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PubMed2026

Safety and Effectiveness of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin for Cancer-Associated Thrombosis: A Systematic Review and Meta-analysis.

BACKGROUND: Cancer-associated thrombosis is a condition associated with high mortality rates, yet limited evidence exists regarding the safety and effectiveness of low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs), focusing on a fixed follow-up period based on clinical practice guideline recommendations. OBJECTIVE: This study aimed to compare the safety and effectiveness of DOACs versus LMWH in patients with cancer-associated thrombosis over a 6-month follow-up period. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched up to 30 June, 2025. Recurrent venous thromboembolism, major bleeding, and all-cause mortality were pooled using a random-effects meta-analysis. RESULTS: Seven randomized controlled trials and 28 cohort studies were included in our systematic review. After applying the criteria for a 6-month follow-up period, five randomized controlled trials and 16 cohort studies with 49,824 patients were analyzed in the meta-analysis. In randomized controlled trials, DOACs showed a lower incidence of venous thromboembolism recurrence (relative risk [RR] 0.66, 95% confidence interval [CI] 0.49-0.87) compared with LMWH, with a non-significant increase in major bleeding (RR 1.28, 95% CI 0.87-1.88) and no significant difference in all-cause mortality (RR 1.00, 95% CI 0.86-1.18). Cohort studies demonstrated a lower incidence of venous thromboembolism recurrence (RR 0.69, 95% CI 0.62-0.76) with DOACs, a non-significant reduction in major bleeding (RR 0.85, 95% CI 0.68-1.07), and a lower risk of all-cause mortality (RR 0.47, 95% CI 0.31-0.72). CONCLUSIONS: In patients with cancer-associated thrombosis, DOACs demonstrated a decrease in recurrent venous thromboembolism without increasing the risk of all-cause mortality. A non-significant increase in the risk of major bleeding was recorded in randomized controlled trials, but not in cohort studies. DOACs may provide greater effectiveness for cancer-associated thrombosis compared with LMWH.

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PubMed2026

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

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PubMed2026

Adjuvant oxaliplatin with S-1 (SOX) versus S-1 for stage II-III gastric cancer (CAPITAL): A randomized, open-label, phase 3 trial.

BACKGROUND: Adjuvant chemotherapy following D2 gastrectomy constitutes the standard-of-care for resectable gastric or gastroesophageal junction (GEJ) carcinoma. The CAPITAL trial is a multicenter, randomized, phase 3 study, aiming to assess the efficacy and safety of adjuvant oxaliplatin plus S-1 (SOX) versus S-1 alone. METHODS: Patients with histologically confirmed pathological stage II-III gastric or GEJ adenocarcinoma after gastrectomy with D2 lymphadenectomy were randomly assigned (1:1) to receive either the SOX regimen (n = 362) or the S-1 regimen (n = 362). The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov (NCT01795027). FINDINGS: The median follow-up was 74.0 months (interquartile range [IQR], 35.5-89.3). The 5-year overall survival rates were 70.9% (95% confidence interval [CI], 66.0-76.1) in the SOX group and 62.9% (95% CI, 57.8-68.5) in the S-1 group (hazard ratio [HR], 0.74; 95% CI, 0.58-0.95; p = 0.018). The 3- and 5-year disease-free survival rates were 71.2% (95% CI, 66.5-76.3) and 66.2% (95% CI, 61.2-71.6) in the SOX group, as compared with 65.1% (95% CI, 60.2-70.5) and 55.6% (95% CI, 50.4-61.3) in the S-1 group (HR, 0.76; 95% CI, 0.61-0.96). Treatment-related adverse events of grade 3-4 occurred in 87 (25%) of 349 patients in the SOX group and 45 (13%) of 347 patients in the S-1 group. The most common grade 3-4 adverse event was neutropenia, occurring in 44 (13%) of 349 patients in the SOX group and 23 (7%) of 347 patients in the S-1 group. CONCLUSIONS: The addition of adjuvant oxaliplatin to S-1 chemotherapy significantly improved overall survival and disease-free survival in patients with gastric cancer. FUNDING: This research was supported by the National Natural Science Foundation of China (82573092 and 82573387).

