Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’ anatomy. However, the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians. Moreover, some potentially useful quantitative information in medical images, especially that which is not visible to the naked eye, is often ignored during clinical practice. In contrast, radiomics performs high-throughput feature extraction from medical images, which enables quantitative analysis of medical images and prediction of various clinical endpoints. Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis, demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine. However, radiomics remains in a developmental phase as numerous technical challenges have yet to be solved, especially in feature engineering and statistical modeling. In this review, we introduce the current utility of radiomics by summarizing research on its application in the diagnosis, prognosis, and prediction of treatment responses in patients with cancer. We focus on machine learning approaches, for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling. Furthermore, we introduce the stability, reproducibility, and interpretability of features, and the generalizability and interpretability of models. Finally, we offer possible solutions to current challenges in radiomics research.

Radiomic model reliability is a central premise for its clinical translation. Presently, it is assessed using test–retest or external data, which, unfortunately, is often scarce in reality. Therefore, we aimed to develop a novel image perturbation-based method (IPBM) for the first of its kind toward building a reliable radiomic model. We first developed a radiomic prognostic model for head-and-neck cancer patients on a training (70%) and evaluated on a testing (30%) cohort using C-index. Subsequently, we applied the IPBM to CT images of both cohorts (Perturbed-Train and Perturbed-Test cohort) to generate 60 additional samples for both cohorts. Model reliability was assessed using intra-class correlation coefficient (ICC) to quantify consistency of the C-index among the 60 samples in the Perturbed-Train and Perturbed-Test cohorts. Besides, we re-trained the radiomic model using reliable RFs exclusively (ICC > 0.75) to validate the IPBM. Results showed moderate model reliability in Perturbed-Train (ICC: 0.565, 95%CI 0.518–0.615) and Perturbed-Test (ICC: 0.596, 95%CI 0.527–0.670) cohorts. An enhanced reliability of the re-trained model was observed in Perturbed-Train (ICC: 0.782, 95%CI 0.759–0.815) and Perturbed-Test (ICC: 0.825, 95%CI 0.782–0.867) cohorts, indicating validity of the IPBM. To conclude, we demonstrated capability of the IPBM toward building reliable radiomic models, providing community with a novel model reliability assessment strategy prior to prospective evaluation.

Purpose: The study aimed to predict acute radiation esophagitis (ARE) with grade ≥ 2 for patients with locally advanced lung cancer (LALC) treated with intensity-modulated radiation therapy (IMRT) using multi-omics features, including radiomics and dosiomics. Methods: 161 patients with stage IIIA−IIIB LALC who received chemoradiotherapy (CRT) or radiotherapy by IMRT with a prescribed dose from 45 to 70 Gy from 2015 to 2019 were enrolled retrospectively. All the toxicity gradings were given following the Common Terminology Criteria for Adverse Events V4.0. Multi-omics features, including radiomics, dosiomics (including dose−volume histogram dosimetric parameters), were extracted based on the planning CT image and three-dimensional dose distribution. All data were randomly divided into training cohorts (N = 107) and testing cohorts (N = 54). In the training cohorts, features with reliably high outcome relevance and low redundancy were selected under random patient subsampling. Four classification models (using clinical factors (CF) only, using radiomics features (RFs) only, dosiomics features (DFs) only, and the hybrid features (HFs) containing clinical factors, radiomics and dosiomics) were constructed employing the Ridge classifier using two-thirds of randomly selected patients as the training cohort. The remaining patient was treated as the testing cohort. A series of models were built with 30 times training–testing splits. Their performances were assessed using the area under the ROC curve (AUC) and accuracy. Results: Among all patients, 51 developed ARE grade ≥ 2, with an incidence of 31.7%. Next, 8990 radiomics and 213 dosiomics features were extracted, and 3, 6, 12, and 13 features remained after feature selection in the CF, DF, RF and DF models, respectively. The RF and HF models achieved similar classification performance, with the training and testing AUCs of 0.796 ± 0.023 (95% confidence interval (CI [0.79, 0.80])/0.744 ± 0.044 (95% CI [0.73, 0.76]) and 0.801 ± 0.022 (95% CI [0.79, 0.81]) (p = 0.74), respectively. The model performances using CF and DF features were poorer, with training and testing AUCs of 0.573 ± 0.026 (95% CI [0.56, 0.58])/ 0.509 ± 0.072 (95% CI [0.48, 0.53]) and 0.679 ± 0.027 (95% CI [0.67, 0.69])/0.604 ± 0.041 (95% CI [0.53, 0.63]) compared with the above two models (p < 0.001), respectively. Conclusions: In LALC patients treated with CRT IMRT, the ARE grade ≥ 2 can be predicted using the pretreatment radiotherapy image features. To predict ARE, the multi-omics features had similar predictability with radiomics features; however, the dosiomics features and clinical factors had a limited classification performance.

