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At least 19 recordsLinked to original sources
PubMed2026

Effect of intraoperative 40-hz gamma-frequency auditory stimulation on postoperative delirium in older adults undergoing major surgery: a randomized clinical trial protocol.

INTRODUCTION: Postoperative delirium (POD) is a common and clinically significant complication among older adults undergoing major surgery under general anesthesia. Gamma-frequency (40-Hz) auditory stimulation has demonstrated potential neuroprotective and cognition-enhancing effects, suggesting a plausible role in perioperative delirium prevention. However, direct clinical evidence supporting intraoperative 40-Hz auditory stimulation in reducing POD remains limited, warranting rigorous evaluation in a randomized trial. PATIENTS AND METHODS: This prospective, parallel-group, randomized controlled trial will enroll 550 older adults scheduled for major noncardiac, nonneurosurgical surgery under general anesthesia. Participants will be randomized in a 1:1 ratio to either the active stimulation group, receiving intraoperative 40-Hz gamma-frequency auditory stimulation delivered via headphones for 2 h following successful anesthesia induction, or the sham stimulation group, wearing headphones without active auditory output. The primary outcome is the incidence of POD on postoperative day 1 though 3, assessed using the Confusion Assessment Method (CAM) or the CAM for the ICU (CAM-ICU). Secondary outcomes include POD severity, sleep quality, pain scores, analgesic consumption, the incidence of postoperative nausea and vomiting (PONV), rescue antiemetic use, duration of post-anesthesia care unit (PACU) stay, length of hospital stay, quality of postoperative recovery, incidence of perioperative adverse events; postoperative morbidity, health-related quality of life, and all-cause 30-day mortality. DISCUSSION: This trial will determine whether intraoperative 40-Hz gamma-frequency auditory stimulation reduces the incidence of POD among older adults undergoing major surgery under general anesthesia. If efficacious, this noninvasive intervention could constitute a feasible perioperative strategy to mitigate delirium risk and enhance postoperative recovery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500115156).

Humans↗
PubMed1979

Controlled clinical trial of pediatric telephone protocols.

A randomized clinical trial of pediatric protocols administered by health assistants demonstrated an alternate method of handling telephone complaints in a large emergency room. The new system advised a higher medical examination rate than the current system in the emergency room probably bacause the current system has deficits with respect to collecting necessary information and making explicit decisions. This higher rate of recommended visits demonstrated in the emergency room was not confirmed in the two pediatric primary-care settings in which the protocol system was also tested. In addition to this use, the telephone protocols may also be useful in training medical and nursing students, in handling telephone complaints similar to a poison control center, in triaging problems in a rural or emergency medical service, and in providing a record of the telephone call.

Age Factors↗
PubMed2026

Privacy-Preserving Linkage of Distributed Biological, Clinical, and Imaging Data Supporting Artificial Intelligence in Pediatric Oncology.

BACKGROUND: Cancer remains the leading cause of disease-related mortality in children over the age of one in Europe, with over 35,000 new pediatric cases and more than 6,000 deaths annually. Due to the rarity of pediatric cancers, clinical trial protocols often substitute for formal treatment guidelines, resulting in many children being enrolled in multiple trials, with biological samples and genomic data stored in various biobanks. Data collection in pediatric oncology is challenging, with sparse data acquired over extended periods, underscoring the need for optimal utilization of all available information through linked, privacy-preserving datasets. METHODS: Here, we report the development of a distributed, privacy-preserving data infrastructure for the PRIMAGE project, a European initiative aimed at supporting artificial intelligence (AI)-driven image analysis for pediatric cancer prognostics. The infrastructure leverages the European Patient Identity (EUPID) Services for Privacy-Preserving Record Linkage, enabling pseudonymized data integration across clinical, biological, and imaging sources. The system incorporates EUPID's hashing and phonetic matching protocols to pseudonymize patient identifiers and link distributed datasets, facilitating secondary data use in compliance with the General Data Protection Regulation. RESULTS: Data from over 700 neuroblastoma patients from European trials and hospitals were linked and uploaded to the PRIMAGE platform, where AI models predict clinical outcomes. CONCLUSION: This infrastructure successfully facilitated AI model development, advancing pediatric oncology research, and offering a scalable framework for future European health data initiatives, such as the European Health Data Space.