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PubMed2026

Outcomes of Stage IVA Cervical Cancer Treated with Radiation Therapy: A Systematic Review and Meta-Analysis.

FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We performed a systematic review and meta-analysis to evaluate survival outcomes, treatment-related morbidity, and prognostic factors in patients with stage IVA cervical cancer treated with definitive radiotherapy. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42024602426), PubMed, Embase, and Web of Science were searched through February 2025. Eleven studies comprising 492 patients met eligibility criteria. Pooled random-effects analyses demonstrated 2-, 3-, and 5-year disease-free survival rates of 41.5% (95% CI, 28.1-55.0), 34.2% (95% CI, 21.1-47.3), and 30.9% (95% CI, 16.0-45.8), respectively. Corresponding overall survival rates were 56.0% (95% CI, 46.2-65.9), 45.9% (95% CI, 35.9-55.9), and 34.8% (95% CI, 26.4-43.3). Weighted median disease-free survival and overall survival were 15.6 and 33.6 months, respectively. The pooled incidence of vesicovaginal or rectovaginal fistula was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 below 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy were consistently associated with improved outcomes. Despite curative-intent treatment, long-term survival remains poor and treatment-related morbidity substantial. Durable pelvic control remains the principal therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy appears essential for optimal outcomes, while future stage IVA-specific studies incorporating image-guided adaptive brachytherapy, advanced radiotherapy techniques, and systemic treatment intensification are needed to improve survival and reduce treatment-related morbidity.

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PubMed2026

Splenic hilum nodal involvement in resected left-sided pancreatic cancer: meta-analysis.

BACKGROUND: Splenectomy is standard of care during left pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) to obtain adequate lymphadenectomy. However, evidence supporting this approach is lacking. Splenic preservation would reduce short-term morbidity and is essential for emerging oncological adjunctive therapies, including immunotherapy and personalized cancer vaccines. This study reviewed the incidence of splenic hilum nodal involvement (SHNI) in left-sided PDAC. METHODS: A systematic review of the PubMed, Embase, and Cochrane databases was performed, identifying studies published from inception to July 2026. Outcomes of interest were the rate of SHNI (station 10), overall survival, and the rate of splenic artery nodal involvement (SANI; station 11). Meta-analyses were conducted using random-effects models. Subgroup analyses for SHNI were performed per tumour localization (pancreatic neck, body, tail). RESULTS: Among 2776 screened studies, 22 with 2260 patients undergoing left pancreatectomy for PDAC were included. The pooled prevalence of SHNI was 3.7% (95% confidence interval (c.i.) 2.2% to 6.2%); 1.1% for pancreatic body PDAC (95% c.i. 0.3% to 4.3%) and 9.7% for pancreatic tail PDAC (95% c.i. 3.5% to 24.0%). SHNI was not significantly associated with survival (pooled hazard ratio 2.05; 95% c.i. 0.89% to 4.72; P = 0.072). The pooled prevalence of SANI was 39.1% (95% c.i. 25.1% to 55.1%). CONCLUSION: In patients undergoing left pancreatectomy for PDAC, the presence of SHNI is rare, particularly in pancreatic body cancer (1.1%). These findings suggest that the relevance of routine splenectomy remains unclear, especially for pancreatic body PDAC. However, because the quality of current evidence is low, further investigation in prospective studies is required.

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PubMed2026

Neighborhood Deprivation and Screening Mammography Utilization: A Retrospective Cross-Sectional Study.

