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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-06-15)
    Abstract: We aim to determine the feasibility of a novel radiomic biomarker that can integrate with other established clinical prognostic factors to predict progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) undergoing first-line immunotherapy. Our study includes 107 patients with stage 4 NSCLC treated with pembrolizumab-based therapy (monotherapy: 30%, combination chemotherapy: 70%). The ITK-SNAP software was used for 3D tumor volume segmentation from pre-therapy CT scans. Radiomic features (n = 102) were extracted using the CaPTk software. Impact of heterogeneity introduced by image physical dimensions (voxel spacing parameters) and acquisition parameters (contrast enhancement and CT reconstruction kernel) was mitigated by resampling the images to the minimum voxel spacing parameters and harmonization by a nested ComBat technique. This technique was initialized with radiomic features, clinical factors of age, sex, race, PD-L1 expression, ECOG status, body mass index (BMI), smoking status, recurrence event and months of progression-free survival, and image acquisition parameters as batch variables. Two phenotypes were identified using unsupervised hierarchical clustering of harmonized features. Prognostic factors, including PDL1 expression, ECOG status, BMI and smoking status, were combined with radiomic phenotypes in Cox regression models of PFS and Kaplan Meier (KM) curve-fitting. Cox model based on clinical factors had a c-statistic of 0.57, which increased to 0.63 upon addition of phenotypes derived from harmonized features. There were statistically significant differences in survival outcomes stratified by clinical covariates, as measured by the log-rank test ( p  = 0.034), which improved upon addition of phenotypes ( p  = 0.00022). We found that mitigation of heterogeneity by image resampling and nested ComBat harmonization improves prognostic value of phenotypes, resulting in better prediction of PFS when added to other prognostic variables.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 2
    In: Applied Sciences, MDPI AG, Vol. 11, No. 16 ( 2021-08-15), p. 7488-
    Abstract: We seek the development and evaluation of a fast, accurate, and consistent method for general-purpose segmentation, based on interactive machine learning (IML). To validate our method, we identified retrospective cohorts of 20 brain, 50 breast, and 50 lung cancer patients, as well as 20 spleen scans, with corresponding ground truth annotations. Utilizing very brief user training annotations and the adaptive geodesic distance transform, an ensemble of SVMs is trained, providing a patient-specific model applied to the whole image. Two experts segmented each cohort twice with our method and twice manually. The IML method was faster than manual annotation by 53.1% on average. We found significant (p 〈 0.001) overlap difference for spleen (DiceIML/DiceManual = 0.91/0.87), breast tumors (DiceIML/DiceManual = 0.84/0.82), and lung nodules (DiceIML/DiceManual = 0.78/0.83). For intra-rater consistency, a significant (p = 0.003) difference was found for spleen (DiceIML/DiceManual = 0.91/0.89). For inter-rater consistency, significant (p 〈 0.045) differences were found for spleen (DiceIML/DiceManual = 0.91/0.87), breast (DiceIML/DiceManual = 0.86/0.81), lung (DiceIML/DiceManual = 0.85/0.89), the non-enhancing (DiceIML/DiceManual = 0.79/0.67) and the enhancing (DiceIML/DiceManual = 0.79/0.84) brain tumor sub-regions, which, in aggregation, favored our method. Quantitative evaluation for speed, spatial overlap, and consistency, reveals the benefits of our proposed method when compared with manual annotation, for several clinically relevant problems. We publicly release our implementation through CaPTk (Cancer Imaging Phenomics Toolkit) and as an MITK plugin.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704225-X
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  • 3
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-12-13)
    Abstract: Our study investigates the effects of heterogeneity in image parameters on the reproducibility of prognostic performance of models built using radiomic biomarkers. We compare the prognostic performance of models derived from the heterogeneity-mitigated features with that of models obtained from raw features, to assess whether reproducibility of prognostic scores improves upon application of our methods. We used two datasets: The Breast I-SPY1 dataset—Baseline DCE-MRI scans of 156 women with locally advanced breast cancer, treated with neoadjuvant chemotherapy, publicly available via The Cancer Imaging Archive (TCIA); The NSCLC IO dataset—Baseline CT scans of 107 patients with stage 4 non-small cell lung cancer (NSCLC), treated with pembrolizumab immunotherapy at our institution. Radiomic features (n = 102) are extracted from the tumor ROIs. We use a variety of resampling and harmonization scenarios to mitigate the heterogeneity in image