The expanding clinical use of Antibody-Drug Conjugates (ADCs) necessitates a clearer understanding of their real-world toxicity profiles across diverse clinical settings. This retrospective pharmacovigilance study analyzed 19,697 adverse event (AE) reports for seven approved ADCs from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2025). Using disproportionality analysis validated by multivariable logistic regression, we identified safety signals for both monotherapy and combination regimens. The analysis revealed that toxicity profiles are strongly driven by an ADC's molecular structure and treatment setting. Target-specific 'on-target, off-tumor' effects were prominent, linking Nectin cell adhesion molecule 4 (NECTIN-4) targeting to skin reactions, Trophoblast cell-surface antigen 2 (TROP2) to gastrointestinal toxicities, and both folate receptor α (FRα) and tissue factor (TF) to ocular disorders. Furthermore, payload and linker types drove distinct toxicities; topoisomerase I inhibitors were associated with increased respiratory toxicity and mortality, while non-cleavable linkers conferred a significantly stronger risk of hepatobiliary toxicity. Combination regimens not only amplified specific risks, such as endocrine disorders with immune checkpoint inhibitors (ICIs), but also fundamentally reshaped toxicity kinetics, accelerating AE onset with ICIs while significantly delaying it with other combinations. This real-world analysis confirms that ADC toxicities are highly specific to their molecular design and clinical context, highlighting that understanding these complex structural and kinetic interplays is essential for optimizing safety management in clinical practice.

Differences in socioeconomic status and ethnicity are linked to disparities in health outcomes, which can affect how consistently patients treat abnormal screening results and cause minority groups to be diagnosed at more advanced stages of disease.

To compare epidemiological and clinical parameters between Jewish and Arab women who were diagnosed with cervical cancer at Ziv Medical Center during a 10-year period.

We conducted a retrospective study of consecutive women diagnosed with cervical cancer at a single institution between 2014 and 2024.

Overall, 83 women diagnosed with cervical cancer in the last 10 years at Ziv Medical Center were included in the study: 53 Jewish (64.6%), 30 Arab (36.2%). The groups were similar in mean age at diagnosis, body mass index, smoking status, Pap history performance prior to the diagnosis, menopause status at diagnosis, stage at diagnosis, and treatment. Arab women had higher parity (< 0.001). According to the results of our study, the percentage of cervical cancer patients undergoing Pap screening, prior to diagnosis from the Arab and Jewish sectors, were 16.7% and 17%, respectively, compared to the national screening rate of 54%. Most of the women were diagnosed at an advanced stage (≥ IIB): 83.3% and 69.8%, respectively, compared to 25% in developed countries.

Jewish and Arab women diagnosed with cervical cancer in northern Israel do not differ in epidemiological and clinical parameters, including age at diagnosis and stage. These findings may be attributed to the low performance rate of Pap screening tests in both groups.

This article presents the "Stronger Than Yourself" program, developed within the integrative medicine service of the Oncology Department of Schneider Children's Medical Center of Israel. The program was designed to improve treatment adherence among pediatric oncology patients, with particular emphasis on oral medication intake. We describe the case of a 7.5-year-old girl diagnosed with acute lymphoblastic leukemia (ALL), who persistently refused to take her prescribed medication and struggled to cooperate with the medical team. Her condition required a tailored intervention to enable continuation of essential treatment. The "Stronger Than Yourself" program combines principles of empowerment and self-control, active parental guidance, and the use of mind-body modalities, such as touch, movement, guided imagery, and mindfulness. Through an individualized integrative intervention, her emotional and behavioral barriers were reduced, resulting in significant improvement in cooperation and full regular medication adherence. Since its launch in 2017, the program has supported more than 200 children, with the vast majority achieving independent and sustained medication intake. The model has been recognized by the professional community and presented internationally. This case demonstrates the potential of a focused integrative approach to address common barriers to medication adherence in pediatric oncology, to reduce distress, and strengthen coping in children and families. Further research is warranted to consolidate the model and extend its implementation in other pediatric care settings.

