PubMed · 8600711
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C T Donovan. 1996. Preventing chemo errors.. https://pubmed.ncbi.nlm.nih.gov/8600711/
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Drug response differs substantially in cancer patients due to inter- and intra-tumor heterogeneity. Particularly, transcriptome context, especially tumor microenvironment, has been shown playing a significant role in shaping the actual treatment outcome. In this study, we develop a deep variational autoencoder (VAE) model to compress thousands of genes into latent vectors in a low-dimensional space. We then demonstrate that these encoded vectors could accurately impute drug response, outperform standard signature-gene based approaches, and appropriately control the overfitting problem. We apply rigorous quality assessment and validation, including assessing the impact of cell line lineage, cross-validation, cross-panel evaluation, and application in independent clinical data sets, to warrant the accuracy of the imputed drug response in both cell lines and cancer samples. Specifically, the expression-regulated component (EReX) of the observed drug response achieves high correlation across panels. Using the well-trained models, we impute drug response of The Cancer Genome Atlas data and investigate the features and signatures associated with the imputed drug response, including cell line origins, somatic mutations and tumor mutation burdens, tumor microenvironment, and confounding factors. In summary, our deep learning method and the results are useful for the study of signatures and markers of drug response.
PURPOSE: To determine the frequency and types of dental abnormalities among children treated at a young age for cancer, as represented by neuroblastoma. PATIENTS AND METHODS: We retrospectively reviewed the dental records and panoramic radiographs of 542 children who were treated for neuroblastoma at our institution over a 31-year period. Patients in our study had to meet the following criteria: they were treated on an institutional protocol, they had undergone panoramic radiography, and their dental follow-up continued for at least 2 years after diagnosis. We evaluated the frequency of clinically or radiographically apparent microdontia, excessive caries, root stunting, hypodontia, and enamel hypoplasia in our study population. RESULTS: Of the 52 patients who met the study criteria, 71% developed dental abnormalities, comprising microdontia in 38%, excessive caries in 29%, root stunting in 17%, hypodontia in 17%, and enamel hypoplasia in 17%. In nearly half (23) of our patients, neuroblastoma was diagnosed on or before their first birthday. CONCLUSION: Children treated for neuroblastoma are at high risk for abnormal dental development. The abnormalities in these patients may require extensive dental care and can compromise their quality of life. Frequent dental examinations and an intense oral hygiene program before, during, and after treatment may improve overall dental health.
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