Survival among lung cancer patients: comparison of the U.S. military health system and the surveillance, epidemiology, and end results (SEER) program by health insurance status.

Purpose: The U.S. military health system (MHS) provides beneficiaries with universal health care while health care access varies in the U.

Selection of optimal quantile protein biomarkers based on cell-level immunohistochemistry data.

Background: Protein biomarkers of cancer progression and response to therapy are increasingly important for improving personalized medicine. Advanced quantitative pathology platforms enable measurement of protein expression in tissues at the single-cell level. However, this rich quantitative cell-by-cell biomarker information is most often not exploited.

Integration of Multi-omic Data in a Molecular Tumor Board Reveals EGFR-Associated ALK-Inhibitor Resistance in a Patient With Inflammatory Myofibroblastic Cancer.

Inflammatory myofibroblastic tumors (IMTs) are intermediate-grade mesenchymal neoplasms commonly characterized by chromosomal rearrangements causing constitutive activation of anaplastic lymphoma kinase (ALK) and/or ALK mutations causing reduced sensitivity to ALK tyrosine kinase inhibitors (TKI). We present a patient with an IMT who initially responded to first-line alectinib, but who later suffered disease relapse and presently survives with moderate residual disease after receiving second-line lorlatinib. Biopsy specimens were analyzed using next generation sequencing (DNA-seq and RNA-seq) and reverse phase protein microarray (RPPA) as part of an institutional Molecular Tumor Board (MTB) study.

Precision diagnosis and staging of TDP-43 proteinopathies: harnessing the power of artificial intelligence.

This scientific commentary refers to ‘Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies’ by Young . (https://doi.org/10.

Development and characterization of an ETV1 rabbit monoclonal antibody for the immunohistochemical detection of ETV1 expression in cancer tissue specimens.

Background: Aberrant ETV1 overexpression arising from gene rearrangements or mutations occur frequently in prostate cancer, round cell sarcomas, gastrointestinal stromal tumors, gliomas, and other malignancies. The absence of specific monoclonal antibodies (mAb) has limited its detection and our understanding of its oncogenic function.

Methods: An ETV1 specific rabbit mAb (29E4) was raised using an immunogenic peptide.

Cerebrospinal fluid: A unique source of circulating tumor DNA with broad clinical applications.

Malignancies involving the central nervous system present unique challenges for diagnosis and monitoring due to the difficulties and risks of direct biopsies and the low specificity and/or sensitivity of other techniques for assessment. In recent years, liquid biopsy of the cerebrospinal fluid (CSF) has emerged as a convenient alternative that combines minimal invasiveness with the ability to detect disease-defining or therapeutically actionable genetic alterations from circulating tumor DNA (ctDNA). Since CSF can be obtained by lumbar puncture, or an established ventricular access device at multiple time points, ctDNA analysis enables initial molecular characterization and longitudinal monitoring throughout a patient's disease course, promoting optimization of treatment regimens.

Prostate cancer autoantibodies - applications in diagnosis, prognosis, monitoring disease progression and immunotherapy.

Although PSA testing is widely used in prostate cancer diagnosis, it remains an imperfect assay due to its lack of accuracy. While several urine or tissue-based gene expression assays are available to identify patients with higher risk of adverse disease and to aid in deciding treatment options, there is still a critical need for reliable biomarkers to monitor disease progression and treatment response. Autoantibodies (AAbs) produced by the humoral immune response against tumor associated antigens offer an attractive alternative, as they target a wide variety of prostate cancer specific antigens and can be collected by using clinically non-invasive methods.

Chemotherapy Treatment Costs and Clinical Outcomes of Colon Cancer in the U.S. Military Health System's Direct and Private Sector Care Settings.

Introduction: Identifying low-value cancer care may be an important step in containing costs associated with treatment. Low-value care occurs when the medical services, tests, or treatments rendered do not result in clinical benefit. These may be impacted by care setting and patients' access to care and health insurance.

Quantile Index Biomarkers Based on Single-Cell Expression Data.

Current histocytometry methods enable single-cell quantification of biomolecules in tumor tissue sections by multiple detection technologies, including multiplex fluorescence-based immunohistochemistry or in situ hybridization. Quantitative pathology platforms can provide distributions of cellular signal intensity (CSI) levels of biomolecules across the entire cell populations of interest within the sampled tumor tissue. However, the heterogeneity of CSI levels is usually ignored, and the simple mean signal intensity value is considered a cancer biomarker.

Factors Associated With Survival Disparities Between Non-Hispanic Black and White Patients With Uterine Cancer.

Importance: Disparities in survival exist between non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) patients with uterine cancer.

Objective: To investigate factors associated with racial disparities in survival between Black and White patients with uterine cancer.

