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Adjuvant apatinib therapy following concurrent chemoradiotherapy in patients with high-risk nasopharyngeal carcinoma: A multicenter, prospective phase 2 study.

PURPOSE: To assess the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with apatinib in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: This multicenter, prospective, phase II study enrolled patients with newly histologically confirmed LA-NPC, who were randomly assigned to receive CCRT followed by adjuvant apatinib (investigational arm) or CCRT alone (control arm). The investigational arm received 250 mg/day of oral apatinib administered every 28 days for up to six cycles after CCRT. The primary endpoint was 3-year progression-free survival (PFS) and secondary endpoints of overall survival (OS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) of 3-year, and safety. RESULTS: From July 2018 to September 2020, 44 and 44 patients were randomized into the CCRT-alone and CCRT and apatinib groups, respectively. The median follow-up duration 56 (range: 40.0-58.6) months. The survival outcomes were the 3-year PFS, OS, and DMFS rates in the adjuvant apatinib following CCRT group were significantly higher than those observed in the CCRT-alone group((PFS, 78.6%vs. 54.5%, p = 0.027; OS, 88.1% vs. 75.0%, p = 0.029; DMFS, 85.4%vs. 59.1%, p = 0.009). The 3-year LRFS was similar between the groups. The grade 3-4 treatment-related adverse events(TRAEs) were higher in the former group than in the latter. The most common grade 3-4 non-hematology-related adverse events were hypertension (14.3%), hand-foot syndrome (9.5%), increased transaminase levels (7.1%), and headache (7.1%). CONCLUSION: Apatinib significantly improved the treatment effects of CCRT for high-risk LA-NPC patients. Therefore, CCRT and adjuvant apatinib may represent a promising option for this patient population.

Adjuvant therapy

Induction Paclitaxel-Cisplatin-Capecitabine for Nasopharyngeal Carcinoma.

BACKGROUND: We previously reported higher failure-free survival (FFS) with induction paclitaxel, cisplatin, and capecitabine (TPC) compared with cisplatin and fluorouracil (PF) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We now report 5-year FFS, with prespecified secondary outcomes. METHODS: In this multicenter, randomized trial, patients with high-risk LA-NPC (T4N0-2M0 or TanyN3M0) received two 21-day cycles of induction chemotherapy with TPC or PF, followed by concurrent chemoradiotherapy. The primary endpoint was FFS; secondary endpoints included distant metastasis-free, locoregional relapse-free, and overall survival (OS), tumor response, and safety. RESULTS: Among 238 patients (TPC, n=118; PF, n=120), with median follow-up of 89.1 months, 5-year FFS was 77.6% in the TPC group and 62.9% in the PF group (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.82). At 5 years, distant metastasis-free survival was 87.8% in the TPC group and 78.8% in the PF group (HR, 0.51; 95% CI, 0.28-0.95); locoregional relapse-free survival was 92.0% and 82.1%, respectively (HR, 0.43; 95% CI, 0.21-0.88); and OS was 89.6% and 82.2%, respectively (HR, 0.51; 95% CI, 0.27-0.95). Among patients with pretreatment Epstein-Barr virus (EBV) DNA <3000 copies/ml, 5-year OS was 92.3% in the TPC group and 84.4% in the PF group. Among those with higher EBV DNA levels, rates were 84.2% in TPC group and 81.1% in PF group. Grade 3 or 4 adverse events occurred in 68 patients (57.6%) receiving TPC and 79 patients (65.8%) receiving PF. Treatment adherence was similar in the two groups. CONCLUSIONS: Among patients with high-risk LA-NPC, TPC induction chemotherapy was associated with higher 5-year FFS than PF. (Funded by National Natural Science Foundation of China and State Key Laboratory of Respiratory Disease; ClinicalTrials.gov number, NCT02940925.).

