Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support methods.Digital drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted agents.DDA has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical trial.The aim of this study was to evaluate the utility of DDA in pediatric oncology.Methods Between 2017 and 2020,103 high-risk pediatric cancer patients(<21 years)were involved in our precision oncology program,and samples from 100 patients were eligible for further analysis.Tissue or blood samples were analyzed by whole-exome(WES)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision support.Finally,a molecular tumor board(MTB)evaluated the results to provide therapy recommendations.Results Of the 100 cases with comprehensive molecular diagnostic data,88 yielded WES and 12 panel sequencing results.DDA identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug resistance.Actionability reached 88%(29/33)by 2020 due to the continuous updates of the evidence database.MTB approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed therapies.Filtering of WES results for targeted panels missed important mutations affecting therapy selection.Conclusions DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine care of high-risk pediatric cancers.Knowledgebase updates enable automatic interpretation of a continuously expanding gene set,a“virtual”panel,filtered out from genome-wide analysis to always maximize the performance of precision treatment planning.

Microsatellite instability and expression of DNA mismatch repair genes in malignant astrocytic tumors from adult and pediatric patients

Microsatellite instability (MSI) is used as a molecular marker for defective DNA mismatch repair (MMR) genes.We report here alterations of MSI in 15 malignant astrocytomas (WHO grade Ⅲ) and glioblastomas (GBM; WHO grade Ⅳ) of pediatric patients (2-21 years) and 12 GBM from adults (44-68 years) by comparative analysis of BAT25/BAT26 loci and 10 other microsatellite markers. High-level microsatellite instability (MSI-H) occurred in 4 of the 15 pediatric cases (26.7%) and in 1 of the 12 adult GBM cases (8.3%). Low-level mi-

Theatment strategies for pediatric patients with primary cardiac tumors

Objective To analyze the experience of treatment strategies for pediatric patients with primary cardiac tumors. Methods The clinical data of 27 patients with primary cardiac tumors which detected by echocardiography from May 1999 to May 2009 was analyzed retrospectively. There were 20 male and 7 female patients,aged from 24 d to 12. 6 years. There were 59. 2% less than 1 year old at the time of diagnosis. A single tumor were present in 22 cases and multiple in 5 cases. Surgery was performed on 22 patients due to the varied

Radiomics and artificial intelligence applications in pediatric brain tumors

Background The study of central nervous system(CNS)tumors is particularly relevant in the pediatric population because of their relatively high frequency in this demographic and the significant impact on disease-and treatment-related morbidity and mortality.While both morphological and non-morphological magnetic resonance imaging techniques can give important information concerning tumor characterization,grading,and patient prognosis,increasing evidence in recent years has highlighted the need for personalized treatment and the development of quantitative imaging parameters that can predict the nature of the lesion and its possible evolution.For this purpose,radiomics and the use of artificial intelligence software,aimed at obtaining valuable data from images beyond mere visual observation,are gaining increasing importance.This brief review illustrates the current state of the art of this new imaging approach and its contributions to understanding CNS tumors in children.Data sources We searched the PubMed,Scopus,and Web of Science databases using the following key search terms:(“radiomics”AND/OR“artificial intelligence”)AND(“pediatric AND brain tumors”).Basic and clinical research literature related to the above key research terms,i.e.,studies assessing the key factors,challenges,or problems of using radiomics and artificial intelligence in pediatric brain tumors management,was collected.Results A total of 63 articles were included.The included ones were published between 2008 and 2024.Central nervous tumors are crucial in pediatrics due to their high frequency and impact on disease and treatment.MRI serves as the cornerstone of neuroimaging,providing cellular,vascular,and functional information in addition to morphological features for brain malignancies.Radiomics can provide a quantitative approach to medical imaging analysis,aimed at increasing the information obtainable from the pixels/voxel grey-level values and their interrelationships.The“radiomic workflow”involves a series of iterative steps for reproducible and consistent extraction of imaging data.These steps include image acquisition for tumor segmentation,feature extraction,and feature selection.Finally,the selected features,via training predictive model(CNN),are used to test the final model.Conclusions In the field of personalized medicine,the application of radiomics and artificial intelligence(AI)algorithms brings up new and significant possibilities.Neuroimaging yields enormous amounts of data that are significantly more than what can be gained from visual studies that radiologists can undertake on their own.Thus,new partnerships with other specialized experts,such as big data analysts and AI specialists,are desperately needed.We believe that radiomics and AI algorithms have the potential to move beyond their restricted use in research to clinical applications in the diagnosis,treatment,and follow-up of pediatric patients with brain tumors,despite the limitations set out.

