Deep learning for predicting immunotherapeutic efficacy in advanced non-small cell lung cancer patients: a retrospective study combining progression-free survival risk and overall survival risk.

Background: Radiomics based on computed tomography (CT) images is potential in promoting individualized treatment of non-small cell lung cancer (NSCLC), however, its role in immunotherapy needs further exploration. The aim of this study was to develop a CT-based radiomics score to predict the efficacy of immune checkpoint inhibitor (ICI) monotherapy in patients with advanced NSCLC. Methods: Two hundred and thirty-six ICI-treated patients were retrospectively included and divided into a training cohort (n=188) and testing cohort (n=48) at a ratio of 8 to 2. The efficacy outcomes of ICI were evaluated based on overall survival (OS) and progression-free survival (PFS). We designed a survival network and combined it with a Cox regression model to obtain patients' OS risk score (OSRS) and PFS risk score (PFSRS). Results: Based on OSRS and PFSRS, patients were divided into high- and low-risk groups in the training cohort and the test cohort with distinctly different [training cohort, log-rank P<0.001, hazard ratio (HR): 4.14; test cohort, log-rank P=0.014, HR: 4.54] and PFS (training cohort, log-rank P<0.001, HR: 4.52; test cohort, log-rank P<0.001, HR: 6.64). Further joint evaluation of OSRS and PFSRS showed that both were significant in the Cox regression model (P<0.001), and multi-overall survival risk score (MOSRS) displayed more outstanding stratification capabilities than OSRS in both the training (P<0.001) and test cohorts (P=0.002). None of the clinical characteristics were significant in the Cox regression model, and the score that predicted the best immune response was not as good as the risk score from follow-up information in the performance of prognostic stratification. Conclusions: We developed a CT imaging-based score with the potential to become an independent prognostic factor to screen patients who would benefit from ICI treatment, which suggested that CT radiomics could be applied for individualized immunotherapy of NSCLC. Our findings should be further validated by future larger multicenter study.

Radiomics nomogram for prediction disease-free survival and adjuvant chemotherapy benefits in patients with resected stage I lung adenocarcinoma.

BACKGROUND: Robust imaging biomarkers are needed for risk stratification in stage I lung adenocarcinoma patients in order to select optimal treatment regimen. We aimed to construct and validate a radiomics nomogram for predicting the disease-free survival (DFS) of patients with resected stage I lung adenocarcinoma, and further identifying candidates benefit from adjuvant chemotherapy (ACT). METHODS: Using radiomics approach, we analyzed 554 patients' computed tomography (CT) images from three multicenter cohorts. Prognostic radiomics features were extracted from computed tomography (CT) images and selected using least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for DFS stratification. The biological basis of radiomics was explored in the Radiogenomics dataset (n=79) by gene set enrichment analysis (GSEA). Then a nomogram that integrated the signature with these significant clinicopathologic factors in the multivariate analysis were constructed in the training cohort (n=238), and its prognostic accuracy was evaluated in the validation cohort (n=237). Finally, the predictive value of nomogram for ACT benefits was assessed. RESULTS: The radiomics signature with higher score was significantly associated with worse DFS in both the training and validation cohorts (P<0.001). The GSEA presented that the signature was highly correlated to characteristic metabolic process and immune system during cancer progression. Multivariable analysis revealed that age (P=0.031), pathologic TNM stage (P=0.043), histologic subtype (P=0.010) and the signature (P<0.001) were independently associated with patients' DFS. The integrated radiomics nomogram showed good discrimination performance, as well as good calibration and clinical utility, for DFS prediction in the validation cohort. We further found that the patients with high points (point ≥8.788) defined by the radiomics nomogram obtained a significant favorable response to ACT (P=0.04) while patients with low points (point <8.788) showed no survival difference (P=0.7). CONCLUSIONS: The radiomics nomogram could be used for prognostic prediction and ACT benefits identification for patient with resected stage I lung adenocarcinoma.

Region growing algorithm combined with morphology and skeleton analysis for segmenting airway tree in CT images.

