Clinical Applications of Bone Marrow CD34 Immunohistochemistry (BM CD34 IHC) Assay: International Council for Standardization in Hematology (ICSH) Guidelines.

Introduction: Investigation of bone marrow (BM) trephine biopsies and/or clot sections by CD34 immunohistochemistry (IHC) testing has been used by pathologists for several decades, and its clinical value has been well established with QBEND10 being the most frequently used primary antibody (Ab) clone. However, most other parameters related to the IHC protocol as well as the readout vary widely between clinical laboratories and in the published literature. The ICSH Working Group having reviewed the published evidence has established guidelines that will help to harmonize performance and reporting of CD34 IHC on BM biopsies.

Intraoperative Molecular Imaging With Pafolacianine: Histologic Characteristics of Identified Nodules.

Background: With increased early detection efforts, surgery for early-stage lung cancer is expected to rise. Pafolacianine is the first FDA approved targeted optical imaging agent indicated as an adjunct for intraoperative identification of malignant and nonmalignant pulmonary lesions in adult patients with known or suspected cancer in the lung.

Methods: This is a retrospective review of the malignant and nonmalignant lesions identified by pafolacianine with intraoperative molecular imaging (IMI) in the multi-center Phase 2 and Phase 3 ELUCIDATE clinical trials.

First-Line PD-1 Blockade Combined With Chemotherapy for Stage IV Penile Squamous Cell Carcinoma: A Multicenter Retrospective Study.

Background: The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC).

Patients And Methods: A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.

Do Appendiceal Neuroendocrine Tumors Metastasize Post Appendectomy or Right Hemicolectomy?

Background: Neuroendocrine tumors (NETs) of the appendix are typically detected incidentally during appendectomy. Recent studies reported no metachronous metastases among patients with primary tumors <2 cm, regardless of lymph node status or referral for completion hemicolectomy. However, questions persist regarding the possibility of metastases developing decades after surgical resection, particularly because appendiceal NETs are frequently diagnosed in young adults and children.

A fully linearized ADMM algorithm for optimization based image reconstruction.

Background And Objective: Optimization based image reconstruction algorithm is an advanced algorithm in medical imaging. However, the corresponding solving algorithm is challenging because the model is usually large-scale and non-smooth. This work aims to devise a simple and convergent solver for optimization model.

PARP1 promotes tumor proliferation in lenalidomide-resistant multiple myeloma via the downregulation of microRNA-192-5p-AKT signaling.

Background: Lenalidomide-based therapies are recommended as first-line treatment for multiple myeloma (MM) patients, regardless of the transplant eligibility. Resistance to lenalidomide is a clinical problem that urgently needs to be addressed. The expression of poly(ADP-ribose) polymerase 1 (PARP1) is abnormally high in a variety of tumor tissues including MM.

SyntheVAEiser: augmenting traditional machine learning methods with VAE-based gene expression sample generation for improved cancer subtype predictions.

The accuracy of machine learning methods is often limited by the amount of training data that is available. We proposed to improve machine learning training regimes by augmenting datasets with synthetically generated samples. We present a method for synthesizing gene expression samples and test the system's capabilities for improving the accuracy of categorical prediction of cancer subtypes.

Physical activity and incident cardiovascular disease in breast cancer survivors: the pathways study.

Purpose: Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail.

Methods: The Pathways Study is a prospective cohort study of 4,504 women diagnosed with invasive breast cancer between 2005 and 2013.

Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography.

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system x radiotracer, [F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC.

Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology.

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.

NCCN Guidelines® Insights: Survivorship, Version 2.2024.

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel's current recommendations regarding sexual health and fertility.

Direct Oral Anticoagulants in Budd-Chiari Syndrome.

Aims: Budd-Chiari syndrome (BCS) is managed by interventions aimed at relieving hepatic venous obstruction and anticoagulation. Despite robust data supporting the tolerability and efficacy of direct oral anticoagulants (DOACs) in patients with other venous thromboembolism, its utility in BCS is not well documented. This study aims to evaluate the efficacy and tolerability of DOACs in Primary BCS from the available literature.

Cell types or cell states? An investigation of adrenergic and mesenchymal cell phenotypes in neuroblastoma.

Neuroblastoma exhibits two cellular phenotypes: therapy-sensitive adrenergic (ADRN) and therapy-resistant mesenchymal (MES). To understand treatment response, it is important to elucidate how these phenotypes impact the dynamics of cancer cell populations and whether they represent distinct cell types or dynamic cell states. Here, we use an integrated experimental and mathematical modeling approach.

