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18 pages, 3505 KiB  
Article
Delta Radiomics and Tumor Size: A New Predictive Radiomics Model for Chemotherapy Response in Liver Metastases from Breast and Colorectal Cancer
by Nicolò Gennaro, Moataz Soliman, Amir A. Borhani, Linda Kelahan, Hatice Savas, Ryan Avery, Kamal Subedi, Tugce A. Trabzonlu, Chase Krumpelman, Vahid Yaghmai, Young Chae, Jochen Lorch, Devalingam Mahalingam, Mary Mulcahy, Al Benson, Ulas Bagci and Yuri S. Velichko
Tomography 2025, 11(3), 20; https://doi.org/10.3390/tomography11030020 - 20 Feb 2025
Viewed by 269
Abstract
Background/Objectives: Radiomic features exhibit a correlation with tumor size on pretreatment images. However, on post-treatment images, this association is influenced by treatment efficacy and varies between responders and non-responders. This study introduces a novel model, called baseline-referenced Delta radiomics, which integrates the [...] Read more.
Background/Objectives: Radiomic features exhibit a correlation with tumor size on pretreatment images. However, on post-treatment images, this association is influenced by treatment efficacy and varies between responders and non-responders. This study introduces a novel model, called baseline-referenced Delta radiomics, which integrates the association between radiomic features and tumor size into Delta radiomics to predict chemotherapy response in liver metastases from breast cancer (BC) and colorectal cancer (CRC). Materials and Methods: A retrospective study analyzed contrast-enhanced computed tomography (CT) scans of 83 BC patients and 84 CRC patients. Among these, 57 BC patients with 106 liver lesions and 37 CRC patients with 109 lesions underwent post-treatment imaging after systemic chemotherapy. Radiomic features were extracted from up to three lesions per patient following manual segmentation. Tumor response was assessed by measuring the longest diameter and classified according to RECIST 1.1 criteria as progressive disease (PD), partial response (PR), or stable disease (SD). Classification models were developed to predict chemotherapy response using pretreatment data only, Delta radiomics, and baseline-referenced Delta radiomics. Model performance was evaluated using confusion matrix metrics. Results: Baseline-referenced Delta radiomics performed comparably or better than established radiomics models in predicting tumor response in chemotherapy-treated patients with liver metastases. The sensitivity, specificity, and balanced accuracy in predicting response ranged from 0.66 to 0.97, 0.81 to 0.97, and 80% to 90%, respectively. Conclusions: By integrating the relationship between radiomic features and tumor size into Delta radiomics, baseline-referenced Delta radiomics offers a promising approach for predicting chemotherapy response in liver metastases from breast and colorectal cancer. Full article
(This article belongs to the Special Issue Imaging in Cancer Diagnosis)
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<p>Pipeline of this study.</p>
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<p>Flowcharts illustrate the construction of the datasets.</p>
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<p>Scatter plot demonstration of association between radiomic features and the tumor size. The red line represents the fitted result.</p>
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<p>Confusion matrices for pretreatment radiomics, Delta radiomics, and functional radiomics response assessment models computed for patients with liver metastasis from (<b>top</b>) colorectal cancer and (<b>bottom</b>) breast cancer.</p>
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<p>Receiver operating characteristic (ROC) curves for predicting chemotherapy response in liver metastases from colorectal cancer (<b>left</b>) and breast cancer (<b>right</b>) using pretreatment radiomics, Delta radiomics, and baseline-referenced Delta radiomics.</p>
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<p>Feature significance for pretreatment radiomics, Delta radiomics, and baseline-referenced Delta radiomics response assessment models computed for patients with liver metastasis from (<b>top</b>) colorectal cancer and (<b>bottom</b>) breast cancer.</p>
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<p>Change in the value of the three most significant features (<a href="#tomography-11-00020-f005" class="html-fig">Figure 5</a>) for Delta radiomics and baseline-referenced Delta radiomics response assessment models computed for patients with liver metastasis from (<b>top</b>) colorectal cancer and (<b>bottom</b>) breast cancer.</p>
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<p>Changes in the value of radiomic features from (<b>top</b>) Delta radiomics and (<b>bottom</b>) baseline-referenced Delta radiomics models in patients with liver metastasis from colorectal cancer treated with chemotherapy alone or chemotherapy in combination with bevacizumab.</p>
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18 pages, 3633 KiB  
Article
Radiomics-Based Prediction of Treatment Response to TRuC-T Cell Therapy in Patients with Mesothelioma: A Pilot Study
by Hubert Beaumont, Antoine Iannessi, Alexandre Thinnes, Sebastien Jacques and Alfonso Quintás-Cardama
Cancers 2025, 17(3), 463; https://doi.org/10.3390/cancers17030463 - 29 Jan 2025
Viewed by 695
Abstract
Background/Objectives: T cell receptor fusion constructs (TRuCs), a next generation engineered T cell therapy, hold great promise. To accelerate the clinical development of these therapies, improving patient selection is a crucial pathway forward. Methods: We retrospectively analyzed 23 mesothelioma patients (85 target tumors) [...] Read more.