RATIONALE AND OBJECTIVES: Access to screening mammography reduces breast cancer mortality disparities. The Area Deprivation Index (ADI) is a validated measure of neighborhood socioeconomic disadvantage linked to adverse health outcomes. There is limited data evaluating mammography utilization among patients residing in areas of higher deprivation. This study evaluated the association between ADI and screening mammography utilization within an accountable care organization (ACO) affiliated with a multicenter academic medical center in the Upper Midwest. METHODS: This retrospective cross-sectional study included women aged 40-85 years attributed to the ACO in 2022, based on Wisconsin Collaborative for Healthcare Quality criteria. The primary outcome was receipt of screening mammography within two years. The primary exposure was ADI, analyzed by decile (ordinal) and as low (deciles 1-5) versus high (deciles 6-10) deprivation. The logistic regression models evaluated associations between ADI and screening, unadjusted and adjusted for age, race, ethnicity, and preferred language. RESULTS: Among 7463 participants with geographic data, 74.4% completed screening. Screening rates were 75.7% in low-deprivation areas versus 66.2% in high-deprivation areas. Increasing ADI decile was associated with reduced screening in unadjusted (OR 0.891, 95% CI 0.87-0.91, p<0.001) and adjusted analyses (OR 0.897, 95% CI 0.88-0.92, p<0.001). Black participants (OR 0.444, p<0.001) and individuals preferring non-English languages (OR 0.333, p<0.001) had lower screening odds after adjustment. CONCLUSION: Higher neighborhood deprivation is independently associated with lower screening mammography utilization. Targeted, equity-focused interventions addressing neighborhood, racial, and language-related barriers are needed to reduce screening disparities.

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PubMed2026

Cost-effectiveness analysis of a virtually administered pain coping skills training intervention in women with breast cancer in underserved areas.

OBJECTIVES: Women with cancer who live in medically underserved areas could benefit from behavioral pain interventions, but access is limited. A randomized trial reported that a 4-session virtual program incorporating pain coping skills training (mPCST) was effective in improving pain outcomes compared to an attention-control condition. We performed a cost-effectiveness analysis of mPCST vs. control. METHODS: Data on medical resource use, therapist time, and participants' attendance at intervention sessions and time associated with travel and using a mobile app were collected. The 5-level EuroQol 5-Dimension (EQ-5D-5L), a preference-weighted measure of health-related quality of life (HRQOL), was administered at baseline, after the intervention period, and 3 and 6 months later. Medicare payments were used to value medical resource use and therapist time to deliver mPCST. Patient time was valued using the average US wage. RESULTS: Medical resource utilization was similar for both groups, but hospitalizations trended higher in the mPCST group. EQ-5D-5L preference weights were higher by an average of 0.066 (p = 0.04) with mPCST across the follow-up period, representing an incremental gain of 0.04 quality-adjusted life years (QALYs) (95% CI: 0.00-0.08). When including the base-case cost of mPCST of \$500 vs. \$0 for the control group, the incremental cost-effectiveness ratio (ICER) was \$12,725 per QALY (95% CI: 5,566-69,343). Including the value of patient time added \$303 to mPCST costs resulting in an ICER of \$20,438 per QALY (95% CI: 9,051-111,403). SIGNIFICANCE OF RESULTS: mPCST is a cost-effective program that improves HRQOL for women with cancer living in medically underserved areas.

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PubMed2026

Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a heterogenous disease with frequent late-stage diagnosis and high mortality rates, for which no reliable screening tests exist. In recent years, epigenetic biomarkers in the form of DNA methylation in CpG-rich regions have gained increased attention in the scientific community due to their robust nature and accessibility, allowing for diagnosis without the need for invasive surgery. In this study, we investigated the aberrant methylation of promoter regions in early stage EOC through non-parametric methods, with the purpose of characterizing candidate epigenetic biomarkers. The approach was used on a cohort of early stage EOC samples, and results were compared to existing programs for differential methylation. Significant regions were then used to construct a CpG panel for stratifying EOC histotypes through predictive classification in external data. Identified promoter regions were highly reproducible across cohorts, and the constructed CpG model stratified histotypes in external cohorts through predictive classification. Comparisons against other DMP and DMR callers showed a degree of homogeneity between results but also revealed promoter regions that were overlooked despite clear signs of aberrant methylation. Finally, EOC histotypes were found to differ in their methylation distribution types, and results indicate that methods sensitive to non-normally distributed data may be poorly suited to compare groups with different distribution types. The non-parametric approach identified aberrantly methylated promoter regions that were highly reproducible across cohorts. Results from predictive classification indicate that these regions may be useful for the purpose of EOC histotype stratification.