Journal Article↗
PubMed1975

The planning of a clinical trials workshop.

The groundwork involved in the planning and running of a Clinical Trials Workshop using a computerized simulation exercise called 'Instant Experience' is described in detail. 2. Groups of six or seven students, each with an experienced tutor, are set the problem of designing a clinical trial protocol for a given drug. By using a computer programme, results can be generated for these designs according to pre-set rules laid down by the organizers. 3. The game itself acts as a vehicle for emphasizing the practical and theoretical problems associated with clinical trials. Further valuable information can be imparted during the group discussion periods when the trial design is being developed and during analysis of the results. 4. Limitations of this type of workshop include the need for students to have a working knowledge of clinical medicine and pharmacology, the competence of the tutors and organizers and the technical problems associated with computers and a comparatively rigid computer programme. 5. The value of this type of workshop lies in its ability to allow students to apply themselves to practical problems in clinical trials and to make mistakes with no harm to the patient.

Computer-Assisted Instruction↗
PubMed1976

Peritoneoscopic evaluation of the effect of chemotherapeutic agents on liver metastases of breast cancer (report of 2 cases).

Two cases of breast cancer are presented in which massive liver metastases were proved by biopsies prior to treatment. Use of alternate cyclical hormonal cytotoxic combination chemotherapy (EORTC Clinical Trial, protocol, no 10741/3) was followed by a dramatic disappearance of neoplastic tissue. Peritoneoscopy associated with needle biopsy proved extremely useful to provide objective evaluation of the response to chemotherapy.

Antineoplastic Agents↗
PubMed2026

Diagnostic performance of panfungal PCR on tissue specimens for the diagnosis of invasive fungal diseases: a systematic review and meta-analysis of the Fungal PCR Initiative (FPCRI).

UNLABELLED: Invasive fungal diseases are difficult to diagnose because of the limited sensitivity of culture. Panfungal PCR amplicon sequencing assays (targeting ribosomal RNA, such as 18S, 28S, ITS) are recommended for fungal identification in histopathology samples showing fungal elements. However, data describing its overall performance and consistency are lacking. This systematic literature review and meta-analysis assessed the performance of panfungal PCR on formalin-fixed paraffin-embedded (FFPE) and non-fixed (fresh or frozen) tissue samples. A systematic literature search was performed to include studies reporting the use of panfungal PCR for fungal identification in FFPE or non-fixed tissue samples. PCR sensitivity and specificity were assessed using the reference standard of histopathology showing fungal elements. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled estimates were obtained using random-effects meta-analysis. Twenty-eight studies were included. In FFPE samples (18 studies, 852 samples), sensitivity and specificity were 75.4% (95% confidence interval [CI], 59.2-86.6) and 93.5% (70.2-98.9), respectively. Sensitivity in non-fixed samples (13 studies, 207 samples) was 86.5% (74.7-93.3), while specificity could not be assessed (insufficient data). Comparative analyses showed a significantly higher sensitivity of panfungal PCR over culture (88.2%; 76-94.7 vs 52.2%; 39-65, P = 0.001). Sub-analyses could not demonstrate the superiority of one PCR target over another due to limited data. Panfungal PCR exhibited adequate sensitivity and good specificity in FFPE samples. Sensitivity was even higher in non-fixed samples and largely superior to culture. Nevertheless, large interstudy variability was observed, warranting interlaboratory studies to define the optimal PCR target and standardized protocols. IMPORTANCE: Invasive fungal diseases are difficult to diagnose because of the low sensitivity of culture. Panfungal PCRs are widely used for fungal identification in tissue specimens but suffer from heterogeneous procedures and performance. This meta-analysis shows an acceptable sensitivity (75.4% and 86.5% in fixed and non-fixed samples, respectively) and good specificity (93.5%) of panfungal PCR, supporting its use, not only on histopathology-positive fixed samples but also in non-fixed samples concomitantly with other diagnostic tools (cultures and fungal-specific PCRs if available). These results provide a strong basis for further standardization of panfungal PCR techniques via interlaboratory assays to assess reproducibility and optimize analytical protocols. CLINICAL TRIALS: This study is registered with PROSPERO as CRD42023461148.