BACKGROUND: Automatic segmentation of pulmonary airway tree is a challenging task in many clinical applications, including developing computer-aided detection and diagnosis schemes of lung diseases. OBJECTIVE: To segment the pulmonary airway tree from the computed tomography (CT) chest images using a novel automatic method proposed in this study. METHODS: This method combines a two-pass region growing algorithm with gray-scale morphological reconstruction and leakage elimination. The first-pass region growing is implemented to obtain a rough airway tree. The second-pass region growing and gray-scale morphological reconstruction are used to detect the distal airways. Finally, leakage detection is performed to remove leakage and refine the airway tree. RESULTS: Our methods were compared with the gold standards. Forty-five clinical CT lung image scan cases were used in the experiments. Statistics on tree division order, branch number, and airway length were adopted for evaluation. The proposed method detected up to 12 generations of bronchi. On average, 148.85 branches were extracted with a false positive rate of 0.75%. CONCLUSIONS: The results show that our method is accurate for pulmonary airway tree segmentation. The strategy of separating the leakage detection from the segmenting process is feasible and promising for ensuring a high branch detected rate with a low leakage volume.

Fusion of quantitative imaging features and serum biomarkers to improve performance of computer-aided diagnosis scheme for lung cancer: A preliminary study.

OBJECTIVES: To develop and test a new multifeature-based computer-aided diagnosis (CADx) scheme of lung cancer by fusing quantitative imaging (QI) features and serum biomarkers to improve CADx performance in classifying between malignant and benign pulmonary nodules. METHODS: First, a dataset involving 173 patients was retrospectively assembled, which includes computed tomography (CT) images and five serum biomarkers extracted from blood samples. Second, a CADx scheme using a four-step-based semiautomatic segmentation method was applied to segment the targeted lung nodules, and compute 78 QI features from each segmented nodule from CT images. Third, two support vector machine (SVM) classifiers were built using QI features and serum biomarkers, respectively. SVM classifiers were trained and tested using the overall dataset with a Relief feature selection method, a synthetic minority oversampling technique and a leave-one-case-out validation method. Finally, to further improve CADx performance, an information-fusion method was used to combine the prediction scores generated by two SVM classifiers. RESULTS: Areas under receiver operating characteristic curves (AUC) generated by QI feature and serum biomarker-based SVMs were 0.81 ± 0.03 and 0.69 ± 0.05, respectively. Using an optimal weighted fusion method to combine prediction scores generated by two SVMs, AUC value significantly increased to 0.85 ± 0.03 (P < 0.05). CONCLUSIONS: This study demonstrates (a) higher CADx performance by using QI features than using the serum biomarkers and (b) feasibility of further improving CADx performance by fusion of QI features and serum biomarkers, which indicates that QI features and serum biomarkers contain the complementary classification information.

Impacts of different methods of conception on the perinatal outcome of intrahepatic cholestasis of pregnancy in twin pregnancies.

Twin pregnancies have a higher prevalence of intrahepatic cholestasis of pregnancy (ICP) than single pregnancies. It is unknown whether in vitro fertilization-embryo transfer (IVF-ET) influences the fetal outcomes in twin pregnancies complicated by ICP. This study aimed to explore the impact of IVF-ET on the perinatal outcomes of ICP in twin pregnancy. Clinical data from 142 twin pregnant women complicated with ICP were retrospectively analyzed, including 51 patients who conceived through IVF-ET (IVF group) and 91 patients with spontaneous conception (SC group). Several biochemical indicators and perinatal outcomes were analyzed. Compared to the SC group, the IVF group had a higher incidence of early-onset ICP (P = 0.015) and more frequent clinical symptoms (P = 0.020), including skin pruritus, skin scratch, and jaundice. Furthermore, the IVF group had higher rates of neonatal asphyxia (IVF vs. SC, 9.80% vs. 1.10%, P = 0.023) and premature delivery (IVF vs. SC, 96.08% vs. 83.52%, P = 0.027) compared to the SC group. The IVF-conceived twin pregnancy group had a higher risk of early-onset ICP and suffered from clinical symptoms and poor perinatal outcomes.

Automatic detection of pulmonary nodules in CT images by incorporating 3D tensor filtering with local image feature analysis.

