Search Results (672)

Rising cancer incidence and survival rates have led to an unprecedented demand for psychosocial care. Yet, limited financial and practical resources present a barrier to the provision of evidence-based care. Clinical practice guidelines (CPGs) are well-positioned to enhance the quality and efficiency of psychosocial oncology care; however, little is known about their use and perceptions in the field. The present study explored the use and perceptions of CPGs among 172 Canadian psychosocial oncology clinicians via a cross-sectional, online survey. Findings revealed substantial variation in awareness, with over 20% of participants reporting no familiarity with CPGs, and low to moderate use of CPGs (M = 2.97, SD = 2.96) among users. Key barriers included a lack of formal training, limited applicability to local contexts, and systemic constraints such as high workloads. Conversely, participants highly endorsed facilitators, including accessible training programs, relevant tools/interventions, and greater institutional and community engagement. Clinician perspectives are paramount to the dissemination and implementation of psychosocial oncology CPGs. Our findings suggest that successful implementation requires broader accessibility, widespread adaptation, and greater community engagement. By addressing these systemic constraints, CPGs may be better positioned to bridge the gap between evidence and real-world service provision. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a biologically heterogeneous disease. Beyond VHL inactivation, alterations in chromatin remodeling genes BAP1 and PBRM1 define distinct tumor phenotypes with prognostic implications. We sought to characterize the clinicopathological features and oncological outcomes associated with IHC-defined loss of these markers in a contemporary surgical cohort. Methods: We retrospectively analyzed 214 patients undergoing partial or radical nephrectomy for ccRCC (2010–2021). Loss of BAP1 and PBRM1 expression was assessed by automated immunohistochemistry. Tumors with retained expression were classified as wild-type and compared with those showing loss of at least one marker. Survival outcomes were evaluated using Kaplan–Meier analysis, multivariable Cox models, and Restricted Mean Survival Time (RMST). Results: IHC-defined loss was identified in 19 patients (8.9%): BAP1 in 12 (5.6%) and PBRM1 in 7 (3.3%). Tumors with IHC-defined loss showed more aggressive features, including larger size (7.7 vs. 4.7 cm; p = 0.009), higher necrosis (36.8% vs. 18.5%; p = 0.050), and more advanced stage (pT3–pT4: 47.4% vs. 16.4%; p < 0.001). Kaplan–Meier analysis demonstrated significantly worse survival outcomes in the IHC-loss group across all endpoints (p ≤ 0.011). RMST analysis at 60 months confirmed significantly worse outcomes across all endpoints (p ≤ 0.005). Conclusions: Loss of BAP1 or PBRM1 identifies a biologically aggressive ccRCC subset with worse oncological outcomes. IHC-based molecular profiling is a practical and accessible tool for risk stratification in surgically treated ccRCC. Full article

