Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

Identifying early gastric cancer under magnifying narrow-band images with deep learning: a multicenter study.

BACKGROUND AND AIMS: Narrow-band imaging with magnifying endoscopy (ME-NBI) has shown advantages in the diagnosis of early gastric cancer (EGC). However, proficiency in diagnostic algorithms requires substantial expertise and experience. In this study, we aimed to develop a computer-aided diagnostic model for EGM (EGCM) to analyze and assist in the diagnosis of EGC under ME-NBI. METHODS: A total of 1777 ME-NBI images from 295 cases were collected from 3 centers. These cases were randomly divided into a training cohort (n = 170), an internal test cohort (ITC, n = 73), and an external test cohort (ETC, n = 52). EGCM based on VGG-19 architecture (Visual Geometry Group [VGG], Oxford University, Oxford, UK) with a single fully connected 2-classification layer was developed through fine-tuning and validated on all cohorts. Furthermore, we compared the model with 8 endoscopists with varying experience. Primary comparison measures included accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: EGCM acquired AUCs of .808 in the ITC and .813 in the ETC. Moreover, EGCM achieved similar predictive performance as the senior endoscopists (accuracy: .770 vs .755, P = .355; sensitivity: .792 vs .767, P = .183; specificity: .745 vs .742, P = .931) but better than the junior endoscopists (accuracy: .770 vs .728, P < .05). After referring to the results of EGCM, the average diagnostic ability of the endoscopists was significantly improved in terms of accuracy, sensitivity, PPV, and NPV (P < .05). CONCLUSIONS: EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists.

Integrating No.3 lymph nodes and primary tumor radiomics to predict lymph node metastasis in T1-2 gastric cancer.

BACKGROUND: This study aimed to develope and validate a radiomics nomogram by integrating the quantitative radiomics characteristics of No.3 lymph nodes (LNs) and primary tumors to better predict preoperative lymph node metastasis (LNM) in T1-2 gastric cancer (GC) patients. METHODS: A total of 159 T1-2 GC patients who had undergone surgery with lymphadenectomy between March 2012 and November 2017 were retrospectively collected and divided into a training cohort (n = 80) and a testing cohort (n = 79). Radiomic features were extracted from both tumor region and No. 3 station LNs based on computed tomography (CT) images per patient. Then, key features were selected using minimum redundancy maximum relevance algorithm and fed into two radiomic signatures, respectively. Meanwhile, the predictive performance of clinical risk factors was studied. Finally, a nomogram was built by merging radiomic signatures and clinical risk factors and evaluated by the area under the receiver operator characteristic curve (AUC) as well as decision curve. RESULTS: Two radiomic signatures, reflecting phenotypes of the tumor and LNs respectively, were significantly associated with LN metastasis. A nomogram incorporating two radiomic signatures and CT-reported LN metastasis status showed good discrimination of LN metastasis in both the training cohort (AUC 0.915; 95% confidence interval [CI] 0.832-0.998) and testing cohort (AUC 0.908; 95% CI 0.814-1.000). The decision curve also indicated its potential clinical usefulness. CONCLUSIONS: The nomogram received favorable predictive accuracy in predicting No.3 LNM in T1-2 GC, and the nomogram showed positive role in predicting LNM in No.4 LNs. The nomogram may be used to predict LNM in T1-2 GC and could assist the choice of therapy.

Development and validation of a novel MR imaging predictor of response to induction chemotherapy in locoregionally advanced nasopharyngeal cancer: a randomized controlled trial substudy (NCT01245959).

BACKGROUND: In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone. METHODS: All patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts. RESULTS: Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25-0.74, p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction <  0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06-0.51, p <  0.001) and low ICTOS (n = 175, p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors. CONCLUSION: An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01245959 . Registered 23 November 2010.

Deep learning-based radiomics model can predict extranodal soft tissue metastasis in gastric cancer.