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PubMed2026

Meaning in Life in Palliative Cancer Care: Psychosocial and Existential Outcomes-A Systematic Review.

BackgroundExistential distress, marked by hopelessness, loss of meaning, and spiritual suffering, is prevalent among patients with advanced illness, and is associated with psychological burden and a wish to hasten death (WTHD).PurposeThis systematic review aimed to synthesize current evidence on meaning in life (MIL) in adult palliative care (PC) populations, focusing on its associations with quality of life (QOL), mental health, existential and spiritual well-being (SWB), and WTHD.MethodsMEDLINE, Web of Science, Scopus, and the Cochrane Library were searched for eligible studies (English, 2016-2024) involving adult cancer patients receiving PC. MIL was examined as a central intervention component or outcome. Risk of bias was assessed: findings were synthesized narratively. The review was registered in PROSPERO.ResultsEight studies (n = 1733 participants) were included: four cross-sectional, two randomized controlled trials, one longitudinal observational study, and one qualitative study. Several studies had small samples and substantial attrition. Risk of bias was high (n = 7), and moderate in one cross-sectional study. MIL was inversely associated with depression, anxiety, demoralization, and WTHD; and positively associated with QOL and SWB. MIL may also mediate psychological outcomes (eg, purpose, coherence, and personal values). However, heterogeneity in MIL conceptualization and measurement, combined with low methodological quality, limited comparability and certainty of findings.ConclusionMIL may be relevant to psychosocial/existential outcomes in PC. Conclusions are constrained by a small and methodologically weak evidence base. Further high-quality, longitudinal research is needed before MIL-centered interventions can be recommended for routine clinical practice.

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PubMed2026

Treatment of Hot Flashes in Men With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: Hot flashes are common and often debilitating side effects of castration therapy; a cornerstone in the treatment of metastatic prostate cancer (PCa) as well as in localized or locally advanced PCa when combined with radiotherapy. The evidence for relieving vasomotor symptoms is limited. This systematic review presents both pharmacological and non-pharmacological interventions for treating hot flashes in men with PCa undergoing castration therapy, primarily androgen deprivation therapy (ADT). METHODS: a systematic literature search was conducted in PubMed using ("hot flash*" OR "hot flush*" OR "vasomotor*") AND ("prostate") as keywords. Studies with intervention for hot flashes due to castration therapy, estimation of treatment response (e.g., reduction in frequency or impact on quality of life) and patients with PCa (any stage) were eligible. RESULTS: Of 469 papers, 35 were included in the review. The included studies evaluated cyproterone acetate, estrogen or estrogen derivatives, progesterone derivatives, selective serotonin reuptake inhibitors (SSRIs), gabapentin, oxybutynin, and clonidine, as well as non-pharmacological interventions such as acupuncture, cognitive behavioral therapy (CBT), and dietary supplements (e.g., Dong Quai/Angelica Sinensis, Serelys Homme, soy protein, and Salvia officinalis). Across all blinded pharmacological interventions, the relative reduction in hot flash frequency ranged from -21% to -84%, and the placebo effect was between -19% and -30%. CONCLUSION: Hormonal agents such as cyproterone acetate and estrogen appear to be the most effective treatments, although they are associated with side effects. Non-pharmacological options like acupuncture and CBT may offer some benefit, while dietary supplements seem to be ineffective. Future studies are needed also to evaluate newer treatments, such as fezolinetant, in this patient population.

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PubMed2026

Wearable Sleep Monitoring in Pediatric Acute Lymphoblastic Leukemia: Associations With Subjective Sleep Ratings and Neurocognitive Functioning.