Background: Multiple Myeloma (MM) remains the most common indication for Autologous Stem Cell Transplant (ASCT). ASCT use is disproportionately lower in older adults, Black patients with MM, as well as those living in rural areas and of low socioeconomic status (SES). Low utilization of ASCT is linked to poor outcomes. There are numerous barriers to ASCT access and limited interventions to address disparate outcomes in patients with MM. Methods: This is an ambispective study conducted at a single institution to identify and mitigate barriers to ASCT utilization. In aim one, we retrospectively evaluated ASCT utilization and overall survival (OS) for MM patients accounting for clinical, geographic (Rural Urban Commuting Area—RUCA), and socioeconomic factors (Yost). In aim two, based on the observations of the retrospective study, we conducted a prospective feasibility study to improve access for vulnerable patients with MM (older adults, Black patients, rural and/or Appalachian residence) using a virtual ASCT consultative model with patient navigation, coordinated with local oncology centers. Poisson regression estimated the relative risk of receiving ASCT. OS was calculated from MM diagnosis to the date of death censoring survivors at last contact and analyzed using Kaplan-Meir. Cox proportional hazard models estimated the hazard ratio for risk of death. The multivariable model was built including significant risk factors from the univariable models to estimate the independent effect of each risk factor. Results: Among 1799 patients, median age of diagnosis was 61 (range 17–87), race was self-identified as White (85.6%), Black (13.1%), or other (1.3%) and it was primarily metropolitan (n = 1205, 71.2%) and 1169 (65%) received a transplant. The hazard of death was lower for those who received a transplant (vs. no transplant, HR = 0.63, 95%CI 0.53–0.74, p < 0.001), patients identified as Black (vs. White, HR = 0.66, 95%CI 0.51–0.85, p = 0.001) and higher SES areas (quartile 2–4 vs. quartile 1, HR = 0.69, 95%CI 0.58–0.83, p < 0.001). Prospectively with patient navigation and virtual consultation (n = 35), half of the patients sought virtual consultation, 68% of patients were eligible for transplant, 43% went on to receive ASCT, of which 42% of patients were non-metropolitan and 15% of patients were from an Appalachian county. Using this strategy, no difference was observed in ASCT utilization by age (31% in age > 70 vs. 45% in age 65–70 vs. 78% in age < 65, p = 0.10), geographical area (47% in metro vs. 50% in non-metro, p = 0.99), or race (46% in White vs. 60% in Black, p = 0.66). Conclusions: Implementing patient navigation and virtual transplant consultation can effectively enhance access to ASCT among underserved MM populations while reducing the influence of racial and geographic differences. Full article

Background: The therapeutic landscape of metastatic prostate cancer has rapidly evolved with the integration of biomarker-driven strategies, particularly targeting homologous recombination repair (HRR) alterations. Poly(ADP-ribose) polymerase inhibitors (PARPi) have demonstrated clinically meaningful benefit, especially in Breast Cancer genes 1/2-altered tumors, through synthetic lethality. However, the expansion of PARPi across multiple Treatment settings has introduced substantial complexity in patient selection, Treatment sequencing, and biomarker interpretation. This review aims to move beyond a descriptive synthesis of clinical trials and provide a clinically applicable, decision-oriented framework for the use of PARP inhibitors in metastatic prostate cancer. Methods: We conducted a narrative review of pivotal phase II and III trials published between 2020 and 2026 evaluating PARPi as monotherapy or in combination strategies. Evidence was critically analyzed with a focus on biomarker relevance, Treatment positioning, and real-world applicability. Evidence Synthesis: PARPi consistently improve radiographic progression-free survival, with the most robust and clinically meaningful benefit observed in BRCA-altered disease. In contrast, non-BRCA HRR alterations demonstrate heterogeneous and often limited predictive value, highlighting the limitations of a binary biomarker approach. Combination strategies in first-line metastatic castration-resistant prostate cancer (mCRPC) have expanded therapeutic options but raise important concerns regarding toxicity, overTreatment, and unclear benefit in biomarker-unselected populations. In parallel, variability in molecular testing strategies and access continues to limit real-world implementation. Conclusions: PARP inhibitors represent a cornerstone of precision oncology in metastatic prostate cancer, but their optimal use requires a refined, biomarker-informed approach. In this context, we propose a pragmatic 2026 clinical decision framework integrating molecular characteristics, prior Treatment exposure, and clinical factors. This approach aims to bridge the gap between clinical trial evidence, guideline recommendations, and real-world practice. Full article