Humans

Frequent mutations in the BIRC3 gene promote metastatic potential of nasopharyngeal carcinoma cells through the TRAF2-NF-&#x3ba;B pathway.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer characterized by highly locoregionally invasive behavior attributable to the latent infection with Epstein-Barr virus (EBV) and genomic instability. It is well established that EBV-encoded oncogenic molecules actively contribute to the malignant behavior of NPC cells. However, the mechanism by which aberrant genomic alterations enable NPC cells to become aggressive remains largely unknown. In the present study, whole-exome sequencing (WES) revealed that the gene encoding the baculoviral IAP repeat-containing 3 (BIRC3) protein was frequently mutated in circulating tumor cells (CTCs) but not in paired primary tumor cells from patients with metastatic NPC. A minigene assay indicated that the c.637&#xa0;A&#xa0;>&#xa0;G mutation disrupted normal mRNA splicing, resulting in the partial deletion of Exons 2 and 3 and altered stability of BIRC3 mRNA. In vitro experiments demonstrated that ectopic expression of the BIRC3c.637A>G mutant enhanced NPC cell invasive properties, including proliferation, resistance to apoptosis, migration, and invasion. Furthermore, overexpression of wild-type BIRC3 promoted invasive characteristics in NPC cells through the TRAF2-NF-&#x3ba;B signaling axis. In summary, BIRC3 acts as a regulator of the malignant features of NPC cells. Frequent BIRC3 mutations in CTCs, such as the c.637&#xa0;A&#xa0;>&#xa0;G mutation, further enhance the metastatic potential of disseminated NPC cells by inducing aberrant alternative splicing. These findings suggest the therapeutic feasibility of targeting the BIRC3/TRAF2/NF-&#x3ba;B axis in the treatment of NPC.

Humans

Somatic mutations: recent advances in brain aging and neurodegeneration.

Somatic mutations are genetic variants that occur after the single-cell phase of development and have been implicated in disease pathogenesis. While most DNA lesions are detected and repaired, examination of healthy tissue has revealed that some lesions escape repair, leading to somatic mutations that accumulate at a consistent rate, including in human brain tissue and postmitotic neurons. Emerging methodological and analytical advances have revealed the presence of persistent mutagenic mechanisms during healthy brain aging as well as mutational pattern shifts in the context of neurodegenerative diseases. Here, we highlight recent methodological advances, summarize our current understanding of somatic mutagenesis in neurotypical brain aging, and examine the role of somatic mutations in neurodegenerative diseases.

Humans

Assessing comorbidities and predicting risk: A primer for APRNs.

Today's clinical environments are rife with tools designed to comprehensively account for medical complexity and comorbidities while predicting risk for a host of adverse health-related outcomes. Therefore, it is imperative that advanced practice registered nurses (APRNs) understand the structure and function of these tools, their similarities and differences, their limitations, and strategies for appropriate incorporation into practice. This article offers a practical overview for APRNs, emphasizing clinical implications and guidance for aligning assessment tools with the clinical population of interest to improve care delivery, quality, and patient outcomes.

Humans

Advanced/Novel Stenting for Pediatric Dynamic Airway Collapse.

Pediatric dynamic airway collapse is a complex condition that can impact all levels of the pediatric airway. These conditions can pose life threatening risk to pediatric patients and carry lasting impacts. While traditionally, tracheostomy has been used to address all levels of dynamic collapse, recent advances have allowed for more individualized, anatomy-specific stenting and splinting strategies for treatment. This article covers pathophysiology and the latest evidence on strategies to address nasopharyngeal, oropharyngeal, proximal trachea, and tracheobronchial dynamic collapse.

Humans

Recent advances in electrode materials for electrochemical detection of zearalenone.

Zearalenone (ZEN) is an estrogenic mycotoxin commonly found in cereals, animal feed, and processed foods, making it an important concern for food safety and public health. Conventional chromatographic and immunological methods can detect ZEN; however, they often require expensive instruments, lengthy sample preparation, and skilled personnel, which restrict their use for rapid and on-site testing. Electrochemical sensors have attracted enormous interest of the scientific community because of their high sensitivity, rapid response, low cost, miniaturization potential, and compatibility with portable systems. The analytical performance of the electrochemical sensors is strongly influenced by electrode materials, morphology, conductivity, porosity, surface functionality, and the efficiency of bioreceptor immobilization. Despite several reviews on mycotoxin detection, a systematic assessment connecting electrode-material design, modification strategies, sensing mechanisms, and electroanalytical performance specifically for ZEN sensing remain limited. This review critically evaluates recent advances in metal oxides, carbon-based materials, metal-organic- and covalent organic frameworks, MXenes, polymers, and hybrid composites for electrochemical ZEN detection. Particular attention has been given to their roles in electron transfer, analyte enrichment, selectivity, and real-sample analysis. The review also compares the major limitations of current sensing systems, including complex fabrication, matrix interference, insufficient long-term stability, poor inter-electrode reproducibility, and limited scalability. Finally, future directions for developing robust, cost-effective, portable, and commercially viable ZEN sensors are discussed.