Background/Objectives: T cell receptor fusion constructs (TRuCs), a next generation engineered T cell therapy, hold great promise. To accelerate the clinical development of these therapies, improving patient selection is a crucial pathway forward. Methods: We retrospectively analyzed 23 mesothelioma patients (85 target tumors) treated in a phase 1/2 single arm clinical trial (NCT03907852). Five imaging sites were involved, the settings for the evaluations were Blinded Independent Central Reviews (BICRs) with double reads. The reproducibility of 3416 radiomics and delta-radiomics (Δradiomics) was assessed. The univariate analysis evaluated correlations at the target tumor level with (1) tumor diameter response; (2) tumor volume response, according to the Quantitative Imaging Biomarker Alliance; and (3) the mean standard uptake value (SUV) response, as defined by the positron emission tomography response criteria in solid tumors (PERCISTs). A random forest model predicted the response of the target pleural tumors. Results: Tumor anatomical distribution was 55.3%, 17.6%, 14.1%, and 10.6% in the pleura, lymph nodes, peritoneum, and soft tissues, respectively. Radiomics/Δradiomics reproducibility differed across tumor localizations. Radiomics were more reproducible than Δradiomics. In the univariate analysis, none of the radiomics/Δradiomics correlated with any response criteria. With an accuracy ranging from 0.75 to 0.9, three radiomics/Δradiomics were able to predict the response of target pleural tumors. Pivotal studies will require a sample size of 250 to 400 tumors. Conclusions: The prediction of responding target pleural tumors can be achieved using a machine learning-based radiomics/Δradiomics analysis. Tumor-specific reproducibility and the average values indicated that using tumor models to create an effective patient model would require combining several target tumor models. Full article
(This article belongs to the Special Issue Biomarkers and Targeted Therapy in Malignant Pleural Mesothelioma)
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<p>Analysis workflow. From the original clinical trial, only mesothelioma patients were considered. This study consisted of a data analysis (blue), radiomics and Δradiomics analysis (green), and model design (orange). The outcome was a pilot evaluation of the predictive performances of target tumors responses.</p>
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<p>Distribution of patients by modality and center at baseline. Five imaging centers participated in the evaluation of patients treated in this study. CT and PET imaging were performed in 23 and 17 patients, respectively. A single imaging center performed only CT (Center #1).</p>
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<p>Distribution of acquisition parameters at baseline. (Left) CT acquisition parameters. From inner to outer circle: manufacturer (Siemens or GE), models, Kvp (90, 120, 130), reconstruction kernel (Standard, Br40, Soft), slice thickness (2.5; 5), and voxel size (0.6; 1.0). (Right) PET acquisition parameters. From inner to outer circle: manufacturers (Siemens (Siemens Healthineers, Forchheim, Germany), GE (GE Healthcare, Milwaukee, WI, US)), models, reconstruction kernel (AllPass, XYZ Gauss (2.0, 3.5, 5.0)), slice thickness (2.0; 5.5), and voxel size (1.5; 6.9). Representativeness was deemed significant for generalization.</p>
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<p>Distribution of target tumors in patients’ anatomy. Out of 85 tumors, 55.3% (<span class="html-italic">n</span> = 47) were found in the pleura, 17.6% (<span class="html-italic">n</span> = 15) in the lymph nodes, 14.1% (<span class="html-italic">n</span> = 12) in the peritoneum, and 10.6% (<span class="html-italic">n</span> = 9) in soft tissues. Two additional tumors, one adrenal tumor and one liver tumor, were classified as “miscellaneous”.</p>
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<p>Radiomic/Δradiomic features according to different CCCs threshold values. The number of radiomics (<b>a</b>) and Δradiomics (<b>b</b>) were calculated for different threshold values of CCC. Radiomics reproducibility depended on tumor localization, with soft tissues (range: 238; 139) and lymph nodes (range: 43; 0) being the most and least reproducible, respectively. The reproducibility of Δradiomics depended on tumor localization, with soft tissues (range: 101; 53) and lymph nodes (range: 3; 0) being the most and least reproducible, respectively.</p>
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<p>Sample cluster map of reproducible pleural tumors radiomics. Left: correlation matrix of 21 radiomics that were deemed reproducible (CCC &gt; 0.8); some of them were highly inter-correlated (yellow clusters). Right: after removing highly inter-correlated radiomics (correlation &gt; 0.9), 8 reproducible and non-redundant pleura radiomics were preselected.</p>
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<p>Number of radiomic/Δradiomic candidates. We considered a different threshold of CCC values ranging from 0.7 to 0.9 for radiomics (<b>a</b>) and 0.6 to 0.9 for Δradiomics (<b>b</b>). For radiomics and Δradiomics, peritoneum and lymph node tumors were the most and least reproducible tumors, respectively.</p>
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<p>Sample variability of segmentation and radiomics values. One pleura and one soft tissue tumor were segmented by Reader 1 and Reader 2. The volume, the joint entropy, and the sum of variance (computed from GLCM) were derived from the segmentations. The inter-reader variability of the segmentations leads to a variability in volume of 20% and 30%, in joint entropy of 16% and 7%, and in sum of variance of 41% and 56%, respectively, the pleura and the soft tissue tumors.</p>
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1 pages, 156 KiB  
Correction
Correction: Peisen et al. Can Delta Radiomics Improve the Prediction of Best Overall Response, Progression-Free Survival, and Overall Survival of Melanoma Patients Treated with Immune Checkpoint Inhibitors? Cancers 2024, 16, 2669
by Felix Peisen, Annika Gerken, Alessa Hering, Isabel Dahm, Konstantin Nikolaou, Sergios Gatidis, Thomas K. Eigentler, Teresa Amaral, Jan H. Moltz and Ahmed E. Othman
Cancers 2025, 17(1), 1; https://doi.org/10.3390/cancers17010001 - 24 Dec 2024
Viewed by 377
Abstract
There was an error in the original publication [...] Full article
15 pages, 7455 KiB  
Article
Multiomics-Based Outcome Prediction in Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy (PULSAR)
by Haozhao Zhang, Michael Dohopolski, Strahinja Stojadinovic, Luiza Giuliani Schmitt, Soummitra Anand, Heejung Kim, Arnold Pompos, Andrew Godley, Steve Jiang, Tu Dan, Zabi Wardak, Robert Timmerman and Hao Peng
Cancers 2024, 16(19), 3425; https://doi.org/10.3390/cancers16193425 - 9 Oct 2024
Cited by 1 | Viewed by 1102
Abstract
Objectives: This retrospective study aims to develop a multiomics approach that integrates radiomics, dosiomics, and delta features to predict treatment responses in brain metastasis (BM) patients undergoing PULSAR. Methods: A retrospective study encompassing 39 BM patients with 69 lesions treated with [...] Read more.