The global rise in multidrug-resistant (MDR) fungal pathogens has positioned Candida auris and Candida glabrata as major threats to public health. In recent years, these pathogens have increasingly been reported beyond traditional hospital settings, including neonatal intensive care units, long-term care facilities, oncology wards, and post-pandemic critical care environments. International surveillance bodies, including the Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), World Health Organization (WHO), and regional monitoring networks, have documented escalating antifungal resistance, complex outbreak dynamics, and persistent gaps in infection control implementation. C. auris has emerged as a major etiological agent of healthcare-associated outbreaks, particularly in intensive care and neonatal units. Surveillance data indicate that a high proportion of C. auris isolates exhibit resistance to azoles, often exceeding 80% in some regions, while echinocandin resistance remains variable. Resistance patterns have evolved from predominantly azole resistance to broader multidrug-resistant phenotypes, including treatment-emergent echinocandin resistance. Six genetically distinct clades (I–VI) have been identified, with Clades I, III, and IV associated with large-scale outbreaks, whereas available data suggests that Clades II, V, and VI are more geographically restricted, although evidence for the recently described clades remains limited. C. glabrata is increasingly recognized as a major cause of invasive candidiasis, with rising resistance reported across multiple regions. While reduced azole susceptibility was historically predominant, emerging evidence highlights rising dual azole–echinocandin resistance, adaptive microevolution during antifungal therapy, and biofilm-associated tolerance mechanisms. Despite these advances, significant gaps persist in global resistance surveillance and in the mechanistic understanding of virulence and antifungal adaptation. Current mitigation strategies include antifungal stewardship programs, expanded resistance testing, and strengthened surveillance systems. Advances in rapid diagnostic technologies such as matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry, polymerase chain reaction (PCR)-based assays, and genomic surveillance have improved pathogen identification and outbreak detection, although accessibility remains limited in resource-constrained settings. This review examines emerging epidemiological, genomic, and antifungal resistance trends in C. auris and C. glabrata and highlights key priorities for improving diagnosis, surveillance, stewardship, and management of multidrug-resistant Candida infections. Full article

Chronic myeloid leukemia (CML) represents a paradigm of targeted therapy, driven by the BCR::ABL1 fusion kinase. Over the past four decades, therapeutic strategies have evolved from early molecular targeting approaches and interferon-α to tyrosine kinase inhibitors (TKIs), dramatically improving survival and transforming CML into a largely controllable disease. To provide a comprehensive overview of this evolution, we conducted a narrative literature search across the PubMed and Embase databases, selecting peer-reviewed articles, international guidelines, and landmark clinical trials based on their historical and clinical relevance. Through this expert-driven synthesis, focusing on key milestones in CML therapy, including antisense strategies, interferon-based treatment, first-, second-, and third-generation TKIs, and the development of allosteric inhibitors, this paper analyzes current management strategies, treatment-free remission (TFR), and emerging therapies. The introduction of imatinib established proof of principle for oncogene-targeted therapy, leading to sustained survival improvements. Second- and third-generation TKIs further enhanced response depth and addressed resistance, including the T315I mutation. More recently, the development of the allosteric inhibitor asciminib introduced a novel mechanism of action and expanded therapeutic options for pretreated patients. Furthermore, the achievement of deep molecular responses has enabled TFR in approximately 40–60% of selected patients, redefining treatment goals toward functional cure. Emerging agents, including next-generation ATP-competitive and allosteric inhibitors, are showing promising activity in resistant disease and may further improve outcomes. Thus, CML represents a unique model of translational oncology, demonstrating how mechanistic insight can drive therapeutic innovation. Future strategies will focus on increasing TFR rates, overcoming resistance, targeting leukemic stem cells, and improving global access to therapy and monitoring, with the ultimate aim of achieving functional cure in the majority of patients. Full article

The family of uterine mesenchymal neoplasms is diverse in etiology and clinical impact. While histomorphology remains central to diagnostic classification, numerous biomarkers have been developed to aid in refining diagnoses and informing optimal treatment strategies. Indeed, a growing number of neoplasms are being primarily classified on the basis of key pathognomonic genetic events, and this number is expected to continue expanding as access to next-generation sequencing rapidly democratizes. Moreover, several quantitative biomarker tests have been developed to aid in the prognostic stratification of tumours with ambiguous morphologic features, providing critical insights to clinicians seeking optimal oncologic management while minimizing unnecessary treatment morbidity. In this review, we discuss key advances in the utilization of biomarkers for diagnostic classification, prognostication, and the prediction of response to targeted therapeutics in uterine mesenchymal neoplasms, with the aim of highlighting the most clinically impactful biomarkers used by pathologists to enhance the clinical care of patients. Full article

