Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

Clonal Hematopoiesis in Women With Breast Cancer.

Purpose: Clonal hematopoiesis (CH) has been associated with a variety of adverse outcomes, most notably hematologic malignancy and ischemic cardiovascular disease. A series of recent studies also suggest that CH may play a role in the outcomes of patients with solid tumors, including breast cancer. Here, we review the clinical and biological data that underlie potential connections between CH, inflammation, and breast cancer, with a focus on the prevalence and impact of clonal hematopoiesis of indeterminate potential in patients with breast cancer.

The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.

The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting.

Perceptions of Palliative Care Among Patients With Kidney Allograft Dysfunction: A Qualitative Study.

Rationale & Objective: Nearly half of kidney transplant recipients develop allograft failure within 10 years of transplantation and experience high mortality, significant symptom burden, and complex communication challenges. These patients may benefit from palliative care, but palliative care is infrequently provided in this population. This study explores palliative care perceptions and needs among patients with poorly functioning and declining kidney allografts.

Multicenter Retrospective Analysis of Pediatric Differentiated Thyroid Carcinoma: Treatment Practices and Outcomes Prior to Pediatric American Thyroid Association Guidelines Implementation.

Background: Differentiated thyroid carcinoma (DTC) is the most common pediatric thyroid malignancy, with papillary thyroid carcinoma (PTC) representing 90% of the cases. In 2015, the American Thyroid Association (ATA) developed management guidelines for pediatric DTC.

Procedure: Patients less than 21 years of age diagnosed with DTC between 2000 and 2015 at Texas Children's Hospital, Seattle Children's Hospital, Children's Healthcare of Atlanta, Children's Hospital Colorado, and Nationwide Children's Hospital were retrospectively analyzed to evaluate treatment practices before the implementation of the ATA guidelines.

Distinct molecular and clinical features of specific variants of KRAS codon 12 in pancreatic adenocarcinoma.

PURPOSE Oncogenic mutations in KRAS have been identified in > 85% of pancreatic ductal adenocarcinoma (PDAC) cases. G12D, G12V, and G12R are the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRAS G12D and G12R.

Phase I study of adavosertib with radiation therapy and temozolomide in newly diagnosed glioblastoma and intratumoral drug levels in recurrent glioblastoma.

Purpose: Adavosertib is an oral small molecular inhibitor of Wee1. The Adult Brain Tumor Consortium performed a phase I study of adavosertib, radiation (RT) and temozolomide (TMZ) in newly diagnosed glioblastoma (GBM) as well as a surgical window of opportunity study in recurrent GBM.

Patients And Methods: The maximum tolerated dose (MTD) of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in 2 separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ.

Genomic Profiling of Cardiac Angiosarcoma Reveals Novel Targetable KDR Variants, Recurrent MED12 Mutations and a High Burden of Germline POT1Alterations.

Purpose: Cardiac angiosarcoma (CAS) is a rare, aggressive malignancy with limited treatment options. Both sporadic and familial cases occur, with recent links to germline POT1 mutations. The genomic landscape of this disease is poorly understood.

Racial discrimination among women seeking breast cancer care.

Discrimination can contribute to worse health outcomes, but its prevalence in breast cancer is not well studied. We aimed to understand how women with stage I-III breast cancer faced discrimination in health care and everyday settings through the Everyday Discrimination Scale, cross-sectional survey. 296 women, 178 (60%) Non-Hispanic White (NHW), 76 (26%) Non-Hispanic Black (NHB), and 42 (14%) Hispanic participated.

Utility of ursodiol prophylaxis against sinusoidal obstruction syndrome (SOS)/ veno-occlusive disease (VOD) in acute leukemia patients receiving gemtuzumab-ozogamicin (GO) or inotuzumab-ozogamicin (InO).

Purpose: Sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) is a serious complication in hematopoietic stem-cell transplant (HSCT) patients. Gemtuzumab-ozogamicin (GO) and InO are known to cause SOS/VOD in leukemic and transplant populations. Due to limited data on ursodiol prophylaxis in non-HSCT patients, we aimed to assess hepatotoxicity, SOS/VOD incidences, time to hepatotoxicity, and confirmed SOS/VOD in adults receiving GO or InO ± ursodiol.

