Objective: Genetic phenotype plays a central role in making treatment decisions of lung adenocarcinoma, especially the tyrosine-kinase-inhibitors-sensitive mutations of the epidermal growth factor receptor (EGFR) gene. We constructed three-dimensional convolutional neural networks (CNN) to analyze underlying patterns in CT images that could indicate that EGFR gene mutation status but are invisible to human eyes. Methods: From 2012 to 2015, 503 Chinese patients with lung adenocarcinoma that had underwent surgery were included. Pathological types and EGFR mutation status were tested from surgical resections. EGFR mutations (exon 19 deletion or exon 21 L858R) were found in 215/345 (62.3%) and 91/158 (57.6%) patients in the training and independent validation set, respectively. CT images were taken before any invasive operation. The patients were randomly chosen to train the CNNs or validate the CNNs’ performance. The performance was quantified using area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: The CNNs showed an AUC of 0.776 (range: 0.702–0.849, p< 0.0001) in the independent validation set and a fusion model of CNNs and clinical features (sex and smoking history) showed an AUC of 0.838 (range: 0.778–0.899, p< 0.0001), accuracy of 77.2%, sensitivity of 75.8% and specificity of 79.1% at the best diagnostic decision point. Conclusion: The CNN exhibits potential ability to identify EGFR mutation status in patients with lung adenocarcinoma which might help make clinical decisions. Advances in knowledge: The CNN showed some diagnostic power and its performance could be further improved by increasing the training set, optimizing the network structure and training strategy. Medical image based CNN has the potential to reflect spatial heterogeneity.

Background: Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8⁺ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice. Methods: Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8⁺ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status. Results: CD8⁺ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8⁺ T cells during late course of this infiltrating period, indicating that 3–7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion. Conclusions: We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.

After neoadjuvant chemoradiotherapy (NCRT) in locally advanced esophageal squamous cell cancer (ESCC), roughly 40% of the patients may achieve pathologic complete response (pCR). Those patients may benefit from organ-saving strategy if the probability of pCR could be correctly identified before esophagectomy. A reliable approach to predict pathological response allows future studies to investigate individualized treatment plans.Method: All eligible patients treated in our center from June 2012 to June 2019 were retrospectively collected. Radiomics features extracted from pre-/post-NCRT CT images were selected by univariate logistic and LASSO regression. A radiomics signature (RS) developed with selected features was combined with clinical variables to construct RS+clinical model with multivariate logistic regression, which was internally validated by bootstrapping. Performance and clinical usefulness of RS+clinical model were assessed by receiver operating characteristic (ROC) curves and decision curve analysis, respectively.Results: Among the 121 eligible patients, 51 achieved pCR (42.1%) after NCRT. Eighteen radiomics features were selected and incorporated into RS. The RS+clinical model has improved prediction performance for pCR compared with the clinical model (corrected area under the ROC curve, 0.84 vs. 0.70). At the 60% probability threshold cutoff (i.e., the patient would opt for observation if his probability of pCR was >60%), net 13% surgeries could be avoided by RS+clinical model, equivalent to implementing organ-saving strategy in 31.37% of the 51 true-pCR cases.Conclusion: The model built with CT radiomics features and clinical variables shows the potential of predicting pCR after NCRT; it provides significant clinical benefit in identifying qualified patients to receive individualized organ-saving treatment plans.