Drug repurposing is often promoted as a faster, lower-risk alternative to de novo discovery, yet substantial barriers continue to limit successful implementation. We performed a scoping review of articles included in PubMed and ScienceDirect with the aim to identify and categorize challenges and analyze the intersections between them. Our review included 73 articles which revealed scientific, clinical, regulatory, economic, and implementation barriers, with the principal being the clinical translation of generated candidates. Scientific challenges include the necessity for new Phase II/III trials to validate efficacy, safety, and optimal dosing in new therapeutic contexts. Across disease areas, domain-specific barriers include subgroup-dependent responses in oncology, resistance and penetration challenges in anti-infectives, and data scarcity in rare diseases. Computational and AI-assisted approaches face fragmented data, model robustness, and insufficient validation. In addition, off-patent drugs face evidence requirements as rigorous as those for de novo entities, yet lack the market exclusivity incentives required to attract private investment. Additionally, an “institutional bottleneck” hinders academic researchers from bringing findings “on-label” due to a lack of regulatory infrastructure and collaborative frameworks. We conclude that drug repurposing requires a distinct translational paradigm involving multi-stakeholder collaboration and early regulatory engagement to bridge the gap between laboratory discovery and patient access. Full article

Background: Cancer predisposition syndromes (CPS) are increasingly recognized in pediatric oncology. In many cases, malignancy in children represents one manifestation of a broader genetic syndrome, often accompanied by dysmorphic features or other distinctive clinical findings. Methods: Clinical documentation and genetic test reports of pediatric patients evaluated over a six-year period (2020–2025) at a genetic counseling unit in a tertiary university hospital in Varna, Bulgaria, were retrospectively reviewed. Referral patterns, clinical characteristics, and genetic findings in children assessed for suspected CPS were analyzed. Results: In total, 430 children underwent genetic testing during the study period; among them, 42 fulfilled the criteria for CPS and were subsequently included in the analysis. Patients were categorized into three groups: those with malignancy (21.4%), those with high-risk hematologic/immune features without malignancy (9.5%), and those referred based on phenotypic features alone (69.0%). Most referrals originated outside oncology services, primarily from general pediatric clinics and outpatient settings, highlighting the importance of non-oncologists in early CPS recognition. Multisystem phenotypic features were common, with 69.0% of patients exhibiting involvement of two or more clinical domains. Genetic testing, predominantly using multigene panels and exome sequencing, identified clinically relevant variants in established CPS genes, most frequently in autosomal dominant conditions within this diagnosis-confirmed cohort. The most common diagnostic categories included NF1 spectrum disorders and RASopathies. Conclusions: These findings emphasize that CPS identification often relies on recognition of non-oncologic features rather than malignancy alone. Genetic counseling plays a central role in diagnosis, risk assessment, and cascade testing. Strengthening awareness among general pediatricians and improving access to genetic services are critical for optimizing early detection and prevention strategies. Full article

Background: Health accessibility is a key determinant of equitable cancer care. In many countries, specialized oncology services are concentrated in urban and socioeconomically advantaged regions, forcing many patients to travel long distances for treatment. Consequently, geographic and social characteristics may be impactful in determining cancer healthcare outcomes. Objective: The aim of this study was to evaluate the association between the municipal-level Social Progress Index (SPI) and geographic travel burden, stage at diagnosis, treatment, and survival in patients with pancreatic cancer in São Paulo state, Brazil. Methods: We conducted a population-based study using data from “Fundação Oncocentro” on adults with pancreatic adenocarcinoma (2005–2025). The SPI (0–100 scale), a composite measure of municipal social and environmental development, was the primary exposure. It is structured into 3 dimensions and 12 components: Basic Human Needs (nutrition, medical care, water and sanitation, housing, safety); Foundations of Well-being (education, information access, health, environmental quality); and Opportunity (rights, freedom of choice, social inclusion, higher education). Municipal residence and cancer center locations were geocoded, and travel distance (km) was estimated. Multivariable Cox, logistic, and linear regression models assessed associations between SPI and overall survival, stage IV at diagnosis, surgery, and travel distance. Results: A total of 13,478 patients were included (mean follow-up 15.1 ± 27.2 months; mean age 62.3 years; 50.4% male). Stage IV disease was frequent (46.3%), and surgery was performed in 33% of cases. Over half of patients (53.2%) traveled more than 10 km for treatment. Increasing SPI was strongly associated with shorter travel distance (β −62.6 km per SPI unit; p < 0.001) and higher odds of surgery (OR 1.04; p < 0.001) and remained independently associated with a higher likelihood of undergoing surgical treatment (adjusted OR 1.04; p < 0.001). The proportion of stage IV disease did not decrease with increasing SPI and was slightly higher in the highest quartile (49.3%). In survival analysis, SPI demonstrated a protective effect in univariate modeling (HR 0.987; p < 0.001), but lost significance in multivariable analysis (p = 0.125). Travel burden was not retained as an independent predictor of survival after adjustment. Conclusions: Municipal-level SPI was a strong determinant of healthcare access and the likelihood of receiving surgical treatment for pancreatic cancer. Social and geographic vulnerability directly influence care pathways, revealing structural inequities in access to treatment. SPI-based stratification may serve as a practical tool to identify priority regions for transport support and equitable allocation of oncology services. Full article