Trophoblast cell surface antigen 2 (Trop-2) is a targetable transmembrane glycoprotein commonly overexpressed in breast cancer (BC). This study combines a systematic review and meta-analysis with a retrospective analysis of an independent early BC patient cohort, aiming to investigate the expression patterns of Trop-2 and their clinical significance in BC.

A systematic literature search was conducted up to October 2025 to identify studies evaluating Trop-2 protein expression levels and clinical outcomes in patients with BC receiving Trop-2-directed antibody-drug conjugates (ADCs) or chemotherapy. Random-effects meta-analyses were performed to estimate pooled Trop-2 positivity rates and to assess progression-free (PFS) and overall survival (OS) across Trop-2 expression levels. Additionally, an association analysis between Trop-2 protein and gene expression was performed in an early BC patient cohort (n = 564) using immunohistochemistry and gene expression data. Trop-2 protein expression was assessed using both conventional observer-based methods and digital quantitative image analysis.

A total of 41 studies fulfilled the inclusion criteria. The overall pooled Trop-2 protein positivity rate was 72% [95% Confidence Interval (CI), 67-77%; 41 studies, n = 9170]. Trop-2-directed ADCs improved PFS versus chemotherapy across different H-score groups, with the greatest benefit in tumours with high H-score [3 studies; n = 575; Hazard Ratio (HR) = 0.33, 95% CI 0.20-0.56, p < 0.0001]. For OS, the benefit was observed in the low H-score group (2 studies; n = 272; HR = 0.75, 95% CI 0.57-0.98, p = 0.034). In the study cohort, Trop-2 protein by observer-read assessment was detected in 396/454 patients (87.22%). Digital pathology identified 54 (11.90%) tumours with low, 326 (71.80%) with medium, and 74 (16.30%) with high H-scores. Observer-read and digital assessments were significantly associated (Pearson's chi-square test, p < 0.001). Higher Trop-2 protein and gene expression were associated with worse distant recurrence-free interval (HR_adj = 1.45, 95% CI 1.01-2.08, p = 0.04 and HR_adj = 1.33, 95% CI 1.05-1.68, p = 0.02, respectively), particularly in Luminal B subtype.

Trop-2 was detectable across all BC subtypes, exhibiting a wide range of expression levels. Our study suggests that Trop-2 may have a potential prognostic significance in early BC.

The tumour microenvironment (TME) influences breast cancer progression and treatment response. We investigated whether TME composition predicts tamoxifen benefit in postmenopausal women with oestrogen receptor-positive, HER2-negative (ER+HER2-) breast cancer.

This study included 513 patients from the Stockholm Tamoxifen (STO-3) trial, which randomised postmenopausal, lymph node-negative women to tamoxifen or no endocrine therapy. Bulk tumour transcriptomes were deconvoluted with the ConsensusTME algorithm to estimate the relative abundance of 18 immune and stromal cell types. A summary score of combined immune cells was created on a per patient basis and evaluated alongside fibroblast and endothelial stromal compartments. Patients were categorised into immune and stromal tertiles on the basis of these scores. Associations between TME composition and tumour characteristics were evaluated using Spearman correlations and Fisher's exact test. Tamoxifen benefit was analysed by univariable Kaplan-Meier (log-rank) and multivariable Cox proportional hazards adjusting for age, tumour size, grade, progesterone receptor, Ki-67, and radiotherapy. Differential expression was assessed with limma and pathway enrichment with fgsea using Hallmark gene sets from MSigDB.

Low immune abundance was significantly associated with higher ER expression (Kruskal-Wallis test p < 0.001). Among tamoxifen-treated patients, those with low immune scores showed improved distant recurrence-free interval (DRFI) relative to untreated patients (log-rank p < 0.001). Similarly, intermediate endothelial (p < 0.001) and low/intermediate fibroblast abundances (p = 0.042, p = 0.009) were associated with favourable DRFI. In multivariable models, low immune (adjusted HR = 0.17, 95% CI 0.08-0.40), intermediate endothelial (aHR = 0.21, 95% CI 0.09-0.51), and low/intermediate fibroblast tertiles (aHR = 0.50, 95% CI 0.27-0.93; aHR = 0.36, 95% CI 0.17-0.77) retained significance. Transcriptomic analysis revealed enrichment of oestrogen-response, MYC-target, and oxidative-phosphorylation pathways in low-immune and low-fibroblast tumours, while interferon-γ response and allograft rejection pathways were downregulated.