Objectives: This retrospective study aims to develop a multiomics approach that integrates radiomics, dosiomics, and delta features to predict treatment responses in brain metastasis (BM) patients undergoing PULSAR. Methods: A retrospective study encompassing 39 BM patients with 69 lesions treated with PULSAR was undertaken. Radiomics, dosiomics, and delta features were extracted from both pre-treatment and intra-treatment MRI scans alongside dose distributions. Six individual models, alongside an ensemble feature selection (EFS) model, were evaluated. The classification task focused on distinguishing between two lesion groups based on whether they exhibited a volume reduction of more than 20% at follow-up. Performance metrics, including sensitivity, specificity, accuracy, precision, F1 score, and the area under the receiver operating characteristic (ROC) curve (AUC), were assessed. Results: The EFS model integrated the features from pre-treatment radiomics, pre-treatment dosiomics, intra-treatment radiomics, and delta radiomics. It outperformed six individual models, achieving an AUC of 0.979, accuracy of 0.917, and F1 score of 0.821. Among the top nine features of the EFS model, six features came from post-wavelet transformation and three from original images. Conclusions: The study demonstrated the feasibility of employing a data-driven multiomics approach to predict treatment outcomes in BM patients receiving PULSAR treatment. Integrating multiomics with intra-treatment decision support in PULSAR shows promise for optimizing patient management and reducing the risks of under- or over-treatment. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
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<p>Comparison of workflows between (<b>A</b>) fractionated stereotactic radiotherapy (fSRT) and (<b>B</b>) PULSAR. PULSAR includes an intra-treatment MRI assessment to evaluate the change in GTV (increased, unchanged, or decreased), enabling more personalized treatment and timely adjustment.</p>
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<p>Six lesions illustrate the temporal evolution of GTV at various treatment stages. In Group A (lesions with red contours), three lesions exhibit non-decreased GTV at follow-up compared to the initial, but they display different GTV changes at the intra-treatment time point, with intra-treatment assessments of (<b>A</b>) decreased, (<b>B</b>) unchanged, and (<b>C</b>) increased GTV. In contrast, Group B (lesions with blue contours) depicts three lesions with a decreased GTV at follow-up compared to the initial, with intra-treatment variations categorized as (<b>D</b>) decreased, (<b>E</b>) unchanged, and (<b>F</b>) increased GTV.</p>
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<p>Lesion volumetric changes examined at three time points (pre-treatment, intra-treatment, and follow-up) for two subsets, namely lesions smaller than 4000 mm<sup>3</sup> (<b>A</b>) and those larger than 4000 mm<sup>3</sup> (<b>B</b>). The line graphs on the left display the relative GTV changes for each lesion during PULSAR. The accompanying heatmaps on the right provide a detailed quantitative representation of these changes, with color intensity reflecting the relative increase or decrease in tumor volume.</p>
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<p>(<b>A</b>) ROC curves for six individual models. For each model, the plot shows the aggregated training (solid line) and test (dashed line) ROC curves generated from 50 iterations of 5-fold stratified cross-validation. The mean AUC with a 95% confidence interval is reported for each model. (<b>B</b>) Performance evaluation of the EFS model. The left panel displays the coefficient values of the nine selected features. The middle panel presents the correlation of the nine features. The right panel shows the ROC curve.</p>
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<p>(<b>A</b>) Probability scores for lesions obtained across different models. The horizontal axis represents the lesion index, and the vertical axis represents the probability score of a lesion under different models. The models (from top to bottom) are 1st radiomics, 2nd radiomics, delta radiomics, 1st dosiomics, 2nd dosiomics, delta dosiomics, and the EFS model. The EFS model shows the most effective separation between the two groups. (<b>B</b>) UMAP visualization of the EFS model’s nine features, projected into a three-dimensional space to illustrate the separation between Group A and Group B lesions. An SVM hyperplane serves as the decision boundary between the groups. (<b>C</b>) A lesion (contour in blue) with decreased GTV at follow-up compared to the initial. (<b>D</b>) A lesion (contour in red) with non-decreased GTV at follow-up compared to the initial. Panels include initial MRI, intra-treatment MRI, initial dose map, intra-treatment dose map, and wavelet-transformed images.</p>
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12 pages, 1529 KiB  
Article
Can Delta Radiomics Improve the Prediction of Best Overall Response, Progression-Free Survival, and Overall Survival of Melanoma Patients Treated with Immune Checkpoint Inhibitors?
by Felix Peisen, Annika Gerken, Alessa Hering, Isabel Dahm, Konstantin Nikolaou, Sergios Gatidis, Thomas K. Eigentler, Teresa Amaral, Jan H. Moltz and Ahmed E. Othman
Cancers 2024, 16(15), 2669; https://doi.org/10.3390/cancers16152669 - 26 Jul 2024
Cited by 2 | Viewed by 1075 | Correction
Abstract
Background: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the [...] Read more.