Computer-aided detection (CAD) technology has been developed and demonstrated its potential to assist radiologists in detecting pulmonary nodules especially at an early stage. In this paper, we present a novel scheme for automatic detection of pulmonary nodules in CT images based on a 3D tensor filtering algorithm and local image feature analysis. We first apply a series of preprocessing steps to segment the lung volume and generate the isotropic volumetric CT data. Next, a unique 3D tensor filtering approach and local image feature analysis are used to detect nodule candidates. A 3D level set segmentation method is used to correct and refine the boundaries of nodule candidates subsequently. Then, we extract the features of the detected candidates and select the optimal features by using a CFS (Correlation Feature Selection) subset evaluator attribute selection method. Finally, a random forest classifier is trained to classify the detected candidates. The performance of this CAD scheme is validated using two datasets namely, the LUNA16 (Lung Nodule Analysis 2016) database and the ANODE09 (Automatic Nodule Detection 2009) database. By applying a 10-fold cross-validation method, the CAD scheme yielded a sensitivity of 79.3% at an average of 4 false positive detections per scan (FP/Scan) for the former dataset, and a sensitivity of 84.62% and 2.8 FP/Scan for the latter dataset, respectively. Our detection results show that the use of 3D tensor filtering algorithm combined with local image feature analysis constitutes an effective approach to detect pulmonary nodules.

Computer-aided diagnosis of lung cancer: the effect of training data sets on classification accuracy of lung nodules.

This study aims to develop a computer-aided diagnosis (CADx) scheme for classification between malignant and benign lung nodules, and also assess whether CADx performance changes in detecting nodules associated with early and advanced stage lung cancer. The study involves 243 biopsy-confirmed pulmonary nodules. Among them, 76 are benign, 81 are stage I and 86 are stage III malignant nodules. The cases are separated into three data sets involving: (1) all nodules, (2) benign and stage I malignant nodules, and (3) benign and stage III malignant nodules. A CADx scheme is applied to segment lung nodules depicted on computed tomography images and we initially computed 66 3D image features. Then, three machine learning models namely, a support vector machine, naïve Bayes classifier and linear discriminant analysis, are separately trained and tested by using three data sets and a leave-one-case-out cross-validation method embedded with a Relief-F feature selection algorithm. When separately using three data sets to train and test three classifiers, the average areas under receiver operating characteristic curves (AUC) are 0.94, 0.90 and 0.99, respectively. When using the classifiers trained using data sets with all nodules, average AUC values are 0.88 and 0.99 for detecting early and advanced stage nodules, respectively. AUC values computed from three classifiers trained using the same data set are consistent without statistically significant difference (p > 0.05). This study demonstrates (1) the feasibility of applying a CADx scheme to accurately distinguish between benign and malignant lung nodules, and (2) a positive trend between CADx performance and cancer progression stage. Thus, in order to increase CADx performance in detecting subtle and early cancer, training data sets should include more diverse early stage cancer cases.

[A study of global ecological adaptability and field selection practices of Panax ginseng].

Through the development of ecological suitability analysis of producing area and the selection criteria of farmland cultivation in the global range of ginseng, we aim to provide scientific basis for rational planning, production layout and standardized planting of farmland. We analyze the data based on the ecological factors from 271 sample plots of Panax ginseng, including both the traditional producing regions recorded in past dynasties medicinal works and the popular production regions in the world, using global geographic information system for medicinal plant(GMPGIS) developed by ICMM (Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences). We concluded that the suitable producing areas in global for P. ginseng mainly included America, Canada, China, Russia, Japan, North Korea, France, Italy, Ukraine, and South Korea. In addition, the suitable producing areas in China mainly included Heilongjiang, Jilin, Liaoning, Shanxi, Gansu, Hubei, Sichuan, Inner Mongolia, Shandong, and Shanxi. Besides, based on the references and the experience of ginseng-producing and our many years' work on the 1,000-hectare plantation of P. ginseng, we established a standard land selection protocol for cultivation of P. ginseng. The use of GMPGIS to select the most optimum ginseng production regions provides a new scientific basis for introduction, cultivation, tending, protection, cultivation normalization for P. ginseng and the standard land selection protocol would lay a solid foundation for the high quality P. ginseng production.

