Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

Imaging segmentation mechanism for rectal tumors using improved U-Net.

OBJECTIVE: In radiation therapy, cancerous region segmentation in magnetic resonance images (MRI) is a critical step. For rectal cancer, the automatic segmentation of rectal tumors from an MRI is a great challenge. There are two main shortcomings in existing deep learning-based methods that lead to incorrect segmentation: 1) there are many organs surrounding the rectum, and the shape of some organs is similar to that of rectal tumors; 2) high-level features extracted by conventional neural networks often do not contain enough high-resolution information. Therefore, an improved U-Net segmentation network based on attention mechanisms is proposed to replace the traditional U-Net network. METHODS: The overall framework of the proposed method is based on traditional U-Net. A ResNeSt module was added to extract the overall features, and a shape module was added after the encoder layer. We then combined the outputs of the shape module and the decoder to obtain the results. Moreover, the model used different types of attention mechanisms, so that the network learned information to improve segmentation accuracy. RESULTS: We validated the effectiveness of the proposed method using 3773 2D MRI datasets from 304 patients. The results showed that the proposed method achieved 0.987, 0.946, 0.897, and 0.899 for Dice, MPA, MioU, and FWIoU, respectively; these values are significantly better than those of other existing methods. CONCLUSION: Due to time savings, the proposed method can help radiologists segment rectal tumors effectively and enable them to focus on patients whose cancerous regions are difficult for the network to segment. SIGNIFICANCE: The proposed method can help doctors segment rectal tumors, thereby ensuring good diagnostic quality and accuracy.

Comprehensively analysis of splicing factors to construct prognosis prediction classifier in prostate cancer.

Splicing factors (SFs) are proteins that control the alternative splicing (AS) of RNAs, which have been recognized as new cancer hallmarks. Their dysregulation has been found to be involved in many biological processes of cancer, such as carcinogenesis, proliferation, metastasis and senescence. Dysregulation of SFs has been demonstrated to contribute to the progression of prostate cancer (PCa). However, a comprehensive analysis of the prognosis value of SFs in PCa is limited. In this work, we systematically analysed 393 SFs to deeply characterize the expression patterns, clinical relevance and biological functions of SFs in PCa. We identified 53 survival-related SFs that can stratify PCa into two de nove molecular subtypes with distinct mRNA expression and AS-event expression patterns and displayed significant differences in pathway activity and clinical outcomes. An SF-based classifier was established using LASSO-COX regression with six key SFs (BCAS1, LSM3, DHX16, NOVA2, RBM47 and SNRPN), which showed promising prognosis-prediction performance with a receiver operating characteristic (ROC) >0.700 in both the training and testing datasets, as well as in three external PCa cohorts (DKFZ, GSE70769 and GSE21035). CRISPR/CAS9 screening data and cell-level functional analysis suggested that LSM3 and DHX16 are essential factors for the proliferation and cell cycle progression in PCa cells. This study proposes that SFs and AS events are potential multidimensional biomarkers for the diagnosis, prognosis and treatment of PCa.

An MRI-based scoring system for pretreatment risk stratification in locally advanced rectal cancer.

BACKGROUND: Accurately assessing the risk of recurrence in patients with locally advanced rectal cancer (LARC) before treatment is important for the development of treatment strategies. The purpose of this study is to develop an MRI-based scoring system to predict the risk of recurrence in patients with LARC. METHODS: This was a multicenter observational study that enrolled participants who underwent neoadjuvant chemoradiotherapy. To evaluate the risk of recurrence in these patients, we developed the mrDEC scoring system and assessed inter-reader agreement. Additionally, we plotted Kaplan-Meier curves to compare the 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates among patients with different mrDEC scores. RESULTS: A total of 1287 patients with LARC were included in this study. We observed substantial inter-reader agreement for mrDEC. Based on the mrDEC scores ranging from 0 to 3, the patients were categorized into four groups. The 3-year DFS rates for the groups were 91.0%, 79.5%, 65.5%, and 44.0% (P < 0.0001), respectively, and the 5-year OS rates were 92.9%, 87.1%, 74.8%, and 44.5%, respectively (P < 0.0001). CONCLUSIONS: The mrDEC scoring system proved to be an effective tool for predicting the prognosis of patients with LARC and can assist clinicians in clinical decision-making.