Background: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the endpoints best overall response (BOR), progression-free survival (PFS), and overall survival (OS), encompassing various immunotherapies. Additionally, this study investigated whether reducing the number of segmented metastases per patient affects predictive capacity. Methods: The total tumour load, excluding cerebral metastases, from 146 baseline and 146 first follow-up CTs of melanoma patients treated with first-line immunotherapy was volumetrically segmented. Twenty-one random forest models were trained and compared for the endpoints BOR; PFS at 6, 9, and 12 months; and OS at 6, 9, and 12 months, using as input either only clinical parameters, whole-tumour-load delta radiomics plus clinical parameters, or delta radiomics from the largest ten metastases plus clinical parameters. Results: The whole-tumour-load delta radiomics model performed best for BOR (AUC 0.81); PFS at 6, 9, and 12 months (AUC 0.82, 0.80, and 0.77); and OS at 6 months (AUC 0.74). The model using delta radiomics from the largest ten metastases performed best for OS at 9 and 12 months (AUC 0.71 and 0.75). Although the radiomic models were numerically superior to the clinical model, statistical significance was not reached. Conclusions: The findings indicate that delta radiomics may offer additional value for predicting BOR, PFS, and OS in metastatic melanoma patients undergoing first-line immunotherapy. Despite its complexity, volumetric whole-tumour-load segmentation could be advantageous. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
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<p>Workflow diagram.</p>
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<p>AUCs for the prediction of binarised best overall response. <b>Left graph</b> represents the model using only clinical parameters; <b>middle graph</b> represents the model using clinical parameters plus radiomic features from all metastases per patient; <b>right graph</b> represents the model using clinical parameters plus radiomic features from the largest ten metastases per patient.</p>
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<p>AUCs for the prediction of progression-free survival at twelve months. (<b>Left graph</b>) represents the model using only clinical parameters; (<b>middle graph</b>) represents the model using clinical parameters plus radiomic features from all metastases per patient; (<b>right graph</b>) represents the model using clinical parameters plus radiomic features from the largest ten metastases per patient.</p>
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<p>AUC curves for the prediction of overall survival for twelve months. (<b>Left graph</b>) represents the model using only clinical parameters; (<b>middle graph</b>) represents the model using clinical parameters plus radiomic features from all metastases per patient; (<b>right graph</b>) represents the model using clinical parameters plus radiomic features from the largest ten metastases per patient.</p>
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14 pages, 2930 KiB  
Article
Utility of CT Radiomics and Delta Radiomics for Survival Evaluation in Locally Advanced Nasopharyngeal Carcinoma with Concurrent Chemoradiotherapy
by Yen-Cho Huang, Shih-Ming Huang, Jih-Hsiang Yeh, Tung-Chieh Chang, Din-Li Tsan, Chien-Yu Lin and Shu-Ju Tu
Diagnostics 2024, 14(9), 941; https://doi.org/10.3390/diagnostics14090941 - 30 Apr 2024
Cited by 1 | Viewed by 1341
Abstract
Background: A high incidence rate of nasopharyngeal carcinoma (NPC) has been observed in Southeast Asia compared to other parts of the world. Radiomics is a computational tool to predict outcomes and may be used as a prognostic biomarker for advanced NPC treated with [...] Read more.
Background: A high incidence rate of nasopharyngeal carcinoma (NPC) has been observed in Southeast Asia compared to other parts of the world. Radiomics is a computational tool to predict outcomes and may be used as a prognostic biomarker for advanced NPC treated with concurrent chemoradiotherapy. Recently, radiomic analysis of the peripheral tumor microenvironment (TME), which is the region surrounding the gross tumor volume (GTV), has shown prognostic usefulness. In this study, not only was gross tumor volume (GTVt) analyzed but also tumor peripheral regions (GTVp) were explored in terms of the TME concept. Both radiomic features and delta radiomic features were analyzed using CT images acquired in a routine radiotherapy process. Methods: A total of 50 patients with NPC stages III, IVA, and IVB were enrolled between September 2004 and February 2014. Survival models were built using Cox regression with clinical factors (i.e., gender, age, overall stage, T stage, N stage, and treatment dose) and radiomic features. Radiomic features were extracted from GTVt and GTVp. GTVp was created surrounding GTVt for TME consideration. Furthermore, delta radiomics, which is the longitudinal change in quantitative radiomic features, was utilized for analysis. Finally, C-index values were computed using leave-one-out cross-validation (LOOCV) to evaluate the performances of all prognosis models. Results: Models were built for three different clinical outcomes, including overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). The range of the C-index in clinical factor models was (0.622, 0.729). All radiomics models, including delta radiomics models, were in the range of (0.718, 0.872). Among delta radiomics models, GTVt and GTVp were in the range of (0.833, 0.872) and (0.799, 0.834), respectively. Conclusions: Radiomic analysis on the proximal region surrounding the gross tumor volume of advanced NPC patients for survival outcome evaluation was investigated, and preliminary positive results were obtained. Radiomic models and delta radiomic models demonstrated performance that was either superior to or comparable with that of conventional clinical models. Full article
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<p>The workflow summary of radiomic application for clinical outcome prediction in this study.</p>
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<p>Patient selection criteria.</p>
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<p>Illustration of extracting radiomic features and building the machine learning model.</p>
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<p>Contours of GTVt (cyan color) in the axial, sagittal, and coronal planes. The window of Hounsfield units (HUs) was set between −200 and 400 to remove air and bone area (water = 0 HU). “L” stands for left side, “P” stands for posterior, and “R” stands for right side.</p>
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<p>Segmentation of GTVp (i.e., tumor microenvironment showing in orange color). This peripheral region of tumor microenvironment is expanded 3 mm outside of GTV. “L” stands for left side, “P” stands for posterior, and “R” stands for right side.</p>
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<p>Kaplan–Meier survival curves from the clinical factor model analysis for three outcomes. Risks were stratified by clinical factors into two groups, and patients were dichotomized by the cut-off of risk in the survival curves.</p>
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<p>Kaplan–Meier survival curves from the GTVt delta radiomics model analysis for three outcomes.</p>
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<p>Kaplan–Meier survival curves from the GTVp delta radiomics model analysis for three outcomes.</p>
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16 pages, 750 KiB  
Article
Evaluating Outcome Prediction via Baseline, End-of-Treatment, and Delta Radiomics on PET-CT Images of Primary Mediastinal Large B-Cell Lymphoma
by Fereshteh Yousefirizi, Claire Gowdy, Ivan S. Klyuzhin, Maziar Sabouri, Petter Tonseth, Anna R. Hayden, Donald Wilson, Laurie H. Sehn, David W. Scott, Christian Steidl, Kerry J. Savage, Carlos F. Uribe and Arman Rahmim
Cancers 2024, 16(6), 1090; https://doi.org/10.3390/cancers16061090 - 8 Mar 2024
Cited by 6 | Viewed by 2243
Abstract
Objectives: Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression [...] Read more.