BACKGROUND: The potential prognostic value of extranodal soft tissue metastasis (ESTM) has been confirmed by increasing studies about gastric cancer (GC). However, the gold standard of ESTM is determined by pathologic examination after surgery, and there are no preoperative methods for assessment of ESTM yet. PURPOSE: This multicenter study aimed to develop a deep learning-based radiomics model to preoperatively identify ESTM and evaluate its prognostic value. METHODS: A total of 959 GC patients were enrolled from two centers and split into a training cohort (N = 551) and a test cohort (N = 236) for ESTM evaluation. Additionally, an external survival cohort (N = 172) was included for prognostic analysis. Four models were established based on clinical characteristics and multiphase computed tomography (CT) images for preoperative identification of ESTM, including a deep learning model, a hand-crafted radiomic model, a clinical model, and a combined model. C-index, decision curve, and calibration curve were utilized to assess the model performances. Survival analysis was conducted to explore the ability of stratifying overall survival (OS). RESULTS: The combined model showed good discrimination of the ESTM [C-indices (95% confidence interval, CI): 0.770 (0.729-0.812) and 0.761 (0.718-0.805) in training and test cohorts respectively], which outperformed deep learning model, radiomics model, and clinical model. The stratified analysis showed this model was not affected by patient's tumor size, the presence of lymphovascular invasion, and Lauren classification (p < 0.05). Moreover, the model score showed strong consistency with the OS [C-indices (95%CI): 0.723 (0.658-0.789, p < 0.0001) in the internal survival cohort and 0.715 (0.650-0.779, p < 0.0001) in the external survival cohort]. More interestingly, univariate analysis showed the model score was significantly associated with occult distant metastasis (p < 0.05) that was missed by preoperative diagnosis. CONCLUSIONS: The model combining CT images and clinical characteristics had an impressive predictive ability of both ESTM and prognosis, which has the potential to serve as an effective complement to the preoperative TNM staging system.

Radiomics and Deep Learning in Nasopharyngeal Carcinoma: A Review.

Nasopharyngeal carcinoma is a common head and neck malignancy with distinct clinical management compared to other types of cancer. Precision risk stratification and tailored therapeutic interventions are crucial to improving the survival outcomes. Artificial intelligence, including radiomics and deep learning, has exhibited considerable efficacy in various clinical tasks for nasopharyngeal carcinoma. These techniques leverage medical images and other clinical data to optimize clinical workflow and ultimately benefit patients. In this review, we provide an overview of the technical aspects and basic workflow of radiomics and deep learning in medical image analysis. We then conduct a detailed review of their applications to seven typical tasks in the clinical diagnosis and treatment of nasopharyngeal carcinoma, covering various aspects of image synthesis, lesion segmentation, diagnosis, and prognosis. The innovation and application effects of cutting-edge research are summarized. Recognizing the heterogeneity of the research field and the existing gap between research and clinical translation, potential avenues for improvement are discussed. We propose that these issues can be gradually addressed by establishing standardized large datasets, exploring the biological characteristics of features, and technological upgrades.

RemixFormer++: A Multi-modal Transformer Model for Precision Skin Tumor Differential Diagnosis with Memory-efficient Attention.

Diagnosing malignant skin tumors accurately at an early stage can be challenging due to ambiguous and even confusing visual characteristics displayed by various categories of skin tumors. To improve diagnosis precision, all available clinical data from multiple sources, particularly clinical images, dermoscopy images, and medical history, could be considered. Aligning with clinical practice, we propose a novel Transformer model, named Remix-Former++ that consists of a clinical image branch, a dermoscopy image branch, and a metadata branch. Given the unique characteristics inherent in clinical and dermoscopy images, specialized attention strategies are adopted for each type. Clinical images are processed through a top-down architecture, capturing both localized lesion details and global contextual information. Conversely, dermoscopy images undergo a bottom-up processing with two-level hierarchical encoders, designed to pinpoint fine-grained structural and textural features. A dedicated metadata branch seamlessly integrates non-visual information by encoding relevant patient data. Fusing features from three branches substantially boosts disease classification accuracy. RemixFormer++ demonstrates exceptional performance on four single-modality datasets (PAD-UFES-20, ISIC 2017/2018/2019). Compared with the previous best method using a public multi-modal Derm7pt dataset, we achieved an absolute 5.3% increase in averaged F1 and 1.2% in accuracy for the classification of five skin tumors. Furthermore, using a large-scale in-house dataset of 10,351 patients with the twelve most common skin tumors, our method obtained an overall classification accuracy of 92.6%. These promising results, on par or better with the performance of 191 dermatologists through a comprehensive reader study, evidently imply the potential clinical usability of our method.

A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma. METHODS: This multicenter, retrospective study included 921 patients with locally recurrent nasopharyngeal carcinoma. A machine learning signature and nomogram based on pretreatment magnetic resonance imaging features were developed for predicting overall survival in a training cohort and validated in 2 independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA-sequencing analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving concordance indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables statistically improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with statistically distinct overall survival rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-sequencing analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: A magnetic resonance imaging-based radiomic signature predicted overall survival more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for locally recurrent nasopharyngeal carcinoma patients.