MRI-based Quantification of Intratumoral Heterogeneity for Predicting Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer.

Background Breast cancer is highly heterogeneous, resulting in different treatment responses to neoadjuvant chemotherapy (NAC) among patients. A noninvasive quantitative measure of intratumoral heterogeneity (ITH) may be valuable for predicting treatment response. Purpose To develop a quantitative measure of ITH on pretreatment MRI scans and test its performance for predicting pathologic complete response (pCR) after NAC in patients with breast cancer. Materials and Methods Pretreatment MRI scans were retrospectively acquired in patients with breast cancer who received NAC followed by surgery at multiple centers from January 2000 to September 2020. Conventional radiomics (hereafter, C-radiomics) and intratumoral ecological diversity features were extracted from the MRI scans, and output probabilities of imaging-based decision tree models were used to generate a C-radiomics score and ITH index. Multivariable logistic regression analysis was used to identify variables associated with pCR, and significant variables, including clinicopathologic variables, C-radiomics score, and ITH index, were combined into a predictive model for which performance was assessed using the area under the receiver operating characteristic curve (AUC). Results The training data set was comprised of 335 patients (median age, 48 years [IQR, 42-54 years]) from centers A and B, and 590, 280, and 384 patients (median age, 48 years [IQR, 41-55 years]) were included in the three external test data sets. Molecular subtype (odds ratio [OR] range, 4.76-8.39 [95% CI: 1.79, 24.21]; all P < .01), ITH index (OR, 30.05 [95% CI: 8.43, 122.64]; P < .001), and C-radiomics score (OR, 29.90 [95% CI: 12.04, 81.70]; P < .001) were independently associated with the odds of achieving pCR. The combined model showed good performance for predicting pCR to NAC in the training data set (AUC, 0.90) and external test data sets (AUC range, 0.83-0.87). Conclusion A model that combined an index created from pretreatment MRI-based imaging features quantitating ITH, C-radiomics score, and clinicopathologic variables showed good performance for predicting pCR to NAC in patients with breast cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rauch in this issue.

Using Machine Learning Methods to Assess Lymphovascular Invasion and Survival in Breast Cancer: Performance of Combining Preoperative Clinical and MRI Characteristics.

BACKGROUND: Preoperative assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) is of high clinical relevance for treatment decision-making and prognosis. PURPOSE: To investigate the associations of preoperative clinical and magnetic resonance imaging (MRI) characteristics with LVI and disease-free survival (DFS) by using machine learning methods in patients with IBC. STUDY TYPE: Retrospective. POPULATION: Five hundred and seventy-five women (range: 24-79 years) with IBC who underwent preoperative MRI examinations at two hospitals, divided into the training (N = 386) and validation datasets (N = 189). FIELD STRENGTH/SEQUENCE: Axial fat-suppressed T2-weighted turbo spin-echo sequence and dynamic contrast-enhanced with fat-suppressed T1-weighted three-dimensional gradient echo imaging. ASSESSMENT: MRI characteristics (clinical T stage, breast edema score, MRI axillary lymph node status, multicentricity or multifocality, enhancement pattern, adjacent vessel sign, and increased ipsilateral vascularity) were reviewed independently by three radiologists. Logistic regression (LR), eXtreme Gradient Boosting (XGBoost), k-Nearest Neighbor (KNN), and Support Vector Machine (SVM) algorithms were used to establish the models by combing preoperative clinical and MRI characteristics for assessing LVI status in the training dataset, and the methods were further applied in the validation dataset. The LVI score was calculated using the best-performing of the four models to analyze the association with DFS. STATISTICAL TESTS: Chi-squared tests, variance inflation factors, receiver operating characteristics (ROC), Kaplan-Meier curve, log-rank, Cox regression, and intraclass correlation coefficient were performed. The area under the ROC curve (AUC) and hazard ratios (HR) were calculated. A P-value <0.05 was considered statistically significant. RESULTS: The model established by the XGBoost algorithm had better performance than LR, SVM, and KNN models, achieving an AUC of 0.832 (95% confidence interval [CI]: 0.789, 0.876) in the training dataset and 0.838 (95% CI: 0.775, 0.901) in the validation dataset. The LVI score established by the XGBoost model was an independent indicator of DFS (adjusted HR: 2.66, 95% CI: 1.22-5.80). DATA CONCLUSION: The XGBoost model based on preoperative clinical and MRI characteristics may help to investigate the LVI status and survival in patients with IBC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Dual parallel net: A novel deep learning model for rectal tumor segmentation via CNN and transformer with Gaussian Mixture prior.

