Search Results (499)

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and is generally associated with an excellent prognosis. Historically, treatment strategies were uniform and frequently aggressive, including total thyroidectomy and routine radioiodine ablation, even in low-risk cases. Current Perspective: Over the past decade, the management of PTC has shifted toward a de-escalation paradigm. This transition is driven by high evidence showing that the majority of PTCs follow an indolent course, with low recurrence and mortality rates. As a result, there is increasing emphasis on tailoring the extent of surgery and adjuvant therapy to individual patient risk profiles. Active surveillance, hemithyroidectomy, and selective use of radioiodine now represent valid alternatives to traditional radical approaches, particularly for low-risk tumors. Clinical Implications: The goal of this evolution is to balance oncologic safety with quality of life, reducing overtreatment and minimizing long-term complications such as hypoparathyroidism or recurrent laryngeal nerve injury. Personalized treatment decisions are now guided by tumor biology, molecular markers, and refined risk stratification systems. Conclusions: This article will review the current evidence supporting this shift, highlight the challenges of implementation in clinical practice, and discuss future trends in the management of papillary thyroid carcinoma. Full article

The treatment paradigm for HER2-positive metastatic breast cancer has evolved from continuous chemotherapy-based regimens to a model of finite chemotherapy induction followed by sustained antibody-driven disease control. The CLEOPATRA trial established dual HER2 blockade with trastuzumab and pertuzumab plus a taxane as the biological and clinical anchor of this approach, demonstrating that chemotherapy is administered for a defined induction period, after which antibody maintains disease suppression. An increasing body of clinical evidence indicates that antibody-based regimens can be combined with targeted agents, including CDK4/6 inhibitors or HER2 tyrosine kinase inhibitors, to achieve durable disease control without the need for continuous chemotherapy. In the PATINA trial, the addition of palbociclib to trastuzumab, pertuzumab, and endocrine therapy was associated with a clinically meaningful improvement in progression-free survival in hormone receptor-positive, HER2-positive metastatic breast cancer. At the same time, quality of life was maintained despite higher rates of hematologic toxicity. More recently, HER2-CLIMB-05 demonstrated that the addition of tucatinib to dual HER2 antibody therapy significantly prolonged progression-free survival, supporting a model of sustained, multi-agent HER2 pathway suppression. The monarcHER trial provided biological proof of concept that antibody plus CDK4/6 inhibition can achieve disease control without chemotherapy in hormone receptor-positive, HER2-positive disease. Collectively, these advances support a translational framework in which antibody therapy serves as a central component of treatment strategies, with targeted partners selected according to tumor biology and prior therapy. This review summarizes the biological basis, clinical evidence, and future perspectives of antibody-driven maintenance in HER2-positive metastatic breast cancer. Full article

Background: POLE-mutated endometrial carcinomas are associated with exceptionally favorable outcomes, forming the basis for treatment de-escalation in early-stage disease. Nevertheless, rare adverse clinical courses have been reported. This study describes an unusual case of late metastatic recurrence in a POLE-mutated tumor and provides a review of similar cases in the literature. Methods: We present a detailed clinical, radiological, pathological, and molecular description of a patient who developed metastatic recurrence 16 years after initial surgery. A systematic literature search was conducted to identify reports of recurrence, progression, or cancer-related death in POLE-mutated endometrial carcinoma, with extraction of recurrence patterns, genomic features, treatment, and outcomes. Results: The patient experienced sequential pulmonary, cerebral, and leptomeningeal metastases despite harboring a canonical POLE hotspot mutation, proficient mismatch repair status, wild-type TP53, no additional known driver mutation beyond PTEN alterations. The literature review identified a small number of similarly adverse cases. Reported recurrences were heterogeneous, though distant and occasionally central nervous system involvement were noted. Conclusions: While POLE-mutated tumors overall retain an excellent prognosis, rare cases may follow an atypical and aggressive course. Improved molecular annotation and integrated risk-stratification models are needed to better identify this minority of higher-risk patients. Full article

