Validation and Implementation of a Somatic-Only Tumor Exome for Routine Clinical Application.

Next-generation sequencing-based genomic testing is standard of care for tumor workflows. However, its application across different institutions continues to be challenging given the diversity of needs and resource availability among different institutions globally. Moreover, the use of a variety of different panels, including those from a few individual genes to those involving hundreds of genes, results in a relatively skewed distribution of care for patients. It is imperative to obtain a higher level of standardization without having to be restricted to specific kits or requiring repeated validations, which are generally expensive. We show the validation and clinical implementation of the DH-CancerSeq assay, a tumor-only whole-exome-based sequencing assay with integrated informatics, while providing similar input requirements, sensitivity, and specificity to a previously validated targeted gene panel and maintaining similar turnaround times for patient care.

Machine Learning-Based Prediction of Distant Recurrence in Invasive Breast Carcinoma Using Clinicopathological Data: A Cross-Institutional Study.

Breast cancer is the most common type of cancer worldwide. Alarmingly, approximately 30% of breast cancer cases result in disease recurrence at distant organs after treatment. Distant recurrence is more common in some subtypes such as invasive breast carcinoma (IBC). While clinicians have utilized several clinicopathological measurements to predict distant recurrences in IBC, no studies have predicted distant recurrences by combining clinicopathological evaluations of IBC tumors pre- and post-therapy with machine learning (ML) models. The goal of our study was to determine whether classification-based ML techniques could predict distant recurrences in IBC patients using key clinicopathological measurements, including pathological staging of the tumor and surrounding lymph nodes assessed both pre- and post-neoadjuvant therapy, response to therapy via standard-of-care imaging, and binary status of adjuvant therapy administered to patients. We trained and tested four clinicopathological ML models using a dataset (144 and 17 patients for training and testing, respectively) from Duke University and validated the best-performing model using an external dataset (8 patients) from Dartmouth Hitchcock Medical Center. The random forest model performed better than the C-support vector classifier, multilayer perceptron, and logistic regression models, yielding AUC values of 1.0 in the testing set and 0.75 in the validation set (p < 0.002) across both institutions, thereby demonstrating the cross-institutional portability and validity of ML models in the field of clinical research in cancer. The top-ranking clinicopathological measurement impacting the prediction of distant recurrences in IBC were identified to be tumor response to neoadjuvant therapy as evaluated via SOC imaging and pathology, which included tumor as well as node staging.

ImaGene: a web-based software platform for tumor radiogenomic evaluation and reporting.

Summary: Radiographic imaging techniques provide insight into the imaging features of tumor regions of interest, while immunohistochemistry and sequencing techniques performed on biopsy samples yield omics data. Relationships between tumor genotype and phenotype can be identified from these data through traditional correlation analyses and artificial intelligence (AI) models. However, the radiogenomics community lacks a unified software platform with which to conduct such analyses in a reproducible manner. To address this gap, we developed ImaGene, a web-based platform that takes tumor omics and imaging datasets as inputs, performs correlation analysis between them, and constructs AI models. ImaGene has several modifiable configuration parameters and produces a report displaying model diagnostics. To demonstrate the utility of ImaGene, we utilized data for invasive breast carcinoma (IBC) and head and neck squamous cell carcinoma (HNSCC) and identified potential associations between imaging features and nine genes (WT1, LGI3, SP7, DSG1, ORM1, CLDN10, CST1, SMTNL2, and SLC22A31) for IBC and eight genes (NR0B1, PLA2G2A, MAL, CLDN16, PRDM14, VRTN, LRRN1, and MECOM) for HNSCC. ImaGene has the potential to become a standard platform for radiogenomic tumor analyses due to its ease of use, flexibility, and reproducibility, playing a central role in the establishment of an emerging radiogenomic knowledge base. Availability and implementation: www.ImaGene.pgxguide.org, https://github.com/skr1/Imagene.git. Supplementary information: Supplementary data are available at https://github.com/skr1/Imagene.git.