Impact of Gender of the Child on Health Care-Seeking Behavior of Caregivers of Childhood Patients With Cancer: A Mixed-Methods Study.

Purpose: Gender bias against girls may affect health-seeking behavior and outcomes of childhood cancer. This study aimed to study the nature and extent of gender bias in health care among caregivers of childhood patients with cancer and also in community.

Methods: This cross-sectional mixed-methods study was conducted in a tertiary cancer hospital and an urban community between July 2021 and July 2023.

Outcomes following transition from ibrutinib to zanubrutinib in patients with Waldenström macroglobulinemia from ASPEN.

Zanubrutinib is a next-generation covalent Bruton tyrosine kinase (BTK) inhibitor designed to provide complete and sustained BTK occupancy for efficacy across disease-relevant tissues, with fewer off-target adverse events (AEs) than other covalent BTK inhibitors. In the phase 3 ASPEN study (BGB-3111-302), comparable efficacy and a favorable safety profile versus ibrutinib were demonstrated in patients with MYD88-mutated Waldenström macroglobulinemia (WM), leading to approval of zanubrutinib for patients with WM. BGB-3111-LTE1 (LTE1) is a long-term extension study to which eligible patients, including patients from comparator treatment arms, could enroll following participation in various parent studies of zanubrutinib to treat B-cell malignancies.

Real-world outcomes of neoadjuvant chemoimmunotherapy in patients with nonsmall cell lung cancer: Predictors of surgery, pathologic complete response, and event-free survival.

Background: Trials of neoadjuvant chemoimmunotherapy (chemoIO) have changed the standard of care for resectable nonsmall cell lung cancer (NSCLC). This study characterizes the outcomes of off-trial patients who received treatment with neoadjuvant chemoIO.

Methods: The authors analyzed records of patients with stage IB-III NSCLC who received neoadjuvant chemoIO with an intent to proceed to surgical resection at three US academic institutions.

Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B).

Purpose: WU-KONG1B (ClinicalTrials.gov identifier: NCT03974022) is a multinational phase II, dose-randomized study to assess the antitumor efficacy of sunvozertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertion mutations (exon20ins).

Methods: Eligible patients with advanced-stage exon20ins NSCLC were randomly assigned by 1:1 ratio to receive sunvozertinib 200 mg or 300 mg once daily (200 and 300 mg-rand cohorts).

Colorectal Cancer Surgical Pathology: Comparative Study in Lebanon Before and After the Economic Collapse.

Background And Objectives: Colorectal cancer (CRC) screening and early detection reduce mortality. Curative treatment is based on surgical resection, and pathological analysis plays a key role in management. In Lebanon, the impact of the COVID-19 pandemic on healthcare has been compounded by an unprecedented socio-economic crisis in 2020.

Randomized Sham Controlled Trial of Targeted Lung Denervation in Patients with COPD (AIRFLOW-3).

Rationale: AIRFLOW-3 was a 1:1 randomized, double blind, sham controlled trial of the d'Nerva Targeted Lung Denervation (TLD) System in patients with COPD.

Objective: Evaluate the impact of TLD on COPD exacerbations compared to optimal medical treatment.

Methods: AIRFLOW-3 patients were symptomatic (CAT ≥10) with moderate to very severe airflow obstruction (25% ≤ FEV ≤ 80% predicted) and GOLD E status (≥2 moderate or ≥1 severe exacerbation over prior 12 months).

Fixed-Duration Epcoritamab Plus R2 Drives Favorable Outcomes in Relapsed or Refractory Follicular Lymphoma.

Epcoritamab is a subcutaneous CD3xCD20 bispecific antibody approved as monotherapy for relapsed/refractory (R/R) follicular lymphoma (FL). We evaluated fixed-duration epcoritamab with rituximab plus lenalidomide (R2) in R/R FL in arm 2 of EPCORE® NHL-2 (phase 1b/2; NCT04663347). Patients received epcoritamab (2 step-up doses, then 48-mg full doses) for up to 2 years and R2 for up to 12 cycles (28 days/cycle).

Systematic engineering of TROP2-targeted CAR T-cell therapy overcomes resistance pathways in solid tumors.