Segmentation of rectal cancerous regions from Magnetic Resonance (MR) images can help doctor define the extent of the rectal cancer and judge the severity of rectal cancer, so rectal tumor segmentation is crucial to improve the accuracy of rectal cancer diagnosis. However, accurate segmentation of rectal cancerous regions remains a challenging task due to the shape of rectal tumor has significant variations and the tumor and surrounding tissue are indistinguishable. In addition, in the early research on rectal tumor segmentation, most deep learning methods were based on convolutional neural networks (CNNs), and traditional CNN have small receptive field, which can only capture local information while ignoring the global information of the image. Nevertheless, the global information plays a crucial role in rectal tumor segmentation, so traditional CNN-based methods usually cannot achieve satisfactory segmentation results. In this paper, we propose an encoder-decoder network named Dual Parallel Net (DuPNet), which fuses transformer and classical CNN for capturing both global and local information. Meanwhile, as for capture features at different scales as well as to avoid accuracy loss and parameters reduction, we design a feature adaptive block (FAB) in skip connection between encoder and decoder. Furthermore, in order to utilize the apriori information of rectal tumor shape effectively, we design a Gaussian Mixture prior and embed it in self-attention mechanism of the transformer, leading to robust feature representation and accurate segmentation results. We have performed extensive ablation experiments to verify the effectiveness of our proposed dual parallel encoder, FAB and Gaussian Mixture prior on the dataset from the Shanxi Cancer Hospital. In the experimental comparison with the state-of-the-art methods, our method achieved a Mean Intersection over Union (MIoU) of 89.34% on the test set. In addition to that, we evaluated the generalizability of our method on the dataset from Xinhua Hospital, the promising results verify the superiority of our method.

An integrated deep learning model for the prediction of pathological complete response to neoadjuvant chemotherapy with serial ultrasonography in breast cancer patients: a multicentre, retrospective study.

BACKGROUND: The biological phenotype of tumours evolves during neoadjuvant chemotherapy (NAC). Accurate prediction of pathological complete response (pCR) to NAC in the early-stage or posttreatment can optimize treatment strategies or improve the breast-conserving rate. This study aimed to develop and validate an autosegmentation-based serial ultrasonography assessment system (SUAS) that incorporated serial ultrasonographic features throughout the NAC of breast cancer to predict pCR. METHODS: A total of 801 patients with biopsy-proven breast cancer were retrospectively enrolled from three institutions and were split into a training cohort (242 patients), an internal validation cohort (197 patients), and two external test cohorts (212 and 150 patients). Three imaging signatures were constructed from the serial ultrasonographic features before (pretreatment signature), during the first-second cycle of (early-stage treatment signature), and after (posttreatment signature) NAC based on autosegmentation by U-net. The SUAS was constructed by subsequently integrating the pre, early-stage, and posttreatment signatures, and the incremental performance was analysed. RESULTS: The SUAS yielded a favourable performance in predicting pCR, with areas under the receiver operating characteristic curve (AUCs) of 0.927 [95% confidence interval (CI) 0.891-0.963] and 0.914 (95% CI 0.853-0.976), compared with those of the clinicopathological prediction model [0.734 (95% CI 0.665-0.804) and 0.610 (95% CI 0.504-0.716)], and radiologist interpretation [0.632 (95% CI 0.570-0.693) and 0.724 (95% CI 0.644-0.804)] in the external test cohorts. Furthermore, similar results were also observed in the early-stage treatment of NAC [AUC 0.874 (0.793-0.955)-0.897 (0.851-0.943) in the external test cohorts]. CONCLUSIONS: We demonstrate that autosegmentation-based SAUS integrating serial ultrasonographic features throughout NAC can predict pCR with favourable performance, which can facilitate individualized treatment strategies.