Background: Using high robust radiomic features in modeling is recommended, yet its impact on radiomic model is unclear. This study evaluated the radiomic model’s robustness and generalizability after screening out low-robust features before radiomic modeling. The results were validated with four datasets and two clinically relevant tasks.Materials and methods: A total of 1,419 head-and-neck cancer patients’ computed tomography images, gross tumor volume segmentation, and clinically relevant outcomes (distant metastasis and local-regional recurrence) were collected from four publicly available datasets. The perturbation method was implemented to simulate images, and the radiomic feature robustness was quantified using intra-class correlation of coefficient (ICC). Three radiomic models were built using all features (ICC > 0), good-robust features (ICC > 0.75), and excellent-robust features (ICC > 0.95), respectively. A filter-based feature selection and Ridge classification method were used to construct the radiomic models. Model performance was assessed with both robustness and generalizability. The robustness of the model was evaluated by the ICC, and the generalizability of the model was quantified by the train-test difference of Area Under the Receiver Operating Characteristic Curve (AUC).Results: The average model robustness ICC improved significantly from 0.65 to 0.78 (P< 0.0001) using good-robust features and to 0.91 (P< 0.0001) using excellent-robust features. Model generalizability also showed a substantial increase, as a closer gap between training and testing AUC was observed where the mean train-test AUC difference was reduced from 0.21 to 0.18 (P< 0.001) in good-robust features and to 0.12 (P< 0.0001) in excellent-robust features. Furthermore, good-robust features yielded the best average AUC in the unseen datasets of 0.58 (P< 0.001) over four datasets and clinical outcomes.Conclusions: Including robust only features in radiomic modeling significantly improves model robustness and generalizability in unseen datasets. Yet, the robustness of radiomic model has to be verified despite building with robust radiomic features, and tightly restricted feature robustness may prevent the optimal model performance in the unseen dataset as it may lower the discrimination power of the model.

An individual's level of lower limb motor function is associated with his or her disability level after stroke, and motor improvement may lead to a better prognosis and quality of life. Data from animal models show that Qizhitongluo (QZTL) capsule facilitates recovery after focal brain injury. We aimed to validate the efficacy and safety of the QZTL capsule for promoting lower limb motor recovery in poststroke patients. In this randomized, multicenter, double-blind, placebo- and active-controlled trial from 13 sites in China, participants with ischemic stroke and Fugl-Meyer motor scale (FMMS) scores of <95 were eligible for inclusion. Patients were randomly assigned in a 2:1:1 ratio to the QZTL group, Naoxintong (NXT) group or placebo group for 12 weeks at 15-28 days after the onset of stroke. The primary outcome was the change in the Lower Limb FMMS (FMMS-LL) score from baseline over the 12-week intervention period. 622 participants were randomly assigned to the QZTL group (309), NXT group (159), or placebo group (154). The FMMS-LL score increased by 4.81 points (95 % CI, 4.27-5.35) in the QZTL group, by 3.77 points (95 % CI, 3.03-4.51) in the NXT group and by 3.00 points (95 % CI, 3.03-4.51) in the placebo group at week 12. The QZTL group showed significantly larger improvements compared with the placebo group at each interview from weeks 4-12 (difference, 0.89 [0.30,1.49] at week 4, P = 0.0032; difference, 1.83[1.01,2.66] at 90 days poststroke, P < 0.0001; difference, 1.81[0.88,2.74] at week 12, P = 0.0001). The QZTL capsule is an effective treatment for lower limb motor impairment. The finding indicates that the QZTL capsule may be used as a potential new strategy for stroke rehabilitation.

Significant lymph node shrinkage is common in patients with nasopharyngeal carcinoma (NPC) throughout radiotherapy (RT) treatment, causing ill-fitted thermoplastic masks (IfTMs). To deal with this, an ad hoc adaptive radiotherapy (ART) may be required to ensure accurate and safe radiation delivery and to maintain treatment efficacy. Presently, the entire procedure for evaluating an eligible ART candidate is time-consuming, resource-demanding, and highly inefficient. In the artificial intelligence paradigm, the pre-treatment identification of NPC patients at risk for IfTMs has become greatly demanding for achieving efficient ART eligibility screening, while no relevant studies have been reported. Hence, we aimed to investigate the capability of computed tomography (CT)-based neck nodal radiomics for predicting IfTM-triggered ART events in NPC patients via a multi-center setting. Contrast-enhanced CT and the clinical data of 124 and 58 NPC patients from Queen Elizabeth Hospital (QEH) and Queen Mary Hospital (QMH), respectively, were retrospectively analyzed. Radiomic (R), clinical (C), and combined (RC) models were developed using the ridge algorithm in the QEH cohort and evaluated in the QMH cohort using the median area under the receiver operating characteristics curve (AUC). Delong’s test was employed for model comparison. Model performance was further assessed on 1000 replicates in both cohorts separately via bootstrapping. The R model yielded the highest “corrected” AUC of 0.784 (BCa 95%CI: 0.673–0.859) and 0.723 (BCa 95%CI: 0.534–0.859) in the QEH and QMH cohort following bootstrapping, respectively. Delong’s test indicated that the R model performed significantly better than the C model in the QMH cohort (p < 0.0001), while demonstrating no significant difference compared to the RC model (p = 0.5773). To conclude, CT-based neck nodal radiomics was capable of predicting IfTM-triggered ART events in NPC patients in this multi-center study, outperforming the traditional clinical model. The findings of this study provide valuable insights for future study into developing an effective screening strategy for ART eligibility in NPC patients in the long run, ultimately alleviating the workload of clinical practitioners, streamlining ART procedural efficiency in clinics, and achieving personalized RT for NPC patients in the future.