BACKGROUND: Sleep disturbances are associated with increased fatigue, reduced quality of life, and neurocognitive dysfunction and have emerged as a common complication among pediatric cancer survivors. Sleep disturbances are particularly concerning given their potential to exacerbate existing neurocognitive impacts of cancer treatments. This pilot study examined the feasibility and acceptability of a home-wearable EEG-based sleep device (Sleep ProfilerTM) for acute lymphoblastic leukemia (ALL) survivors as well as associations between specific sleep parameters and neurocognitive functioning. PROCEDURE: Children (ages 8-12; M = 10 years, SD = 1.6; N = 23) >6 months post-treatment for ALL were enrolled at clinical visits and wore the Sleep ProfilerTM for two consecutive nights at home, followed by neurocognitive testing of attention, inhibitory control, working memory, and processing speed. Parents completed subjective measures of child sleep, anxiety, depression, and acceptability. Feasibility reflected the percentage of children wearing the device at least one night and the percentage of nights with good EEG quality data. RESULTS: All participants wore the device both nights, with 84% meeting the threshold for good quality measurement. Few children met recommended quantity and quality sleep thresholds based on objective measurement, including 5 patients with elevated snoring levels; 43.5% of subjective ratings fell above the threshold for sleep disturbance. Greater sleep latency was associated with worse inhibitory control (r = -0.42, p = 0.046), and total sleep time was positively associated with inhibitory control and attention. CONCLUSIONS: Findings confirm the feasibility and acceptability of home EEG sleep monitoring in school-age survivors, and associations of sleep latency and snoring with reduced neurocognitive functioning may offer modifiable risk factors for aspects of neuropsychological dysfunction common in pediatric survivorship. CLINICAL TRIAL REGISTRATION: At the time this study was conducted, we were not required to register the study on ClinicalTrials.gov. It was a single-institution feasibility study without intervention, which was not considered a clinical trial.

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PubMed2026

Cost-Effectiveness of Electronic Patient-Reported Outcome Measure Interventions in Cancer: Systematic Review and Parameter Extraction for Economic Modeling.

BACKGROUND: Complex digital interventions that integrate electronic patient-reported outcome measures (ePROM) into clinical practice in cancer have the potential to improve quality of life, increase survival, and reduce health resource use and costs. Such systems can help patients with cancer self-manage chemotherapy symptoms, reduce clinicians' workloads through automated decision support, and resolve problems earlier. However, more research on the cost-effectiveness of ePROM monitoring is needed. OBJECTIVE: This paper comprises two complementary components: (1) a systematic literature review summarizing and evaluating the quantitative and qualitative evidence related to the cost-effectiveness of ePROM monitoring and (2) a health economic model parameter extraction. We also conducted supplementary targeted searches and scoping to provide context to our findings. METHODS: We searched Ovid (including MEDLINE and Embase), Scopus, and the International Health Technology Assessment Database for original English-language papers published on or before March 2025 using search strings that combined terms related to ePROMs, health economics, and cancer/oncology. We included papers reporting health economic-related outcomes for ePROM interventions designed for adult cancer populations and excluded screening tools and conference abstracts. RESULTS: We included 34 publications from 27 unique studies and identified and analyzed 26 ePROM-integrated interventions within these. Most (23/26) of the included interventions explicitly described some form of alert handling and automated decision support based on remote ePROM monitoring. Of the 34 publications, 5 presented full cost-effectiveness analysis results, of which 3 were highly uncertain and lacked clear differences in costs and health outcomes between ePROMs and standard care; conversely, 2 presented strong evidence of cost-effectiveness due to quality-of-life improvements, reduced hospitalizations, and potentially more autonomy in health-related travel (eg, ePROM-monitored patients can drive or walk to the hospital instead of using taxis or ambulances). A further 5 publications reported partial health economic results (eg, cost-consequence and budget impact), of which 1 detected no difference in strategies; in contrast, 4 reported lower health resource use and costs of ePROMs, mainly due to hospitalization reductions. Overall, 12 of the 27 studies included a qualitative component but mostly focused on user experience and design-related themes; only 2 of these addressed economic-specific themes (eg, changes in workflow and resource use due to ePROM implementation and integration), indicating some potential for time saving due to ePROM monitoring. CONCLUSIONS: Some ePROM-integrated interventions demonstrated cost-effectiveness in cancer care, but the evidence base remains limited. Where evidence does exist, cost-effectiveness appears driven by reduced hospitalization and improved quality of life. Qualitative research within the included studies rarely addressed economic questions. We provide a detailed parameter extraction for use in future economic modeling and recommend research priorities, including quantitative mapping of ePROM symptom data onto health resource use patterns, and qualitative work exploring how ePROM implementation affects clinical workloads and patient-perspective costs.