Chemotherapy induces ACE2 expression in breast cancer via the ROS-AKT-HIF-1α signaling pathway: a potential prognostic marker for breast cancer patients receiving chemotherapy.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system and a well-known functional receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The COVID-19 pandemic has brought ACE2 into the spotlight, and ACE2 expression in tumors and its relationship with SARS-COV-2 infection and prognosis of cancer patients have received extensive attention. However, the association between ACE2 expression and tumor therapy and prognosis, especially in breast cancer, remains ambiguous and requires further investigation. We have previously reported that ACE2 is elevated in drug-resistant breast cancer cells, but the exact function of ACE2 in drug resistance and progression of this malignant disease has not been explored. METHODS: The expression of ACE2 and HIF-1α in parental and drug-resistant breast cancer cells under normoxic and hypoxic conditions was analyzed by Western blot and qRT-PCR methods. The protein levels of ACE2 in plasma samples from breast cancer patients were examined by ELISA. The relationship between ACE2 expression and breast cancer treatment and prognosis was analyzed using clinical specimens and public databases. The reactive oxygen species (ROS) levels in breast cancer cells were measured by using a fluorescent probe. Small interfering RNAs (siRNAs) or lentivirus-mediated shRNA was used to silence ACE2 and HIF-1α expression in cellular models. The effect of ACE2 knockdown on drug resistance in breast cancer was determined by Cell Counting Kit 8 (CCK-8)-based assay, colony formation assay, apoptosis and EdU assay. RESULTS: ACE2 expression is relatively low in breast cancer cells, but increases rapidly and specifically after exposure to anticancer drugs, and remains high after resistance is acquired. Mechanistically, chemotherapeutic agents increase ACE2 expression in breast cancer cells by inducing intracellular ROS production, and increased ROS levels enhance AKT phosphorylation and subsequently increase HIF-1α expression, which in turn upregulates ACE2 expression. Although ACE2 levels in plasma and cancer tissues are lower in breast cancer patients compared with healthy controls, elevated ACE2 in patients after chemotherapy is a predictor of poor treatment response and an unfavorable prognostic factor for survival in breast cancer patients. CONCLUSION: ACE2 is a gene in breast cancer cells that responds rapidly to chemotherapeutic agents through the ROS-AKT-HIF-1α axis. Elevated ACE2 modulates the sensitivity of breast cancer cells to anticancer drugs by optimizing the balance of intracellular ROS. Moreover, increased ACE2 is not only a predictor of poor response to chemotherapy, but is also associated with a worse prognosis in breast cancer patients. Thus, our findings provide novel insights into the spatiotemporal differences in the function of ACE2 in the initiation and progression of breast cancer.

Automated whole-slide images assessment of immune infiltration in resected non-small-cell lung cancer: towards better risk-stratification.

BACKGROUND: High immune infiltration is associated with favourable prognosis in patients with non-small-cell lung cancer (NSCLC), but an automated workflow for characterizing immune infiltration, with high validity and reliability, remains to be developed. METHODS: We performed a multicentre retrospective study of patients with completely resected NSCLC. We developed an image analysis workflow for automatically evaluating the density of CD3+ and CD8+ T-cells in the tumour regions on immunohistochemistry (IHC)-stained whole-slide images (WSIs), and proposed an immune scoring system "I-score" based on the automated assessed cell density. RESULTS: A discovery cohort (n = 145) and a validation cohort (n = 180) were used to assess the prognostic value of the I-score for disease-free survival (DFS). The I-score (two-category) was an independent prognostic factor after adjusting for other clinicopathologic factors. Compared with a low I-score (two-category), a high I-score was associated with significantly superior DFS in the discovery cohort (adjusted hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.33-0.86; P = 0.010) and validation cohort (adjusted HR, 0.57; 95% CI 0.36-0.92; P = 0.022). The I-score improved the prognostic stratification when integrating it into the Cox proportional hazard regression models with other risk factors (discovery cohort, C-index 0.742 vs. 0.728; validation cohort, C-index 0.695 vs. 0.685). CONCLUSION: This automated workflow and immune scoring system would advance the clinical application of immune microenvironment evaluation and support the clinical decision making for patients with resected NSCLC.

Multi-scale pathology image texture signature is a prognostic factor for resectable lung adenocarcinoma: a multi-center, retrospective study.

