Tumor Absorbed Dose Predicts Survival and Local Tumor Control in Colorectal Liver Metastases Treated with 90Y Radioembolization.

Background: To evaluate predictors of outcomes in colorectal liver metastases (CLM) patients undergoing 90Y radioembolization (TARE), focusing on the impact of tumor absorbed dose.

Materials And Methods: Patients' characteristics and dosimetry assessments were analyzed in 231 patients undergoing 329 TARE sessions from 09/2009 to 07/2023. Response was assessed using RECIST1.

Two-Step Semi-Automated Classification of Choroidal Metastases on MRI: Orbit Localization via Bounding Boxes Followed by Binary Classification via Evolutionary Strategies.

Background And Purpose: The choroid of the eye is a rare site for metastatic tumor spread, and as small lesions on the periphery of brain MRI studies, these choroidal metastases are often missed. To improve their detection, we aimed to use artificial intelligence to distinguish between brain MRI scans containing normal orbits and choroidal metastases.

Materials And Methods: We present a novel hierarchical deep learning framework for sequential cropping and classification on brain MRI images to detect choroidal metastases.

Isatuximab for Relapsed and/or Refractory AL Amyloidosis: Results of a Prospective Phase 2 Trial (SWOG S1702).

Isatuximab is an IgG1k monoclonal antibody that binds with high affinity to CD38 expressed on plasma cells. Anti-CD38 antibodies have shown efficacy as monotherapy and in combination in a variety of settings for patients with multiple myeloma and light chain (AL) amyloidosis. This multi-center, cooperative group phase 2 trial was designed to evaluate hematologic response, organ response, and safety of isatuximab monotherapy for the treatment of relapsed AL amyloidosis.

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.

Plasma lipidome dysregulation in frontotemporal dementia reveals shared, genotype-specific, and severity-linked alterations.

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

The Discovery of RP-2119: A Potent, Selective, and Orally Bioavailable Polθ ATPase Inhibitor.

DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.

The International Association for the Study of Lung Cancer Staging Project: The Impact of Common Molecular Alterations on Overall Survival in NSCLC in Initial Analyses of the IASLC Ninth Edition Staging Database.

Introduction: TNM staging systems create prognostic categories by anatomic extent of disease. Whether therapeutically important molecular alterations in NSCLC augment the prognostic information of TNM staging is unclear. To study this, we analyzed molecular data from the ninth edition of the lung cancer staging system.

The International Association for the Study of Lung Cancer Staging Project: The Impact of Smoking Status on Lung Cancer Staging in the Ninth Edition of the TNM Classification.

Introduction: Cigarette smoking negatively affects lung cancer prognosis. Incorporating smoking history into stage-stratified survival analyses may improve prognostication.

Methods: Using the International Association for the Study of Lung Cancer ninth edition NSCLC database, we evaluated the association between smoking status at diagnosis and overall survival (OS) using Kaplan-Meier plots and multivariate Cox proportional hazard regression models adjusted for age, region, sex, histologic type, performance status, and TNM stage.

Extrachromosomal DNA-Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma.

Unlabelled: Oncogenes amplified on extrachromosomal DNA (ecDNA) contribute to treatment resistance and poor survival across cancers. Currently, the spatiotemporal evolution of ecDNA remains poorly understood. In this study, we integrate computational modeling with samples from 94 treatment-naive human glioblastomas (GBM) to investigate the spatiotemporal evolution of ecDNA.

Guidelines for meta-analyses and systematic reviews in urology.

In an effort to improve the quality of systematic reviews and meta-analysis in the clinical urology literature, a group of statisticians developed a set of guidelines to address common errors of analysis, reporting and interpretation. One key focus is the assessment and interpretation of between-studies heterogeneity. Application of the guidelines will help avoid 'cookie cutter science' and lead to more considered analysis and interpretation of systematic reviews and meta-analyses.

False equivalence: differences in the activity of ampicillin-sulbactam and amoxicillin-clavulanate in several Enterobacterales species.

Background And Objectives: The β-lactam/β-lactamase inhibitor combinations ampicillin-sulbactam (SAM) and amoxicillin-clavulanate (AMC) are frequently used to treat Enterobacterales infections and are often assumed to be interchangeable, leading some clinical microbiology laboratories to report antimicrobial susceptibility testing (AST) results for only one of these agents. Given differences in β-lactamase inhibition between sulbactam and clavulanate, we hypothesized that the activities of SAM and AMC may differ.

Methods: To understand the prevalence of discordant SAM and AMC susceptibility results in Enterobacterales species, we analysed AST results obtained by broth microdilution (MicroScan WalkAway, Beckman Coulter) for Enterobacterales isolates recovered from clinical specimens between 2018 and 2022 at an academic medical centre in New York City.

Flap Complications Following Maxillectomy, Reconstructive Surgery, and Postoperative Proton Radiotherapy: A Cohort Study and Considerations for Risk Mitigation.

