Impact of enzalutamide on patient-reported fatigue in patients with prostate cancer: data from the pivotal clinical trials.

Background: Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)).

Methods: Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression.

Clinical Activity of Ripretinib in Patients with Advanced Gastrointestinal Stromal Tumor Harboring Heterogeneous Mutations in the Phase III INVICTUS Study.

Purpose: Most patients with gastrointestinal stromal tumor (GIST) have activating mutations in and are initially responsive to tyrosine kinase inhibitors (TKI). The acquisition of secondary mutations leads to refractory/relapsed disease. This study reports the results of an analysis from the phase III INVICTUS study (NCT03353753) characterizing the genomic heterogeneity of tumors from patients with advanced GIST and evaluating ripretinib efficacy across mutation subgroups.

Adult Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: A Clinical Case Series in a Predominantly Hispanic Cohort.

Hemophagocytic lymphohistiocytosis (HLH) is a systemic inflammation disorder secondary to immune dysregulation. Patients may present with fevers, splenomegaly, bone marrow failure and hemophagocytosis, among other clinical and laboratory findings. Lymphoma-associated HLH (LA-HLH) is a puzzling diagnosis given both conditions overlapping presentation.

Establishment of Patient-Derived Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor Models for Predicting Therapeutic Response.

Purpose: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract, with mutant succinate dehydrogenase () subunits (A-D) comprising less than 7.5% (i.e.

Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour.

Purpose: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor α kinase signalling. Ripretinib showed preliminary efficacy in patients with advanced gastrointestinal stromal tumour (GIST) in a phase I study across a range of doses. Results were confirmed in the phase III INVICTUS study, and ripretinib 150 mg once daily (QD) was subsequently approved as a ≥fourth-line therapy.

Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.

Purpose: Primary or secondary mutations in or platelet-derived growth factor receptor alpha () underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V-mutant and later-line KIT-mutant GIST.

Early and Next-Generation KIT/PDGFRA Kinase Inhibitors and the Future of Treatment for Advanced Gastrointestinal Stromal Tumor.

The majority of gastrointestinal stromal tumors (GIST) harbor an activating mutation in either the KIT or PDGFRA receptor tyrosine kinases. Approval of imatinib, a KIT/PDGFRA tyrosine kinase inhibitor (TKI), meaningfully improved the treatment of advanced GIST. Other TKIs subsequently gained approval: sunitinib as a second-line therapy and regorafenib as a third-line therapy.

Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study.

Background: Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumors (GISTs) as at least fourth-line therapy. In INVICTUS, ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.

Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy.

Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation.

Correlation of Regulatory T Cell Numbers with Disease Tolerance upon Virus Infection.

The goal of a successful immune response is to clear the pathogen while sparing host tissues from damage associated with pathogen replication and active immunity. Regulatory T cells (Treg) have been implicated in maintaining this balance as they contribute both to the organization of immune responses as well as restriction of inflammation and immune activation to limit immunopathology. To determine if Treg abundance prior to pathogen encounter can be used to predict the success of an antiviral immune response, we used genetically diverse mice from the collaborative cross infected with West Nile virus (WNV).

The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2+ breast cancer.

Despite the availability of multiple human epidermal growth factor receptor 2-targeted (HER2-targeted) treatments, therapeutic resistance in HER2+ breast cancer remains a clinical challenge. Intratumor heterogeneity for HER2 and resistance-conferring mutations in the PIK3CA gene (encoding PI3K catalytic subunit α) have been investigated in response and resistance to HER2-targeting agents, while the role of divergent cellular phenotypes and tumor epithelial-stromal cell interactions is less well understood. Here, we assessed the effect of intratumor cellular genetic heterogeneity for ERBB2 (encoding HER2) copy number and PIK3CA mutation on different types of neoadjuvant HER2-targeting therapies and clinical outcome in HER2+ breast cancer.

Distinguishing granulomas from adenocarcinomas by integrating stable and discriminating radiomic features on non-contrast computed tomography scans.

Objective: To identify stable and discriminating radiomic features on non-contrast CT scans to develop more generalisable radiomic classifiers for distinguishing granulomas from adenocarcinomas.

Methods: In total, 412 patients with adenocarcinomas and granulomas from three institutions were retrospectively included. Segmentations of the lung nodules were performed manually by an expert radiologist in a 2D axial view.

10-Year Study of Christian Church Support for Domestic Violence Victims: 2005-2015.