Humans↗
PubMedDate not supplied

[Preoperative radiotherapy in breast cancer. Description of a clinical trial record and first results].

The protocol of a clinical trial, studying the value of preoperative radiotherapy (RT) in operable breast cancer is described. Results are compared to those of 2 control groups: patients treated either with surgery only or with surgery + postoperative RT. So far, in each of the 3 groups 250 patients have been entered, their total number being expected to reach about 350 per group. Two year results (on 209 evaluable cases) did not reveal any difference in survival between the groups, but a markedly lowered incidence of locally recurrent disease (from 16% to 4%) in the irradiated patients. No increase in mortality or metastasis was noted after RT. Side effects of RT were considered mild and not of such a degree as to necessitate its discontinuation.

Breast Neoplasms↗
PubMed2026

AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.

BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.

Humans↗
PubMed2025

DigiNet: Optimizing personalized care for patients with stage IV non-small cell lung cancer (NSCLC) through a digitally connected provider network-analysis plan of a prospective multicenter cohort trial.

PURPOSE: The German sector-based healthcare system poses a major challenge to continuous patient monitoring and long-term follow-up, both essential for generating high-quality, longitudinal real-world data. The national Network for Genomic Medicine (nNGM) bridges the inpatient and outpatient care sectors to provide comprehensive molecular diagnostics and personalized treatment for non-small cell lung cancer (NSCLC) patients in Germany. Building on the established nNGM infrastructure, the DigiNet study aims to evaluate the impact of digitally integrated, personalized care on overall survival (OS) and the optimization of treatment pathways, compared to routine care. METHODS: DigiNet is a prospective, controlled, non-randomized multicenter cohort study including patients with stage IV NSCLC in two study regions (East and West) in Germany. The results of molecular diagnostics and clinical information, along with the entire treatment data are documented in a shared database. A board of lung cancer specialists monitors critical events. Patients digitally complete quality of life questionnaires, with results visualized for physicians. To assess the impact of this personalized digital care, a population-based control group will be identified by matching cohorts within the involved cancer registries. The primary endpoint is OS, and secondary endpoints comprise time on first-line treatment and hospitalization rates. Furthermore, a health economic and business economic evaluation will be conducted. Qualitative interviews with patients and physicians will be performed to assess barriers and facilitating factors for implementing the DigiNet intervention. ETHICS: The study protocol was reviewed and approved by the Ethics Committee of the University Hospital of Cologne (21-1521). TRIAL REGISTRATION: NCT05818449, registered retrospectively on December 12, 2022.

Humans↗
PubMed2024

Translation of culturally and contextually informed diabetes training for Aboriginal primary health care providers on Aboriginal client outcomes: Protocol of a cluster randomized crossover trial of effectiveness.