BACKGROUND: Tumor histomorphology analysis plays a crucial role in predicting the prognosis of resectable lung adenocarcinoma (LUAD). Computer-extracted image texture features have been previously shown to be correlated with outcome. However, a comprehensive, quantitative, and interpretable predictor remains to be developed. METHODS: In this multi-center study, we included patients with resectable LUAD from four independent cohorts. An automated pipeline was designed for extracting texture features from the tumor region in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) at multiple magnifications. A multi-scale pathology image texture signature (MPIS) was constructed with the discriminative texture features in terms of overall survival (OS) selected by the LASSO method. The prognostic value of MPIS for OS was evaluated through univariable and multivariable analysis in the discovery set (n = 111) and the three external validation sets (V1, n = 115; V2, n = 116; and V3, n = 246). We constructed a Cox proportional hazards model incorporating clinicopathological variables and MPIS to assess whether MPIS could improve prognostic stratification. We also performed histo-genomics analysis to explore the associations between texture features and biological pathways. RESULTS: A set of eight texture features was selected to construct MPIS. In multivariable analysis, a higher MPIS was associated with significantly worse OS in the discovery set (HR 5.32, 95%CI 1.72-16.44; P = 0.0037) and the three external validation sets (V1: HR 2.63, 95%CI 1.10-6.29, P = 0.0292; V2: HR 2.99, 95%CI 1.34-6.66, P = 0.0075; V3: HR 1.93, 95%CI 1.15-3.23, P = 0.0125). The model that integrated clinicopathological variables and MPIS had better discrimination for OS compared to the clinicopathological variables-based model in the discovery set (C-index, 0.837 vs. 0.798) and the three external validation sets (V1: 0.704 vs. 0.679; V2: 0.728 vs. 0.666; V3: 0.696 vs. 0.669). Furthermore, the identified texture features were associated with biological pathways, such as cytokine activity, structural constituent of cytoskeleton, and extracellular matrix structural constituent. CONCLUSIONS: MPIS was an independent prognostic biomarker that was robust and interpretable. Integration of MPIS with clinicopathological variables improved prognostic stratification in resectable LUAD and might help enhance the quality of individualized postoperative care.

Multiparametric MRI-based radiomics nomogram for preoperative prediction of lymphovascular invasion and clinical outcomes in patients with breast invasive ductal carcinoma.

OBJECTIVE: To develop a multiparametric MRI-based radiomics nomogram for predicting lymphovascular invasion (LVI) status and clinical outcomes in patients with breast invasive ductal carcinoma (IDC). METHODS: A total of 160 patients with pathologically confirmed breast IDC (training cohort: n = 112; validation cohort: n = 48) who underwent preoperative breast MRI were included. Imaging features were extracted from T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) maps, and contrast-enhanced T1-weighted imaging (cT1WI) sequences. A four-step procedure was applied for feature selection and radiomics signature building. Univariate and multivariate logistic regression analyses were conducted to identify the features associated with LVI, which were then incorporated into the radiomics nomogram. The performance of the nomogram was evaluated by its discrimination, calibration, and clinical usefulness. Kaplan-Meier survival curves based on the two radiomics models were used to estimate disease-free survival (DFS). RESULTS: The fusion radiomics signature of the T2WI, cT1WI, and ADC maps achieved a better predictive efficacy for LVI than either of them alone. The proposed radiomics nomogram, incorporating the fusion radiomics signature and MRI-reported peritumoral edema, showed satisfactory capabilities of calibration and discrimination in both training and validation datasets, with AUCs of 0.919 (95% CI: 0.871-0.967) and 0.863 (95% CI: 0.726-0.999), respectively. The radiomics signature and nomogram-defined high-risk groups had a shorter DFS than those in the low-risk groups (both p < 0.05). Higher Rad-scores were independently associated with a worse DFS in the whole cohort (p < 0.05). CONCLUSIONS: The proposed nomogram, incorporating multiparametric MRI-based radiomics signature and MRI-reported peritumoral edema, achieved a satisfactory preoperative prediction of LVI and clinical outcomes in IDC patients. KEY POINTS: • The fusion radiomics signature of the T2WI, cT1WI, and ADC maps achieved a better predictive efficacy for LVI than either of them alone. • The proposed nomogram achieved a favorable prediction of LVI in IDC patients with AUCs of 0.919 and 0.863 in the training and validation datasets, respectively. • The radiomics model could classify patients into high- and low-risk groups with significant differences in DFS.

MRI characteristics of breast edema for assessing axillary lymph node burden in early-stage breast cancer: a retrospective bicentric study.