Objectives: Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients. Material and Methods: Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [18F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE). Results: To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (p-value> 0.05). Conclusion: This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [18F]FDG PET-CT scans. Full article
(This article belongs to the Special Issue PET/CT in Cancers Outcomes Prediction)
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<p>Our suggested approach: (<b>a</b>) Diagrammatic representation of Radiomics flow chart applied in this study. (<b>b</b>) RIM features are extracted on scans from different time points (baseline and End of Treatment (EoT)) on both PET and CT scans (Only PET scan is shown in (<b>b</b>) for visualization). (RIM: radial mean intensity).</p>
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15 pages, 1816 KiB  
Systematic Review
Progress in Serial Imaging for Prognostic Stratification of Lung Cancer Patients Receiving Immunotherapy: A Systematic Review and Meta-Analysis
by Hwa-Yen Chiu, Ting-Wei Wang, Ming-Sheng Hsu, Heng-Shen Chao, Chien-Yi Liao, Chia-Feng Lu, Yu-Te Wu and Yuh-Ming Chen
Cancers 2024, 16(3), 615; https://doi.org/10.3390/cancers16030615 - 31 Jan 2024
Viewed by 1804
Abstract
Immunotherapy, particularly with checkpoint inhibitors, has revolutionized non-small cell lung cancer treatment. Enhancing the selection of potential responders is crucial, and researchers are exploring predictive biomarkers. Delta radiomics, a derivative of radiomics, holds promise in this regard. For this study, a meta-analysis was [...] Read more.
Immunotherapy, particularly with checkpoint inhibitors, has revolutionized non-small cell lung cancer treatment. Enhancing the selection of potential responders is crucial, and researchers are exploring predictive biomarkers. Delta radiomics, a derivative of radiomics, holds promise in this regard. For this study, a meta-analysis was conducted that adhered to PRISMA guidelines, searching PubMed, Embase, Web of Science, and the Cochrane Library for studies on the use of delta radiomics in stratifying lung cancer patients receiving immunotherapy. Out of 223 initially collected studies, 10 were included for qualitative synthesis. Stratifying patients using radiomic models, the pooled analysis reveals a predictive power with an area under the curve of 0.81 (95% CI 0.76–0.86, p < 0.001) for 6-month response, a pooled hazard ratio of 4.77 (95% CI 2.70–8.43, p < 0.001) for progression-free survival, and 2.15 (95% CI 1.73–2.66, p < 0.001) for overall survival at 6 months. Radiomics emerges as a potential prognostic predictor for lung cancer, but further research is needed to compare traditional radiomics and deep-learning radiomics. Full article
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<p>PRISMA flowchart of the included studies.</p>
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<p>Quality assessment. (<b>a</b>) Risk of bias for individual studies. (<b>b</b>) Summary of risk of biases [<a href="#B32-cancers-16-00615" class="html-bibr">32</a>,<a href="#B33-cancers-16-00615" class="html-bibr">33</a>,<a href="#B34-cancers-16-00615" class="html-bibr">34</a>,<a href="#B35-cancers-16-00615" class="html-bibr">35</a>,<a href="#B36-cancers-16-00615" class="html-bibr">36</a>,<a href="#B37-cancers-16-00615" class="html-bibr">37</a>,<a href="#B38-cancers-16-00615" class="html-bibr">38</a>,<a href="#B39-cancers-16-00615" class="html-bibr">39</a>,<a href="#B40-cancers-16-00615" class="html-bibr">40</a>,<a href="#B41-cancers-16-00615" class="html-bibr">41</a>].</p>
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<p>Forest plots of the predictive performance of radiomics models in progression-free survival and overall survival of NSCLC patients treated with immunotherapy [<a href="#B32-cancers-16-00615" class="html-bibr">32</a>,<a href="#B33-cancers-16-00615" class="html-bibr">33</a>,<a href="#B34-cancers-16-00615" class="html-bibr">34</a>,<a href="#B35-cancers-16-00615" class="html-bibr">35</a>,<a href="#B36-cancers-16-00615" class="html-bibr">36</a>,<a href="#B37-cancers-16-00615" class="html-bibr">37</a>,<a href="#B38-cancers-16-00615" class="html-bibr">38</a>,<a href="#B39-cancers-16-00615" class="html-bibr">39</a>,<a href="#B41-cancers-16-00615" class="html-bibr">41</a>]. (<b>a</b>) The 6-month response, (<b>b</b>) hazard ratio for progression-free survival, (<b>c</b>) hazard ratio for overall survival.</p>
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<p>Funnel plots of the pooled predictive performance of radiomics models in progression-free survival and overall survival of NSCLC patients treated with immunotherapy. (<b>a</b>) The 6-month response AUC, (<b>b</b>) hazard ratio for progression-free survival, (<b>c</b>) hazard ratio for overall survival.</p>
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15 pages, 1862 KiB  
Article
Evaluating the Potential of Delta Radiomics for Assessing Tyrosine Kinase Inhibitor Treatment Response in Non-Small Cell Lung Cancer Patients
by Ting-Wei Wang, Heng-Sheng Chao, Hwa-Yen Chiu, Yi-Hui Lin, Hung-Chun Chen, Chia-Feng Lu, Chien-Yi Liao, Yen Lee, Tsu-Hui Shiao, Yuh-Min Chen, Jing-Wen Huang and Yu-Te Wu
Cancers 2023, 15(21), 5125; https://doi.org/10.3390/cancers15215125 - 24 Oct 2023
Cited by 5 | Viewed by 1863
Abstract
Our study aimed to harness the power of CT scans, observed over time, in predicting how lung adenocarcinoma patients might respond to a treatment known as EGFR-TKI. Analyzing scans from 322 advanced stage lung cancer patients, we identified distinct image-based patterns. By integrating [...] Read more.