BACKGROUND: Indigenous populations globally have significantly high rates of type 2 diabetes compared to their non-Indigenous counterparts. This study aims to implement and evaluate the effectiveness of a culturally and contextually informed Aboriginal Diabetes Workforce Training Program on Aboriginal primary health care workforce knowledge, attitude, confidence, skill and practice relating to diabetes care. METHODS: A Cluster Randomised Crossover Control Trial with two arms (Group A and Group B) will be conducted with Aboriginal primary health care services in South Australia. These services primarily provide primary health care to Aboriginal and Torres Strait Islander people. All healthcare service sites will be randomised into groups A and B to receive the training program. The training program consists of three components: 1) Peer support network, 2) E-Learning modules and 3) onsite support. Aboriginal Health Workers of participating sites will be invited to participate in the monthly online peer support network and all chronic disease staff are eligible to participate in the E-Learning modules and onsite support. The Peer Support Network runs for the entirety of the study, 17 months. Training components 2 and 3 occur simultaneously and are 2.5 months in length, with a six-month washout period between the two randomised groups undertaking the training. All primary outcomes of the study relate to diabetes management in a primary health care settings and measure participants' knowledge, attitude, confidence, practice and skills. These will be collected at seven time points across the entire study. Secondary outcomes measure satisfaction of the peer support network using a survey, interviews to understand enablers and barriers to participation, health service systems characteristics through focus groups, and medical record review to ascertain diabetes patients' care received and their clinical outcomes up to 12 months post training intervention. DISCUSSION: The findings will explore the effectiveness of the training program on Aboriginal primary health care provider knowledge, attitude, confidence, skill and practice relating to diabetes care. The final findings will be published in 2027. TRIAL REGISTRATION: The study was prospectively registered in The Australian New Zealand Clinical Trials Registry (ANZCTR), with registration number ACTRN12623000749606 at ANZCTR - Registration. Universal Trial Number (UTN) U1111-1283-5257.

Humans↗
PubMed2025

Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) study protocol.

INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people over 55 years of age globally, being neovascular AMD (nAMD) its most aggressive form. Its treatment consists of the use of drugs that block vascular endothelial growth factor (anti-VEGF). Proteomics may allow the identification of differentially expressed proteins between responders and non-responders to each anti-VEGF drug. Thus, the objective of Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) is to find new proteomic biomarkers, predictive of response to antiangiogenic treatment in patients with nAMD. METHODS AND ANALYSIS: PHARPRO-AMD is a nationwide, multicentre, prospective, observational study. Treatment-naïve patients with nAMD starting anti-VEGF therapy will be enrolled and followed up for 2 years. During this period, clinical variables will be gathered to classify treatment response. In addition, blood, tear and vitreous and aqueous humour samples will be collected and will undergo a ZenoSWATH proteomic analysis. Relevant biomarkers identified and response classification will be used to perform a multivariate logistic regression and construct receiver operating characteristic curves. RESULTS: The study is expected to identify a panel of proteomic biomarkers predictive of anti-VEGF treatment response. Integrating data from invasive and non-invasive biological samples may enhance clinical applicability. Once validated, these biomarkers could support the design of future clinical trials on biomarker-guided therapies, helping to optimise treatment regimens and improve visual outcomes. CONCLUSIONS: The PHARPRO-AMD study aims to provide proof-of-concept for biomarker-guided anti-VEGF therapy in nAMD, potentially improving vision outcomes. A notable limitation is the exclusion of patients with visual acuity above 73 Early Treatment of Diabetic Retinopathy Study letters, a criterion chosen to reduce potential ceiling effects and improve response assessment accuracy. ETHICS AND DISSEMINATION: Approved by the Galician Network of Ethics Committees, with nationwide validity. Anonymised data will be deposited in open-access repositories and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Spanish Clinical Studies Registry (REec) (0033-2024-OBS).