Religious beliefs play a significant role in the lives of victims of domestic violence. Victims find strength in their faith and would rather endure the violence at all costs to keep a family or a marriage together, than to compromise their faith by leaving. This 10 -year study explored the climate of support for victims of domestic violence among Christian clergy and church members between 2005 and 2015.

Post-Operative Superior Mesenteric Artery Syndrome Following Retroperitoneal Sarcoma Resection.

Superior mesenteric artery (SMA) syndrome is an uncommon phenomenon caused by the compression of the third portion of the duodenum between the aorta and the SMA. Here, we present a previously healthy 15-year-old male who presented with early satiety and 20 kg weight loss. Computed tomography (CT) demonstrated a massive retroperitoneal liposarcoma displacing the entire small intestine into the right upper quadrant.

Angiokines Associated with Targeted Therapy Outcomes in Patients with Non-Clear Cell Renal Cell Carcinoma.

Purpose: Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC) to inform treatment selection but also to identify novel therapeutic targets. We thus sought to profile circulating angiokines in the context of a randomized treatment trial of everolimus versus sunitinib.

Patients And Methods: ASPEN (NCT01108445) was an international, randomized, open-label phase II trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC with no prior systemic therapy.

CDK 4/6 inhibitors are associated with a high incidence of thrombotic events in women with breast cancer in real-world practice.

Purpose: Cyclin-dependent kinase (CDK) 4/6 inhibitors are integral treatment for advanced hormone receptor positive breast cancer; however, venous thromboembolic events (VTE) occurred in 1%-5% of clinical trial patients. Thrombosis rates in the real-world setting remain unclear. We aimed to define the rate of thromboembolic events, risk factors for thrombosis on CDK 4/6 inhibitors and evaluate the Khorana VTE risk score as a predictive tool for VTE in patients on CDK 4/6 therapy.

Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice.

The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2.

Mistrust Reported by US Mexicans With Cancer at End of Life and Hospice Enrollment.

Hospice research with Hispanics mostly focuses on cultural barriers. Mindful of social justice and structural violence, we used critical grounded theory in a postcolonial theory framework to develop a grounded theory of hospice decision making in US Mexicans with terminal cancer. Findings suggest that hospice avoidance is predicted by mistrust, rather than culture, whereas hospice enrollers felt a sense of belonging.

Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial.

Background: PDGFRA D842V mutations occur in 5-10% of gastrointestinal stromal tumours (GISTs), and previously approved tyrosine kinase inhibitors (TKIs) are inactive against this mutation. Consequently, patients have a poor prognosis. We present an updated analysis of avapritinib efficacy and long-term safety in this patient population.

Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy.

Background: Most gastrointestinal stromal tumors (GIST) driven by KIT or platelet-derived growth factor receptor A (PDGFRA) mutations develop resistance to available tyrosine kinase inhibitor (TKI) treatments. NAVIGATOR is a two-part, single-arm, dose escalation and expansion study designed to evaluate safety and antineoplastic activity of avapritinib, a selective, potent inhibitor of KIT and PDGFRA, in patients with unresectable or metastatic GIST.

Materials And Methods: Eligible patients were 18 years or older with histologically or cytologically confirmed unresectable GIST and Eastern Cooperative Oncology Group performance status ≤2 and initiated avapritinib at 300 mg or 400 mg once daily.

Identification of Wee1 as a target in combination with avapritinib for gastrointestinal stromal tumor treatment.

Management of gastrointestinal stromal tumors (GISTs) has been revolutionized by the identification of activating mutations in KIT and PDGFRA and clinical application of RTK inhibitors in advanced disease. Stratification of GISTs into molecularly defined subsets provides insight into clinical behavior and response to approved targeted therapies. Although these RTK inhibitors are effective in most GISTs, resistance remains a significant clinical problem.

Molecular Crosstalk Between MYC and HIF in Cancer.

The transcription factor c-MYC (MYC thereafter) is a global regulator of gene expression. It is overexpressed or deregulated in human cancers of diverse origins and plays a key role in the development of cancers. Hypoxia-inducible factors (HIFs), a central regulator for cells to adapt to low cellular oxygen levels, is also often overexpressed and activated in many human cancers.

Novel blood-based early cancer detection: diagnostics in development.

Cancer affects millions of Americans, and the number of cases is steadily rising. The increase in diagnosis of cancer cases comes with an associated increase in personal and economic burden. Earlier detection can improve treatment outcomes and may reduce the burden of cancer.