Epithelial neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of malignancies with limited treatment options. Comprehensive molecular characterization may reveal novel therapeutic opportunities for these clinically challenging tumors.

Within a nationwide precision oncology program, we performed whole-genome/exome and transcriptome sequencing in 168 patients with a diagnosis of advanced NEN from diverse anatomic origins, followed by evaluation of real-world outcomes associated with molecularly guided interventions.

Our analysis revealed substantial molecular heterogeneity across advanced NENs, including distinct genetic profiles between low-grade and high-grade tumors, as well as alterations specific to particular tissues of origin. Candidate therapeutic targets included elevated tumor mutational burden induced by temozolomide exposure, rare actionable kinase mutations, overexpression of targetable antigens, and signatures of homologous recombination deficiency, providing a rationale for immune checkpoint blockade, kinase inhibitors, antibody-drug conjugates, poly(ADP-ribose) polymerase (PARP) inhibitors, and platinum-based therapies, respectively. Overall, 144 patients (85.7%) received molecularly guided treatment recommendations, of which 85 were implemented in 57 patients (39.6%). Among 68 evaluable therapy outcomes, 47 (69.1%) demonstrated clinical benefit (objective response, n = 25; disease stabilization, n = 22). At the patient level, 34 of the 57 treated (59.6%) experienced clinical benefit from at least one therapy (objective response, n = 18; disease stabilization, n = 16).

Comprehensive genomic and transcriptomic profiling identified distinct molecular alteration patterns and therapeutic vulnerabilities among different classes of epithelial NENs from various tissues, warranting further investigation in anatomic-site-specific studies. Our outcome data underscore the clinical utility of broad molecular profiling in patients with advanced NENs lacking further standard treatment options.

Funding for the study was institutional.

Perform an updated meta-analysis of RCTs that evaluated survival and recurrence in patients with clinically node-negative breast cancer with sentinel lymph node metastasis who underwent sentinel lymph node dissection (SLND) alone compared to axillary lymph node dissection (ALND).

A systematic search was conducted in PubMed, Embase, and Cochrane databases for studies on clinical T1-T3, N0, M0 primary breast cancer patients with pSLN undergoing SLND or ALND. The primary outcomes of interest are disease-free survival, overall survival, and recurrence rate; surgical adverse effects and mortality rate are evaluated as secondary outcomes.

We included eight RCTs, in which 3952 patients underwent SLND, and 3871 underwent ALND in the presence of sentinel lymph node metastasis. We observed that overall survival and disease-free survival were non-inferior in the experimental group. When analyzing recurrence rates, axillary recurrence was the only type for which ALND appeared to have a protective effect. In contrast, local and distal recurrence were more common in the group undergoing complete axillary dissection. In terms of morbidity, patients who underwent SLND alone had fewer adverse surgical effects. The reduction in lymphedema was statistically significant only at the 5-year endpoint after randomization. However, the occurrence was lower in the experimental group at all time points analyzed in the studies.

Our findings show that SLND reduces surgical complications associated with ALND and improves quality of life without decreasing local control and overall survival in patients with T1-T2/T3 breast cancer with clinically negative nodes and the presence of 1-2 pSLN.

Thin melanoma (TM, ≤1.0 mm Breslow thickness) and Melanoma In Situ (MIS) constitute the majority of melanoma diagnoses worldwide and are responsible for melanoma-related deaths in these early-stage tumors. Despite their favorable prognosis, MIS and TM represent an opportunity for improving patient outcomes through early detection, accurate risk stratification, and long-term surveillance for metastasis and new skin neoplasms.

Provide an update of current evidence regarding epidemiology, risk factors, prognostic indicators, genetic background, and clinical management of MIS and TM.

A comprehensive review of the literature and international guidelines was conducted, integrating epidemiologic data, clinical prognostic parameters, and molecular insights relevant to MIS and TM.

MIS and TM account for over 80% of all melanomas, with increasing incidence and relatively stable mortality rates. Prognosis is primarily determined by Breslow depth and ulceration, while factors such as mitotic rate, anatomic site, and age further refine risk assessment. Genetic alterations contribute to tumorigenesis but are not yet integrated into routine management. Long-term dermatological surveillance is needed, as new neoplasms, recurrence, and metastasis can develop during follow-up.

MIS and TM are increasingly diagnosed, and dermatologists need to be a part of early detection, multidisciplinary management, and lifelong surveillance, which remain the cornerstone of reducing melanoma-related mortality.

The substantial heterogeneity among the included studies limits direct comparison and quantitative synthesis of the available data.

Breast cancer is one of the most prevalent cancers worldwide, with a 5-year survival rate exceeding 90%. Despite advances in treatment, survivors frequently experience persistent cancer- and treatment-related symptoms that negatively impact their quality of life. Body-oriented interventions (BOIs) have demonstrated effectiveness in symptom management; however, systematic reviews focused exclusively on BOIs for women who survived breast cancer (WSBC) remain limited. This systematic review protocol outlines the methodology for evaluating the scientific evidence on the effects of BOIs on cancer- and treatment-related symptoms in WSBC.