TME composition modulates tamoxifen benefit in postmenopausal ER+HER2- breast cancer. Low immune, intermediate endothelial, and low/intermediate fibroblast abundances are associated with improved benefit from tamoxifen, suggesting that both immune and stromal compartments influence endocrine treatment efficacy.

Conventional image-guided radiotherapy (IGRT) typically relies on a computed tomography (CT)-based treatment planning process (planning CT, pCT) performed prior to the start of treatment. During this process, a patient-specific treatment plan is generated, which is then delivered to the patient with a linear accelerator on a daily basis, usually with image guidance to compensate for variations in patient setup. However, daily interfractional anatomical variations in target position, shape, and volume, as well as in surrounding organs at risk (OARs), can only be addressed indirectly by adding safety margins, resulting in larger irradiated volumes and potentially increased toxicity. Online adaptive radiotherapy (oART) is a promising and innovative technique to reduce such margins and, consequently, treatment-related toxicity. It uses daily imaging to generate a "plan of the day" that is aligned with the current patient anatomy, often supported by artificial intelligence (AI), while the patient remains on the treatment couch. Through daily image-guided re-optimization of the radiation treatment (RT) plan on the anatomy of the day, target coverage may also be improved. This approach is particularly attractive in the pelvic region, where high interfractional anatomical variability, for example due to peristalsis or changes in bladder and rectal filling, is frequently observed.

This prospective registry-based cohort study will include patients with pelvic or thoracic tumors with an indication for RT treated with IGRT or oART using the Varian Ethos™ system. The primary endpoint is defined as a 10% reduction in the rate of acute RT related toxicity (≥Common Terminology Criteria for Adverse Events (CTCAE) II°, v5.0) using oART. Secondary endpoints encompass clinical outcomes including late toxicities, tumor control rates, and patient-reported outcomes (PROs), as well as technical factors such as target volume, coverage, dose to OARs and anatomical variability score. While the cohort study compares IGRT versus oART for primary and secondary clinical endpoints, it also evaluates the real oART scenario against two hypothetical control scenarios for technical endpoints.

The introduction of oART promises a reduction in toxicities and improved target volume coverage, potentially resulting in enhanced tumor control rates. It is poised to be a pioneering technology in the field of radiation oncology. Given the absence of a direct comparison between IGRT and oART thus far, the prospective registry-based cohort study PRoART aims to address this gap.

Clinical trial number NCT06185062, Clinicaltrials.gov. Registered 12/14/2023. Last update 07/29/2026.

Acute kidney failure from light chain cast nephropathy is a serious complication of multiple myeloma. Plasma exchange (PLEX) has been used to remove circulating free light chains (FLCs), but its benefit in the modern treatment era remains uncertain. We performed a retrospective multicenter cohort study using the TriNetX Research Network to identify newly diagnosed multiple myeloma cases presenting between 2014 and 2024 with acute kidney failure and FLC levels > 1500 mg/L. Patients were classified by receipt of PLEX within 7 days. Propensity score matching incorporated demographics, comorbidities, laboratory values, and initial myeloma-directed therapies. The primary outcome was dialysis dependence at 90 days. Secondary outcomes included dialysis dependence at 180 days, mortality, renal recovery (creatinine < 2.0 mg/dL), ICU admission within 7 days, and dialysis-free survival. Among 5454 eligible patients, 251 (4.6%) received PLEX. After matching, 248 patients were included in each group. PLEX was not associated with reduced dialysis dependence at 90 (16.1% vs. 18.1%; OR 0.87, 95% CI 0.54-1.39) or 180 days (18.5% vs. 20.2%; OR 0.90, 95% CI 0.58-1.41). Mortality, ICU admission, and dialysis-free survival were also similar. PLEX was not associated with improved dialysis independence or survival, supporting rapid initiation of effective anti-myeloma therapy.