Journal Article

Major cardiovascular event risk of advanced therapies in inflammatory bowel diseases: systematic review and meta-analysis.

BACKGROUND: Patients with chronic immune-mediated disorders (IMIDs), including inflammatory bowel disease (IBD), are at increased risk of cardiovascular disease. While advanced therapies show cardioprotective effects in other IMIDs, their impact on major adverse cardiovascular events (MACE) in IBD remains unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating MACE risk with advanced therapies in IBD. METHODS: Systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials identified 43 studies (36 RCTs, including 9 long-term follow-up (LTF) studies, and 7 observational studies) published between 2002 and 2024. Primary analyses estimated odds ratios (OR) for MACE comparing advanced therapy to placebo, with secondary analyses stratifying studies by drug class and length of follow-up. Sensitivity analyses were conducted using alternative methods to account for zero-event data. RESULTS: Placebo-controlled RCTs showed a nonsignificant trend toward reduced MACE risk (OR 0.60; 95% CI 0.24-1.51), with similar findings across sensitivity analyses accounting for sparse and zero-event data. Class-specific trends suggested lower MACE risk with IL-12/IL-23 inhibitors (OR 0.35; 95% CI 0.05-2.21), JAK inhibitors (OR 0.57; 95% CI 0.16-2.06), and a potential increase with Anti-TNF agents (OR: 3.04; 95% CI 0.31-29.47), though none reached statistical significance. LTF studies showed consistent findings. Observational studies suggested lower MACE risk with Anti-TNF therapies (OR 0.29; 95% CI 0.21-0.40), but not with IL-12/IL-23 (OR 4.41; 95% CI 0.49-39.28) or JAK inhibitors (OR 1.57; 95% CI 0.86-2.84). CONCLUSION: Advanced therapies did not demonstrate a clear increase or decrease in cardiovascular risk in IBD. The discrepancies between RCTs and observational studies underscore the urgent need for rigorous-designed observational research with long-term follow-up to evaluate the real-world impact of advanced therapies on MACE risk.

Humans

The Natural History of Residual and Recurrent Disease in Advanced Juvenile Nasopharyngeal Angiofibroma: A Systematic Review.

OBJECTIVE: This systematic review explores the natural history of residual and recurrent juvenile nasopharyngeal angiofibromas (JNAs) to inform clinical decision-making. DATA SOURCES: PubMed, Embase, Scopus, and Web of Science. REVIEW METHODS: A systematic literature review was conducted according to PRISMA guidelines across PubMed, Embase, Scopus, and Web of Science from inception to February 20, 2025 and was re-run on September 21, 2025. Studies included patients with advanced JNA and documented follow-up of residual or recurrent disease. Descriptive statistics, chi-squared analysis, and analysis of variance were used to evaluate treatment outcomes across different modalities including surgery, radiotherapy, gamma knife surgery, and medical therapies. RESULTS: Twenty-one studies encompassing 131 male patients (mean age 16.3&#x2009;years) were included. Residual or recurrent disease demonstrated complete involution in 41%, stable disease in 29%, and reduction in size in 25% of cases. Only 2% of patients had progressive disease. A statistically significant association was observed between treatment modality and outcome (p&#x2009;=&#x2009;0.015), with radiotherapy, either alone, or as part of a multimodal approach, showing the highest rates of spontaneous involution. CONCLUSION: Residual and recurrent JNAs often remain stable or regress without further intervention. Close surveillance with imaging is a safe and effective strategy for asymptomatic patients, minimizing the risks of additional treatment in a young patient population with disease near critical anatomical structures.

Humans

Treatment of OSA using mandibular advancement versus CPAP in improving cardiovascular health.