Total hip arthroplasty (THA) is among the most effective orthopedic interventions for osteoarthritis, yet post-operative rehabilitation is frequently delayed due to informational and organizational barriers. Geographic information system (GIS) technology offers a promising approach to improving rehabilitation access coordination, though its integration into patient-facing mobile platforms remains insufficiently studied. This two-arm, parallel-group, superiority randomized controlled trial enrolled 142 adult patients (≥18 years) within seven days of primary THA at the National Research Oncology Center LLC, Astana, Kazakhstan. Participants were randomized 1:1 to the GIS-integrated Health-GIS mobile coordination platform (experimental group) or standard general practitioner (GP)-mediated referral (control group). Key exclusion criteria included severe cognitive or visual impairment, absence of smartphone access or digital literacy, and medical contraindications to rehabilitation. The primary outcomes were time to second-stage rehabilitation initiation and health-related quality of life assessed by the SF-12 (Physical and Mental Component Summaries). Secondary outcomes included the Harris Hip Score (HHS), Visual Analogue Scale (VAS) for pain, System Usability Scale (SUS), and quality-adjusted life years (QALYs) over a 12-month follow-up. Of 142 randomized participants (61% male, 39% female), 131 completed follow-up and were included in the modified intention-to-treat analysis (experimental: n = 66; control: n = 65). The experimental group initiated second-stage rehabilitation significantly earlier (median 43 vs. 59 days; p = 0.021). At 12 months, the experimental group demonstrated superior SF-12 Physical Component Summary scores (48.21 vs. 42.84; p < 0.001), while Mental Component Summary scores did not differ significantly between groups (46.96 vs. 47.05; p = 0.669). Quality-adjusted life years were significantly higher in the experimental group (0.74 ± 0.04 vs. 0.72 ± 0.04; p = 0.008). Harris Hip Scores were significantly better in the experimental group at 6 weeks (p < 0.001) and 6 months (p = 0.009), converging by 12 months (p = 0.068). No statistically significant between-group differences in pain intensity (VAS) were observed at any time point (baseline: p = 0.814; 6 weeks: p = 0.336; 6 months: p = 0.066; 12 months: p = 0.105). Platform usability was rated as good-to-excellent by clinicians (SUS: 86.9 at 6 months) and acceptable by patients (mean SUS: 71.4). A GIS-integrated mobile coordination platform significantly reduced time to rehabilitation initiation and improved physical health-related quality of life and health utility following THA compared to standard referral practice. These findings support platform-based care coordination as an effective complement to surgical care, with important implications for rehabilitation access policy. Future multi-center studies and formal cost-effectiveness analyses are warranted to establish generalizability. Trial Registration: ClinicalTrials.gov, NCT07201116, registered 23 September 2025. Full article