Background: Minimal residual disease (MRD) assessment is an emerging tool for refining the risk of relapse following definitive therapy in non-small-cell lung cancer (NSCLC). However, data regarding its clinical impact on the decision-making process remain limited. We evaluated MRD feasibility and its impact in the real-world setting. Methods: A pooled retrospective analysis of longitudinal MRD data in NSCLC patients (n = 34: Signatera™ (Exome), n = 25, Guardant Reveal™, n = 9) was implemented. Co-primary endpoints: MRD feasibility and clinical impact on management (changes in surveillance intensity or therapy escalation/de-escalation). Secondary endpoints: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy for recurrence detection, and MRD lead time. Results: MRD was feasible in 32/34 patients (94.1%); longitudinal testing included two samples in 15 patients (44.1%) and three samples in 2 patients (5.9%). Signatera™ (Exome) failed in 2/25 (8.0%) due to insufficient tissue. MRD influenced management in 20/34 (58.8%) patients, most commonly supporting therapy de-escalation (15/34, 44.1%), followed by imaging surveillance modification (3/34, 8.8%) and therapy escalation (2/34, 5.9%). In univariable analysis, tumor grade and STAS were associated with MRD-driven management impact, but neither remained significant in multivariable analysis. With a median follow-up of 18.9 months (IQR 8.5–30.7), MRD was positive in 6/32 (18.8%), while recurrence/progression occurred in 10/32 (31.3%) patients. MRD yielded 21 true negatives, five true positives, five false negatives (including two isolated brain recurrences), and one false positive, corresponding to a sensitivity of 50.0%, specificity of 95.5%, PPV of 83.3%, NPV of 80.8%, and an accuracy of 81.3%. The median MRD lead time (n = 5) was 1.31 months (range, 0.46–5.52). Conclusions: In this real-world cohort, MRD testing was feasible and frequently guided clinical decisions, mainly supporting treatment de-escalation. MRD was highly specific but less sensitive. Prospective studies are needed to define optimal testing intervals and validate MRD-guided strategies. Full article

The management of urothelial carcinoma (UC) is undergoing a paradigm shift from static anatomical staging to molecularly guided dynamic approaches that integrate time as a critical therapeutic variable. This evolution is driven by liquid biopsies, particularly circulating tumor DNA, which allow real-time tumor interrogation. We conducted this expert review to synthesize landmark evidence, enabling technologies, and implementation challenges in dynamic precision oncology for UC. In this non-systematic narrative review, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for articles published between January 2015 and February 2026. Studies were selected based on their relevance to dynamic precision oncology, clinical actionability, and translational implementation, prioritizing landmark randomized controlled trials providing level 1–2 evidence, large prospective cohorts, and key translational studies. Enfortumab vedotin plus pembrolizumab established the new first-line standard for metastatic UC, achieving a median overall survival of 33.8 months versus 15.9 months (hazard ratio [HR] 0.51, 95% confidence interval 0.43–0.61). Circulating tumor DNA demonstrates robust prognostic value for molecular residual disease (MRD) detection (Level 2a evidence), stratifying recurrence risk with hazard ratios of approximately 4.5. Critically, the IMvigor011 trial has now provided Level 1b evidence that ctDNA-guided adjuvant atezolizumab improves both disease-free survival (DFS) (HR 0.64, p = 0.0047) and OS (HR 0.59, p = 0.0131) in ctDNA(+) patients, while validating treatment de-escalation in ctDNA(−) patients (1-year DFS 95%). Erdafitinib in patients harboring FGFR2/3 alterations (HR 0.64) confirms the value of genomic profiling. Major limitations include the inherent selection bias of this non-systematic approach, substantial platform heterogeneity, and lack of standardization. In conclusion, dynamic precision oncology has transformed UC management, with the IMvigor011 trial establishing ctDNA-guided MRD status as the first phase 3-validated predictive biomarker framework for adjuvant therapy selection in a solid tumor. Implementation requires adherence to established standardization frameworks, cross-platform and cross-agent validations, and tiered implementation strategies to ensure equitable access across diverse resource settings. Full article

