Tânia Pereira

Abstract
Lung cancer is still the leading cause of cancer death in the world. For this reason, novel approaches for early and more accurate diagnosis are needed. Computer-aided decision (CAD) can be an interesting option for a noninvasive tumour characterisation based on thoracic computed tomography (CT) image analysis. Until now, radiomics have been focused on tumour features analysis, and have not considered the information on other lung structures that can have relevant features for tumour genotype classification, especially for epidermal growth factor receptor (EGFR), which is the mutation with the most successful targeted therapies. With this perspective paper, we aim to explore a comprehensive analysis of the need to combine the information from tumours with other lung structures for the next generation of CADs, which could create a high impact on targeted therapies and personalised medicine. The forthcoming artificial intelligence (AI)-based approaches for lung cancer assessment should be able to make a holistic analysis, capturing information from pathological processes involved in cancer development. The powerful and interpretable AI models allow us to identify novel biomarkers of cancer development, contributing to new insights about the pathological processes, and making a more accurate diagnosis to help in the treatment plan selection.

Abstract

Abstract
The evolution of personalized medicine has changed the therapeutic strategy from classical chemotherapy and radiotherapy to a genetic modification targeted therapy, and although biopsy is the traditional method to genetically characterize lung cancer tumor, it is an invasive and painful procedure for the patient. Nodule image features extracted from computed tomography (CT) scans have been used to create machine learning models that predict gene mutation status in a noninvasive, fast, and easy-to-use manner. However, recent studies have shown that radiomic features extracted from an extended region of interest (ROI) beyond the tumor, might be more relevant to predict the mutation status in lung cancer, and consequently may be used to significantly decrease the mortality rate of patients battling this condition. In this work, we investigated the relation between image phenotypes and the mutation status of Epidermal Growth Factor Receptor (EGFR), the most frequently mutated gene in lung cancer with several approved targeted-therapies, using radiomic features extracted from the lung containing the nodule. A variety of linear, nonlinear, and ensemble predictive classification models, along with several feature selection methods, were used to classify the binary outcome of wild-type or mutant EGFR mutation status. The results show that a comprehensive approach using a ROI that included the lung with nodule can capture relevant information and successfully predict the EGFR mutation status with increased performance compared to local nodule analyses. Linear Support Vector Machine, Elastic Net, and Logistic Regression, combined with the Principal Component Analysis feature selection method implemented with 70% of variance in the feature set, were the best-performing classifiers, reaching Area Under the Curve (AUC) values ranging from 0.725 to 0.737. This approach that exploits a holistic analysis indicates that information from more extensive regions of the lung containing the nodule allows a more complete lung cancer characterization and should be considered in future radiogenomic studies.

Abstract
Statistics have demonstrated that one of the main factors responsible for the high mortality rate related to lung cancer is the late diagnosis. Precision medicine practices have shown advances in the individualized treatment according to the genetic profile of each patient, providing better control on cancer response. Medical imaging offers valuable information with an extensive perspective of the cancer, opening opportunities to explore the imaging manifestations associated with the tumor genotype in a non-invasive way. This work aims to study the relevance of physiological features captured from Computed Tomography images, using three different 2D regions of interest to assess the Epidermal growth factor receptor (EGFR) mutation status: nodule, lung containing the main nodule, and both lungs. A Convolutional Autoencoder was developed for the reconstruction of the input image. Thereafter, the encoder block was used as a feature extractor, stacking a classifier on top to assess the EGFR mutation status. Results showed that extending the analysis beyond the local nodule allowed the capture of more relevant information, suggesting the presence of useful biomarkers using the lung with nodule region of interest, which allowed to obtain the best prediction ability. This comparative study represents an innovative approach for gene mutations status assessment, contributing to the discussion on the extent of pathological phenomena associated with cancer development, and its contribution to more accurate Artificial Intelligence-based solutions, and constituting, to the best of our knowledge, the first deep learning approach that explores a comprehensive analysis for the EGFR mutation status classification. CCBYNCND

Abstract
Liquid biopsy is an emerging technology with a potential role in the screening and early detection of lung cancer. Several liquid biopsy-derived biomarkers have been identified and are currently under ongoing investigation. In this article, we review the available data on the use of circulating biomarkers for the early detection of lung cancer, focusing on the circulating tumor cells, circulating cell-free DNA, circulating micro-RNAs, tumor-derived exosomes, and tumor-educated platelets, providing an overview of future potential applicability in the clinical practice. While several biomarkers have shown exciting results, diagnostic performance and clinical applicability is still limited. The combination of different biomarkers, as well as their combination with other diagnostic tools show great promise, although further research is still required to define and validate the role of liquid biopsies in clinical practice.