Design, Setting, And Patients: This cohort study used data from the National Cancer Database on 274 838 Black and White patients who received a diagnosis of uterine cancer from January 1, 2004, to December 31, 2017, with follow-up through December 2020.

Nondisparate Survival of Non-Hispanic Black Women With Breast Cancer Despite Less Favorable Pathology: Effect of Access to and Provision of Care Within a Military Health Care System.

Introduction: Breast cancer mortality rates are 40% higher in non-Hispanic Blacks (NHBs) than in non-Hispanic White (NHWs) in the United States. All women treated within the Murtha Cancer Center at Walter Reed National Military Medical Center (MCC/WRNMMC) have health insurance and are provided multidisciplinary health care. Pathological factors and outcomes of NHBs and NHWs treated within the MCC/WRNMMC were evaluated to determine whether equal-access health care reduces disparate phenotypes and survival between the racial groups.

NSC243928 Treatment Induces Anti-Tumor Immune Response in Mouse Mammary Tumor Models.

NSC243928 induces cell death in triple-negative breast cancer cells in a LY6K-dependent manner. NSC243928 has been reported as an anti-cancer agent in the NCI small molecule library. The molecular mechanism of NSC243928 as an anti-cancer agent in the treatment of tumor growth in the syngeneic mouse model has not been established.

Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency and, while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multiomics approach to interrogate molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means.

Survival Disparities in US Black Compared to White Women with Hormone Receptor Positive-HER2 Negative Breast Cancer.

Black women in the US have significantly higher breast cancer mortality than White women. Within biomarker-defined tumor subtypes, disparate outcomes seem to be limited to women with hormone receptor positive and HER2 negative (HR+/HER2-) breast cancer, a subtype usually associated with favorable prognosis. In this review, we present data from an array of studies that demonstrate significantly higher mortality in Black compared to White women with HR+/HER2-breast cancer and contrast these data to studies from integrated healthcare systems that failed to find survival differences.

Lymphocyte antigen 6K signaling to aurora kinase promotes advancement of the cell cycle and the growth of cancer cells, which is inhibited by LY6K-NSC243928 interaction.

Lymphocyte antigen 6K (LY6K) is a small GPI-linked protein that is normally expressed in testes. Increased expression of LY6K is significantly associated with poor survival outcomes in many solid cancers, including cancers of the breast, ovary, gastrointestinal tract, head and neck, brain, bladder, and lung. LY6K is required for ERK-AKT and TGF-β pathways in cancer cells and is required for in vivo tumor growth.

Use of Longitudinal Serum Analysis and Machine Learning to Develop a Classifier for Cancer Early Detection.

Early detection of solid tumors through a simple screening process, such as the proteomic analysis of biofluids, has the potential to significantly alter the management and outcomes of cancers. The application of advanced targeted proteomics measurements and data analysis strategies to uniformly collected serum or plasma samples would enable longitudinal studies of cancer risk, progression, and response to therapy that have the potential to significantly reduce cancer burden in general. In this article, we describe a generalizable workflow combining robust, multiplexed targeted proteomics measurements applied to longitudinal samples from the Department of Defense Serum Repository with a Random Forest machine learning method for developing and initially evaluating the performance of candidate biomarker panels for early detection of cancers.

Prospective Long-term Health-related Quality of Life Outcomes After Surgery, Radiotherapy, or Active Surveillance for Localized Prostate Cancer.

Background: Localized prostate cancer (PCa) treatment is associated with reduced health-related quality of life (HRQoL). Current literature is limited by short-term follow-up.

Objective: To prospectively evaluate the 5-yr HRQoL outcomes in men undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), or active surveillance (AS).

Development of fluorophore labeled or biotinylated anticancer small molecule NSC243928.

Small molecule NSC243928 binds with LY6K, a potential target for the treatment of triple-negative breast cancer, and induces cancer cell death with an unclear mechanism. We have developed chemical tools to identify the molecular mechanisms of NSC243928-LY6K interaction. Herein, we report on the development and synthesis of biotinylated and fluorophore-tethered derivatives of NSC243928 guided by docking studies and molecular dynamics.

Five-year survival of patients with late-stage prostate cancer: comparison of the Military Health System and the U.S. general population.

Background: While the 5-year survival rate for local and regional prostate cancer is nearly 100%, it decreases dramatically for advanced tumours. Accessibility to health care is an important factor for cancer prognosis. The U.

Cancers of unknown primary: Survival by histologic type, demographic features, and treatment in the U.S. Military Health System.

Background: Cancers of unknown primary (CUP), a group of heterogenous metastatic cancers lacking a known primary site, have poor prognosis. This study compared survival of CUP by histologic type, patient characteristics, and treatment in the U.S.