OBJECTIVES: To investigate whether breast edema characteristics at preoperative T2-weighted imaging (T2WI) could help evaluate axillary lymph node (ALN) burden in patients with early-stage breast cancer. METHODS: This retrospective study included women with clinical T1 and T2 stage breast cancer and preoperative MRI examination in two independent cohorts from May 2014 to December 2020. Low (< 3 LNs+) and high (≥ 3 LNs+) pathological ALN (pALN) burden were recorded as endpoint. Breast edema score (BES) was evaluated at T2WI. Univariable and multivariable analyses were performed by the logistic regression model. The added predictive value of BES was examined utilizing the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 1092 patients were included in this study. BES was identified as the independent predictor of pALN burden in primary (n = 677) and validation (n = 415) cohorts. The analysis using MRI-ALN status showed that BES significantly improved the predictive performance of pALN burden (AUC: 0.65 vs 0.71, p < 0.001; IDI = 0.045, p < 0.001; continuous NRI = 0.159, p = 0.050). These results were confirmed in the validation cohort (AUC: 0.64 vs 0.69, p = 0.009; IDI = 0.050, p < 0.001; continuous NRI = 0.213, p = 0.047). Furthermore, BES was positively correlated with biologically invasive clinicopathological factors (p < 0.05). CONCLUSIONS: In individuals with early-stage breast cancer, preoperative MRI characteristics of breast edema could be a promising predictor for pALN burden, which may aid in treatment planning. KEY POINTS: • In this retrospective study of 1092 patients with early-stage breast cancer from two cohorts, the MRI characteristic of breast edema has independent and additive predictive value for assessing axillary lymph node burden. • Breast edema characteristics at T2WI positively correlated with biologically invasive clinicopathological factors, which may be useful for preoperative diagnosis and treatment planning for individual patients with breast cancer.

Deep learning predicts resistance to neoadjuvant chemotherapy for locally advanced gastric cancer: a multicenter study.

BACKGROUND: Accurate pre-treatment prediction of neoadjuvant chemotherapy (NACT) resistance in patients with locally advanced gastric cancer (LAGC) is essential for timely surgeries and optimized treatments. We aim to evaluate the effectiveness of deep learning (DL) on computed tomography (CT) images in predicting NACT resistance in LAGC patients. METHODS: A total of 633 LAGC patients receiving NACT from three hospitals were included in this retrospective study. The training and internal validation cohorts were randomly selected from center 1, comprising 242 and 104 patients, respectively. The external validation cohort 1 comprised 128 patients from center 2, and the external validation cohort 2 comprised 159 patients from center 3. First, a DL model was developed using ResNet-50 to predict NACT resistance in LAGC patients, and the gradient-weighted class activation mapping (Grad-CAM) was assessed for visualization. Then, an integrated model was constructed by combing the DL signature and clinical characteristics. Finally, the performance was tested in internal and external validation cohorts using area under the receiver operating characteristic (ROC) curves (AUC). RESULTS: The DL model achieved AUCs of 0.808 (95% CI 0.724-0.893), 0.755 (95% CI 0.660-0.850), and 0.752 (95% CI 0.678-0.825) in validation cohorts, respectively, which were higher than those of the clinical model. Furthermore, the integrated model performed significantly better than the clinical model (P < 0.05). CONCLUSIONS: A CT-based model using DL showed promising performance for predicting NACT resistance in LAGC patients, which could provide valuable information in terms of individualized treatment.

Development and validation of a MRI-based radiomics signature for prediction of KRAS mutation in rectal cancer.