Background: Blood cultures are frequently obtained in the emergency department (ED), yet organism identification and subsequent antibiotic optimization commonly occur after hospital admission. Inappropriate empiric therapy remains common and is associated with adverse outcomes. MALDI-TOF MS can shorten the time to organism identification; however, real-world effectiveness may depend on laboratory cadence and stewardship support, and evidence for once-daily batch workflows without active antimicrobial stewardship is limited. Method: We performed a retrospective before–after cohort study at a tertiary medical center in central Taiwan, comparing positive blood cultures (PBCs) obtained in the ED before MALDI-TOF MS implementation (1 May–31 July 2018; conventional identification) and after implementation (1 September–30 November 2018; MALDI-TOF MS). Primary endpoints were appropriate antibiotic therapy at 24, 48, and 72 h after the first PBC report. Secondary endpoints included timing, location, and classification (escalation vs. de-escalation) of the first antibiotic modification. Results: After exclusions, 323 unique PBCs were analyzed (182 pre-implementation; 141 post-implementation). Baseline characteristics and clinical outcomes were similar, including in-hospital mortality (14.8% vs. 14.9%). Time to the initial positive report (Gram stain) and the final report (identification with antimicrobial susceptibility testing) did not differ significantly between periods. Appropriate antibiotic use at 24/48/72 h was comparable (75.3% vs. 76.6%, 82.4% vs. 80.1%, and 86.3% vs. 84.4%). The timing and pattern of the first antibiotic modification were also similar. In a secondary stratified analysis, patients modified before culture positivity had higher acuity and worse outcomes. Conclusions: Once-daily MALDI-TOF MS implementation was not associated with improved antibiotic appropriateness or modification patterns in ED bacteremia without active real-time stewardship oversight. Higher-frequency processing and real-time stewardship linkage may be required to translate faster diagnostics into timely therapeutic action. Full article

Automated customer service and algorithmic governance are common in digital marketplaces, yet trust can erode when logistics, refunds, and escalation fail. Complaint-based risk and trust narratives in Turkey’s e-commerce marketplaces are analyzed for January 2019–December 2025 using 118,173 de-identified Turkish and English texts from Şikayetvar, a leading Turkish online consumer-complaint portal, and reviews of official marketplace apps on Google Play and the Apple App Store. BERTopic is implemented in Python with multilingual transformer embeddings, UMAP, HDBSCAN, and c-TF-IDF representations. The selected model identifies 35 micro-topics grouped into five macro-themes: fulfillment disruptions, remediation frictions, product-integrity risks, escalation failures, and governance threats. Monthly probability-weighted prevalence is estimated, and marketplace differences are evaluated with divergence measures, permutation tests, and multinomial regression controlling for time and language. Changepoint tests indicate a shift toward fulfillment grievances in April 2020, rising governance threats from June 2022, and increasing escalation failures linked to automated support from February 2023. These patterns suggest that barriers to human escalation convert operational incidents into platform-level trust judgments, offering monitoring signals for service recovery, marketplace governance, and AI oversight. By isolating escalation failures as a distinct complaint domain, the study links service automation to procedural justice mechanisms that translate operational breakdowns into platform-level trust and risk judgments. Full article

Management of locoregionally advanced human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV(+) OPSCC) can include induction chemotherapy followed by definitive chemoradiation. The standard induction regimen of cisplatin, docetaxel, and 5-fluorouracil (TPF) is associated with high toxicity. Given the chemosensitivity of HPV(+) OPSCC, platinum doublets are frequently used as induction therapy with potentially less toxicity. This retrospective study aimed to compare outcomes between treatment-naive HPV(+) OPSCC patients receiving induction TPF and those receiving an induction platinum doublet. Data collected included tumor characteristics, response after chemoradiation, hospitalization rates, and overall survival (OS). Fifty-five patients (18 TPF and 37 platinum doublet) were included. There was no significant difference in response after completion of definitive chemoradiation (TPF: CR 83.3%, PR 5.6%, progression or metastasis 11.1% vs. platinum doublet: CR 75.7%, PR 16.2%, progression or metastasis 8.1%; p = 0.5241). There were also no differences in hospitalizations for adverse events (38.9% in TPF vs. 40.5% in platinum doublet, p = 0.907) or recurrence (11.1% in TPF vs. 2.7% in platinum doublet, p = 0.198). The 5-year OS was 84.6% in the TPF group and 81.5% in the platinum doublet group (p = 0.581). Induction platinum doublet regimens offer comparable OS, response, and hospitalization rates to TPF in locally advanced HPV(+) OPSCC. Induction with a platinum doublet may be a viable de-escalation strategy for patients who are not candidates for TPF. Full article

