Objective: The treatment of anaplastic thyroid cancer (ATC) has continued to rapidly evolve over time. Increased utilization of novel, personalized therapies based upon the tumour's somatic mutation status has recently been integrated. The aim of this case series is to describe a series of patients that underwent rapid genomic testing upon their diagnosis of ATC, allowing for the early integration of novel therapies.Design: A fast track pathway for genomic tumour analysis of patients with ATC was implemented at a single academic cancer hospital in January of 2020.Patients: All patients were evaluated by head and neck surgery, endocrinology, and medical oncology upon diagnosis of ATC.Measurements: Genetic work-up was completed, which prompted a recommendation for dual BRAF/MEK inhibition with dabrafenib and trametinib for tumours with BRAF V600E mutation. For patients whose tumours were BRAF V600E wild-type, pembrolizumab with lenvatinib was offered.Results: A total of four patients were included in this series. Two patients (50%) had tumours that were BRAF V600E positive. Among patients that were BRAF V600E positive, both patients initiated urgent dabrafenib and trametinib dual tyrosine kinase inhibitor (TKI) therapy; with one patient demonstrating near-complete clinical response allowing for posttreatment surgery, while the other demonstrated decreased tumour burden. Among patients who were BRAF V600E wild-type, lenvatinib and pembrolizumab were recommended off-label; one patient demonstrated decreased tumour burden, but developed severe pure red cell aplasia, while the other patient is demonstrating an early clinical response. Conclusions:The integration of early genomic analysis and personalized neoadjuvant TKI therapy into the treatment of ATC can greatly benefit patient care outcomes and optimize tumour control.

BackgroundInfectious diarrheal illness is a significant contributor to healthcare costs in the US pediatric population. New multi-pathogen PCR-based panels have shown increased sensitivity over previous methods; however, they are costly and clinical utility may be limited in many cases. Clinical Prediction Rules (CPRs) may help optimize the appropriate use of these tests. Furthermore, Natural Language Processing (NLP) is an emerging tool to extract clinical history for decision support. Here, we examine NLP for the validation of a CPR for pediatric diarrhea.MethodsUsing data from a prospective clinical trial at 5 US pediatric hospitals, 961 diarrheal cases were assessed for etiology and relevant clinical variables. Of 65 variables collected in that study, 42 were excluded in our models based on a scarcity of documentation in reviewed clinical charts. The remaining 23 variables were ranked by random forest (RF) variable importance and utilized in both an RF and stepwise logistic regression (LR) model for viral-only etiology. We investigated whether NLP could accurately extract data from clinical notes comparable to study questionnaires. We used the eHOST abstraction software to abstract 6 clinical variables from patient charts that were useful in our CPR. These data will be used to train an NLP algorithm to extract the same variables from additional charts, and be combined with data from 2 other variables coded in the EMR to externally validate our model.ResultsBoth RF and LR models achieved cross-validated area under the receiver operating characteristic curves of 0.74 using the top 5 variables (season, age, bloody diarrhea, vomiting/nausea, and fever), which did not improve significantly with the addition of more variables. Of 270 charts abstracted for NLP training, there were 41 occurrences of bloody diarrhea annotated, 339 occurrences of vomiting, and 145 occurrences of fever. Inter-annotator agreement over 9 training sets ranged between 0.63 and 0.83.ConclusionWe have constructed a parsimonious CPR involving only 5 inputs for the prediction of a viral-only etiology for pediatric diarrheal illness using prospectively collected data. With the training of an NLP algorithm for automated chart abstraction we will validate the CPR. NLP could allow a CPR to run without manual data entry to improve care. Disclosures All authors: No reported disclosures.

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