Objective To identify CT-acquisition parameters accounting for radiomics variability and to develop a post-acquisition CT-image correction method to reduce variability and improve radiomics classification in both phantom and clinical applications. Methods CT-acquisition protocols were prospectively tested in a phantom. The multi-centric retrospective clinical study included CT scans of patients with colorectal/renal cancer liver metastases. Ninety-three radiomics features of first order and texture were extracted. Intraclass correlation coefficients (ICCs) between CT-acquisition protocols were evaluated to define sources of variability. Voxel size, ComBat, and singular value decomposition (SVD) compensation methods were explored for reducing the radiomics variability. The number of robust features was compared before and after correction using two-proportion z test. The radiomics classification accuracy (K-means purity) was assessed before and after ComBat- and SVD-based correction. Results Fifty-three acquisition protocols in 13 tissue densities were analyzed. Ninety-seven liver metastases from 43 patients with CT from two vendors were included. Pixel size, reconstruction slice spacing, convolution kernel, and acquisition slice thickness are relevant sources of radiomics variability with a percentage of robust features lower than 80%. Resampling to isometric voxels increased the number of robust features when images were acquired with different pixel sizes (p < 0.05). SVD-based for thickness correction and ComBat correction for thickness and combined thickness–kernel increased the number of reproducible features (p < 0.05). ComBat showed the highest improvement of radiomics-based classification in both the phantom and clinical applications (K-means purity 65.98 vs 73.20). Conclusion CT-image post-acquisition processing and radiomics normalization by means of batch effect correction allow for standardization of large-scale data analysis and improve the classification accuracy. Key Points • The voxel size (accounting for the pixel size and slice spacing), slice thickness, and convolution kernel are relevant sources of CT-radiomics variability. • Voxel size resampling increased the mean percentage of robust CT-radiomics features from 59.50 to 89.25% when comparing CT scans acquired with different pixel sizes and from 71.62 to 82.58% when the scans were acquired with different slice spacings. • ComBat batch effect correction reduced the CT-radiomics variability secondary to the slice thickness and convolution kernel, improving the capacity of CT-radiomics to differentiate tissues (in the phantom application) and the primary tumor type from liver metastases (in the clinical application).

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Glioblastoma is the most common primary brain tumor. Standard therapy consists of maximum safe resection combined with adjuvant radiochemotherapy followed by chemotherapy with temozolomide, however prognosis is extremely poor. Assessment of the residual tumor after surgery and patient stratification into prognostic groups (i.e., by tumor volume) is currently hindered by the subjective evaluation of residual enhancement in medical images (magnetic resonance imaging [MRI]). Furthermore, objective evidence defining the optimal time to acquire the images is lacking. We analyzed 144 patients with glioblastoma, objectively quantified the enhancing residual tumor through computational image analysis and assessed the correlation with survival. Pathological enhancement thickness on post-surgical MRI correlated with survival (hazard ratio: 1.98, p < 0.001). The prognostic value of several imaging and clinical variables was analyzed individually and combined (radiomics AUC 0.71, p = 0.07; combined AUC 0.72, p < 0.001). Residual enhancement thickness and radiomics complemented clinical data for prognosis stratification in patients with glioblastoma. Significant results were only obtained for scans performed between 24 and 72 h after surgery, raising the possibility of confounding non-tumor enhancement in very early post-surgery MRI. Regarding the extent of resection, and in agreement with recent studies, the association between the measured tumor remnant and survival supports maximal safe resection whenever possible.

Immunotherapy by immune checkpoint inhibitors (ICI) has become a standard treatment strategy for many types of solid tumors. However, the majority of cancer patients will not respond and predicting response to this therapy is still a challenge. Artificial intelligence (AI) methods can extract meaningful information from complex data, such as image data. In clinical routine, radiology or histopathology images are ubiquitously available. AI has been used to predict the response to immunotherapy from radiology or histopathology images, either directly or indirectly via surrogate markers. While none of these methods are currently used in clinical routine, academic and commercial developments are pointing towards potential clinical adoption in the near future. Here, we summarize the state of the art in AI-based image biomarkers for immunotherapy response based on radiology and histopathology images. We point out limitations, caveats, and pitfalls, including biases, generalizability, and explainability which are relevant for researchers and healthcare providers alike, and outline key clinical use cases of this new class of predictive biomarkers.

Dimensionality reduction is key to alleviate machine learning artifacts in clinical applications with Small Sample Size (SSS) unbalanced datasets. Existing methods rely on either the probabilistic distribution of training data or the discriminant power of the reduced space, disregarding the impact of repeatability and uncertainty in features.In the present study is proposed the use of reproducibility of radiomics features to select features with high inter-class correlation coefficient (ICC). The reproducibility includes the variability introduced in the image acquisition, like medical scans acquisition parameters and convolution kernels, that affects intensity-based features and tumor annotations made by physicians, that influences morphological descriptors of the lesion.For the reproducibility of radiomics features three studies were conducted on cases collected at Vall Hebron Oncology Institute (VHIO) on responders to oncology treatment. The studies focused on the variability due to the convolution kernel, image acquisition parameters, and the inter-observer lesion identification. The features selected were those features with a ICC higher than 0.7 in the three studies.The selected features based on reproducibility were evaluated for lesion malignancy classification using a different database. Results show better performance compared to several stateof-the-art methods including Principal Component Analysis (PCA), Kernel Discriminant Analysis via QR decomposition (KDAQR), LASSO, and an own built Convolutional Neural Network.