Methylation-Based Characterization of a New IDH2 Mutation in Sinonasal Undifferentiated Carcinoma.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172K, R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the Gene Expression Omnibus database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sinonasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, showed the position of our sample to be within 1.02 standard deviation of the other IDH-mutant SNUCs. A molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

Corrigendum to "Robustness of radiomic features in magnetic resonance imaging for patients with glioblastoma: Multi-center study" [Phys. Imaging Radiat. Oncol. 22 (2022) 131-136].

[This corrects the article DOI: 10.1016/j.phro.2022.05.006.].

Robustness of radiomic features in magnetic resonance imaging for patients with glioblastoma: Multi-center study.

Background and purpose: Radiomics offers great potential in improving diagnosis and treatment for patients with glioblastoma multiforme. However, in order to implement radiomics in clinical routine, the features used for prognostic modelling need to be stable. This comprises significant challenge in multi-center studies. The aim of this study was to evaluate the impact of different image normalization methods on MRI features robustness in multi-center study. Methods: Radiomics stability was checked on magnetic resonance images of eleven patients. The images were acquired in two different hospitals using contrast-enhanced T1 sequences. The images were normalized using one of five investigated approaches including grey-level discretization, histogram matching and z-score. Then, radiomic features were extracted and features stability was evaluated using intra-class correlation coefficients. In the second part of the study, improvement in the prognostic performance of features was tested on 60 patients derived from publicly available dataset. Results: Depending on the normalization scheme, the percentage of stable features varied from 3.4% to 8%. The histogram matching based on the tumor region showed the highest amount of the stable features (113/1404); while normalization using fixed bin size resulted in 48 stable features. The histogram matching also led to better prognostic value (median c-index increase of 0.065) comparing to non-normalized images. Conclusions: MRI normalization plays an important role in radiomics. Appropriate normalization helps to select robust features, which can be used for prognostic modelling in multicenter studies. In our study, histogram matching based on tumor region improved both stability of radiomic features and their prognostic value.

Improved Survival Prediction by Combining Radiological Imaging and S-100B Levels Into a Multivariate Model in Metastatic Melanoma Patients Treated With Immune Checkpoint Inhibition.

Purpose: We explored imaging and blood bio-markers for survival prediction in a cohort of patients with metastatic melanoma treated with immune checkpoint inhibition. Materials and Methods: 94 consecutive metastatic melanoma patients treated with immune checkpoint inhibition were included into this study. PET/CT imaging was available at baseline (Tp0), 3 months (Tp1) and 6 months (Tp2) after start of immunotherapy. Radiological response at Tp2 was evaluated using iRECIST. Total tumor burden (TB) at each time-point was measured and relative change of TB compared to baseline was calculated. LDH, CRP and S-100B were also analyzed. Cox proportional hazards model and logistic regression were used for survival analysis. Results: iRECIST at Tp2 was significantly associated with overall survival (OS) with C-index=0.68. TB at baseline was not associated with OS, whereas TB at Tp1 and Tp2 provided similar predictive power with C-index of 0.67 and 0.71, respectively. Appearance of new metastatic lesions during follow-up was an independent prognostic factor (C-index=0.73). Elevated LDH and S-100B ratios at Tp2 were significantly associated with worse OS: C-index=0.73 for LDH and 0.73 for S-100B. Correlation of LDH with TB was weak (r=0.34). A multivariate model including TB change, S-100B, and appearance of new lesions showed the best predictive performance with C-index=0.83. Conclusion: Our analysis shows only a weak correlation between LDH and TB. Additionally, baseline TB was not a prognostic factor in our cohort. A multivariate model combining early blood and imaging biomarkers achieved the best predictive power with regard to survival, outperforming iRECIST.

Quantification of the spatial distribution of primary tumors in the lung to develop new prognostic biomarkers for locally advanced NSCLC.

The anatomical location and extent of primary lung tumors have shown prognostic value for overall survival (OS). However, its manual assessment is prone to interobserver variability. This study aims to use data driven identification of image characteristics for OS in locally advanced non-small cell lung cancer (NSCLC) patients. Five stage IIIA/IIIB NSCLC patient cohorts were retrospectively collected. Patients were treated either with radiochemotherapy (RCT): RCT1* (n = 107), RCT2 (n = 95), RCT3 (n = 37) or with surgery combined with radiotherapy or chemotherapy: S1* (n = 135), S2 (n = 55). Based on a deformable image registration (MIM Vista, 6.9.2.), an in-house developed software transferred each primary tumor to the CT scan of a reference patient while maintaining the original tumor shape. A frequency-weighted cumulative status map was created for both exploratory cohorts (indicated with an asterisk), where the spatial extent of the tumor was uni-labeled with 2 years OS. For the exploratory cohorts, a permutation test with random assignment of patient status was performed to identify regions with statistically significant worse OS, referred to as decreased survival areas (DSA). The minimal Euclidean distance between primary tumor to DSA was extracted from the independent cohorts (negative distance in case of overlap). To account for the tumor volume, the distance was scaled with the radius of the volume-equivalent sphere. For the S1 cohort, DSA were located at the right main bronchus whereas for the RCT1 cohort they further extended in cranio-caudal direction. In the independent cohorts, the model based on distance to DSA achieved performance: AUCRCT2 [95% CI] = 0.67 [0.55-0.78] and AUCRCT3 = 0.59 [0.39-0.79] for RCT patients, but showed bad performance for surgery cohort (AUCS2 = 0.52 [0.30-0.74]). Shorter distance to DSA was associated with worse outcome (p = 0.0074). In conclusion, this explanatory analysis quantifies the value of primary tumor location for OS prediction based on cumulative status maps. Shorter distance of primary tumor to a high-risk region was associated with worse prognosis in the RCT cohort.