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PubMed2026

Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation.

The successful culture of human embryonic stem (hES) cells from inner cell mass cells of blastocyst stage 'spare' embryos in 1998, followed by induced pluripotent stem (iPS) cells in 2006, which allowed somatic cells to be reprogrammed to pluripotency using the Yamanaka factors, transformed regenerative biology and inspired extensive global efforts towards developing pluripotent stem cell-based applications. However, hES and iPS cells, as well as organoids generated from them, largely retain fetal-like characteristics, which limits their relevance for clinical translation. Concurrently, the prevailing assumption published in leading journals that adult tissues lack endogenous stem cells has led to the belief that mature cells dedifferentiate and reprogram during in vivo regeneration upon chronic injury, and that the appearance of embryonic/fetal markers in diabetes, heart failure, cancer, and many other chronic disease states reflects dedifferentiation of mature cells. We suggest that the prevailing concepts of dedifferentiation and reprogramming, both in vitro and in vivo, require careful re-evaluation. Adult somatic cells possibly do not truly dedifferentiate, neither in vitro nor in vivo. Instead, tissue-resident, pluripotent, very small embryonic-like stem cells (VSELs) in multiple organs account for the observed biology. In vitro "reprogramming" responses to Yamanaka factors likely reflect selective activation and expansion of VSELs/early progenitors rather than the dedifferentiation/ reprogramming of mature adult somatic cells. Likewise, the embryonic/fetal-like signatures reported in multiple disease states including cancer reflect expansion of immature tissue-specific progenitors that arise from VSELs but fail to differentiate normally due to a damaged microenvironment in vivo. Therapeutic strategies involving transplantation of MSCs, MUSE cells, or their secreted exosomes improve disease outcomes, possibly by restoring the damaged niche that supports functional tissue repair by VSELs. Although direct evidence to support this is lacking at present, recognising the central role of VSELs/progenitors and their niche in maintaining tissue homeostasis in vivo could resolve existing roadblocks and guide more effective endogenous regenerative therapies for diseased tissues and age-related dysfunctions.

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PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

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PubMed2026

Performance of Photon-counting CT for Assessing Pretreatment Breast Cancer: Comparison with Mammography, MRI, and 18F-FDG PET/CT.

Background Photon-counting CT (PCCT) offers improved spatial resolution, contrast to noise ratio, and dose efficiency, but its clinical utility remains incompletely defined for breast cancer. Purpose To evaluate the feasibility of PCCT for pretreatment breast cancer assessment through comparisons with MRI, full-field digital mammography (FFDM), and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT. Materials and Methods In this prospective study (March-May 2025), female participants with breast lesions categorized as Breast Imaging Reporting and Data System 4C or higher at US or FFDM underwent breast MRI and multiphasic contrast-enhanced PCCT. 18F-FDG PET/CT was performed in a subset with locally advanced disease. Four radiologists independently evaluated lesion morphologic characteristics, additional findings, and clinical TNM stage. Agreement was analyzed using intraclass correlation coefficients (ICCs) and κ statistics. The diagnostic performance for additional lesions and nodal metastasis was compared with the reference standard (pathologic examination). Results Among 126 participants (mean age, 58.1 years ± 12.3 [SD]), interreader agreement across PCCT, MRI, and FFDM was good to excellent. PCCT agreed with MRI for lesion characterization (κ = 0.57-0.96) and clinical T categorization (κ = 0.86-0.88), with highest agreement with pathologic size (ICC, 0.70-0.81). For 46 pathologically confirmed additional lesions, PCCT was more sensitive than FFDM (difference, 44% [95% CI: 19, 66]) and similar to MRI (difference, 7% [95% CI: -5, 21]). Additionally, 44% (95% CI: 27, 52) of microcalcifications were missed at PCCT versus FFDM. For pathologically confirmed nodal metastasis, PCCT was more sensitive (difference, 10% [95% CI: 1, 20]) and accurate (difference, 6% [95% CI: 1, 11]) than MRI. For clinical N category, PCCT agreed with PET/CT (κ = 0.82 [95% CI: 0.62, 0.96]; n = 19). Two distant metastases identified at PCCT were consistent with 18F-FDG PET/CT and pathologic findings. Conclusion PCCT demonstrated similar performance to MRI for lesion characterization and detection of additional lesions, with better performance for nodal metastasis evaluation; however, detection of microcalcifications was limited. © RSNA, 2026 Supplemental material is available for this article.