Artificial intelligence in gastric cancer: applications and challenges.

Gastric cancer (GC) is one of the most common malignant tumors with high mortality. Accurate diagnosis and treatment decisions for GC rely heavily on human experts' careful judgments on medical images. However, the improvement of the accuracy is hindered by imaging conditions, limited experience, objective criteria, and inter-observer discrepancies. Recently, the developments of machine learning, especially deep-learning algorithms, have been facilitating computers to extract more information from data automatically. Researchers are exploring the far-reaching applications of artificial intelligence (AI) in various clinical practices, including GC. Herein, we aim to provide a broad framework to summarize current research on AI in GC. In the screening of GC, AI can identify precancerous diseases and assist in early cancer detection with endoscopic examination and pathological confirmation. In the diagnosis of GC, AI can support tumor-node-metastasis (TNM) staging and subtype classification. For treatment decisions, AI can help with surgical margin determination and prognosis prediction. Meanwhile, current approaches are challenged by data scarcity and poor interpretability. To tackle these problems, more regulated data, unified processing procedures, and advanced algorithms are urgently needed to build more accurate and robust AI models for GC.

Knowledge-guided multi-task attention network for survival risk prediction using multi-center computed tomography images.

Accurate preoperative prediction of overall survival (OS) risk of human cancers based on CT images is greatly significant for personalized treatment. Deep learning methods have been widely explored to improve automated prediction of OS risk. However, the accuracy of OS risk prediction has been limited by prior existing methods. To facilitate capturing survival-related information, we proposed a novel knowledge-guided multi-task network with tailored attention modules for OS risk prediction and prediction of clinical stages simultaneously. The network exploits useful information contained in multiple learning tasks to improve prediction of OS risk. Three multi-center datasets, including two gastric cancer datasets with 459 patients, and a public American lung cancer dataset with 422 patients, are used to evaluate our proposed network. The results show that our proposed network can boost its performance by capturing and sharing information from other predictions of clinical stages. Our method outperforms the state-of-the-art methods with the highest geometrical metric. Furthermore, our method shows better prognostic value with the highest hazard ratio for stratifying patients into high- and low-risk groups. Therefore, our proposed method may be exploited as a potential tool for the improvement of personalized treatment.

Deep learning-based AI model for signet-ring cell carcinoma diagnosis and chemotherapy response prediction in gastric cancer.

PURPOSE: We aimed to develop a noninvasive artificial intelligence (AI) model to diagnose signet-ring cell carcinoma (SRCC) of gastric cancer (GC) and identify patients with SRCC who could benefit from postoperative chemotherapy based on preoperative contrast-enhanced computed tomography (CT). METHODS: A total of 855 GC patients with 855 single GCs were included, of which 249 patients were diagnosed as SRCC by histopathologic examinations. The AI model was generated with clinical, handcrafted radiomic, and deep learning features. Model diagnostic performance was measured by area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, while predictive performance was measured by Kaplan-Meier curves. RESULTS: In the test cohort (n = 257), the AUC, sensitivity, and specificity of our AI model for diagnosing SRCC were 0.786 (95% CI: 0.721-0.845), 77.3%, and 69.2%, respectively. For the entire cohort, patients with AI-predicted high risk had a significantly shorter median OS compared with those with low risk (median overall survival [OS], 38.8 vs. 64.2 months, p = 0.009). Importantly, in pathologically confirmed advanced SRCC patients, AI-predicted high-risk status was indicative of a shorter overall survival (median overall survival [OS], 31.0 vs. 54.4 months, p = 0.036) and marked chemotherapy resistance, whereas AI-predicted low-risk status had substantial chemotherapy benefit (median OS [without vs. with chemotherapy], 26.0 vs. not reached, p = 0.013). CONCLUSIONS: The CT-based AI model demonstrated good performance for diagnosing SRCC, stratifying patient prognosis, and predicting chemotherapy responses. Advanced SRCC patients with AI-predicted low-risk status may benefit substantially from adjuvant chemotherapy.

Multi-Focus Network to Decode Imaging Phenotype for Overall Survival Prediction of Gastric Cancer Patients.

