Predicting response to cancer immunotherapy using noninvasive radiomic biomarkers.

INTRODUCTION: Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds-urging the quest for predictive biomarkers. We hypothesize that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response. PATIENTS AND METHODS: In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients. RESULTS: The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P < 0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P = 0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P < 0.001), resulting in a 1-year survival difference of 24% (P = 0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy. CONCLUSIONS: These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.

Opportunistic osteoporosis screening in multi-detector CT images via local classification of textures.

Our study proposed an automatic pipeline for opportunistic osteoporosis screening using 3D texture features and regional vBMD using multi-detector CT images. A combination of different local and global texture features outperformed the global vBMD and showed high discriminative power to identify patients with vertebral fractures. INTRODUCTION: Many patients at risk for osteoporosis undergo computed tomography (CT) scans, usable for opportunistic (non-dedicated) screening. We compared the performance of global volumetric bone mineral density (vBMD) with a random forest classifier based on regional vBMD and 3D texture features to separate patients with and without osteoporotic fractures. METHODS: In total, 154 patients (mean age 64 ± 8.5, male; n = 103) were included in this retrospective single-center analysis, who underwent contrast-enhanced CT for other reasons than osteoporosis screening. Patients were dichotomized regarding prevalent vertebral osteoporotic fractures (noFX, n = 101; FX, n = 53). Vertebral bodies were automatically segmented, and trabecular vBMD was calculated with a dedicated phantom. For 3D texture analysis, we extracted gray-level co-occurrence matrix Haralick features (HAR), histogram of gradients (HoG), local binary patterns (LBP), and wavelets (WL). Fractured vertebrae were excluded for texture-feature and vBMD data extraction. The performance to identify patients with prevalent osteoporotic vertebral fractures was evaluated in a fourfold cross-validation. RESULTS: The random forest classifier showed a high discriminatory power (AUC = 0.88). Parameters of all vertebral levels significantly contributed to this classification. Importantly, the AUC of the proposed algorithm was significantly higher than that of volumetric global BMD alone (AUC = 0.64). CONCLUSION: The presented classifier combining 3D texture features and regional vBMD including the complete thoracolumbar spine showed high discriminatory power to identify patients with vertebral fractures and had a better diagnostic performance than vBMD alone.

Integrated noninvasive diagnostics for prediction of survival in immunotherapy.

Background: Integrating complementary diagnostic data sources promises enhanced robustness in the predictive performance of artificial intelligence (AI) models, a crucial requirement for future clinical validation/implementation. In this study, we investigate the potential value of integrating data from noninvasive diagnostic modalities, including chest computed tomography (CT) imaging, routine laboratory blood tests, and clinical parameters, to retrospectively predict 1-year survival in a cohort of patients with advanced non-small-cell lung cancer, melanoma, and urothelial cancer treated with immunotherapy. Patients and methods: The study included 475 patients, of whom 444 had longitudinal CT scans and 475 had longitudinal laboratory data. An ensemble of AI models was trained on data from each diagnostic modality, and subsequently, a model-agnostic integration approach was adopted for combining the prediction probabilities of each modality and producing an integrated decision. Results: Integrating different diagnostic data demonstrated a modest increase in predictive performance. The highest area under the curve (AUC) was achieved by CT and laboratory data integration (AUC of 0.83, 95% confidence interval 0.81-0.85, P < 0.001), whereas the performance of individual models trained on laboratory and CT data independently yielded AUCs of 0.81 and 0.73, respectively. Conclusions: In our retrospective cohort, integrating different noninvasive data modalities improved performance.

Radiomics in immuno-oncology.

With the ongoing advances in imaging techniques, increasing volumes of anatomical and functional data are being generated as part of the routine clinical workflow. This surge of available imaging data coincides with increasing research in quantitative imaging, particularly in the domain of imaging features. An important and novel approach is radiomics, where high-dimensional image properties are extracted from routine medical images. The fundamental principle of radiomics is the hypothesis that biomedical images contain predictive information, not discernible to the human eye, that can be mined through quantitative image analysis. In this review, a general outline of radiomics and artificial intelligence (AI) will be provided, along with prominent use cases in immunotherapy (e.g. response and adverse event prediction) and targeted therapy (i.e. radiogenomics). While the increased use and development of radiomics and AI in immuno-oncology is highly promising, the technology is still in its early stages, and different challenges still need to be overcome. Nevertheless, novel AI algorithms are being constructed with an ever-increasing scope of applications.

CT texture analysis in colorectal liver metastases and the surrounding liver parenchyma and its potential as an imaging biomarker of disease aggressiveness, response and survival.

OBJECTIVES: To study the ratio between the CT texture of colorectal liver metastases (CRLM) and the surrounding liver parenchyma and assess the potential of various texture measures and ratios as predictive/prognostic imaging markers. MATERIALS: Seventy patients with colorectal cancer and synchronous CRLM were included. All visible metastases, as well as the whole-volume of the surrounding liver, were separately delineated on the portal venous phase primary staging CT. Texture features entropy (E) and uniformity (U) were extracted and ratios between the texture features (T) of the metastases and background liver (Tmetastases/Tliver) calculated. Texture features were compared with clinical outcome parameters: [1] extent of disease (i.e. number of metastases), [2] response to chemotherapy (in 56/70 patients who underwent chemotherapy and CT for response evaluation), and [3] overall survival. RESULTS: The Emetastases/Eliver ratio was lower in patients with limited disease (P = 0.02) and associated with overall survival, albeit not statistically significant when tested in multivariable analyses (HR 1.90; P = 0.07); Umetastases/Uliver was higher in patients with limited disease (P = 0.02). Emetastases showed a trend towards a higher value in patients that responded well to chemotherapy (P = 0.08). CONCLUSION: The ratio between the texture of liver metastases and the surrounding liver appears to reflect relevant changes in tissue microarchitecture and may be of value to assess the extent of disease and help predict overall survival.