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.

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.

Anti-tumor activity of trastuzumab deruxtecan in pediatric solid tumors with variable HER2 expression.

Trastuzumab deruxtecan (T-DXd) is a HER2-targeting antibody-drug conjugate (ADC) with efficacy across adult cancers exhibiting variable HER2 expression. Prior studies demonstrating HER2 expression in osteosarcoma (OS) motivated a clinical trial of T-DXd in pediatric and adolescent/young adults with OS but was terminated early for inactivity. We evaluated the activity of T-DXd using OS patient-derived xenograft (PDX) models and found a 22% objective response rate despite no detectable HER2 expression across PDXs tested.

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).

Changes in Cost of Guideline-Concordant Cancer Treatment: Observations and Implications.

Purpose: Cost of cancer care in the United States is substantial. Previous studies have explored pricing comparisons at the level of individual cancer drugs but not that of clinical indications. This study evaluates cost patterns for providing the best guideline-concordant therapy for solid tumor treatment indications.

PAX3-FOXO1 Drives Targetable Cell State-Dependent Metabolic Vulnerabilities in Rhabdomyosarcoma.

PAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. Here, we showed that PAX3-FOXO1+ RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved in de novo pyrimidine synthesis, including dihydrofolate reductase (DHFR). Consequently, PAX3-FOXO1+ cells displayed increased sensitivity to inhibition of DHFR by the chemotherapeutic drug methotrexate, and this dependence was rescued by provision of pyrimidine nucleotides.

Enkephalin-producing regulatory T cells in the skin restrain local inflammation through control of nociception.

The skin integrates diverse signals discerned by sensory neurons and immune cells to elicit adaptive responses to a range of stresses. Considering interactions between nervous and immune systems, we examined whether regulatory T (T) cells, which suppress systemic and local inflammation, can modulate activation of peripheral neurons. Acute T cell "loss of function" increased neuronal activation to noxious stimuli independently of their immunosuppressive function.

Seizure-Related Homolog Protein 6 (SEZ6): Biology and Therapeutic Target in Neuroendocrine Carcinomas.

Seizure-related homolog protein 6 (SEZ6) is a cell surface type 1 transmembrane protein involved in neuronal development, expression of which in adult tissues is almost exclusively limited to the central nervous system. Aberrant expression of SEZ6 has been associated with neurodevelopmental and psychiatric disorders including epilepsy, schizophrenia, and Alzheimer's disease. More recently, SEZ6 overexpression has been detected in small cell lung cancer (SCLC) and other high-grade neuroendocrine malignancies, although our understanding of the function of SEZ6 as a driver of cancer is limited.

Evaluating Breast Cancer Intravoxel Incoherent Motion MRI Biomarkers across Software Platforms.

Purpose To evaluate intravoxel incoherent motion (IVIM) biomarkers across different MRI vendors and software programs for breast cancer characterization in a two-site study. Materials and Methods This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included 106 patients (with 18 benign and 88 malignant lesions) who underwent bilateral diffusion-weighted imaging (DWI) between February 2009 and March 2013. DWI was performed using 1.

"An HIV Free Generation": A Qualitative Inquiry Into Mapping Intersectional Discourses of Preexposure Prophylaxis for Women Among Female Nurses in Rural South Africa.

South Africa has one of the highest HIV prevalence rates in the world, with women and girls bearing the greatest burden. Although HIV preexposure prophylaxis (PrEP) is effective, data on its implementation in rural South Africa remain limited. Our study explores how female nurses in Msinga, South Africa, navigate communal hopes and anxieties regarding PrEP for women.

Genetically determined body mass index is associated with diffuse large B-cell lymphoma in polygenic and Mendelian randomization analyses.

Obesity has been associated with non-Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome-wide association studies of European ancestry (N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.

Enhancing Early Detection of Pancreatic Cancer in Genetically Predisposed Individuals: Integrating Advanced Imaging Modalities with Emerging Biomarkers and Liquid Biopsy.

Purpose: Pancreatic cancer is one of the most lethal malignancies, with a five-year survival rate rarely exceeding 10%. Due to its asymptomatic onset, it is frequently diagnosed at an advanced and often inoperable stage. This review assesses current strategies for early detection, including genomic testing, advanced imaging technologies, and biomarker-based platforms, with a focus on their clinical utility and integration into surveillance protocols.

Genetic suppression of precocious transcription termination identifies mutations in essential subunits of the fission yeast cleavage and polyadenylation machinery.

The fission yeast phosphate acquisition (PHO) regulon is repressed under phosphate-replete conditions by upstream lncRNA-mediated transcriptional interference. Inositol-1-pyrophosphates control phosphate homeostasis via their action as agonists of precocious PHO lncRNA 3'-processing/termination. Inositol pyrophosphatase-inactivating mutations that increase inositol-1-pyrophosphates elicit derepression of the PHO genes and a severe growth defect in YES medium.

Lesion Analysis of F-Metafluorobenzylguanidine PET Imaging in Neuroblastoma.

A PET analog of metaiodobenzylguanidine (MIBG)-F-metafluorobenzylguanidine (F-MFBG)-allows for rapid same-day imaging. We previously reported on the safety and feasibility of F-MFBG PET imaging in patients with neuroendocrine tumors. We now report a comprehensive analysis of lesion detection with F-MFBG imaging in patients with neuroblastoma compared with I-MIBG imaging.

Target volume delineation of the neck for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, the Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology collaboratively developed evidence-based guidelines and a comprehensive contouring atlas for neck target volume delineation in nasopharyngeal carcinoma. These guidelines address five key challenges in modern radiotherapy practice: margin design of clinical target volume; nodal target volume delineation after induction chemotherapy; delineation of equivocal nodes evident on imaging; low-risk clinical target volume delineation based on regional stepwise extension patterns; and modifications for anatomical boundaries of lymphatic areas. Developed through a rigorous systematic review and expert appraisal process by a panel of 50 international, multidisciplinary members from 17 countries and regions, these guidelines incorporate the latest advances in nasopharyngeal carcinoma diagnosis and treatment.

Primary target volume delineation for radiotherapy in nasopharyngeal carcinoma: CSTRO, CACA, CSCO, HNCIG, ESTRO, and ASTRO guidelines and contouring atlas.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology jointly developed evidence-based guidelines and a contouring atlas for primary target volume delineation for radiotherapy in nasopharyngeal carcinoma. The guidelines systematically address three crucial challenges: margin design of clinical target volumes; target volume delineation after induction chemotherapy; and low-risk clinical target volume delineation based on local stepwise extension patterns. Based on a comprehensive systematic review and critical appraisal by an international multidisciplinary panel of 50 nasopharyngeal carcinoma specialists from 17 countries and regions, these guidelines are in keeping with advances in nasopharyngeal carcinoma diagnosis and treatment, embodying contemporary treatment concepts, and elaborating on the differences in practice.