OBJECTIVE: To develop a T2-weighted (T2W) image-based radiomics signature for the individual prediction of KRAS mutation status in patients with rectal cancer. METHODS: Three hundred four consecutive patients from center I with pathologically diagnosed rectal adenocarcinoma (training dataset, n = 213; internal validation dataset, n = 91) were enrolled in our retrospective study. The patients from center II (n = 86) were selected as an external validation dataset. A total of 960 imaging features were extracted from high-resolution T2W images for each patient. Five steps, mainly univariate statistical tests, were applied for feature selection. Subsequently, three classification methods, i.e., logistic regression (LR), decision tree (DT), and support vector machine (SVM) algorithm, were applied to develop the radiomics signature for KRAS prediction in the training dataset. The predictive performance was evaluated by receiver operating characteristics curve (ROC) analysis, calibration curve, and decision curve analysis (DCA). RESULTS: Seven radiomics features were screened as a KRAS-associated radiomics signature of rectal cancer. Our best prediction model was obtained with SVM classifiers with AUC of 0.722 (95%CI, 0.654-0.790) in the training dataset. This was validated in the internal and external validation datasets with good calibration, and the corresponding AUCs were 0.682 (95% CI, 0.569-0.794) and 0.714 (95% CI, 0.602-0.827), respectively. DCA confirmed its clinical usefulness. CONCLUSIONS: The proposed T2WI-based radiomics signature has a moderate performance to predict KRAS status, and may be useful for supplementing genomic analysis to determine KRAS expression in rectal cancer patients. KEY POINTS: • T2WI-based radiomics showed a moderate diagnostic significance for KRAS status. • The best prediction model was obtained with SVM classifier. • The baseline clinical and histopathological characteristics were not associated with KRAS mutation.

MLW-gcForest: a multi-weighted gcForest model towards the staging of lung adenocarcinoma based on multi-modal genetic data.

BACKGROUND: Lung cancer is one of the most common types of cancer, among which lung adenocarcinoma accounts for the largest proportion. Currently, accurate staging is a prerequisite for effective diagnosis and treatment of lung adenocarcinoma. Previous research has used mainly single-modal data, such as gene expression data, for classification and prediction. Integrating multi-modal genetic data (gene expression RNA-seq, methylation data and copy number variation) from the same patient provides the possibility of using multi-modal genetic data for cancer prediction. A new machine learning method called gcForest has recently been proposed. This method has been proven to be suitable for classification in some fields. However, the model may face challenges when applied to small samples and high-dimensional genetic data. RESULTS: In this paper, we propose a multi-weighted gcForest algorithm (MLW-gcForest) to construct a lung adenocarcinoma staging model using multi-modal genetic data. The new algorithm is based on the standard gcForest algorithm. First, different weights are assigned to different random forests according to the classification performance of these forests in the standard gcForest model. Second, because the feature vectors generated under different scanning granularities have a diverse influence on the final classification result, the feature vectors are given weights according to the proposed sorting optimization algorithm. Then, we train three MLW-gcForest models based on three single-modal datasets (gene expression RNA-seq, methylation data, and copy number variation) and then perform decision fusion to stage lung adenocarcinoma. Experimental results suggest that the MLW-gcForest model is superior to the standard gcForest model in constructing a staging model of lung adenocarcinoma and is better than the traditional classification methods. The accuracy, precision, recall, and AUC reached 0.908, 0.896, 0.882, and 0.96, respectively. CONCLUSIONS: The MLW-gcForest model has great potential in lung adenocarcinoma staging, which is helpful for the diagnosis and personalized treatment of lung adenocarcinoma. The results suggest that the MLW-gcForest algorithm is effective on multi-modal genetic data, which consist of small samples and are high dimensional.

Diffusion kurtosis imaging-derived histogram metrics for prediction of KRAS mutation in rectal adenocarcinoma: Preliminary findings.

BACKGROUND: Although histological examination is the standard method for assessing genetic status, the development of a noninvasive method, which can display the heterogeneity of the whole tumor to supplement genotype analysis, might be important for personalized treatment strategies. PURPOSE: To evaluate the potential role of diffusion kurtosis imaging (DKI)-derived parameters using histogram analysis derived from whole-tumor volumes for prediction of the status of KRAS mutations in patients with rectal adenocarcinoma. STUDY TYPE: Retrospective. SUBJECTS: In all, 148 consecutive patients with histologically confirmed rectal adenocarcinoma who were treated at our institution. SEQUENCE: DKI was performed with a 3.0 T MRI system using a single-shot echo-planar imaging sequence with b values of 0, 700, 1400, and 2100 sec/mm2 . ASSESSMENT: D, K, and apparent diffusion coefficient (ADC) values were measured using whole-tumor volume histogram analysis and were compared between different KRAS mutations status. STATISTICAL TESTS: Student's t-test or Mann-Whitney U-test, and receiver operating characteristic (ROC) curves were used for statistical analysis. RESULTS: All the percentile metrics of ADC and D values were significantly lower in the mutated group than those in the wildtype group (all P < 0.05), except for the minimum value of ADC and D (both P > 0.05), while K-related percentile metrics were higher in the mutated group compared with those in the wildtype group (all P < 0.05). Regarding the comparison of the diagnostic performance of all the histogram metrics, K75th showed the highest AUC value of 0.871, and the corresponding values for sensitivity, specificity, positive predictive value, and negative predictive value were 81.43%, 78.21%, 77.03%, and 82.43%, respectively. DATA CONCLUSION: DKI metrics with whole-tumor volume histogram analysis is associated with KRAS mutations, and thus may be useful for predicting the KRAS status of rectal cancers for guiding targeted therapy. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:930-939.