The aim of this study is to examine the scientific evidence on the effects of BOIs on cancer- and treatment-related symptoms, well-being, and quality of life in WSBC.

This protocol follows PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidelines. We will conduct searches in 6 electronic databases: PubMed, Cochrane, Web of Science, Scopus, APA PsycNet, and Portal Regional da BVS. Studies will be considered for inclusion if they are written in English, French, Portuguese, or Spanish, with no restrictions on publication date; they consist of WSBC (aged 18 to 64 years); they are randomized controlled trials, quasi-randomized controlled trials, and pilot studies focusing on BOIs; they include a control group receiving no intervention, standard care, or a non-BOI; and the primary outcomes of interest include preintervention and postintervention measures of cancer- and treatment-related symptoms, well-being, and quality of life. The methodological quality of the studies and the risk of bias will be assessed using the PEDro scale and version 2 of the Cochrane risk-of-bias tool, respectively. The synthesis of results will be measured through the Best Evidence Synthesis. Two experienced independent reviewers will conduct study selection, data extraction, methodological quality assessment, and scientific evidence assessment. Disagreements will be resolved by a third reviewer.

This protocol describes the prespecified methodology for the systematic review. At the time of publication of this protocol, the corresponding full systematic review manuscript was under peer review. The outcomes will synthesize the scientific evidence on the effects of BOIs on cancer- and treatment-related symptoms in WSBC. It is anticipated that this systematic review will identify benefits and directions for future research to support the integration of BOIs tailored to this population.

Considering that previous systematic reviews focused on the effects of BOIs in survivors of all cancer types, challenges related to study risk of bias such as heterogeneity in intervention types, study designs, and outcome measures are anticipated, potentially leading to some inconsistency and imprecision. To mitigate these issues, PRISMA guidelines will be followed, and methodological quality and best evidence strength will be rigorously assessed. This review will systematically synthesize the effects of BOIs on cancer- and treatment-related symptoms in WSBC. These findings will provide health professionals with reliable evidence and methodological guidance for further research.

PROSPERO CRD42023452519; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=452519.

DERR1-10.2196/76858.

Pathological vertebral compression fractures exert a significant impact on cancer patients' quality of life. Procedures that combine percutaneous vertebral augmentation with radiofrequency ablation (RFA) have expanded the therapeutic options for treating complex fractures accompanied by severe height loss and spinal compromise.

A woman in her sixties with squamous cell carcinoma of the anal canal developed a T10 metastatic burst fracture with > 80% vertebral height loss and spinal cord compression despite radiation therapy. We performed sequential RFA for local tumor control, followed by balloon kyphoplasty to create cavity space, and SpineJack® (Stryker) deployment for maximum vertebral height restoration. Complete pain relief was achieved, with significant restoration of vertebral anatomy and correction of both antero- and retropulsion. The patient remained asymptomatic at follow-up.

The use of second- and third-generation percutaneous vertebral augmentation in combination with RFA represents a promising multimodal approach for managing complex metastatic burst fractures when conventional treatments fail.

Immune checkpoint inhibitors (ICIs) have fundamentally transformed the treatment landscape for localized colorectal cancer (CRC), particularly for the mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) subgroups. This review evaluates the current clinical evidence and evolving paradigms of immunotherapy in early-stage CRC. In localized MSI-H colon and rectal cancers, neoadjuvant immunotherapy has demonstrated unprecedented efficacy, yielding near-universal major pathologic responses and high rates of pathologic complete responses. For MSI-H rectal cancer, these deep and sustained clinical complete responses have established nonoperative management as a viable, organ-preserving standard of care for highly selected patients undergoing rigorous multidisciplinary surveillance. Despite these rapid advancements, critical questions remain regarding optimal regimen selection, treatment duration, and the integration of circulating tumor DNA (ctDNA) for molecular residual disease monitoring. Although ctDNA is a promising dynamic biomarker, it currently cannot replace definitive pathologic assessment outside of clinical trials. Furthermore, extending the benefits of immunotherapy to the majority of patients with microsatellite-stable (MSS) CRC represents a significant unmet clinical need. Current evidence for ICIs in localized MSS disease remains limited, although investigational combination strategies incorporating radiation, chemotherapy, and novel immune modulators are yielding hypothesis-generating signals. Future progress hinges on precision de-escalation protocols and biomarker-driven, response-adapted trial designs to validate surrogate end points and optimize patient outcomes across all localized CRC subtypes.