Gastric cancer (GC) is the third leading cause of cancer-associated deaths globally. Accurate risk prediction of the overall survival (OS) for GC patients shows significant prognostic value, which helps identify and classify patients into different risk groups to benefit from personalized treatment. Many methods based on machine learning algorithms have been widely explored to predict the risk of OS. However, the accuracy of risk prediction has been limited and remains a challenge with existing methods. Few studies have proposed a framework and pay attention to the low-level and high-level features separately for the risk prediction of OS based on computed tomography images of GC patients. To achieve high accuracy, we propose a multi-focus fusion convolutional neural network. The network focuses on low-level and high-level features, where a subnet to focus on lower-level features and the other enhanced subnet with lateral connection to focus on higher-level semantic features. Three independent datasets of 640 GC patients are used to assess our method. Our proposed network is evaluated by metrics of the concordance index and hazard ratio. Our network outperforms state-of-the-art methods with the highest concordance index and hazard ratio in independent validation and test sets. Our results prove that our architecture can unify the separate low-level and high-level features into a single framework, and can be a powerful method for accurate risk prediction of OS.

A deep learning-based radiomic nomogram for prognosis and treatment decision in advanced nasopharyngeal carcinoma: A multicentre study.

BACKGROUND: Induction chemotherapy (ICT) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Currently, the choice of them remains equivocal in clinical practice. We aimed to develop a deep learning-based model for treatment decision in NPC. METHODS: A total of 1872 patients with stage T3N1M0 NPC were enrolled from four Chinese centres and received either ICT+CCRT or CCRT. A nomogram was constructed for predicting the prognosis of patients with different treatment regimens using multi-task deep learning radiomics and pre-treatment MR images, based on which an optimal treatment regimen was recommended. Model performance was assessed by the concordance index (C-index) and the Kaplan-Meier estimator. FINDINGS: The nomogram showed excellent prognostic ability for disease-free survival in both the CCRT (C-index range: 0.888-0.921) and ICT+CCRT (C-index range: 0.784-0.830) groups. According to the prognostic difference between treatments using the nomogram, patients were divided into the ICT-preferred and CCRT-preferred groups. In the ICT-preferred group, patients receiving ICT+CCRT exhibited prolonged survival over those receiving CCRT in the internal and external test cohorts (hazard ratio [HR]: 0.17, p<0.001 and 0.24, p=0.02); while the trend was opposite in the CCRT-preferred group (HR: 6.24, p<0.001 and 12.08, p<0.001). Similar results for treatment decision using the nomogram were obtained in different subgroups stratified by clinical factors and MR acquisition parameters. INTERPRETATION: Our nomogram could predict the prognosis of T3N1M0 NPC patients with different treatment regimens and accordingly recommend an optimal treatment regimen, which may serve as a potential tool for promoting personalized treatment of NPC. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, Beijing Natural Science Foundation, Strategic Priority Research Program of CAS, Project of High-Level Talents Team Introduction in Zhuhai City, Beijing Natural Science Foundation, Beijing Nova Program, Youth Innovation Promotion Association CAS.

Multi-Habitat Based Radiomics for the Prediction of Treatment Response to Concurrent Chemotherapy and Radiation Therapy in Locally Advanced Cervical Cancer.

Objectives: To develop a radiomic model based on multiparametric magnetic resonance imaging (MRI) for predicting treatment response prior to commencing concurrent chemotherapy and radiation therapy (CCRT) for locally advanced cervical cancer. Materials and methods: The retrospective study enrolled 120 patients (allocated to a training or a test set) with locally advanced cervical cancer who underwent CCRT between December 2014 and June 2017. All patients enrolled underwent MRI with nine sequences before treatment and again at the end of the fourth week of treatment. Responses were evaluated by MRI according to RECIST standards, and patients were divided into a responder group or non-responder group. For every MRI sequence, a total of 114 radiomic features were extracted from the outlined tumor habitat. On the training set, the least absolute shrinkage and selection operator method was used to select key features and to construct nine habitat signatures. Then, three kinds of machine learning models were compared and applied to integrate these predictive signatures and the clinical characteristics into a radiomic model. The discrimination ability, reliability, and calibration of our radiomic model were evaluated. Results: The radiomic model, which consisted of three habitat signatures from sagittal T2 image, axial T1 enhanced-MRI image, and ADC image, respectively, has shown good predictive performance, with area under the curve of 0.820 (95% CI: 0.713-0.927) in the training set and 0.798 (95% CI: 0.678-0.917) in the test set. Meanwhile, the model proved to perform better than each single signature or clinical characteristic. Conclusions: A radiomic model employing features from multiple tumor habitats held the ability for predicting treatment response in patients with locally advanced cervical cancer before commencing CCRT. These results illustrated a potential new tool for improving medical decision-making and therapeutic strategies.