Paediatric medulloblastoma is the most common malignant brain tumour in children, exhibiting substantial biological heterogeneity that drives variable treatment outcomes. Despite advances in multimodal therapy, treatment-related morbidity remains a critical concern, underscoring the need for biomarkers to guide precision therapy. This review synthesises current knowledge on biomarkers of treatment response, encompassing molecular, epigenetic, transcriptomic, protein, and imaging-based markers. WNT-activated tumours show excellent prognosis and are candidates for therapy de-escalation; SHH-driven tumours demonstrate age-dependent outcomes influenced by TP53 status; Group 3 tumours carry the poorest prognosis; and Group 4 tumours display highly variable outcomes. DNA methylation profiles, transcriptional programs, and non-coding RNAs provide additional predictive insights. Protein biomarkers and advanced imaging, including liquid biopsy and radiomics, offer minimally invasive approaches for real-time monitoring of treatment efficacy. The review also addresses challenges such as intra-tumour heterogeneity, limited tissue availability, technical variability, and ethical considerations in paediatric oncology. Finally, we explore future directions, highlighting integrative, longitudinal, and ethically grounded biomarker strategies that have the potential to optimise therapy, minimise long-term toxicity, and improve both survival and quality of life for children with medulloblastoma. Full article

Background: The CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) has transformed cystic fibrosis (CF) care, but national-level real-world data on long-term effectiveness, durability of response, and treatment de-escalation remain limited. Methods: We conducted a nationwide longitudinal study using the Italian Cystic Fibrosis Registry. People with CF aged ≥6 years who initiated ETI between October 2019 and December 2022 and received ≥3 months of continuous therapy were included. Lung function (percent predicted FEV₁, ppFEV₁), nutritional status (BMI or BMI z-score), hospital days, complications, microbiology, and chronic treatments were assessed during the two years before and up to two years after ETI initiation. Longitudinal changes were analyzed using generalized estimating equations with multiple imputation for missing data. Results: The cohort included 2276 individuals (mean age 27.9 ± 13.3 years; 49% female). Mean ppFEV₁ declined during the pre-ETI period but increased by 9.9 percentage points at 12 months after ETI initiation (p < 0.001) and remained 6.8 percentage points above baseline at 24 months. A decline between 12 and 24 months was observed overall, except in individuals with severe baseline lung disease (ppFEV₁ < 40%), who maintained stable improvements. Mean annual hospital days decreased by approximately 65% and remained low throughout follow-up. Nutritional status improved, with a mean BMI increase of approximately 1.05 kg/m² compared with immediate pre-treatment in adults and a BMI z-score increase of 0.2 SD compared with pre-treatment timepoints in children. Use of most standard CF therapies declined substantially, particularly among individuals with ppFEV₁ ≥ 40%. The prevalence of allergic bronchopulmonary aspergillosis decreased, while liver disease prevalence increased modestly, largely reflecting transient elevations in liver enzymes. Conclusions: In this nationwide real-world cohort, ETI was associated with sustained improvements in lung function, nutritional status, and hospitalization burden. The attenuation of lung function gains after the first year, particularly in less severe disease, supports the need for individualized monitoring and cautious treatment de-escalation in the ETI era. Full article