Background: Flap complications following maxillectomy, reconstruction, and adjuvant proton beam therapy (PBT) for primary maxillary and sinonasal malignancies are not well described.

Methods: This retrospective cohort study included consecutive patients treated between 2016 and 2023 from a single-institutional database.

Results: Thirteen patients were identified with a median follow-up of 26 months.

A Bayesian Multi-Factorial Design and Analysis for Estimating Combined Effects of Multiple Interventions in a Pragmatic Clinical Trial to Improve Dementia Care.

Factorial study designs can be important for understanding the effectiveness of interventions when multiple interventions are under investigation. In this design setting, a unit of randomization can be assigned to any combination of interventions. The rationale for taking this kind of approach can vary depending on the specific questions targeted by the research.

Guidelines for Meta-analyses and Systematic Reviews in Urology.

Our guideline comprises points addressing the conduct and interpretation of systematic reviews and meta-analyses in urology. Application of the guideline would lead to a more considered interpretation of a smaller number of systematic reviews and meta-analyses, and could thus help in translating evidence into better decision-making for doctors and patients.

Oncologic Anthropology and the African Diaspora: Twenty-Year Anniversary Report, International Center for the Study of Breast Cancer Subtypes (ICSBCS).

The International Center for the Study of Breast Cancer Subtypes (ICSBCS) has played a vital role in defining and overcoming many inequities that exist in breast cancer treatment and outcome on a global basis through capacity-building programs that improve the management of breast cancer patients across the African diaspora. ICSBCS activities also fill critical gaps in disparities research related to the genetics of ancestry. Over the past 20 years, ICSBCS teams have spearheaded landmark studies documenting the relevance of genetic African ancestry to breast cancer risk, while also improving the quality of care delivered to patients in diverse communities.

Radiomic biomarkers associated with immune checkpoint blockade response for advanced renal cell carcinoma.

Purpose: Immune checkpoint blockade (ICB) has transformed outcomes for patients with metastatic renal cell carcinoma (mRCC) and has impacted the timing and use of cytoreductive nephrectomy (CN). As ICB responses vary, we evaluated whether radiographic and radiomic biomarkers were associated with clinical and pathological outcomes.

Methods: This retrospective cohort study included ICB-treated mRCC patients without upfront CN.

Guidelines for Meta-analyses and Systematic Reviews in Urology.

Our guideline comprises points addressing the conduct and interpretation of systematic reviews and meta-analyses in urology. Application of the guideline would lead to a more considered interpretation of a smaller number of systematic reviews and meta-analyses, and could thus help in translating evidence into better decision-making for doctors and patients.

Impact of Population Pharmacogenomics on Cisplatin-Induced Neurotoxicities in Testicular Cancer Survivors.

Background: Cisplatin is a commonly used chemotherapeutic across numerous cancer types that can cause neurotoxicities in patients, including peripheral sensory neuropathy, tinnitus, hearing loss, and vertigo.

Objective: We aimed to evaluate, for the first time, how genetic ancestry impacts cisplatin-induced neurotoxicities and if disparities are related to population differences in allele frequency.

Methods: In a cohort of cisplatin-treated testicular cancer survivors, relationships between genetic ancestry and neurotoxicities, medications, and lifestyle factors were assessed using logistic regression and Kruskal-Wallis tests and multiple pairwise comparisons using the Wilcoxon rank-sum test (Benjamini-Hochberg adjustment).

Building effective relationships in global surgery: an exploratory qualitative study.

Background: The rise in malignant hepatopancreatobiliary tumors disproportionately affects low- and middle-income countries (LMICs) due to systemic challenges. In 2023, the International Hepatopancreatobiliary Association (IHPBA) launched a relationship-building initiative to mitigate outcome disparities by increasing capacity and quality. This study aimed to understand the dynamics and value of such collaborations.

High transposable element expression in sarcomas is associated with increased immune infiltrates and improved outcomes including after immunotherapy.

Background: Response to immune checkpoint inhibition (ICI) in sarcomas is overall low and heterogeneous. Understanding determinants of ICI outcomes may improve efficacy and patient selection. Thus, we investigated whether the expression of transposable elements (TEs), which are epigenetically silenced and can stimulate antitumor immunity, influence ICI outcomes and immune infiltrates in common sarcoma subtypes.

Activity-based probes and chemical proteomics uncover the biological impact of targeting HMGCS1 in the mevalonate pathway.

Mevalonate is a precursor for essential metabolites, such as isoprenoids and sterols. Its synthesis starts with HMGCS1 producing HMG-CoA, which is then converted to mevalonate by HMGCR, a target of statins. Cancer cells often upregulate enzymes in the mevalonate pathway (MVP) to meet their metabolic demands, leading to the development of inhibitors targeting several enzymes in this pathway.