Our study aimed to harness the power of CT scans, observed over time, in predicting how lung adenocarcinoma patients might respond to a treatment known as EGFR-TKI. Analyzing scans from 322 advanced stage lung cancer patients, we identified distinct image-based patterns. By integrating these patterns with comprehensive clinical information, such as gene mutations and treatment regimens, our predictive capabilities were significantly enhanced. Interestingly, the precision of these predictions, particularly related to radiomics features, diminished when data from various centers were combined, suggesting that the approach requires standardization across facilities. This novel method offers a potential pathway to anticipate disease progression in lung adenocarcinoma patients treated with EGFR-TKI, laying the groundwork for more personalized treatments. To further validate this approach, extensive studies involving a larger cohort are pivotal. Full article
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<p>Overall workflow of the study.</p>
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<p>Correlation analysis of the final selected features.</p>
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<p>Time dependent AUC of performance of clinical, radiomics and ensemble methods.</p>
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<p>Kaplan–Meier survival curves of progression free survival stratify by model output (<b>a</b>) test set (<b>b</b>) combined test set. Kaplan-Meier survival curves for high-risk patients (blue line) and low risk patients (orange line). The shaded areas represent the 95% confidence intervals for each group.</p>
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14 pages, 2259 KiB  
Article
Development of a Model Based on Delta-Radiomic Features for the Optimization of Head and Neck Squamous Cell Carcinoma Patient Treatment
by Severina Šedienė, Ilona Kulakienė, Benas Gabrielis Urbonavičius, Erika Korobeinikova, Viktoras Rudžianskas, Paulius Algirdas Povilonis, Evelina Jaselskė, Diana Adlienė and Elona Juozaitytė
Medicina 2023, 59(6), 1173; https://doi.org/10.3390/medicina59061173 - 19 Jun 2023
Cited by 1 | Viewed by 1739
Abstract
Background and Objectives: To our knowledge, this is the first study that investigated the prognostic value of radiomics features extracted from not only staging 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) images, but also post-induction chemotherapy (ICT) PET/CT images. This study aimed to [...] Read more.
Background and Objectives: To our knowledge, this is the first study that investigated the prognostic value of radiomics features extracted from not only staging 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) images, but also post-induction chemotherapy (ICT) PET/CT images. This study aimed to construct a training model based on radiomics features obtained from PET/CT in a cohort of patients with locally advanced head and neck squamous cell carcinoma treated with ICT, to predict locoregional recurrence, development of distant metastases, and the overall survival, and to extract the most significant radiomics features, which were included in the final model. Materials and Methods: This retrospective study analyzed data of 55 patients. All patients underwent PET/CT at the initial staging and after ICT. Along the classical set of 13 parameters, the original 52 parameters were extracted from each PET/CT study and an additional 52 parameters were generated as a difference between radiomics parameters before and after the ICT. Five machine learning algorithms were tested. Results: The Random Forest algorithm demonstrated the best performance (R2 0.963–0.998) in the majority of datasets. The strongest correlation in the classical dataset was between the time to disease progression and time to death (r = 0.89). Another strong correlation (r ≥ 0.8) was between higher-order texture indices GLRLM_GLNU, GLRLM_SZLGE, and GLRLM_ZLNU and standard PET parameters MTV, TLG, and SUVmax. Patients with a higher numerical expression of GLCM_ContrastVariance, extracted from the delta dataset, had a longer survival and longer time until progression (p = 0.001). Good correlations were observed between Discretized_SUVstd or Discretized_SUVSkewness and time until progression (p = 0.007). Conclusions: Radiomics features extracted from the delta dataset produced the most robust data. Most of the parameters had a positive impact on the prediction of the overall survival and the time until progression. The strongest single parameter was GLCM_ContrastVariance. Discretized_SUVstd or Discretized_SUVSkewness demonstrated a strong correlation with the time until progression. Full article
(This article belongs to the Section Oncology)
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<p>Individual thermoplastic mask (<b>a</b>) for immobilization of the patient for the post-ICT head and neck PET/CT scan (<b>b</b>).</p>
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<p>Matrix of <span class="html-italic">p</span>-values. Lower part of the matrix visually depicts datapoint scatter tendencies, while red trendlines depicts the dependencies of variables.</p>
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<p>Correlation coefficient between textural indices and positron emission tomography standard parameters.</p>
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<p>ROC curve of the Random Forest ML algorithm with whole = body imaging radiomics parameters before the ICT dataset.</p>
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<p>Relationship between survival and GLCM_ContrastVariance.</p>
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<p>The heatmap of correlation values of second- and third-grade parameters. Red color represents complete positive correlation, while blue color—complete negative correlation.</p>
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11 pages, 262 KiB  
Review
Image Guided Radiotherapy (IGRT) and Delta (Δ) Radiomics—An Urgent Alliance for the Front Line of the War against Head and Neck Cancers
by Camil Ciprian Mireștean, Roxana Irina Iancu and Dragoș Petru Teodor Iancu
Diagnostics 2023, 13(12), 2045; https://doi.org/10.3390/diagnostics13122045 - 13 Jun 2023
Cited by 4 | Viewed by 2276
Abstract
The identification of a biomarker that is response predictive could offer a solution for the stratification of the treatment of head and neck cancers (HNC) in the context of high recurrence rates, especially those associated with loco-regional failure. Delta (Δ) radiomics, a concept [...] Read more.