Drivers and barriers to health-seeking behaviors and interactions: a qualitative study of Black patients with lung cancer and with peripheral artery disease.

Objective: To identify factors that may influence health-seeking behaviors and health system interactions from the perspective of Black patients with lung cancer (LC) or peripheral artery disease (PAD).

Methods: Semi-structured interviews were conducted virtually with Black patients in the United States. Thematic analysis of interview transcripts was performed.

Psychosocial impact associated with a multicancer early detection test (PATHFINDER): a prospective, multicentre, cohort study.

Background: PATHFINDER was a prospective cohort study of multicancer early detection (MCED) testing in an outpatient ambulatory population. The aim of this study is to report the patient-reported outcomes (PROs) collected as secondary and exploratory measures in the PATHFINDER study.

Methods: PATHFINDER is a prospective, multicentre, cohort study that enrolled existing healthy ambulatory outpatients at seven health networks in the USA, including hospitals, academic medical centres, and integrated health systems.

An implantable system for opioid safety.

Naloxone can effectively rescue victims from opioid overdose, but less than 5% survive due to delayed or absent first responder intervention. Current overdose reversal systems face key limitations, including low user adherence, false positive detection, and slow antidote delivery. Here, we describe a subcutaneously implanted robotic first responder to overcome these challenges.

Artificial intelligence-based biomarkers for treatment decisions in oncology.

The development of new therapeutic strategies such as immune checkpoint inhibitors (ICIs) and targeted therapies has increased the complexity of the treatment landscape for solid tumors. At the current rate of annual FDA approvals, the potential treatment options could increase by tenfold over the next 5 years. The cost of personalized medicine technologies limits its accessibility, thus increasing socioeconomic disparities in the treated population.

Addition of an NK1 receptor antagonist to standard antiemetic prophylaxis in patients with B-cell lymphoma receiving EPOCH.

Introduction: Data on the optimal management of patients with hematologic malignancies and chemotherapy-induced nausea and vomiting (CINV) are lacking, particularly for multiday chemotherapy regimens. We report our institutional experience in patients with B-cell lymphoma receiving multiday dose-adjusted R-EPOCH chemotherapy utilizing two CINV prophylaxis strategies.

Methods: We performed a retrospective, single-center, cohort study evaluating hospitalized patients with aggressive non-Hodgkin B-cell lymphoma receiving DA-R-EPOCH (April 2016 to October 2022).

Rethinking the rise of early onset gastrointestinal cancers: a call to action.

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend.

Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.

Background: Natural killer (NK) cells are important contributors to antitumor immunity in clear-cell renal cell carcinoma (ccRCC). However, their phenotype, function, and association with clinical outcomes in ccRCC remain poorly understood.

Materials And Methods: We analyzed single-cell RNA sequencing data from 13 primary tumors, 1 localized tumor extension, and 1 metastasis from ccRCC patients at different clinical stages.

Comparison of two alternative sequences with cabazitaxel and 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: A retrospective multicenter study (LuCaS).

Background: Cabazitaxel and Lu-PSMA-617 have been shown to improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and androgen receptor pathway inhibitors (ARPI). we aimed to evaluate the impact of sequencing cabazitaxel and Lu-PSMA-617 on survival outcomes in patients with mCRPC.

Patients And Methods: This is a retrospective, multicenter, cohort study which included patients with mCRPC who received sequential treatment with Lu-PSMA-617 and cabazitaxel between January 2015 and December 2023.

Nivolumab to restore T-cell fitness in CAR-T refractory multiple myeloma.

Efficacy and durability remain central shortcomings of T-cell based therapies in multiple myeloma (MM). Here, we employ blood-based transcriptional T-cell profiling to define impaired T-cell fitness as putative biomarker associated with sensitivity to PD1 inhibition in CAR-T refractory MM patients.

Recurrence Patterns and Management after Pleurectomy Decortication for Pleural Mesothelioma.

Objective: We hypothesize that recurrence following pleurectomy decortication (PD) is primarily local. We explored factors associated with tumor recurrence patterns, disease-free interval (DFI), and post-recurrence survival (PRS).

Summary Background Data: Tumor recurrence is a major barrier for long-term survival after pleural mesothelioma (PM) surgery.