Humans↗
PubMed2025

Study Protocol for HeartMagic: A Prospective Observational Cohort Characterizing Subtypes of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure (HF) is a life-threatening syndrome with significant morbidity and mortality. Although evidence-based drug treatments have effectively reduced morbidity and mortality in HF with reduced ejection fraction (EF), few therapies have been demonstrated to improve outcomes in HF with preserved EF. This may be caused by the existence of several HF with preserved EF subtypes that each need different treatments. There is therefore an unmet need for a comprehensive approach to subtype patients with HF with preserved EF. This protocol details the approach employed in the HeartMagic (Heart Failure Studied With a Machine Learning, Genomics, and Imaging Combination) study to address this gap. METHODS: This prospective multicenter observational cohort study will include 500 consecutive patients with HF with preserved EF at 2 Swiss university hospitals, along with 50 age-matched patients with HF with reduced EF and 50 healthy controls. In addition to routine clinical workup, participants undergo genomic, transcriptomic, and metabolomic analyses, and the anatomy, composition, and function of the heart are quantified by comprehensive echocardiography and magnetic resonance imaging. Quantitative magnetic resonance imaging is also applied to characterize the kidney. The primary outcome is a composite of 1-year cardiovascular mortality or rehospitalization. Machine learning-based multimodal clustering will be employed to identify distinct HF with preserved EF subtypes. Statistical analysis will include group comparisons, survival analysis, and integrative multimodal clustering combining clinical, imaging, ECG, genomic, transcriptomic, and metabolomic data to identify and validate HF with preserved EF subtypes. CONCLUSIONS: The integration of comprehensive magnetic resonance imaging with extensive genomic and metabolomic profiling in this study will result in an unprecedented panoramic view of HF with preserved EF and help distinguish functional subgroups, which may provide a basis for personalized therapies.

Aged↗
PubMed2024

Associations between (pharmaco-)genetic markers and postoperative pain after inguinal hernia repair - a prospective study protocol.

BACKGROUND: Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background. Additionally, genetic polymorphisms in enzymes involved in pain mechanisms, as well as the metabolism of analgesics might influence pain perception, pain development, and response to pain medications. Key enzymes include the catechol-o-methyltransferase (COMT), the µ-opioid receptor 1 (OPRM1), and the cytochrome P450 2D6 (CYP2D6). CYP2D6 plays a crucial role in metabolizing analgesics such as tramadol, codeine, and oxycodone. It is also suspected to be involved in the synthesis of catecholamines and endogenous morphines suggesting a potential role in pathophysiology of pain. We hypothesize that the CYP2D6 activity influences the development of postoperative pain after hernia surgery. METHODS: This study is a prospective, observational, multicenter association study investigating adult patients scheduled for inguinal hernia surgery using a robotic-assisted (rTAPP) approach. Patients are enrolled during the preoperative surgical consultation. A buccal swab is collected for genetic testing at this time. Pain at the site of the hernia is assessed using the validated EuraHSQoL score preoperatively and at 2, 4, and 6 weeks postoperatively. Additionally, information on co-medication and details of the surgery will be collected. The planned number of participants is 350 patients. The primary objective is to analyze the association between different genotype-predicted CYP2D6 phenotypes and patient-reported pain intensity 6 weeks after surgery. Secondary objectives include the association between further genetic variants, such as the COMT rs4680 and OPRM1 rs1799971 genotype, and pain severity. Additionally, the potential of pharmacogenetic panel testing to optimize analgesic therapy in hernia surgery patients will be explored. DISCUSSION: The findings of this study are expected to provide valuable insights into identifying patients at higher risk for postoperative pain before surgery. This knowledge could pave the way for tailored interventions during and after surgery for these specific patients. TRIAL REGISTRATION: Deutsches Register Klinischer Studien https://www.drks.de/DRKS00034796 Registered on August 07, 2024.

Genetic Association Studies↗
PubMed2026

Longitudinal Clinical, Physiological, and Molecular Profiling of Female Patients With Metastatic Cancer: Protocol and Feasibility of a Multicenter High-Definition Oncology Study.