Australia has one of the highest rates of skin cancer globally, and outdoor workers represent a key high-risk population due to prolonged occupational sun exposure. Despite a robust legislative framework mandating comprehensive workplace sun protection, evidence indicates suboptimal implementation and compliance in Australian workplaces. This perspective critically analyses the documented gap between policy and practice, examining the individual, cultural and organisational barriers to effective sun protection. We argue that current workplace policies are insufficient without rigorous enforcement, adequate penalties and a genuine shift in workplace culture. Furthermore, we highlight the pivotal role of occupational health physicians and general practitioners in bridging this gap through patient identification, targeted education, and early skin cancer detection. Closing the policy-practice gap requires a concerted, multi-pronged effort from policymakers, employers, workers, and clinicians to move beyond mere compliance and foster a culture of sun safety.

Robot-assisted partial nephrectomy (RAPN) is an important nephron-sparing approach for renal tumors, with increasing emphasis on postoperative renal functional preservation. Preservation of renal function is clinically relevant in patients with reduced renal reserve or factors associated with future renal decline. However, the global research landscape and emerging trends in this field remain unclear. This study performed a bibliometric analysis of publications related to robot-assisted partial nephrectomy and renal function preservation, with emphasis on functional outcomes and CKD-related concepts identified within the literature. Publications from 2008 to 2026 were retrieved from the Web of Science Core Collection on May 10, 2026. Only English-language articles and reviews were included. Data were analyzed using Excel, VOSviewer, CiteSpace, Charticulator, and Scimago Graphica. A total of 276 publications were included, comprising 245 articles and 31 reviews. Publication output showed steady growth, with peaks in 2017 and 2022. Urology and nephrology were the dominant category. The United States led in publications, citations, and H-index, followed by Italy and China, with collaboration centered mainly on the United States and Italy. Cleveland Clinic and Temple University were leading institutions. Keyword analysis identified partial nephrectomy, ischemia, warm ischemia time, eGFR, small renal mass, and trifecta as major themes. The field has evolved from technical exploration toward ischemia reduction, nephron preservation, standardized outcome reporting, and individualized risk stratification. Future studies should prioritize prospective multicenter designs and standardized renal functional endpoints.

The recognition of mislocalized DNA and RNA by cGAS-STING, RIG-I/MDA5, the OAS-RNase L axis, and endosomal TLR3/7/8 has emerged as a unifying paradigm linking cancer, autoinflammation, and antiviral immunity. Counterbalancing these sensors is a structurally heterogeneous nuclease repertoire whose distinct substrate specificities, subcellular compartments and pH optima constrain ligand availability in space and time. Disruption of this equilibrium drives disease through two mirror-image mechanisms. In cancer, DNASE1 is inactivated by tumor-derived G-actin, DNASE1L3 is transcriptionally silenced in hepatocellular, colorectal and lung adenocarcinomas, and DNASE2 is upregulated in immunologically "cold" tumors, together permitting neutrophil-extracellular-trap-mediated exclusion of cytotoxic T cells and suppression of cytosolic DNA sensing. In autoimmunity, biallelic loss of DNASE1L3, TREX1, RNase H2, ADAR1 or RNase T2 produces the interferonopathies of systemic lupus and Aicardi-Goutières syndrome. Diagnostically, nuclease-specific cleavage signatures have matured into cell-free DNA fragmentomics validated across 13 cancer types in a 3,021-patient cohort; therapeutically, the field now spans engineered actin-resistant DNASE1/DNASE1L3 biologics, selective TREX1 and ADAR1 inhibitors entering first-in-human evaluation, STING-activating nanomedicines, RNase Fc-fusions such as RSLV-132 in phase 2a lupus, and JAK1/2 inhibition as standard of care in Aicardi-Goutières syndrome. We synthesize this evidence as a two-fate problem: whether an endogenous nucleic acid accumulates at these sensors to drive autoinflammation or is cleared by nucleases before detection is set by the balance between sensor engagement and clearance capacity. The therapeutic corollary acts on the ligand rather than the enzyme, restoring ligand availability where disease is malignant and restoring clearance where disease is self-directed.