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PubMed2026

Effects of erector spinae plane block on postoperative pain in patients undergoing implant-based breast reconstruction for breast cancer: a randomized controlled trial.

BACKGROUND: Implant-based breast reconstruction after mastectomy causes acute pain. OBJECTIVE: To determine whether a single-shot T5 erector spinae plane block (ESPB) reduces postoperative pain. DESIGN: Single-center, RCT with allocation concealment; blinded assessors and statisticians. SETTING: Tertiary cancer center in China. PATIENTS: 100 adults scheduled for radical mastectomy with implant reconstruction were randomized (1:1); follow-up complete. INTERVENTION: Before induction, ESPB was given under ultrasound guidance at T5 with 30 mL of 0.375% ropivacaine plus dexmedetomidine 1 μg/kg; controls received no block. Standardized general anesthesia and postoperative PCA for both groups. MAIN OUTCOME MEASURES: Resting NRS at 6 h (MCID=1). Secondary outcomes were opioid consumption, quality of recovery, and PONV. RESULTS: ESPB did not significantly reduce resting pain at 6 h at the median (τ =0.50; adjusted difference -0.9; p = 0.08). At the upper tail, pain intensity was lower (τ = 0.75; -1.8; p <0.01). Repeated measures provided additional time-point information, improving estimation precision and test sensitivity. ESPB get lower pain scores at 6, 12, and 24 hours (all p <0.01). But, the 95% CI includes the MCID, the clinical benefit remains uncertain. Opioid use decreased at 24 h (-13.5 mg; p <0.01) and 48 h (-6.6 mg; p <0.01). Quality of recovery improved at 24 h (difference 5 points; p <0.01), but not later. No differences were observed in intraoperative hemodynamics or PONV. CONCLUSIONS: Single-shot T5 ESPB with perineural dexmedetomidine may reduce postoperative pain and opioid requirements and improve early recovery. Further large trials are warranted. Clinical relevance remains to be confirmed. TRIAL REGISTRATION: ClinicalTrials.gov NCT06143020.

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PubMed2026

High-dose radiotherapy in patients with high-risk prostate cancers treated with long-term androgen deprivation therapy (GETUG AFU 18): a randomised, phase 3 trial.

BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9·5 years (IQR 8·5-10·3), 5-year progression-free survival was 91·4% (95% CI 87·0-94·4) in the dose-escalation group versus 88·1% (83·2-91·6) in the control group, and 10-year progression-free survival was 83·6% (77·8-88·0) versus 72·2% (65·3-78·0; stratified HR 0·56, 95% CI 0·40-0·78, p<0·0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING: French National Cancer Institute and AstraZeneca.

Aged↗

PubMed2026

Distinct functions of mammalian RAD51 paralogs in genome maintenance.

RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) are evolutionarily conserved essential proteins for cell survival and genome maintenance. RAD51 paralogs were originally identified to play a role in homologous recombination-mediated repair of DNA double-strand breaks (DSBs). However, investigations over the last decade have uncovered new roles of RAD51 paralogs beyond DSB repair in replication stress responses, including replication fork progression, fork stability, and its restart. Recent structural studies have not only uncovered the molecular architecture of previously known RAD51 paralog complexes but also identified novel paralog complex assemblies, providing mechanistic insights into their various genome-maintenance functions. Additionally, a role for RAD51 paralogs in resolving R-loops has been identified, and studies with cancer-associated variants suggest that RAD51 paralogs are potential determinants of cancer susceptibility and therapeutic responses. In the present review, we highlight the recently deciphered structures and novel functions of RAD51 paralog complexes and discuss the clinical and therapeutic implications.

Rad51 Recombinase↗