This exploratory study examines how journalists in/coordinating investigations use a chatbot designed to reduce power asymmetries during remote work. Twelve freelancers across Africa, Europe, and India tested Obruche, a chatbot advisor covering risk mitigation, pay equality, tension de-escalation, and intellectual property protection. Drawing on the Unified Theory of Acceptance and Use of Technology, semi-structured interviews were coded for Performance Expectancy, Effort Expectancy, Facilitating Conditions, and Social Influence. Results show journalists gravitate towards chatbots that are cognisant of their location-specific challenges and able to provide information that facilitates access to media outlets or peers for future collaborations. Next-best-action responses that expanded user queries or offered role-play scenarios also left journalists feeling supported, less lonely, and not judged. However, the chatbot’s female persona, scepticism of artificial intelligence, and chatbot novelty may reduce user acceptance. Obruche’s potential areas of intervention are linked to eight types of organisational power. The chatbot mainly assisted journalists to confront or rebalance Control of Knowledge and Information, and Control of Scarce Resources, aiding users’ Ability to Cope with Uncertainty. This research contributes to recent qualitative studies on journalists’ well-being by demonstrating how chatbots can mitigate power imbalances between dispersed teams of journalists. The benefits and concerns presented may inform future designs of similar team-mediation chatbots. Full article

Decisions regarding the use of adjuvant systemic therapy in genitourinary (GU) malignancies—including bladder, kidney, and prostate cancers—are currently driven by clinicopathologic risk factors, which incompletely capture individual risk of residual disease. Consequently, patient selection for adjuvant treatment remains imprecise, leading to both overtreatment of cancers unlikely to recur and undertreatment of those with occult residual disease. Circulating tumor DNA (ctDNA), a minimally invasive liquid biopsy biomarker for minimal residual disease, has emerged as a promising tool to refine adjuvant treatment decision-making. Detection of ctDNA reflects persistent tumor-derived genomic material and often precedes radiographic recurrence, whereas ctDNA negativity is consistently associated with favorable oncologic outcomes. In this review, we summarize the evolving evidence supporting the use of ctDNA to guide adjuvant therapy decisions in bladder, kidney, and prostate cancers. This is not a comprehensive review on all of the potential applications of ctDNA in these malignancies. Rather, we aim to highlight disease-specific, adjuvant-guiding applications, including post-neoadjuvant and post-cystectomy decision-making in bladder cancer and emerging proof-of-concept data in renal cell carcinoma, and explore the potential application of ctDNA in the post-prostatectomy setting. Collectively, these data suggest that ctDNA may enable a paradigm shift toward biologically informed escalation and de-escalation of adjuvant therapy across GU malignancies, while underscoring the need for prospective validation in biomarker-driven clinical trials. Full article

Background: Among individuals with type 2 diabetes (T2D), lifestyle improvements can restore glycemic control, yet few studies have examined deprescribing in settings where it was necessitated by improvements in health. This study aimed to (1) identify instances of medication deprescribing among adults with T2D in a primary care setting where patients had access to lifestyle medicine (LM), (2) document lifestyle changes among deprescribed patients, (3) assess changes in body mass index (BMI), glucose, and hemoglobin A1c (HbA1c) following deprescribing, and (4) assess the safety of deprescribing in the context of LM-informed care by identifying adverse events. Methods: A retrospective review of electronic health records (EHR) was conducted among 650 adults with a diagnosis of T2D per ICD-10 code at two primary care practices. To be included in the study, individuals had to be seen at least two times during the study period, from 2014 to 2023. Using a previously developed deprescribing framework, records were reviewed to identify deprescribing events. Among patients who were identified as deprescribed, BMI, glucose, and HbA1c, were extracted from the EHR, and age-, sex-, and time-adjusted differences in least squares means were calculated. Mentions of lifestyle change in provider notes in the EHR were also extracted pre- vs. post-deprescribing. Results: Forty-one deprescribing events were confirmed, totaling 6.3% of the study population. The most common medication changes included metformin dose reduction 34%, metformin discontinuation 19.5%, and insulin dose reduction 19.5%. Among patients with follow-up data, mean BMI decreased by 2.25 kg/m², p = 0.0003. Mean decreases of 25% in glucose and 13% in HbA1c were also observed, p < 0.0003 and p < 0.0013, respectively. Lifestyle modifications were specifically cited in 51% of records among deprescribed patients, most frequently related to diet and exercise. No serious adverse events were identified in patients who were deprescribed. Conclusions: In a primary care setting where patients had access to lifestyle medicine, a subset of adults with T2D experienced meaningful health improvements and were able to reduce glucose-lowering medications without any serious adverse events noted in the EHR. Full article

