Implementing a context-augmented large language model to guide precision cancer medicine.

The rapid expansion of molecularly informed therapies in oncology, coupled with evolving regulatory FDA approvals, poses a challenge for oncologists seeking to integrate precision cancer medicine into patient care. Large Language Models (LLMs) have demonstrated potential for clinical applications, but their reliance on general knowledge limits their ability to provide up-to-date and niche treatment recommendations. To address this challenge, we developed a RAG-LLM workflow augmented with Molecular Oncology Almanac (MOAlmanac), a curated precision oncology knowledge resource, and evaluated this approach relative to alternative frameworks (i.

Novel biomarkers for guiding treatment for prostate cancer.

Risk stratification is a cornerstone of the clinical management of nonmetastatic prostate cancer. Conventional risk stratification has relied on clinical and pathologic variables, which allow for patients to be placed into risk groups that help guide prognostication and treatment recommendations. However, the performance of conventional risk stratification systems is suboptimal, leading to undertreatment for some patients and overtreatment (with potentially avoidable side-effects) for others.

Immune Spatial Organization Predicts Metastasis Risk in Aggressive Localized Prostate Cancer.

Risk stratification in localized prostate cancer (PCa) remains imprecise. Computational pathology has emerged as an attractive option for improving risk stratification, but current approaches either lack interpretability or focus solely on tumor morphology. Here, we identify, validate, and provide interpretability for an immune microenvironment-derived computational pathology biomarker for high-grade PCa.

Impact of Cribriform Pattern on Progression-Free Survival After Radical Prostatectomy in Gleason Score 8-10 Prostate Cancer.

Background: Although extensive research highlights the detrimental effect of cribriform pattern 4 (CP4) on survival in non-high-risk prostate cancer (PC), its prognostic significance in high-risk PC is not well understood. Methods: The individual patient data from the The Cancer Genome Atlas (TCGA) database following radical prostatectomy was retrospectively examined. A predefined statistical analysis was conducted to evaluate the potential association between CP4 and progression-free survival (PFS).

DirectHRD enables sensitive scar-based classification of homologous recombination deficiency.

Homologous recombination deficiency (HRD) is a predictive biomarker for efficacy of PARP (poly ADP-ribose polymerase) inhibition and platinum chemotherapy for cancer patients but remains challenging to detect. The discovery of patients without pathogenic mutations in known HR genes but exhibiting genomic scars indicative of HRD led to the FDA approval of the first scar-based HRD test. Despite advancements in whole genome sequencing (WGS) and integration of large training datasets with machine learning models, current methods lack the sensitivity required for detecting HRD scars in low tumor purity samples, especially in liquid biopsies.

Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer.

Prostate cancer has substantial heterogeneity in clinical outcomes and therapeutic responses, posing challenges in predicting disease progression and tailoring treatment strategies. Recent studies have highlighted the potential prognostic value of evaluating the tumor microenvironment, including the presence of a histologically overt stromal response (HOST-response) characterized by peri-glandular stromal changes and architectural distortions. This retrospective study examined patient records from The Cancer Genome Atlas database to identify genomic alterations associated with the HOST-response in prostate cancer.

Randomized Phase II Study Evaluating the Addition of Pembrolizumab to Radium-223 in Metastatic Castration-resistant Prostate Cancer.

The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) activity. In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes in patients with mCRPC.

Somatic symptoms in school refusal: a qualitative study among children, adolescents, and their parents during the COVID-19 pandemic.

School refusal (SR) is commonly associated with somatic symptoms that are temporally related to school attendance. Abdominal pain, headache, vomiting, and musculoskeletal pain are frequently encountered and are usually not caused by a physical disease. School refusers, parents and health care workers are often puzzled by these impairing symptoms.

Assessing the Feasibility of Using Artificial Intelligence-Segmented Dominant Intraprostatic Lesion for Focal Intraprostatic Boost With External Beam Radiation Therapy.

Purpose: The delineation of dominant intraprostatic gross tumor volumes (GTVs) on multiparametric magnetic resonance imaging (mpMRI) can be subject to interobserver variability. We evaluated whether deep learning artificial intelligence (AI)-segmented GTVs can provide a similar degree of intraprostatic boosting with external beam radiation therapy (EBRT) as radiation oncologist (RO)-delineated GTVs.