Background: Custom-made subperiosteal implants have re-emerged as a valuable option for the rehabilitation of patients with severe maxillofacial atrophy and post-oncological defects. Despite advances in digital workflows and implant design, their unique anatomical, biological, and prosthetic characteristics pose specific challenges for long-term maintenance, and no dedicated standardized guidelines are currently available. Methods: This narrative review critically appraises the available literature on implant maintenance and related fields. A comprehensive search was conducted across PubMed, Scopus, and Web of Science, including studies on peri-implant maintenance, supportive periodontal therapy, full-arch and zygomatic implant rehabilitations, and subperiosteal implants. Due to the lack of direct evidence, a qualitative narrative synthesis was adopted to develop preliminary clinical considerations for maintenance of custom-made subperiosteal implants. These considerations should be interpreted as an expert-informed perspective rather than validated clinical guidelines. Results: Conventional maintenance protocols developed for endosseous implants are not directly transferable to subperiosteal implants due to differences in the implant–tissue interface, biomechanics, diagnostic parameters, and hygiene accessibility. Key challenges include the absence of a conventional peri-implant sulcus, possible implant exposure, complex prosthetic geometries, and potential susceptibility to biofilm accumulation in areas with limited access. Evidence from related fields highlights the importance of structured maintenance, individualized risk-based follow-up, effective biofilm control, and patient-specific home-care strategies. Conclusions: Preliminary evidence-informed clinical considerations for the maintenance of subperiosteal implants are proposed, with emphasis on plaque control, individualized follow-up, descriptive clinical monitoring, and hygiene-oriented prosthetic and surgical planning. These considerations are not intended as validated guidelines, but as a practical starting point for clinical reasoning in an area where dedicated evidence remains limited. Full article

Background/Objectives: Totally implantable venous access ports (TIVAPs) are commonly used in oncology for long-term venous access, but catheter tip malpositioning can lead to complications. Intracavitary electrocardiography (IC-ECG) provides real-time tip guidance, although data on clinical outcomes and patient satisfaction remain limited. This study evaluates postoperative complications, catheter function, and patient comfort and satisfaction after TIVAP implantation using ultrasound and IC-ECG guidance. Methods: This retrospective single-center study included adults with solid cancers who received TIVAP implants for chemotherapy from June 2021 to September 2024. Procedures used the right internal jugular vein, with ultrasound guidance and the Seldinger technique; catheter tip placement was guided by IC-ECG. Chest X-rays were obtained to assess for early complications and tip position. Primary outcomes were comfort and satisfaction; secondary outcomes included catheter tip position, catheter complications, and usability. Results: Among 213 screened patients, 192 were included (79 females, 113 males; mean age 60.83 ± 12.19 years). The catheter tip was located within the target zone in 149 patients (77.6%). Success rates were 98.44% (n = 189/192) for blood aspiration, 97.90% (n = 186/190) for port ease of use, 98.95% (n = 189/191) for overall satisfaction, and 98.43% (n = 188/191) for willingness to recommend. Discomfort occurred in 6.25% (n = 12/192) of patients. Comfort improved significantly from day1 to day7 (p < 0.001). Complication rates included hematoma (1.56%, n = 3), pneumothorax (0.52%, n = 1), venous thrombosis (1.56%, n = 3), local infection (2.08%, n = 4), systemic infection (0.52%, n = 1), and catheter occlusion (2.08%, n = 4). Catheter blood aspiration success was 93.75% (n = 180/192). Conclusions: In this retrospective cohort, TIVAP implantation via the right internal jugular vein under ultrasound and IC-ECG guidance was associated with low complication rates, favorable catheter function, and high patient satisfaction. Prospective, multicenter, and comparative studies are needed to determine whether ECG-guided tip positioning improves long-term clinical and patient-centered outcomes. Full article