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite advances, substantial variability persists among diagnostic methods and clinical workflows. A narrative review of PubMed, Scopus, and Web of Science databases was conducted up to July 2025. Studies addressing HPV detection techniques in OPSCC—including p16^INK4a^ immunohistochemistry (IHC), HPV DNA and RNA assays, liquid biopsy approaches, and computational surrogates—were critically analyzed regarding diagnostic accuracy, clinical applicability, and emerging innovations. Tissue-based assays remain the diagnostic reference standard. p16 IHC provides high sensitivity but limited specificity and should be confirmed with nucleic acid-based methods such as DNA PCR, in situ hybridization (ISH), or E6/E7 mRNA detection. Combined or “orthogonal” testing minimizes discordance and refines risk stratification. Liquid biopsy detection of circulating HPV DNA using droplet digital PCR or next-generation sequencing has shown high sensitivity and specificity in cohorts of patients with HPV-associated OPSCC, supporting its potential role as a complementary biomarker for treatment monitoring and surveillance. However, circulating HPV DNA alone does not unequivocally identify the anatomic source of HPV DNA and should be interpreted together with clinical, radiologic, and tissue-based findings. Oral rinse and saliva assays show moderate diagnostic performance, while artificial intelligence-based radiomic and histopathologic models are emerging as complementary tools. Reliable HPV attribution in OPSCC requires a multimodal diagnostic strategy integrating p16 IHC, molecular confirmation, and ctHPV-DNA monitoring. Methodological standardization and prospective validation are essential to implement precision-guided, cost-effective workflows in routine clinical practice. Full article

Background: There is growing recognition that certain medical conditions, such as type 2 diabetes (T2D), can be effectively addressed through comprehensive lifestyle changes, thereby reducing reliance on medications; however, little guidance exists on deprescribing following lifestyle change. This study aimed to develop a framework that can be used to better define and standardize across research studies which medication changes in T2D care can be classified as deprescribing. Methods: An iterative development process began with a review of medication data exported from electronic health records (EHR) for n = 650 patients with T2D, 18–89 years, from two primary care practices with LM board-certified physicians. Included patients were seen during the period of 15 May 2014 to 13 March 2023. All reported T2D medications were grouped into the following categories: insulin, non-insulin, or metformin. A consensus-based review process was employed, facilitated by weekly meetings with the research team, whereby patients were classified as “potentially deprescribed,” “not deprescribed,” or “unclear” (not enough information based on limited, exported EHR data). Patients identified as potentially deprescribed or “unclear” were then further assessed through a more detailed review of their EHR. Results: Using the results of this chart review, a framework was developed to identify types of deprescribing, as follows: (1) insulin dose reduced; (2) change from insulin to other non-insulin medication; (3) insulin discontinued; (4) non-insulin T2D medication stopped; (5) dose reduced of the same non-insulin T2D medication; (6) change from any non-insulin medication to metformin or multiple medications + metformin to metformin only; (7) metformin stopped; (8) metformin dose reduced. A total of n = 193 patients were identified as having been potentially deprescribed based on the exported EHR data, and after a more detailed review of individual EHR records, 41 were confirmed as deprescribed. Conclusions: This study is the first to present a novel framework for classifying deprescribing in the context of positive health outcomes. The framework will facilitate future research evaluating the impact of lifestyle changes on diabetes management and promote comparability across settings for medication outcomes. Future research is needed to apply this framework to quantify deprescribing across various settings with greater precision. Full article