiver operating characteristic curve were used to differentiate tumor from nontumor pancreas.

Dual Stromal Targeting Sensitizes Pancreatic Adenocarcinoma for Anti-Programmed Cell Death Protein 1 Therapy.

Background & Aims: The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms.

Methods: A murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-programmed cell death protein 1 (PD-1) antibody, and stromal hyaluronan (HA) degradation by PEGylated recombinant human hyaluronidase (PEGPH20) to assess immune and stromal modulating effects of these agents and their combinations.

Best Practices for the Coordinated Care of Patients With Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy.

Neuroendocrine tumors (NETs) are rare, diverse malignancies; approximately two thirds originate in the gastrointestinal tract and pancreas and are known as gastroenteropancreatic NET. Most cases are diagnosed in the advanced or metastatic setting and overexpress somatostatin receptors. Recommended first-line treatment is somatostatin analogs; however, disease progression is common.