A deep learning MR-based radiomic nomogram may predict survival for nasopharyngeal carcinoma patients with stage T3N1M0.

PURPOSE: To estimate the prognostic value of deep learning (DL) magnetic resonance (MR)-based radiomics for stage T3N1M0 nasopharyngeal carcinoma (NPC) patients receiving induction chemotherapy (ICT) prior to concurrent chemoradiotherapy (CCRT). METHODS: A total of 638 stage T3N1M0 NPC patients (training cohort: n = 447; test cohort: n = 191) were enrolled and underwent MRI scans before receiving ICT + CCRT. From the pretreatment MR images, DL-based radiomic signatures were developed to predict disease-free survival (DFS) in an end-to-end way. Incorporating independent clinical prognostic parameters and radiomic signatures, a radiomic nomogram was built through multivariable Cox proportional hazards method. The discriminative performance of the radiomic nomogram was assessed using the concordance index (C-index) and the Kaplan-Meier estimator. RESULTS: Three DL-based radiomic signatures were significantly correlated with DFS in the training (C-index: 0.695-0.731, all p < 0.001) and test (C-index: 0.706-0.755, all p < 0.001) cohorts. Integrating radiomic signatures with clinical factors significantly improved the predictive value compared to the clinical model in the training (C-index: 0.771 vs. 0.640, p < 0.001) and test (C-index: 0.788 vs. 0.625, p = 0.001) cohorts. Furthermore, risk stratification using the radiomic nomogram demonstrated that the high-risk group exhibited short-lived DFS compared to the low-risk group in the training cohort (hazard ratio [HR]: 6.12, p < 0.001), which was validated in the test cohort (HR: 6.90, p < 0.001). CONCLUSIONS: Our DL-based radiomic nomogram may serve as a noninvasive and useful tool for pretreatment prognostic prediction and risk stratification in stage T3N1M0 NPC.

A deep-learning-based prognostic nomogram integrating microscopic digital pathology and macroscopic magnetic resonance images in nasopharyngeal carcinoma: a multi-cohort study.

BACKGROUND: To explore the prognostic value of radiomics-based and digital pathology-based imaging biomarkers from macroscopic magnetic resonance imaging (MRI) and microscopic whole-slide images for patients with nasopharyngeal carcinoma (NPC). METHODS: We recruited 220 NPC patients and divided them into training (n = 132), internal test (n = 44), and external test (n = 44) cohorts. The primary endpoint was failure-free survival (FFS). Radiomic features were extracted from pretreatment MRI and selected and integrated into a radiomic signature. The histopathological signature was extracted from whole-slide images of biopsy specimens using an end-to-end deep-learning method. Incorporating two signatures and independent clinical factors, a multi-scale nomogram was constructed. We also tested the correlation between the key imaging features and genetic alternations in an independent cohort of 16 patients (biological test cohort). RESULTS: Both radiomic and histopathologic signatures presented significant associations with treatment failure in the three cohorts (C-index: 0.689-0.779, all p < 0.050). The multi-scale nomogram showed a consistent significant improvement for predicting treatment failure compared with the clinical model in the training (C-index: 0.817 versus 0.730, p < 0.050), internal test (C-index: 0.828 versus 0.602, p < 0.050) and external test (C-index: 0.834 versus 0.679, p < 0.050) cohorts. Furthermore, patients were stratified successfully into two groups with distinguishable prognosis (log-rank p < 0.0010) using our nomogram. We also found that two texture features were related to the genetic alternations of chromatin remodeling pathways in another independent cohort. CONCLUSION: The multi-scale imaging features showed a complementary value in prognostic prediction and may improve individualized treatment in NPC.

Multiplanar MRI-Based Predictive Model for Preoperative Assessment of Lymph Node Metastasis in Endometrial Cancer.