Anti-proliferation and radiosensitization effects of chitooligosaccharides on human lung cancer line HepG2.

OBJECTIVE: To observe the anti-proliferation and radiosensitization effect of chitooligosaccharides (COS) on human lung cancer cell line HepG2. METHODS: CCK-8 assay was employed to obtain the inhibition ratio of COS on HepG2 cells at 24 h after treatment. The clonogenic assay was used to analyze the cell viability of RAY group and RAY + COS group with X-ray of 0, 1, 2, 4, 6 and 8 Gy, and the cell survival curve was used to analyze the sensitization ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY + COS group after 24 h treatment. RESULTS: COS inhibited the proliferation of HepG2 cells, and the inhibition rate positively correlated with the concentration of COS. The cell viability decreased with increasing exposure dose in RAY group and RAY + COS group. The cell viabilities of RAY + COS group were lower than those of RAY group at the dose of 4, 6 and 8 Gy (P < 0.05), and the sensitization ratio of COS was 1.19. There were higher percentage at G2/M phase and apoptosis rate, and lower percentage at S phase in RAY + COS group versus the other two groups (P < 0.01). CONCLUSIONS: COS can inhibit the proliferation of HepG2 cells, and enhance the radiosensitization of HepG2 cells, induce apoptosis and G2/M phase arrest.

An Aberrant Left Bronchial Artery Originating from the Proximal Ascending Aorta.

The origin of the bronchial arteries (BAs) has numerous anatomical variations. It is important to recognize these variations when performing interventional radiologic procedures in the thorax. We report the case of a 71-year-old man who underwent transarterial infusion chemotherapy for squamous cell carcinoma of the upper lobe of the left lung via a feeding left BA that originated from the proximal ascending aorta. After two cycles of transarterial infusion chemotherapy, the tumor significantly decreased in size. To the best of our knowledge, this is the first report of an aberrant BA originating from this site.

Endovascular embolization of bronchial artery originating from the upper portion of aortic arch in patients with massive hemoptysis.

PURPOSE: Our experience with endovascular embolization (EVE) of the bronchial artery (BA) originating from the upper portion of the aortic arch (AA) in six patients is described. METHODS: Altogether, 818 patients with hemoptysis underwent multidetector row computed tomography angiography (MDCTA) before EVE or AA angiography during EVE. Aberrant BAs originating from the upper portion of the AA were the source of massive hemoptysis in six patients (0.73 %). MDCT angiograms and/or Digital subtraction angiograms were retrospectively reviewed. Selective catheterization and embolization were performed. RESULTS: The ostia of the BAs were located on the superior surface of the AA between the brachiocephalic trunk and left common carotid artery in three patients, the junction of the aorta and medial surface of the left subclavian artery in two, and the posterior wall of the upper portion of the AA in one. The six BAs comprised two common trunks, three single right sides, and one single left side. The targeted vessels were successfully catheterized and embolized by a coaxial microcatheter system using polyvinyl alcohol particles. Other pathologic BAs and nonbronchial systemic arteries also were embolized. Bleeding was immediately controlled in all patients with no recurrence of hemoptysis. No procedure-related complications occurred. CONCLUSIONS: Application of EVE of anomalous origin of BAs in patients with hemoptysis is important, as demonstrated in the six reported patients. MDCTA before EVE or AA angiography during EVE is critical to avoid missing a rare aberrant BA originating from the upper portion of the AA.

Endovascular coil embolization of a costocervical trunk pseudoaneurysm after bullectomy with pleural abrasion.

Transarterial embolization (TAE) is less invasive than surgery for the treatment of pseudoaneurysms. Costocervical trunk (CCT) pseudoaneurysms are extremely rare. We herein report an unusual case of a 45-year-old man with a CCT pseudoaneurysm caused by a bullectomy with pleural abrasion, which had been performed to manage a spontaneous pneumothorax. The patient presented with chronic chest pain and successfully underwent TAE with a metallic coil. The chest pain completely disappeared 2 weeks after the TAE, and follow-up computed tomography showed that the pseudoaneurysm had almost completely disappeared 9 months after the TAE.