Importance: A comprehensive analysis of childhood cancer and cancer predisposition syndromes (CPSs) incidence can provide insights that lead to improvements and modifications in treatment protocols through personalized therapy, thereby reducing toxicity. Purpose: This study aimed to analyze age-specific hospital-based childhood cancer rates and the distribution of CPSs in a 20-year pediatric cohort from the region. Materials: A total of 2190 patients, aged from birth to 17 years, diagnosed with any type of neoplasm classified by ICD-10 codes at Karol Jonscher’s Clinical Hospital of Poznan University of Medical Sciences (KJCH PUMS) between 1 January 2000, and 31 December 2019, were included, with 193 (8.8%) having an underlying CPS. Results: The pediatric population of the Greater Poland Region has declined over the past two decades. The most common diagnoses can be grouped into three main categories: (1) leukemias, involving 704 patients (32.1%); (2) central nervous system (CNS) tumors, represented by 382 children (17.4%); and (3) lymphomas, including 279 patients (12.7%), together accounting for 1353 cases (61.8%). The age-specific hospital-based case rate for childhood cancer (all types combined) peaked in the 0–28 days age group at 71.8 per 100,000 person-years (95% CI: 52.2–96.4), with a trend to decrease with age and a slight increase among adolescents aged 16–17 years (13.6 per 100,000, 95% CI: 12.0–15.4). The age-specific incidence of CPS-positive cancers declined from 18.0 (95% CI: 8.2–29.4) per 100,000 person-years in the first month of life to 0.7 (95% CI: 0.3–1.2) in 16–17-year-olds. CPS-positive children were diagnosed at significantly younger ages for four cancer types: liver and intrahepatic bile duct tumors (C22: A = 0.097, adjusted p < 0.001), myeloid leukemia (C92: A = 0.179, adjusted p < 0.001), lymphoid leukemia (C91: A = 0.309, adjusted p = 0.007), and renal tumors (C64: A = 0.335, adjusted p = 0.013). Conclusions: CPSs likely play a significant and underestimated role in pediatric cancers, especially during early childhood. Improving access to genetic testing could greatly enhance risk assessment, personalized treatment, and long-term outcomes in pediatric oncology. Full article

Metastatic triple-negative breast cancer (mTNBC) remains one of the most challenging therapeutic settings in oncology. Although it has traditionally been defined by the absence of hormone receptor expression—estrogen receptor (ER) and progesterone receptor (PR)—and HER2 amplification or overexpression, this simplified definition fails to capture the biological complexity that drives its marked clinical heterogeneity, therapeutic resistance, and prognostic variability. Over the past decade, multiple studies have challenged the notion of TNBC as a single disease entity, identifying distinct molecular subtypes, including Basal-like 1 (BL1), Basal-like 2 (BL2), Mesenchymal (M), Mesenchymal Stem-like (MSL), Immunomodulatory (IM), and Luminal Androgen Receptor (LAR), each characterized by specific biological programs and therapeutic vulnerabilities. In parallel, clinically oriented systems such as the Fudan classification have enabled the prospective evaluation of subtype-guided therapeutic strategies in metastatic disease, as illustrated by the FUTURE and FUTURE-SUPER trials. In this review, we examine the molecular classification and clinical behavior of mTNBC subtypes, integrating genomic, transcriptomic, epigenetic, immunologic, stromal, and biomechanical dimensions of tumor heterogeneity. We also discuss emerging tools, including single-cell RNA sequencing, spatial transcriptomics, circulating tumor DNA analysis, long non-coding RNA profiling, and surrogate immunohistochemistry-based classifiers, as well as their potential role in refining patient stratification. From a therapeutic perspective, we review subtype-guided strategies involving chemotherapy, platinum agents, PARP inhibitors, immunotherapy, antiandrogen therapy, PI3K/AKT/mTOR pathway inhibition, antiangiogenic approaches, and antibody–drug conjugates. Redefining mTNBC through biologically driven stratification represents a rational strategy to optimize treatment selection, support clinical trial design, and accelerate the development of precision oncology approaches. However, clinical implementation requires greater methodological standardization, validated predictive biomarkers, accessible diagnostic platforms, and dynamic monitoring strategies capable of capturing subtype evolution under therapeutic pressure. TNBC should therefore not be regarded as a single disease, but as a spectrum of biologically distinct and clinically evolving entities whose integrated characterization may be essential to improving outcomes in this historically poor-prognosis population. Full article