MRI radiomics in the prediction of the volumetric response in meningiomas after gamma knife radiosurgery.

PURPOSE: This report presents the first investigation of the radiomics value in predicting the meningioma volumetric response to gamma knife radiosurgery (GKRS). METHODS: The retrospective study included 93 meningioma patients imaged by three Tesla MRI. Tumor morphology was quantified by calculating 337 shape, first- and second-order radiomic features from MRI obtained before GKRS. Analysis was performed on original 3D MR images and after their laplacian of gaussian (LoG), logarithm and exponential filtering. The prediction performance was evaluated by Pearson correlation, linear regression and ROC analysis, with meningioma volume change per month as the outcome. RESULTS: Sixty calculated features significantly correlated with the outcome. The feature selection based on LASSO and multivariate regression started from all available 337 radiomic and 12 non-radiomic features. It selected LoG-sigma-1-0-mm-3D_firstorder_InterquartileRange and logarithm_ngtdm_Busyness as the predictively most robust and non-redundant features. The radiomic score based on these two features produced an AUC = 0.81. Adding the non-radiomic karnofsky performance status (KPS) to the score has increased the AUC to 0.88. Low values of the radiomic score defined a homogeneous subgroup of 50 patients with consistent absence (0%) of tumor progression. CONCLUSION: This is the first report of a strong association between MRI radiomic features and volumetric meningioma response to radiosurgery. The clinical importance of the early and reliable prediction of meningioma responsiveness to radiosurgery is based on its potential to aid individualized therapy decision making.

Analysis of Spatial Distribution and Prognostic Value of Different Pan Cytokeratin Immunostaining Intensities in Breast Tumor Tissue Sections.

Cancer risk prognosis could improve patient survival through early personalized treatment decisions. This is the first systematic analysis of the spatial and prognostic distribution of different pan cytokeratin immunostaining intensities in breast tumors. The prognostic model included 102 breast carcinoma patients, with distant metastasis occurrence as the endpoint. We segmented the full intensity range (0-255) of pan cytokeratin digitized immunostaining into seven discrete narrow grey level ranges: 0-130, 130-160, 160-180, 180-200, 200-220, 220-240, and 240-255. These images were subsequently examined by 33 major (GLCM), fractal and first-order statistics computational analysis features. Interestingly, while moderate intensities were strongly associated with metastasis outcome, high intensities of pan cytokeratin immunostaining provided no prognostic value even after an exhaustive computational analysis. The intense pan cytokeratin immunostaining was also relatively rare, suggesting the low differentiation state of epithelial cells. The observed variability in immunostaining intensities highlighted the intratumoral heterogeneity of the malignant cells and its association with a poor disease outcome. The prognostic importance of the moderate intensity range established by complex computational morphology analyses was supported by simple measurements of its immunostaining area which was associated with favorable disease outcome. This study reveals intratumoral heterogeneity of the pan cytokeratin immunostaining together with the prognostic evaluation and spatial distribution of its discrete intensities.

Size and Shape Filtering of Malignant Cell Clusters within Breast Tumors Identifies Scattered Individual Epithelial Cells as the Most Valuable Histomorphological Clue in the Prognosis of Distant Metastasis Risk.

Survival and life quality of breast cancer patients could be improved by more aggressive chemotherapy for those at high metastasis risk and less intense treatments for low-risk patients. Such personalized treatment cannot be currently achieved due to the insufficient reliability of metastasis risk prognosis. The purpose of this study was therefore, to identify novel histopathological prognostic markers of metastasis risk through exhaustive computational image analysis of 80 size and shape subsets of epithelial clusters in breast tumors. The group of 102 patients had a follow-up median of 12.3 years, without lymph node spread and systemic treatments. Epithelial cells were stained by the AE1/AE3 pan-cytokeratin antibody cocktail. The size and shape subsets of the stained epithelial cell clusters were defined in each image by use of the circularity and size filters and analyzed for prognostic performance. Epithelial areas with the optimal prognostic performance were uniformly small and round and could be recognized as individual epithelial cells scattered in tumor stroma. Their count achieved an area under the receiver operating characteristic curve (AUC) of 0.82, total area (AUC = 0.77), average size (AUC = 0.63), and circularity (AUC = 0.62). In conclusion, by use of computational image analysis as a hypothesis-free discovery tool, this study reveals the histomorphological marker with a high prognostic value that is simple and therefore easy to quantify by visual microscopy.