parameters. The patients were divided into groups based on batch variables. For each group, the radiomic phenotypes are combined with the clinical covariates into a prognostic model. The performance of the groups is assessed using the c-statistic, derived from a Cox proportional hazards model fitted on all patients within a group. The heterogeneity-mitigation scenario (radiomic features, derived from images that have been resampled to minimum voxel spacing, are harmonized using the image acquisition parameters as batch variables) gave models with highest prognostic scores (for e.g., IO dataset; batch variable: high kernel resolution—c-score: 0.66). The prognostic performance of patient groups is not comparable in case of models built using non-heterogeneity mitigated features (for e.g., I-SPY1 dataset; batch variable: small pixel spacing—c-score: 0.54, large pixel spacing—c-score: 0.65). The prognostic performance of patient groups is closer in case of heterogeneity-mitigated scenarios (for e.g., scenario—harmonize by voxel spacing parameters: IO dataset; thin slice—c-score: 0.62, thick slice—c-score: 0.60). Our results indicate that accounting for heterogeneity in image parameters is important to obtain more reproducible prognostic scores, irrespective of image site or modality. For non-heterogeneity mitigated models, the prognostic scores are not comparable across patient groups divided based on batch variables. This study can be a step in the direction of constructing reproducible radiomic biomarkers, thus increasing their application in clinical decision making.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 661-661
    Abstract: Background: Tumoral molecular characterization and genomic analysis is required for appropriate choice of therapy, requiring tumor biopsies which are invasive and associated with life-threatening complications. Standard of care computed tomography (CT) acquired during lung cancer management has a yet untapped wealth of information on in situ tumor architecture, heterogeneity and peritumoral environment which have prognostic implications. Previously published literature on overall survival (OS) prediction in stage III non-small cell lung cancer (NSCLC) on CT are limited by use of heterogeneous tumor histology, therapy, imaging technique and imaging scanner type, all of which can impact radiomic features and hence potentially obscure a discernible predictive radiomic signature. To address these challenges, we 1) used a well-curated cohort of stage III NSCLC patients, 2) developed radiomic phenotypes predictive of OS, and 3) accounted for differences across image acquisition modalities and vendors. Methods: We retrospectively analyzed 110 thoracic CT scans (82 non-contrast, 28 contrast enhanced; from three vendors) from stage III lung adenocarcinoma patients (68 female, 42 male) acquired between April 2012−October 2018, with median age of 66 (range 60−71) years, and 56 identified events of death. Isotropic interpolation (3mm) was implemented to account for variations in image spatial resolution. Tumor segmentations were performed by one of three experienced radiologists using itk-SNAP. A set of 107 radiomic features subdivided into first order statistics, shape-based and textural, were extracted for each tumor using the Pyradiomics package. Radiomic features with different distributions across vendors were identified and discarded using the Kruskal-Wallis test. Harmonization of radiomic features based on radiocontrast agents was performed using ComBat batch effect correction. Radiomic phenotypes were derived through unsupervised hierarchical clustering of the main principal components of the radiomic features. A baseline Cox model based on the established tumor volume and ECOG status was built and compared with a model integrating such clinical covariates with the radiomic phenotypes using C-statistics. Results: The OS predictive performance of the Cox model integrating radiomic phenotypes and clinical covariates had C-index = 0.68, (95%) CI = [0.61,0.76], an improvement since the baseline model alone had C-index = 0.65, CI = [0.58,0.73] . Radiomic phenotypes derived from non-harmonized features did not add value to the predictive performance of the baseline model. Conclusions: Accounting for differences related to image acquisition, vendors and radiocontrast agents through feature harmonization, can substantially improve the predictive performance of well-known clinical covariates using standard CT used in NSCLC management. Citation Format: Jose M. Luna, Andrew R. Barsky, Russell T. Shinohara, Alexandra D. Dreyfuss, Hannah Horng, Leonid Roshkovan, Michelle Hershman, Babak Haghighi, Peter B. Noel, Keith A. Cengel, Sharyn I. Katz, Eric S. Diffenderfer, Despina Kontos. Robust feature selection and ComBat-based harmonization to improve survival prediction in stage III lung cancer using radiomic phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 661.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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