BACKGROUND: Obstructive sleep apnea is a significant risk factor for hypertension. We assessed the relative effectiveness of mandibular advancement device (MAD) versus continuous positive airway pressure (CPAP) in reducing 24 h ambulatory blood pressure (BP) and other health-related outcomes over 12 months. METHODS: In a randomized, non-inferiority trial, 321 participants with hypertension and increased cardiovascular risk were recruited for polysomnography. Of these, 220 with moderate-to-severe OSA (apnea-hypopnea index (AHI) &#x2265;15 events/hour) were randomized to MAD or CPAP (1:1). We report the final outcomes at the 12-month follow-up. RESULTS: A total of 180 participants (MAD: 89; CPAP: 91) completed the 12-month follow-up. Median usage for MAD and CPAP was 5.5 and 4.9 h per night, respectively. Compared to baseline, the 24 h mean arterial BP at 12 months decreased by 2.3 mmHg (P = 0.200) in the MAD group and by 1.0 mmHg (P = 0.999) in the CPAP group. The difference between-groups was -0.6 mmHg (95% confidence interval: -2.53 to 1.39, non-inferiority P < 0.019). The MAD group demonstrated a larger reduction in asleep BP compared to the CPAP group. The prevalence of excessive daytime sleepiness in the MAD group decreased from 30.3% at baseline to 10.1% at 12-month follow-up (P = 0.001), and from 38.5% to 7.7% in the CPAP group (P < 0.001). The between-group difference was 10.6% (P = 0.097). No significant within-group or between-group differences were observed in the prevalence of arrhythmias and plasma levels of cardiac biomarkers. CONCLUSION: At 12-month, MAD is non-inferior to CPAP for reducing 24 h mean arterial BP in participants with hypertension and increased cardiovascular risk. TRIAL REGISTRATION: NCT04119999.

Humans

Recent advances in supramolecular macrocycle-based artificial light-harvesting systems.

Artificial light-harvesting systems (ALHSs) inspired by the antenna function of natural photosynthesis provide molecular platforms for collecting excitation energy and directing it to emissive or reactive acceptors. In many supramolecular ALHSs, however, practical performance is limited by poorly defined donor-acceptor orientation, aggregation-caused quenching (ACQ), interfacial defects, and limited stability in aqueous or complex media. Supramolecular macrocycles-particularly pillar[n]arenes (PAs), cucurbit[n]urils (CBs), calixarenes (CAs), cyclodextrins (CDs), and supramolecular coordination complexes (SCCs)-offer a useful design space because their cavities, pre-organized scaffolds, and reversible non-covalent interactions can confine chromophores, tune local donor/acceptor ratios, and modulate F&#xf6;rster resonance energy transfer (FRET). This Review systematically examines the unique structural advantages and assembly mechanisms of the five macrocyclic families, with an emphasis on their use in constructing ALHSs-from single-step to cascaded FRET-and in advancing aqueous photocatalysis, near-infrared bioimaging, panchromatic fluorescence modulation, and singlet oxygen generation. The resulting structure-property-application framework is intended to guide the rational design of macrocycle-assisted photofunctional materials while avoiding overextension of the photosynthesis analogy.

Journal Article

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2&#xd7; liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans

A review into the recent advances in the world of amoebiasis.

PURPOSE OF REVIEW: Amoebiasis is a parasitic infection caused by Entamoeba histolytica , affecting 10% of the global population. It is a well recognized cause of morbidity and mortality in low-middle-income countries where it is endemic. However, with increased migration and global travel, amoebiasis is now more common in high-income countries, although diagnosis is often delayed or even missed due to lack of awareness of the latest epidemiology and optimal diagnostic testing. This review discusses the evolving prevalence, and the current international guidelines for the investigation and treatment of amoebiasis, focusing on recent advances. RECENT FINDINGS: The recent literature shows that the primary investigations for amoebiasis remain the same, though newer modalities such as artificial intelligence-powered microscopy and metagenomics have been developed recently, which aids the accuracy and speed of diagnosis. Treatment remains the same, though current research has found potential new drugs and drug targets which show promise. SUMMARY: This review reinforces the importance of early clinical suspicion, diagnosis and treatment for amoebiasis. What was once a disease only seen in endemic countries or travel-associated imported cases is now more common and must not be missed.

Humans

Proteomics in environmental pollution research: Advances, challenges, and future directions.

