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Prediction of Radiation-Induced Hypothyroidism Using Radiomic Data Analysis Does Not Show Superiority over Standard Normal Tissue Complication Models.

ABSTRACT: State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33-35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). We showed that radiomic-based models did not outperform state-of-art NTCP models (p > 0.05). The potential benefit of radiomic-based approach is that it is dose-independent, and models can be used prior to treatment planning allowing faster selection of susceptible population.

SUBMITTER: Smyczynska U

PROVIDER: S-EPMC8582656 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeOsteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no normal tissue complication probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORNI-IV) and grade IV (ORNIV) after RT (±chemotherapy) in patients with HNC.Methods and materialsIncluded patients with HNC were treated with (chemo-)RT between 2005 and 2015. Mandible bone radiation dose-volume parameters and clinical variables (ie, age, sex, tumor site, pre-RT dental extractions, chemotherapy history, postoperative RT, and smoking status) were considered as potential predictors. The patient cohort was randomly divided into a training (70%) and independent test (30%) cohort. Bootstrapped forward variable selection was performed in the training cohort to select the predictors for the NTCP models. Final NTCP model(s) were validated on the holdback test subset.ResultsOf 1259 included patients with HNC, 13.7% (n = 173 patients) developed any grade ORN (ORNI-IV primary endpoint) and 5% (n = 65) ORNIV (secondary endpoint). All dose and volume parameters of the mandible bone were significantly associated with the development of ORN in univariable models. Multivariable analyses identified D30% and pre-RT dental extraction as independent predictors for both ORNI-IV and ORNIV best-performing NTCP models with an area under the curve (AUC) of 0.78 (AUCvalidation = 0.75 [0.69-0.82]) and 0.81 (AUCvalidation = 0.82 [0.74-0.89]), respectively.ConclusionsThis study presented NTCP models based on mandible bone D30% and pre-RT dental extraction that predict ORNI-IV and ORNIV (ie, needing invasive surgical intervention) after HNC RT. Our results suggest that less than 30% of the mandible should receive a dose of 35 Gy or more for an ORNI-IV risk lower than 5%. These NTCP models can improve ORN prevention and management by identifying patients at risk of ORN.

Project description:BackgroundCardioprotection by preventing or repairing mitochondrial damage is an unmet therapeutic need. To understand the role of cardiomyocyte mitochondria in physiopathology, the reliable characterization of the mitochondrial morphology and compartment is pivotal. Previous studies mostly relied on two-dimensional (2D) routine transmission electron microscopy (TEM), thereby neglecting the real three-dimensional (3D) mitochondrial organization. This study aimed to determine whether classical 2D TEM analysis of the cardiomyocyte ultrastructure is sufficient to comprehensively describe the mitochondrial compartment and to reflect mitochondrial number, size, dispersion, distribution, and morphology.MethodsSpatial distribution of the complex mitochondrial network and morphology, number, and size heterogeneity of cardiac mitochondria in isolated adult mouse cardiomyocytes and adult wild-type left ventricular tissues (C57BL/6) were assessed using a comparative 3D imaging system based on focused ion beam-scanning electron microscopy (FIB-SEM) nanotomography. For comparison of 2D vs. 3D data sets, analytical strategies and mathematical comparative approaches were performed. To confirm the value of 3D data for mitochondrial changes, we compared the obtained values for number, coverage area, size heterogeneity, and complexity of wild-type cardiomyocyte mitochondria with data sets from mice lacking the cytosolic and mitochondrial protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3; Bnip3-/- ) using FIB-SEM. Mitochondrial respiration was assessed on isolated mitochondria using the Seahorse XF analyser. A cardiac biopsy was obtained from a male patient (48 years) suffering from myocarditis.ResultsThe FIB-SEM nanotomographic analysis revealed that no linear relationship exists for mitochondrial number (r = 0.02; P = 0.9511), dispersion (r = -0.03; P = 0.9188), and shape (roundness: r = 0.15, P = 0.6397; elongation: r = -0.09, P = 0.7804) between 3D and 2D results. Cumulative frequency distribution analysis showed a diverse abundance of mitochondria with different sizes in 3D and 2D. Qualitatively, 2D data could not reflect mitochondrial distribution and dynamics existing in 3D tissue. 3D analyses enabled the discovery that BNIP3 deletion resulted in more smaller, less complex cardiomyocyte mitochondria (number: P < 0.01; heterogeneity: C.V. wild-type 89% vs. Bnip3-/- 68%; complexity: P < 0.001) forming large myofibril-distorting clusters, as seen in human myocarditis with disturbed mitochondrial dynamics. Bnip3-/- mice also show a higher respiration rate (P < 0.01).ConclusionsHere, we demonstrate the need of 3D analyses for the characterization of mitochondrial features in cardiac tissue samples. Hence, we observed that BNIP3 deletion physiologically acts as a molecular brake on mitochondrial number, suggesting a role in mitochondrial fusion/fission processes and thereby regulating the homeostasis of cardiac bioenergetics.

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Prediction of Radiation-Induced Hypothyroidism Using Radiomic Data Analysis Does Not Show Superiority over Standard Normal Tissue Complication Models.

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