PURPOSE: A substantial proportion of patients receiving genomically matched therapies do not achieve clinical benefit, underscoring the influence of nongenetic factors on cancer outcomes. High-Definition Oncology (HDO) proposes integrating longitudinal, multimodal patient data-spanning clinical, molecular, physiological, and behavioral domains-to enable truly individualized cancer care. This manuscript describes the HDO study design, framework, and feasibility results in women with metastatic cancer. METHODS: We initiated a prospective, multicenter observational study (HDO study; ClinicalTrials.gov identifier: NCT06590506) enrolling 300 female patients with newly diagnosed metastatic breast, lung, or colorectal cancer. Here, we report the study design, standardized workflows, prespecified feasibility criteria, and early internal pilot results. Eleven data modalities are collected longitudinally, including tumor and germline genomics, germline epigenomics, gut microbiome, blood and stool metabolomics and proteomics, exposome characterization, wearable-derived physiological monitoring, digital footprint assessment, medical imaging, and patient-reported outcomes. Standardized workflows govern clinical procedures, data acquisition, biospecimen processing, and quality control across all participating sites. RESULTS: Feasibility was evaluated in the first 30 participants (10% of planned accrual). Patients completed 100% of scheduled clinical visits, 97.4% of planned plasma collections, 80.7% of stool samples, and all tumor biopsies. Wearable devices captured activity, heart rate, sleep, and blood oxygen saturation data during 95.0%, 84.2%, 90.6%, and 70.7% of total patient-days, respectively. Biospecimens met predefined quality control metrics across all molecular modalities. Engagement with mobile applications for pain and emotion reporting exceeded 80%. CONCLUSION: The HDO study demonstrates the feasibility of comprehensive, longitudinal, multimodal data collection in women with metastatic cancer. This internal pilot establishes an integrated framework for future analyses aimed at characterizing disease trajectories, defining molecular and physiological determinants of outcomes, and developing patient-specific computational models.

Humans↗
PubMed2026

Copy Number-low/TP53-mutated Endometrial Cancer With Wild-type p53 Immunoexpression: Implications for Risk Stratification and Management When Using Next-generation Sequencing for Molecular Classification.

Endometrial cancers with the Cancer Genome Atlas (TCGA) molecular profile of TP53-mutated, POLE-wild-type, and microsatellite-stable generally exhibit a high burden of copy number (CN) alterations and carry an increased risk for adverse outcomes, meriting maximal adjuvant therapy. In contrast, the prognosis associated with a TP53 mutation that coexists with a POLE mutation or microsatellite instability aligns with that of ultramutated or hypermutated cancers, respectively. In this study, we characterized a rare molecular subclass of endometrial cancers defined by TP53 mutation but low burden of CN alterations, wild-type p53 immunoexpression (immunohistochemistry [IHC]), and low TP53 variant allele frequency (median 13% and maximum 47%). Among 723 consecutive endometrial cancers prospectively classified using next-generation sequencing, 16 (2.2%) were CN-low/TP53-mutated/p53 wild-type IHC. Two additional cases were identified in a separate retrospective cohort of 32 recurrent low-grade early-stage endometrial cancers, bringing the total to 18 cases. They affected postmenopausal patients, exhibited low-grade endometrioid histotype, and were mostly confined to the uterus without lymphovascular space invasion. The recurrence rate was 6.25% (1/16) in the prospective cohort, and none died, placing their prognosis closer to that of CN-low than CN-high cancers. We conclude that next-generation sequencing-based TCGA classification of TP53-mutated, POLE-wild-type, microsatellite-stable endometrial cancers with TP53 variant allele frequency < 50% requires further evaluation using CN analysis and/or p53 IHC to detect this rare molecular category. IHC-based TCGA classification, such as the ProMisE protocol, will not be able to detect these cases because the p53 IHC pattern is wild-type and there are no distinguishing morphological features; this may be of relevance for analyzing ProMisE protocol-based clinical trials and outcomes studies. Long-term outcome studies are needed to refine risk stratification and treatment decisions for this unique molecular class of endometrial cancers that further contributes to the evolving understanding that the clinical significance of TP53 mutation in endometrial cancer is complex and depends on coexisting molecular alterations.

Humans↗