Environmental proteomics has emerged as a powerful approach for elucidating the molecular mechanisms underlying pollutant-induced biological effects. Although this field has developed rapidly, the systematic review of recent proteomics applications in environmental pollution research remains limited. This review explored the emerging roles of toxicoproteomics in biomarker discovery and mechanistic elucidation, as well as ecotoxicoproteomics in ecological risk assessment and bioremediation strategies. Here, we review the field, highlighting recent trends such as the integration of proteomics with genomics, transcriptomics, and metabolomics to provide a comprehensive view of biological responses to environmental stressors. We further discuss the growing application of artificial intelligence in improving proteomics data interpretation and accelerating biomarker discovery. In addition, recent technological advances in environmental proteomics are highlighted, including next-generation tissue microarray proteomics, nanoscale proteomics, single-cell proteomics, and spatial proteomics. Despite its potential, proteomics faces challenges, such as high operational costs, computational complexity in analysis, and technical limitations in low-abundance protein detection. We propose that the convergence of proteomics with artificial intelligence and multi-omics approaches offers promising solutions to these challenges, enhancing the practical application of proteomics in environmental monitoring and risk assessment.

Proteomics

Advanced mitigation strategies for acrylamide formation in foods: Mechanistic insights, emerging innovations, and future perspectives.

Acrylamide is a heat-induced contaminant formed predominantly in carbohydrate-rich foods during high-temperature processing, posing significant concerns due to its potential carcinogenic, neurotoxic, and genotoxic effects. This review critically examines the mechanisms of acrylamide formation, emphasizing the role of the Maillard reaction and key precursors such as asparagine and reducing sugars, along with the influence of processing conditions including temperature, time, pH, and moisture. Various mitigation strategies are comprehensively discussed, ranging from raw material selection and genetic approaches to enzymatic treatments such as asparaginase and the application of natural and chemical inhibitors. Advances in processing technologies, including optimization of conventional thermal methods and emerging non-thermal techniques such as cold plasma and ultrasound, are evaluated for their effectiveness. The review also highlights the role of food additives, functional ingredients, and fermentation in reducing acrylamide formation. Furthermore, recent developments in analytical techniques, including chromatographic methods, biosensors, and artificial intelligence-based predictive models, are explored for improved detection and control. Risk assessment, toxicological implications, and global regulatory frameworks are also examined. Finally, future perspectives focusing on genetic engineering, personalized nutrition, and digital technologies such as AI and blockchain are discussed to support sustainable and industry-applicable mitigation strategies.

Acrylamide

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans

Daily low-dose carboplatin or weekly carboplatin plus nab-paclitaxel for concurrent chemoradiotherapy in older patients with locally advanced non-small cell lung cancer (JCOG1914): A randomized phase 3 trial.

BACKGROUND: Daily low-dose carboplatin with concurrent thoracic radiotherapy is the standard treatment for older patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. METHODS: This open-label phase 3 trial was conducted at 38 institutions in Japan. Patients aged&#xa0;&#x2265;&#xa0;75&#xa0;years with LA-NSCLC were randomly assigned (1:1) to receive daily carboplatin (30&#xa0;mg/m2) or weekly carboplatin (area under the curve, 2&#xa0;mg&#xb7;min/mL) plus nab-paclitaxel (30&#xa0;mg/m2) with thoracic radiotherapy. Durvalumab maintenance therapy was recommended after treatment completion. The primary endpoint was overall survival, which was used to assess the non-inferiority of weekly carboplatin plus nab-paclitaxel compared to daily low-dose carboplatin. RESULTS: From December 2020 to March 2024, 124 patients were enrolled (carboplatin arm, 61 and carboplatin plus nab-paclitaxel arm, 63). In the planned interim analysis, the Bayesian predictive probability indicating the non-inferiority of carboplatin plus nab-paclitaxel compared with carboplatin in the final analysis was 8.0%, leading to early study termination for futility. The median overall survival was not estimable in the carboplatin arm; the estimated value in the carboplatin plus nab-paclitaxel arm was 26.1&#xa0;months (hazard ratio, 1.56; 95% confidence interval, 0.79-3.11; p&#xa0;=&#xa0;0.200). Two treatment-related and seven non-cancer-related deaths occurred in the carboplatin plus nab-paclitaxel arm. Patients in the carboplatin arm had better quality of life than those in the carboplatin plus nab-paclitaxel arm at 6&#xa0;weeks (odds ratio, 0.39; 95% confidence interval, 0.18-0.81; p&#xa0;=&#xa0;0.012). CONCLUSIONS: Daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard treatment for older patients with unresectable LA-NSCLC in Japan.

Humans