Antibody-based therapies have revolutionized cancer treatment but have several limitations. These include: down-regulation of the target antigen; mutation of the target epitope; or in the case of antibody drug conjugates (ADCs), resistance to the chemotherapy warhead. Since TROP2-targeted therapy with ADCs yields responses in TROP2+ solid tumors but lacks the durability observed with other immunotherapy-based approaches, we developed novel TROP2-targeting chimeric antigen receptor (CAR) T cells as an alternative.

Emerging HER2 Targeting Immunotherapy for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a fatal bile duct malignancy. CCA is intrinsically resistant to standard chemotherapy, responds poorly to it, and has a poor prognosis. Effective treatments for cholangiocarcinoma remain elusive, and a breakthrough in CCA treatment is still awaited.

Contemporary Characteristics and Outcomes of Pediatric Oncology Patients Participating in Early Phase Clinical Trials.

Background: Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development. Currently, there is a paucity of information regarding contemporary outcomes for pediatric patients enrolled in these trials. We describe characteristics and outcomes of patients enrolled in pediatric phase 1 clinical trials over a 9-year period at a single institution.

How I treat Ph+ acute lymphoblastic leukemia.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by the fusion gene which produces a constitutively active tyrosine kinase which drives disease pathogenesis and is associated with resistance to conventional chemotherapy. Intensive cytotoxic chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT), the historical treatment paradigm for Ph+ ALL, was associated with poor outcomes. The introduction of inhibitors of ABL1 revolutionized the treatment of Ph+ ALL.

Precursor plasma cell disorders: Classification, risk stratification, and emerging role of early interception.

Precursor plasma cell disorders include monoclonal gammopathy of undermined significance (MGUS) and smoldering multiple myeloma (SMM). These conditions carry a variable risk of progression to symptomatic myeloma and there are ongoing efforts to improve risk stratification to identify patients that are at highest risk of progression. Advanced imaging plays a crucial role in diagnosis and monitoring, and more sensitive tools to measure serum monoclonal proteins and circulating tumor cells are being developed.

Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model.

Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). However, some patients may still not be treated with venetoclax combinations due to frailty concerns. We evaluated efficacy and safety of venetoclax plus azacitidine vs.

Patterns of immunity changes predict response to stereotactic ablative radiotherapy in early non-small-cell lung cancer.

Background: Stereotactic Ablative Radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC) can stimulate an immune response against cancer. We evaluated changes in peripheral lymphocyte subpopulations and cytokines levels after SABR in patients with early-stage NSCLC. We examined how these changes relate to overall survival (OS) and disease-free survival (DFS).

Advancing preclinical biology for Ewing Sarcoma: an international effort.

Ewing sarcoma (EwS) is an aggressive bone and soft tissue cancer affecting adolescents and young adults. In vitro and in vivo models of EwS have been instrumental in advancing our understanding of EwS biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease where effective treatment options remain limited. Through an international collaborative effort between the Children's Oncology Group (COG) Bone Tumor Committee and the Euro Ewing Consortium (EEC), we review the current landscape of preclinical modeling used in EwS research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and non-mammalian xenografts) model systems.

Staff Perspectives on Normalizing and Sustaining Electronic Patient-Reported Outcomes Monitoring at Six US Health Systems.

Purpose: We assessed the perspectives of staff from six health systems to understand how electronic Symptom Management (eSyM), an eSyM program that supports patients during chemotherapy and after surgery, is normalized and sustained.

Methods: Starting in 2019, we integrated eSyM into routine clinical practice and assessed its effectiveness using a cluster randomized stepped-wedge trial design. At least 1 year after implementation, we administered cross-sectional surveys to elicit the perspectives of physicians, nurses, advanced practice providers (APPs), hospital administrators, information technology, and research staff using the Normalization MeAsure Development (NoMAD) and the Clinical Sustainability Assessment Tool (CSAT).

Biomarkers to optimize PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer.

Although the recently approved prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) [Lu]Lu-PSMA-617 has improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), not all patients respond optimally to this treatment; even measuring response accurately can be difficult. Moreover, there is currently a lack of validated prognostic and predictive biomarkers for [Lu]Lu-PSMA-617 treatment in this patient population. There is, therefore, a growing need to identify biomarkers to help optimize patient selection for [Lu]Lu-PSMA-617 and guide therapy decision-making.

Multi-Trait Polygenic Scores for COPD and COPD Exacerbations Implicate Druggable Proteins.

Objectives: To construct multi-trait polygenic scores (PRS) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validate their performance in diverse cohorts, and identify PRS-related proteins for potential therapeutic targeting.