Molecular Pathway and Immune Profile Analysis of IPMN-Derived Versus PanIN-Derived Pancreatic Ductal Adenocarcinomas.

Intraductal papillary mucinous neoplasms (IPMN) are commonly detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need.

Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Changes in Skin Cancer-Related Behaviors, Distress, and Beliefs in Response to Receipt of Low- to Moderate-Penetrance Genetic Test Results for Skin Cancer Risk.

Little is known about the impact of low- to moderate-penetrance genetic testing for skin cancer, which is a promising approach to skin cancer prevention. To address this deficit, we conducted an analysis comparing changes in skin cancer-related behaviors, distress, and beliefs measured at a baseline and twice after the receipt of skin cancer precision prevention materials containing risk feedback (higher or average risk) among 568 non-Hispanic White (NHW) and 463 Hispanic participants. Regression analyses identified decreased average weekend hours in the sun (β = -0.

Oncogenic RAS in Cancers from the DNA Replication Stress and Senescence Perspective.

Rat Sarcoma (RAS)-driven cancers have been one of the main foci in the field of cancer science for over four decades. Despite significant improvement in understanding the biology of RAS oncogene, the method to target RAS-mutated cancers is still unclear. In recent years, the role for RAS beyond its hyperproliferation has been extensively documented.

Exploring Genomic Biomarkers for Pembrolizumab Response: A Real-World Approach and Patient Similarity Network Analysis Reveal DNA Response and Repair Gene Mutations as a Signature.

: Single-agent immune checkpoint inhibitor (IO) therapy is the standard for non-oncogene-addicted advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score ≥ 50%. Smoking-induced harm generates high tumor mutation burden (H-TMB) in smoking patients (S-pts), while never-smoking patients (NS-pts) typically have low TMB (L-TMB) and are unresponsive to IO. However, the molecular characterization of NS-pts with H-TMB remains unclear.

The Role of Radiation, Immunotherapy, and Chemotherapy in the Management of Locally Advanced or Metastatic Cutaneous Malignancies.

Introduction: Skin cancer impacts a significant proportion of the population. While surgical management is often the mainstay of treatment, advanced or metastatic cutaneous malignancies require additional local and/or systemic therapies.

Methods: A review of the literature was performed studying the use of radiation therapy, chemotherapy, and immunotherapy for locally advanced or metastatic cutaneous malignancies.

Effects of Socioeconomic Deprivation on UTUC Staging, Mortality, and Recurrence.

Objectives: To determine whether the area deprivation index (ADI), a surrogate for socioeconomic status (SES) associated with patient residence, affected UTUC staging, recurrence rates, and mortality.

Methods: Patients undergoing radical nephroureterectomy or ureterectomy for UTUC at a single institution between February 2010 to August 2021 were classified by ADI. A 50 percentile cut-off of ADI classified patients as "advantaged" or "disadvantaged.

Association between Locoregional Failure and NFE2L2/KEAP1/CUL3 Mutations in NRG/RTOG 9512: A Randomized Trial of Radiation Fractionation in T2N0 Glottic Cancer.

Purpose: NFE2L2/KEAP1/CUL3 mutations have been validated for radiation resistance in cell-based assays and animal models. However, clinical validation of these biomarkers has been challenging due to multimodality treatment regimens. This study aims to investigate the association between NFE2L2/KEAP1/CUL3 mutations and patient outcomes, including local failure (LF), locoregional failures (LRF), disease-free survival (DFS) and overall survival (OS), using samples from a phase III trial in which patients were treated with radiation monotherapy at 2 controlled doses.

Reirradiation in the Management of Locally Recurrent Rectal Adenocarcinoma.

Rectal cancer recurrence after prior radiotherapy presents a difficult treatment challenge. Salvage treatment can be curative, however, it often requires multimodal therapy which can come with significant treatment related morbidity. Reirradiation is a common part of treatment considerations in this setting and presents challenges in balancing appropriately aggressive therapy to improve disease control and cure rates with the addition of excess toxicity.

Real-World and Clinical Trial Validation of a Deep Learning Radiomic Biomarker for PD-(L)1 Immune Checkpoint Inhibitor Response in Advanced Non-Small Cell Lung Cancer.

Purpose: This study developed and validated a novel deep learning radiomic biomarker to estimate response to immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC) using real-world data (RWD) and clinical trial data.

Materials And Methods: Retrospective RWD of 1,829 patients with advanced NSCLC treated with PD-(L)1 ICIs were collected from 10 academic and community institutions in the United States and Europe. The RWD included data sets for discovery (Data Set A-Discovery, n = 1,173) and independent test (Data Set B, n = 458).