Neurocognitive Dysfunction After Treatment for Pediatric Brain Tumors:Subtype-Specific Findings and Proposal for Brain Network-Informed Evaluations

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment.As the lesion itself,as well as each treatment,can cause specific neural damage,the long-term neurocognitive outcomes are highly complex and challenging to assess.The number of neurocognitive studies in this population grows exponentially worldwide,motivating modern neuroscience to provide guidance in follow-up before,during and after treatment.In this review,we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types.Based on this information,we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Low-Grade Astrocytomas—Final Report (Protocol BT-13)

Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curative treatment is not available for most of these patients, it is reasonable to conduct clinical studies to evaluate new agents. This Phase II study evaluates efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in LGA. Sixteen children diagnosed with LGA were treated. They included 12 males and 4 females, ages 1.6 - 17.4 years (median 10.6). Efficacy was evaluated in 16 patients. The majority of patients were previously treated, but 1 patient had stereotactic biopsy only. Out of the remaining 15 patients, 6 patients received chemotherapy, and 7 patients had surgery, and 2 patients received RT and chemotherapy after surgery. The patients received treatment with ANP administered daily every 4 hours (median dose of A10 was 7.71 g/kg/d and AS2-1 was 0.26 g/kg/d) until objective response or stable disease was documented and for 8 months thereafter. The duration of ANP IV ranged from 1.4 to 286 weeks with a median of 83 weeks. A complete response was documented in 25.0%, partial response in 12.5%, and stable disease in 37.5%. Overall survival was 67.7% at 5 years, and 54.2% at 10 and 15 years. Progression-free survival was 48.1%, 34.4% and 34.4% at 5, 10, and 15 years respectively. The treatment was associated with grade 3 or grade 4 Adverse Drug Experiences (ADE) in 6 patients. There were two hypernatremias of grade 4 (12%). Grade 3 ADE included urinary frequency (6%), fatigue (6%) and hypernatremia (6%). There were no chronic toxicities, and there was a high quality of survival. ANP shows efficacy with a very good toxicity profile in this cohort of children with low-grade astrocytoma.

Presentation of massive orbital hidrocystoma at birth:case report and review of the literature

Background:Hidrocystoma,or sudoriferous cyst,is an eyelid tumor originating from apocrine or eccrine sweat glands.Its presence in the orbit is relatively rare.Case presentation:A full-term female child with severe right eye extrusion was referred to our department two hours after birth.We performed cyst aspiration under ultrasonic guidance;15 cc straw-colored fluid was obtained and proptosis resolved significantly.Orbital magnetic resonance imaging(MRI)showed a large unilocular retrobulbar mass with hypo-intensity in T1 and hyper-intensity in T2.The case underwent further daily ocular assessment until day 5;when proptosis began to worsen again.On day 6,under general anesthesia,we performed aspiration and then the cyst was completely removed with an intact wall through a trans-conjunctival incision.The diameter of the aspirated cyst was about 4 cm.In pathologic consultation,a cystic cavity lined by a layer of sweat duct like epithelium with apical snouts consistent with the diagnosis of apocrine hidrocystoma was reported.Conclusion:To date,in the literature,six other cases of orbital hidrocystoma have been reported in childhood with protean clinical pictures;none of which presented at birth.Herein,we introduce the first case report at birth and also provide a review on the literature.Our report strongly argues against the well reputed theory of traumatic origin for orbital hidrocystoma;it has been postulated that this tumor may be the result of sweat gland cells implantation through the orbit.We thereby suggest the possible presence of choristomatous ectopic sweat gland cells in the orbit during embryogenesis.