Design: Prospective cohort studies.

Setting: Genetic Epidemiology of COPD (COPDGene; 2007-present), Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE; 2005-2008), Mass General Brigham Biobank (MGBB; 2010-present), All of Us (2016-present), and UK Biobank (UKB; 2006-present).

Multi-modal characterization of transcriptional programs that drive metastatic cascades to solid sites and ascites in ovarian cancer.

Ovarian high-grade serous carcinoma (HGSC) is characterized by extensive intra-peritoneal dissemination and tumor heterogeneity. In the metastatic cascade, tumors utilize several transcriptional programs to translocate and survive in distant tissues. Here, we analyzed multi-modal, real-world data from 350 tumor samples across 160 patients with HGSC to identify transcriptional programs that drive intra-peritoneal metastasis and heterogeneity.

Effect of bone marrow disease on hematologic toxicity and response to [Lu]Lu-PSMA-617 therapy: insights from PSMA-PET/CT imaging.

Purpose: Despite the effectiveness of [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC), hematologic toxicity remains a concern, particularly in patients with bone metastases. This study evaluated whether the extent, intensity, and heterogeneity of bone disease on pretreatment PSMA-PET/CT were associated with hematologic toxicity, PSA response, and overall survival (OS) in mCRPC patients treated with [Lu]Lu-PSMA-617.

Methods: This retrospective study included 96 mCRPC patients who underwent pretreatment PSMA-PET/CT and received standard-of-care [Lu]Lu-PSMA-617.

Prospective study of circulating metabolomic profiles and breast cancer incidence among predominantly premenopausal women.

Background: Associations between premenopausal plasma metabolites and breast cancer incidence are largely unknown.

Methods: We conducted a prospective, matched case-control study in which we measured pre-diagnostic metabolomic profiles among predominantly premenopausal women in the Nurses' Health Study II (n = 2010). Lipids, carbohydrates, and organic acid-related metabolites (n = 218) were profiled via liquid chromatography-tandem mass spectrometry.

Financial instability, insurance, and transportation influence timely head and neck cancer care in the United States: Patient and healthcare worker perspectives.

Introduction: Delays in head and neck cancer (HNC) diagnosis and treatment and financial burdens of care are often rooted in social determinants of health (SDOH), such as financial instability, socioeconomic status (SES), health insurance status, and transportation barriers. While these factors are well recognized, their underlying impact on access to care remains underexplored; this qualitative study aims to investigate how these SDOH facilitate or hinder HNC care through insights from patients and healthcare workers (HCWs) in the United States, to identify targets for intervention.

Methods: Semi-structured interviews were conducted with patients with newly diagnosed HNC, and HCWs caring for these patients, between June 2022 and July 2023.

Enhanced Cancer Radiosensitization via Energy Transfer from Eu-Doped GdF Nanoparticles to Methylene Blue in X-ray Photodynamic Therapy.

We synthesized europium-doped gadolinium fluoride (GdF:Eu) scintillating nanoparticles conjugated to methylene blue (MB) for singlet oxygen (O) generation in X-ray-induced photodynamic therapy (X-PDT). The impact of MB conjugation on GdF:Eu nanoparticles (GdF@B) was analyzed, including size, polydispersity, and surface charge. Time-resolved photoluminescence analysis demonstrated that binding of MB to the nanoparticle surface is essential for enabling efficient resonant energy transfer (ET) from the GdF:Eu core to the MB molecules.

Immunoprofiling at an Institutional Scale Reveals That High Numbers of Intratumoral CD8 and PD-1 Cells Predict Superior Patient Survival Across Major Cancer Types Independent of Major Risk Factors.

Purpose: Retrospective studies have found associations between the number of intratumoral immune cells and patient outcomes for specific cancers treated with targeted therapies. However, the clinical value of routinely quantifying intratumoral immune biomarkers using a digital pathology platform in the pan-cancer setting within an active clinical laboratory has not been established.

Methods: We developed ImmunoProfile, a daily clinical workflow that integrates automated multiplex immunofluorescence tissue staining, digital slide imaging, and machine learning-assisted scoring to quantify intratumoral CD8, PD-1, CD8PD-1, and FOXP3 immune cells and PD-L1 expression in formalin-fixed, paraffin-embedded tissue samples in a standardized and reproducible manner.