The identification of a biomarker that is response predictive could offer a solution for the stratification of the treatment of head and neck cancers (HNC) in the context of high recurrence rates, especially those associated with loco-regional failure. Delta (Δ) radiomics, a concept based on the variation of parameters extracted from medical imaging using artificial intelligence (AI) algorithms, demonstrates its potential as a predictive biomarker of treatment response in HNC. The concept of image-guided radiotherapy (IGRT), including computer tomography simulation (CT) and position control imaging with cone-beam-computed tomography (CBCT), now offers new perspectives for radiomics applied in radiotherapy. The use of Δ features of texture, shape, and size, both from the primary tumor and from the tumor-involved lymph nodes, demonstrates the best predictive accuracy. If, in the case of treatment response, promising Δ radiomics results could be obtained, even after 24 h from the start of treatment, for radiation-induced xerostomia, the evaluation of Δ radiomics in the middle of treatment could be recommended. The fused models (clinical and Δ radiomics) seem to offer benefits, both in comparison to the clinical model and to the radiomic model. The selection of patients who benefit from induction chemotherapy is underestimated in Δ radiomic studies and may be an unexplored territory with major potential. The advantage offered by “in house” simulation CT and CBCT favors the rapid implementation of Δ radiomics studies in radiotherapy departments. Positron emission tomography (PET)-CT Δ radiomics could guide the new concepts of dose escalation on radio-resistant sub-volumes based on radiobiological criteria, but also guide the “next level” of HNC adaptive radiotherapy (ART). Full article
(This article belongs to the Special Issue Radiomics in Oncology 3rd Edition)
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Article
Delta Radiomic Analysis of Mesorectum to Predict Treatment Response and Prognosis in Locally Advanced Rectal Cancer
by Giuditta Chiloiro, Davide Cusumano, Angela Romano, Luca Boldrini, Giuseppe Nicolì, Claudio Votta, Huong Elena Tran, Brunella Barbaro, Davide Carano, Vincenzo Valentini and Maria Antonietta Gambacorta
Cancers 2023, 15(12), 3082; https://doi.org/10.3390/cancers15123082 - 7 Jun 2023
Cited by 7 | Viewed by 1879
Abstract
Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy [...] Read more.
Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (nCRT). Methods: Pre- and post-nCRT MRIs of LARC patients treated at a single institution from May 2008 to November 2016 were retrospectively collected. Radiomic features were extracted from the GTV and mesorectum. The Wilcoxon–Mann–Whitney test and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the features in predicting pCR and 2yDFS. Results: Out of 203 LARC patients, a total of 565 variables were evaluated. The best performing pCR prediction model was based on two GTV features with an AUC of 0.80 in the training set and 0.69 in the validation set. The best performing 2yDFS prediction model was based on one GTV and two mesorectal features with an AUC of 0.79 in the training set and 0.70 in the validation set. Conclusions: The results of this study suggest a possible role for delta radiomics based on mesorectal features in the prediction of 2yDFS in patients with LARC. Full article
(This article belongs to the Special Issue Advances in Radiotherapy and Prognosis of Rectal Cancer)
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<p>GTV (red) and mesorectum (green) delineated on pre-treatment (<b>left</b>) and post-treatment (<b>right</b>) MRI on axial plans.</p>
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<p>ROC (receiver operating characteristic) curves of the models elaborated for pCR (pathological complete response, top line) and 2yDFS (disease free survival at 2 years, bottom line) for training (<b>left</b>) and validation set (<b>right</b>), respectively.</p>
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14 pages, 2168 KiB  
Article
Radiomics and Delta-Radiomics Signatures to Predict Response and Survival in Patients with Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
by François Cousin, Thomas Louis, Sophie Dheur, Frank Aboubakar, Benoit Ghaye, Mariaelena Occhipinti, Wim Vos, Fabio Bottari, Astrid Paulus, Anne Sibille, Frédérique Vaillant, Bernard Duysinx, Julien Guiot and Roland Hustinx
Cancers 2023, 15(7), 1968; https://doi.org/10.3390/cancers15071968 - 25 Mar 2023
Cited by 18 | Viewed by 3755
Abstract
The aim of our study was to determine the potential role of CT-based radiomics in predicting treatment response and survival in patients with advanced NSCLC treated with immune checkpoint inhibitors. We retrospectively included 188 patients with NSCLC treated with PD-1/PD-L1 inhibitors from two [...] Read more.