Advanced biomaterials-based in vitro platforms are increasingly required to overcome the limited predictive power of conventional 2D cell cultures in colorectal cancer (CRC) drug screening. Herein, we report the development of a biomimetic, multicellular 3D CRC model based on gelatin methacrylate (GelMA) hydrogels, designed to recapitulate key structural and biological features of the tumor microenvironment. The platform integrates a vascularized hydrogel compartment with human endothelial cells, combined with cancer-associated fibroblasts and macrophages, enabling controlled tumor-stroma-vessel interactions within a physiologically relevant architecture. The GelMA hydrogels were comprehensively characterized, and their role in regulating endothelial viability, migration, and angiogenic marker expression was systematically evaluated. The drug screening capability of the platform was assessed using 5-fluorouracil (5-FU). Comparative analyses revealed that 3D cultures exhibited attenuated cytotoxicity, oxidative stress, and apoptotic responses relative to 2D monolayers, particularly at lower drug concentrations and prolonged exposure times. These findings demonstrate that GelMA-based microenvironment actively modulates cellular drug responses through multicellular interactions and diffusion-mediated effects, rather than acting as a passive scaffold. Overall, this study establishes a functional 3D in vitro platform that provides improved physiological relevance and predictive capability for preclinical CRC drug screening, while offering a human-relevant alternative aligned with the principles of the 3Rs.

Chronic stress has been implicated in the dysregulation of immunological, neurochemical, and endocrinological functions, yet its impact on hepatic homeostasis and liver carcinogenesis remains elusive. In this study, by using single-nucleus RNA sequencing and histopathological evaluation, we demonstrated that chronic stress induced profound hepatic dysfunction. Notably, using orthotopic murine models of liver cancer, we further found that chronic stress substantially accelerated tumor progression. Mechanistically, we identified β2-adrenergic receptor (ADRB2) signaling as the pivotal molecular pathway driving stress-accelerated cancer progression, which was in line with the poor clinical outcomes observed in patients with cancer exhibiting enhanced adrenergic signaling within tumors. Collectively, our study provides compelling evidence that chronic stress compromises hepatic homeostasis and accelerates liver cancer progression via ADRB2 activation, highlighting the therapeutic potential of targeting this pathway and the clinical importance of stress management in hepatic disorders.

Androgen receptor (AR) signaling is central to prostate cancer progression, yet resistance to AR-targeted therapies remains a major clinical challenge. Understanding the molecular consequences of AR pathway inhibition is therefore essential for improving therapeutic outcomes. Here, we identify a previously unrecognized link between AR antagonism and cuproptosis, a copper-dependent form of regulated cell death. Using integrated genomic profiling, we find that AR-targeted agents transcriptionally activate the key cuproptosis regulator Ferredoxin-1 (FDX1), thereby rendering prostate cancer cells markedly more susceptible to copper-induced lethality. Mechanistically, ligand-bound AR directly engages FDX1 cis-regulatory elements, which are rendered accessible by the pioneer factor GATA2, and drives FDX1 upregulation upon AR antagonist exposure. Consistent with this mechanism, FDX1 expression is elevated in clinical prostate cancer samples following androgen deprivation therapy or AR antagonist treatment. Increased FDX1 enhances intracellular Cu⁺ accumulation, destabilizes Fe-S cluster proteins, and disrupts mitochondrial metabolism, establishing a procuproptotic state. Functionally, combining AR antagonists with copper ionophores synergistically induces cuproptosis and potently suppresses tumor growth in AR-positive prostate cancer cells, three-dimensional (3D) spheroids, patient-derived organoids, and xenograft models, with minimal systemic toxicity. This synergy is abolished by FDX1 loss or copper chelation, confirming dependence on AR-FDX1 axis activation. Together, these findings uncover FDX1 as a mechanistic effector of AR pathway inhibition and propose a well-tolerated combination strategy that exploits cuproptosis to improve therapeutic responses in prostate cancer.

Inflammatory breast cancer (IBC), an aggressive and lethal breast cancer subtype, lacks unequivocal genomic differences or robust biomarkers that differentiate it from non-IBC. Here, TGIRT-seq revealed myriad differences in tumors, PBMC, and plasma RNAs that distinguished IBC patients from non-IBC patients and healthy donors across different tested breast cancer subtypes. By mapping reads to genome and transcriptome reference sequences and quantitating intron-to-exon read depth ratios (IDRs), we developed methods for parallel analysis of transcriptional and posttranscriptional gene regulation. This analysis identified numerous protein-coding genes in IBC patient tumors and PBMCs with high IDRs, suggesting rate-limiting RNA splicing that decreases mRNA production. Mirroring gene expression differences in tumors and PBMCs, overrepresented protein-coding gene RNAs in IBC patient plasma were largely intron RNA fragments, while those in non-IBC patient and healthy donor plasma were largely mRNA fragments. Our findings provide insights into IBC and should enable monitoring disease progression by liquid biopsy.