We retrospectively evaluated the capability of radiomic features to predict tumor growth in lung cancer screening and compared the performance of multi-window radiomic features and single window radiomic features. One hundred fifty lung nodules among 114 screen-detected, incident lung cancer patients from the National Lung Screening Trial (NLST) were investigated. Volume double time (VDT) was calculated as the difference between continuous two scans and used to define indolent and aggressive lung cancers. Lung nodules were semi-automatically segmented using lung and mediastinal windows separately, and subtracting the mediastinal window region from the lung window region generated the difference region. 364 radiomic features were separately exacted from nodules using the lung window, the mediastinal window and the difference region. Multivariable models were conducted to identify the most predictive features in predicting tumor growth. Clinical information was also obtained from the database. Based on our definition, 26% of the cases were indolent lung cancer. The tumor growth pattern could be predicted by radiomic models constructed using features obtained in the lung window, the difference region, and by combining features obtained in both the lung window and difference regions with areas under the receiver operator characteristic (AUROCs) of 0.799, 0.819, and 0.846, respectively. The multi-window feature model showed better performance compared to single window features (P < 0.001). Incorporating clinical factors into the multi-window feature models showed improvement, yielding an accuracy of 84.67% and AUROC of 0.855 for distinguishing indolent from aggressive disease. Multi-window CT based radiomics features are valuable predictors of indolent lung cancers and out performed single CT window setting. Combining clinical information improved predicting performance.

Hypoxic regions (habitats) within tumors are heterogeneously distributed and can be widely variant. Hypoxic habitats are generally pan-therapy resistant. For this reason, hypoxia-activated prodrugs (HAPs) have been developed to target these resistant volumes. The HAP evofosfamide (TH-302) has shown promise in preclinical and early clinical trials of sarcoma. However, in a phase III clinical trial, TH-302 did not improve survival in combination with doxorubicin (dox), most likely due to a lack of patient stratification based on hypoxic status. Herein, our goal was to develop deep-learning (DL) models to identify hypoxic habitats, using multiparametric (mp) MRI and co-registered histology, and to non-invasively monitor response to TH-302 in a patient-derived xenograft (PDX) of rhabdomyosarcoma and a syngeneic model of fibrosarcoma (RIF-1). A DL convolutional neural network showed strong correlations (>0.81) between the true hypoxic portion in histology and the predicted hypoxic portion in multiparametric MRI. TH-302 monotherapy or in combination with Dox delayed tumor growth and increased survival in the hypoxic PDX model (p<0.05), but not in the RIF-1 model, which had lower volume of hypoxic habitats. Control studies showed that RIF-1 resistance was due to hypoxia and not to other causes. Notably, PDX tumors developed resistance to TH-302 under prolonged treatment. In conclusion, response to TH-302 can be attributed to differences in hypoxia status prior therapy. Development of non-invasive MR imaging to assess hypoxia is crucial in determining the effectiveness of TH-302 therapy and to follow response. In further studies, our approach can be used to better plan therapeutic schedules to avoid resistance. One Sentence Summary: Development of non-invasive MR imaging to assess hypoxia is crucial in determining the effectiveness of TH-302 therapy and to follow response.

Background parenchymal enhancement (BPE) on multi-parametric breast magnetic resonance imaging (mpMRI) reflects the volume and intensity of gadolinium uptake. We developed a semi-automated segmentation algorithm to extract and quantify measures of BPE and investigated the agreement of computed measures of BPE with radiologist-assigned categories. We retrospectively identified 123 high risk patients with breast mpMRI performed for screening indications. Pre- and post-gadolinium T1-weighted series with and without fat suppression were co-registered. Using Otsu’s method and an active contours method, the breast tissue was segmented from the chest wall and non-fat voxels were clustered to identify the amount of fibroglandular tissue. Median and inter-quartile ranges for the absolute volume of BPE (BPE cm3) and the percentage of BPE (BPE%) using a threshold PE of 30% were computed within the segmented FGT on the first post-contrast phase. Student’s t-test was used to evaluate BPE volume and BPE% by radiologist-assigned categories. Both BPE volume and BPE% differed significantly between minimal/mild and moderate/marked radiologist assigned categories (p=0.030 and 0.004, respectively). Using our newly developed semi-automated segmentation pipeline, we quantified fibroglandular tissue and BPE. The overlapping ranges of quantitative BPE corresponding to the radiologist-assigned BPE categories showcases the inter-reader variability with visual estimation of BPE.