Methods And Materials: We identified 124 patients who underwent mpMRI followed by EBRT between 2010 and 2013.

MTAP deficiency contributes to immune landscape remodelling and tumour evasion.

Methylthioadenosine phosphorylase (MTAP) deficiency occurs in various malignancies and is associated with poor survival in cancer patients. However, the mechanisms underlying tumour progression due to MTAP loss are yet to be elucidated. Utilizing integrated analyses of the transcriptome, proteome and secretome, we demonstrated that MTAP deficiency alters tumour-intrinsic, immune-related pathways and reprograms cytokine profiles towards a tumour-favourable environment.

Natural history of Myhre syndrome.

Background: Myhre syndrome (MS) is a rare genetic disease characterized by skeletal disorders, facial features and joint limitation, caused by a gain of function mutation in SMAD4 gene. The natural history of MS remains incompletely understood.

Methods: We recruited in a longitudinal retrospective study patients with molecular confirmed MS from the French reference center for rare skeletal dysplasia.

Stereotactic Magnetic Resonance-Guided Adaptive Radiation Therapy (SMART) for Abdominopelvic Oligometastases.

Purpose: Stereotactic body radiation therapy can be an effective treatment for oligometastases. However, safe delivery of ablative radiation is frequently limited by the proximity of mobile organs sensitive to high radiation doses. The goal of this study was to determine the feasibility, safety, and disease control outcomes of stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) in patients with abdominopelvic oligometastases.

Local Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033): A Phase II Randomized Trial of Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab in Women With Stage I HER2-Positive Breast Cancer.

Purpose: Human epidermal growth factor receptor 2 (HER2)-directed therapy improves local control among women with HER2-positive breast cancer. This retrospective analysis evaluates the safety and efficacy of radiation therapy (RT) among patients receiving adjuvant trastuzumab emtansine (T-DM1) or paclitaxel (T) plus trastuzumab (H) in the ATEMPT (Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab) trial; Translational Breast Cancer Research Consortium (TBCRC) 033.

Methods And Materials: Patients with stage I HER2-positive breast cancer were randomized 3:1 to receive adjuvant T-DM1 or TH after mastectomy or breast-conserving surgery (BCS).

Fall of Community-Acquired Pneumonia in Children following COVID-19 Non-Pharmaceutical Interventions: A Time Series Analysis.

Non-pharmaceutical interventions (NPIs) were implemented to reduce the spread of coronavirus disease 2019 (COVID-19). A first national lockdown was decided in France on the 17 March 2020. These measures had an impact on other viral and non-viral infectious diseases.

Educational Setting and SARS-CoV-2 Transmission Among Children With Multisystem Inflammatory Syndrome: A French National Surveillance System.

Multisystem inflammatory syndrome in children (MIS-C) is the most severe form associated with SARS-CoV-2 infection in children. To reduce the spread of SARS-CoV-2 at the population level, educational setting closure have been implemented in many countries. However, the direct benefit of school closure on the MIS-C burden remains to be explored.

The risk of death from prostate cancer in men with Gleason score 3+4 prostate cancer treated using brachytherapy with or without a short course of androgen deprivation therapy.

Objective: We evaluated whether intermediate-risk factors, in addition to age, were associated with risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer.

Materials And Methods: We conducted a prospective cohort study of 1,920 men with Gleason 3+4 adenocarcinoma of the prostate who received brachytherapy (BT) or BT and a median of 4 months of androgen deprivation therapy (ADT). Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether percentage of positive biopsies (PPB), cT2b-T2c stage, prostate-specific antigen (PSA) of 10.

Disparities in Refusal of Locoregional Treatment for Prostate Adenocarcinoma.

Purpose: We assessed sociodemographic factors associated with and survival implications of refusal of potentially survival-prolonging locoregional treatment (LT, including radiotherapy and surgery) despite provider recommendation among men with localized prostate adenocarcinoma.

Methods: The National Cancer Database (2004-2015) identified men with TxN0M0 prostate cancer who either received or refused LT despite provider recommendation. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of refusing LT, with sociodemographic and clinical covariates.

Identifying the Best Candidates for Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as the Primary Staging Approach Among Men with High-risk Prostate Cancer and Negative Conventional Imaging.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.