Introduction: Assessment of lymph node metastasis (LNM) is crucial for treatment decision and prognosis prediction for endometrial cancer (EC). However, the sensitivity of the routinely used magnetic resonance imaging (MRI) is low in assessing normal-sized LNM (diameter, 0-0.8 cm). We aimed to develop a predictive model based on magnetic resonance (MR) images and clinical parameters to predict LNM in normal-sized lymph nodes (LNs). Materials and Methods: A total of 200 retrospective patients were enrolled and divided into a training cohort (n = 140) and a test cohort (n = 60). All patients underwent preoperative MRI and had pathological result of LNM status. In total, 4,179 radiomic features were extracted. Four models including a clinical model, a radiomic model, and two combined models were built. Area under the receiver operating characteristic (ROC) curves (AUC) and calibration curves were used to assess these models. Subgroup analysis was performed according to LN size. All patients underwent surgical staging and had pathological results. Results: All of the four models showed predictive ability in LNM. One of the combined models, ModelCR1, consisting of radiomic features, LN size, and cancer antigen 125, showed the best discrimination ability on the training cohort [AUC, 0.892; 95% confidence interval [CI], 0.834-0.951] and test cohort (AUC, 0.883; 95% CI, 0.786-0.980). The subgroup analysis showed that this model also indicated good predictive ability in normal-sized LNs (0.3-0.8 cm group, accuracy = 0.846; <0.3 cm group, accuracy = 0.849). Furthermore, compared with the routinely preoperative MR report, the sensitivity and accuracy of this model had a great improvement. Conclusions: A predictive model was proposed based on MR radiomic features and clinical parameters for LNM in EC. The model had a good discrimination ability, especially for normal-sized LNs.

Radiomic analysis for preoperative prediction of cervical lymph node metastasis in patients with papillary thyroid carcinoma.

PURPOSE: Cervical lymph node (LN) metastasis of papillary thyroid carcinoma (PTC) is critical for treatment and prognosis. We explored the feasibility of using radiomics to preoperatively predict cervical LN metastasis in PTC patients. METHOD: Total 221 PTC patients (training cohort: n = 154; validation cohort: n = 67; divided randomly at the ratio of 7:3) were enrolled and divided into 2 groups based on LN pathologic diagnosis (N0: n = 118; N1a and N1b: n = 88 and 15, respectively). We extracted 546 radiomic features from non-contrast and venous contrast-enhanced computed tomography (CT) images. We selected 8 groups of candidate feature sets by minimum redundancy maximum relevance (mRMR), and obtained 8 radiomic sub-signatures by support vector machine (SVM) to construct the radiomic signature. Incorporating the radiomic signature, CT-reported cervical LN status and clinical risk factors, a nomogram was constructed using multivariable logistic regression. The nomogram's calibration, discrimination, and clinical utility were assessed. RESULTS: The radiomic signature was associated significantly with cervical LN status (p < 0.01 for both training and validation cohorts). The radiomic signature showed better predictive performance than any radiomic sub-signatures devised by SVM. Addition of radiomic signature to the nomogram improved the predictive value (area under the curve (AUC), 0.807 to 0.867) in the training cohort; this was confirmed in an independent validation cohort (AUC, 0.795 to 0.822). Good agreement was observed using calibration curves in both cohorts. Decision curve analysis demonstrated the radiomic nomogram was worthy of clinical application. CONCLUSIONS: Our radiomic nomogram improved the preoperative prediction of cervical LN metastasis in PTC patients.

Using biparametric MRI radiomics signature to differentiate between benign and malignant prostate lesions.

PURPOSE: To investigate the efficiency of radiomics signature in discriminating between benign and malignant prostate lesions with similar biparametric magnetic resonance imaging (bp-MRI) findings. EXPERIMENTAL DESIGN: Our study consisted of 331 patients underwent bp-MRI before pathological examination from January 2013 to November 2016. Radiomics features were extracted from peripheral zone (PZ), transition zone (TZ), and lesion areas segmented on images obtained by T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and its derivative apparent-diffusion coefficient (ADC) imaging. The individual prediction model, built using the clinical data and biparametric MRI features (Bp signature), was prepared using data of 232 patients and validated using data of 99 patients. The predictive performance was calculated and demonstrated using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. RESULTS: The Bp signature, based on the six selected radiomics features of bp-MRI, showed better discrimination in the validation cohort (area under the curve [AUC], 0.92) than on each subcategory images (AUC, 0.81 on T2WI; AUC, 0.77 on DWI; AUC, 0.89 on ADC). The differential diagnostic efficiency was poorer with the clinical model (AUC, 0.73), built using the selected independent clinical risk factors with statistical significance (P < 0.05), than with the Bp signature. Discrimination efficiency improved when including the Bp signature and clinical factors [i.e., the individual prediction model (AUC, 0.93)]. CONCLUSION: The Bp signature, based on bp-MRI, performed better than each single imaging modality. The individual prediction model including the radiomics signatures and clinical factors showed better preoperative diagnostic performance, which could contribute to clinical individualized treatment.