The aim of our study was to determine the potential role of CT-based radiomics in predicting treatment response and survival in patients with advanced NSCLC treated with immune checkpoint inhibitors. We retrospectively included 188 patients with NSCLC treated with PD-1/PD-L1 inhibitors from two independent centers. Radiomics analysis was performed on pre-treatment contrast-enhanced CT. A delta-radiomics analysis was also conducted on a subset of 160 patients who underwent a follow-up contrast-enhanced CT after 2 to 4 treatment cycles. Linear and random forest (RF) models were tested to predict response at 6 months and overall survival. Models based on clinical parameters only and combined clinical and radiomics models were also tested and compared to the radiomics and delta-radiomics models. The RF delta-radiomics model showed the best performance for response prediction with an AUC of 0.8 (95% CI: 0.65−0.95) on the external test dataset. The Cox regression delta-radiomics model was the most accurate at predicting survival with a concordance index of 0.68 (95% CI: 0.56−0.80) (p = 0.02). The baseline CT radiomics signatures did not show any significant results for treatment response prediction or survival. In conclusion, our results demonstrated the ability of a CT-based delta-radiomics signature to identify early on patients with NSCLC who were more likely to benefit from immunotherapy. Full article
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<p>Radiomics workflow of the study.</p>
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<p>Patient flow diagram.</p>
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<p>The ROC curves for treatment response prediction of the generalized linear (<b>a</b>–<b>e</b>) and the random forest (<b>f</b>–<b>i</b>) models obtained on the external dataset.</p>
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<p>External dataset OS Kaplan–Meier curves with split based on Cox proportional hazard for the clinical model (<b>a</b>); the radiomics single-lesion model (<b>b</b>); the delta-radiomics model (<b>c</b>); the combined radiomics single-lesion model (<b>d</b>); and the combined delta-radiomics model (<b>e</b>).</p>
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18 pages, 1612 KiB  
Article
Association of Multi-Phasic MR-Based Radiomic and Dosimetric Features with Treatment Response in Unresectable Hepatocellular Carcinoma Patients following Novel Sequential TACE-SBRT-Immunotherapy
by Lok-Man Ho, Sai-Kit Lam, Jiang Zhang, Chi-Leung Chiang, Albert Chi-Yan Chan and Jing Cai
Cancers 2023, 15(4), 1105; https://doi.org/10.3390/cancers15041105 - 9 Feb 2023
Cited by 10 | Viewed by 3434
Abstract
This study aims to investigate the association of pre-treatment multi-phasic MR-based radiomics and dosimetric features with treatment response to a novel sequential trans-arterial chemoembolization (TACE) plus stereotactic body radiotherapy (SBRT) plus immunotherapy regimen in unresectable Hepatocellular Carcinoma (HCC) sub-population. Twenty-six patients with unresectable [...] Read more.
This study aims to investigate the association of pre-treatment multi-phasic MR-based radiomics and dosimetric features with treatment response to a novel sequential trans-arterial chemoembolization (TACE) plus stereotactic body radiotherapy (SBRT) plus immunotherapy regimen in unresectable Hepatocellular Carcinoma (HCC) sub-population. Twenty-six patients with unresectable HCC were retrospectively analyzed. Radiomic features were extracted from 42 lesions on arterial phase (AP) and portal-venous phase (PVP) MR images. Delta-phase (DeltaP) radiomic features were calculated as AP-to-PVP ratio. Dosimetric data of the tumor was extracted from dose-volume-histograms. A two-sided independent Mann–Whitney U test was used to assess the clinical association of each feature, and the classification performance of each significant independent feature was assessed using logistic regression. For the 3-month timepoint, four DeltaP-derived radiomics that characterize the temporal change in intratumoral randomness and uniformity were the only contributors to the treatment response association (p-value = 0.038–0.063, AUC = 0.690–0.766). For the 6-month timepoint, DeltaP-derived radiomic features (n = 4) maintained strong clinical associations with the treatment response (p-value = 0.047–0.070, AUC = 0.699–0.788), additional AP-derived radiomic features (n = 4) that reflect baseline tumoral arterial-enhanced signal pattern and tumor morphology (n = 1) that denotes initial tumor burden were shown to have strong associations with treatment response (p-value = 0.028–0.074, AUC = 0.719–0.773). This pilot study successfully demonstrated associations of pre-treatment multi-phasic MR-based radiomics with tumor response to the novel treatment regimen. Full article
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<p>A 76-year-old male patient was diagnosed with advanced-staged HCC. (<b>a</b>) Axial AP T1W MR image with the VOI, (<b>b</b>) Axial PVP T1W MR image with the VOI. SBRT of 30 Gy was prescribed in 5 fractions to the tumor. (<b>c</b>) DVH of gross tumor volume (GTV) and planning target volume (PTV) generated from the treatment planning system and (<b>d</b>) Dose distribution of the SBRT treatment plan.</p>
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Article
Delta Radiomics Model Predicts Lesion-Level Responses to Tyrosine Kinase Inhibitors in Patients with Advanced Renal Cell Carcinoma: A Preliminary Result
by Yuntian Chen, Enyu Yuan, Guangxi Sun, Bin Song and Jin Yao
J. Clin. Med. 2023, 12(4), 1301; https://doi.org/10.3390/jcm12041301 - 6 Feb 2023
Cited by 2 | Viewed by 1609
Abstract
Background: This study aimed to develop and internally validate computed tomography (CT)-based radiomic models to predict the lesion-level short-term response to tyrosine kinase inhibitors (TKIs) in patients with advanced renal cell carcinoma (RCC). Methods: This retrospective study included consecutive patients with RCC that [...] Read more.
Background: This study aimed to develop and internally validate computed tomography (CT)-based radiomic models to predict the lesion-level short-term response to tyrosine kinase inhibitors (TKIs) in patients with advanced renal cell carcinoma (RCC). Methods: This retrospective study included consecutive patients with RCC that were treated using TKIs as the first-line treatment. Radiomic features were extracted from noncontrast (NC) and arterial-phase (AP) CT images. The model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: A total of 36 patients with 131 measurable lesions were enrolled (training: validation = 91: 40). The model with five delta features achieved the best discrimination capability with AUC values of 0.940 (95% CI, 0.890‒0.990) in the training cohort and 0.916 (95% CI, 0.828‒1.000) in the validation cohort. Only the delta model was well calibrated. The DCA showed that the net benefit of the delta model was greater than that of the other radiomic models, as well as that of the treat-all and treat-none criteria. Conclusions: Models based on CT delta radiomic features may help predict the short-term response to TKIs in patients with advanced RCC and aid in lesion stratification for potential treatments. Full article
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<p>Flowchart for selecting the study population.</p>
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<p>Workflow of radiomic analysis.</p>
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<p>Calibration curves of each model in training (<b>a</b>) and validation (<b>b</b>) cohorts.</p>
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<p>Decision curves of each model in training (<b>a</b>) and validation (<b>b</b>) cohorts. The filled area demonstrates the area between decision curve of the delta model, treat-none criteria, and treat-all criteria.</p>
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