Radiomics analysis of multiparametric MRI for prediction of pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVES: To develop and validate a radiomics predictive model based on pre-treatment multiparameter magnetic resonance imaging (MRI) features and clinical features to predict a pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after receiving neoadjuvant chemoradiotherapy (CRT). METHODS: One hundred and eighty-six consecutive patients with LARC (training dataset, n = 131; validation dataset, n = 55) were enrolled in our retrospective study. A total of 1,188 imaging features were extracted from pre-CRT T2-weighted (T2-w), contrast-enhanced T1-weighted (cT1-w) and ADC images for each patient. Three steps including least absolute shrinkage and selection operator (LASSO) regression were performed to select key features and build a radiomics signature. Combining clinical risk factors, a radiomics nomogram was constructed. The predictive performance was evaluated by receiver operator characteristic (ROC) curve analysis, and then assessed with respect to its calibration, discrimination and clinical usefulness. RESULTS: Thirty-one of 186 patients (16.7%) achieved pCR. The radiomics signature derived from joint T2-w, ADC, and cT1-w images, comprising 12 selected features, was significantly associated with pCR status and showed better predictive performance than signatures derived from either of them alone in both datasets. The radiomics nomogram, incorporating the radiomics signature and MR-reported T-stages, also showed good discrimination, with areas under the ROC curves (AUCs) of 0.948 (95% CI, 0.907-0.989) and 0.966 (95% CI, 0.924-1.000), as well as good calibration in both datasets. Decision curve analysis confirmed its clinical usefulness. CONCLUSIONS: This study demonstrated that the pre-treatment radiomics nomogram can predict pCR in patients with LARC and potentially guide treatments to select patients for a "wait-and-see" policy. KEY POINTS: • Radiomics analysis of pre-CRT multiparameter MR images could predict pCR in patients with LARC. • Proposed radiomics signature from joint T2-w, ADC and cT1-w images showed better predictive performance than individual signatures. • Most of the clinical characteristics were unable to predict pCR.

Whole-tumour diffusion kurtosis MR imaging histogram analysis of rectal adenocarcinoma: Correlation with clinical pathologic prognostic factors.

OBJECTIVE: To investigate potential relationships between diffusion kurtosis imaging (DKI)-derived parameters using whole-tumour volume histogram analysis and clinicopathological prognostic factors in patients with rectal adenocarcinoma. MATERIAL AND METHODS: 79 consecutive patients who underwent MRI examination with rectal adenocarcinoma were retrospectively evaluated. Parameters D, K and conventional ADC were measured using whole-tumour volume histogram analysis. Student's t-test or Mann-Whitney U-test, receiver operating characteristic curves and Spearman's correlation were used for statistical analysis. RESULTS: Almost all the percentile metrics of K were correlated positively with nodal involvement, higher histological grades, the presence of lymphangiovascular invasion (LVI) and circumferential margin (CRM) (p<0.05), with the exception of between K10th, K90th and histological grades. In contrast, significant negative correlations were observed between 25th, 50th percentiles and mean values of ADC and D, as well as ADC10th, with tumour T stages (p< 0.05). Meanwhile, lower 75th and 90th percentiles of ADC and D values were also correlated inversely with nodal involvement (p< 0.05). Kmean showed a relatively higher area under the curve (AUC) and higher specificity than other percentiles for differentiation of lesions with nodal involvement. CONCLUSION: DKI metrics with whole-tumour volume histogram analysis, especially K parameters, were associated with important prognostic factors of rectal cancer. KEY POINTS: • K correlated positively with some important prognostic factors of rectal cancer. • K mean showed higher AUC and specificity for differentiation of nodal involvement. • DKI metrics with whole-tumour volume histogram analysis depicted tumour heterogeneity.