Clot-Based Radiomics Predict a Mechanical Thrombectomy Strategy for Successful Recanalization in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MTB) is a reference treatment for acute ischemic stroke, with several endovascular strategies currently available. However, no quantitative methods are available for the selection of the best endovascular strategy or to predict the difficulty of clot removal. We aimed to investigate the predictive value of an endovascular strategy based on radiomic features extracted from the clot on preinterventional, noncontrast computed tomography to identify patients with first-attempt recanalization with thromboaspiration and to predict the overall number of passages needed with an MTB device for successful recanalization. METHODS: We performed a study including 2 cohorts of patients admitted to our hospital: a retrospective training cohort (n=109) and a prospective validation cohort (n=47). Thrombi were segmented on noncontrast computed tomography, followed by the automatic computation of 1485 thrombus-related radiomic features. After selection of the relevant features, 2 machine learning models were developed on the training cohort to predict (1) first-attempt recanalization with thromboaspiration and (2) the overall number of passages with MTB devices for successful recanalization. The performance of the models was evaluated on the prospective validation cohort. RESULTS: A small subset of radiomic features (n=9) was predictive of first-attempt recanalization with thromboaspiration (receiver operating characteristic curve-area under the curve, 0.88). The same subset also predicted the overall number of passages required for successful recanalization (explained variance, 0.70; mean squared error, 0.76; Pearson correlation coefficient, 0.73; P<0.05). CONCLUSIONS: Clot-based radiomics have the ability to predict an MTB strategy for successful recanalization in acute ischemic stroke, thus allowing a potentially better selection of the MTB strategy, as well as patients who are most likely to benefit from the intervention.

Radiomics and Machine Learning Differentiate Soft-Tissue Lipoma and Liposarcoma Better than Musculoskeletal Radiologists.

Distinguishing lipoma from liposarcoma is challenging on conventional MRI examination. In case of uncertain diagnosis following MRI, further invasive procedure (percutaneous biopsy or surgery) is often required to allow for diagnosis based on histopathological examination. Radiomics and machine learning allow for several types of pathologies encountered on radiological images to be automatically and reliably distinguished. The aim of the study was to assess the contribution of radiomics and machine learning in the differentiation between soft-tissue lipoma and liposarcoma on preoperative MRI and to assess the diagnostic accuracy of a machine-learning model compared to musculoskeletal radiologists. 86 radiomics features were retrospectively extracted from volume-of-interest on T1-weighted spin-echo 1.5 and 3.0 Tesla MRI of 38 soft-tissue tumors (24 lipomas and 14 liposarcomas, based on histopathological diagnosis). These radiomics features were then used to train a machine-learning classifier to distinguish lipoma and liposarcoma. The generalization performance of the machine-learning model was assessed using Monte-Carlo cross-validation and receiver operating characteristic curve analysis (ROC-AUC). Finally, the performance of the machine-learning model was compared to the accuracy of three specialized musculoskeletal radiologists using the McNemar test. Machine-learning classifier accurately distinguished lipoma and liposarcoma, with a ROC-AUC of 0.926. Notably, it performed better than the three specialized musculoskeletal radiologists reviewing the same patients, who achieved ROC-AUC of 0.685, 0.805, and 0.785. Despite being developed on few cases, the trained machine-learning classifier accurately distinguishes lipoma and liposarcoma on preoperative MRI, with better performance than specialized musculoskeletal radiologists.

Differentiating kidney stones from phleboliths in unenhanced low-dose computed tomography using radiomics and machine learning.

OBJECTIVES: Distinguishing between kidney stones and phleboliths can constitute a diagnostic challenge in patients undergoing unenhanced low-dose CT (LDCT) for acute flank pain. We sought to investigate the accuracy of radiomics and a machine-learning classifier in differentiating between kidney stones and phleboliths on LDCT. METHODS: Radiomics features were extracted following a semi-automatic segmentation of kidney stones and phleboliths for two independent consecutive cohorts of patients undergoing LDCT for acute flank pain. Radiomics features from the first cohort of patients (n = 369) were ultimately used to train a machine-learning model designed to distinguish kidney stones (n = 211) from phleboliths (n = 201). Classification performance was assessed on the second independent cohort (i.e., testing set) (kidney stones n = 24; phleboliths n = 23) using positive and negative predictive values (PPV and NPV), area under the receiver operating curves (AUC), and permutation testing. RESULTS: Our machine-learning classification model trained on radiomics features achieved an overall accuracy of 85.1% on the independent testing set, with an AUC of 0.902, PPV of 81.5%, and NPV of 90.0%. Classification accuracy was significantly better than chance on permutation testing (p < 0.05, permutation p value). CONCLUSION: Radiomics and machine learning enable accurate differentiation between kidney stones and phleboliths on LDCT in patients presenting with acute flank pain. KEY POINTS: • Combining a machine-learning algorithm with radiomics features extracted for abdominopelvic calcification on LDCT offers a highly accurate method for discriminating phleboliths from kidney stones. • Our radiomics and machine-learning model proved robust for CT acquisition and reconstruction protocol when tested in comparison with an external independent cohort of patients with acute flank pain. • The high performance of the radiomics-based automatic classification model in differentiating phleboliths from kidney stones indicates its potential as a future diagnostic tool for equivocal abdominopelvic calcifications in the setting of suspected renal colic.