Bilateral subclavian origin of the bronchial arteries combined with absence of other origins.

There are numerous anatomical variations of the sites of origin of the bronchial arteries (BAs). A subclavian origin of a BA involves an aberrant artery that originates from the subclavian artery (SCA) or its branches. However, the aberrant artery usually originates directly from the SCA, and an SCA-origin BA arising from the branches of the SCA is rare. We herein present an extremely rare case of a right BA arising from the ipsilateral costocervical trunk, and a left BA arising from the ipsilateral thyrocervical trunk, in the absence of other origins of the BA. This anatomical variation was detected during pretherapeutic evaluation by multidetector-row computed tomography and confirmed by selective angiography. Recognition of these anatomic variations is important to surgical, diagnostic, and interventional radiologic procedures in the thorax.

Endovascular embolization of an aberrant bronchial artery originating from the vertebral artery in a patient with massive hemoptysis.

Endovascular embolization has become an established procedure for the management of massive or recurrent hemoptysis. The bronchial, nonbronchial systemic and pulmonary arteries are possible sources of bleeding, and the major sources of bleeding are the bronchial arteries (BAs). However, the locations of ostia of the BAs have numerous anatomical variations, which can make it technically challenging to identify a bleeding artery. We herein present a rare case of a left BA that originated from the ipsilateral vertebral artery in a patient with massive hemoptysis caused by active tuberculosis. Transarterial embolization was successfully performed, and the hemoptysis has been controlled for 2 months.

Aberrant left inferior bronchial artery originating from the left gastric artery in a patient with acute massive hemoptysis.

Massive hemoptysis is a life-threatening condition, and the major source of bleeding in this condition is the bronchial circulation. Bronchial artery embolization is a safe and effective treatment for controlling hemoptysis. However, the sites of origin of the bronchial arteries (BAs) have numerous anatomical variations, which can result in a technical challenge to identify a bleeding artery. We present a rare case of a left inferior BA that originated from the left gastric artery in a patient with recurrent massive hemoptysis caused by bronchiectasis. The aberrant BA was embolized, and hemoptysis has been controlled for 8 months.

Common trunk of left internal thoracic artery and thyrocervical trunk arising from the ipsilateral vertebral artery.

The sites of origin of the branches of the subclavian artery depict numerous anatomical variations. However, a common trunk of the internal thoracic artery (ITA) and thycocervical trunk (TCT) arising from the vertebral artery is a rare anatomical finding. Herein, we present the first case in which the common trunk of the left ITA and TCT arose from the ipsilateral proximal vertebral artery as discovered on pre-therapeutic evaluation by multidetector-row computed tomography and clearly confirmed by selective angiography. It is important to recognize such anatomic variations for surgical, diagnostic, and interventional radiologic procedures in the head, neck, thorax, and abdomen.

Detection of rib metastases in patients with lung cancer: a comparative study of MRI, CT and bone scintigraphy.

We retrospectively investigated the imaging findings of bone scintigraphy, chest CT and chest MRI in 55 cases of lung cancer. The sensitivity, specificity and accuracy of the detection of rib metastases were compared between imaging modalities on both a per-lesion and a per-patient basis. On a per-lesion basis, MRI sensitivity and accuracy were significantly higher than that of bone scintigraphy and CT (P<0.05). The sensitivities, specificities, and accuracy levels between CT and bone scintigraphy did not differ on either a per-lesion or per-patient basis (P>0.05). MRI appears to be superior for the detection of ribs metastases in lung cancer.

Endovascular embolization of the complete type of anomalous systemic arterial supply to normal basal lung segments: a report of four cases and literature review.

The complete type of anomalous systemic arterial supply to normal basal lung segments is characterized by anomalous systemic artery supply to all or some of the normal basal segments with an absent corresponding pulmonary artery. Surgical intervention generally is required. This study reports on four patients with this anomaly with hemoptysis or a combination of other symptoms who underwent successful transarterial embolization using metallic coils or an Amplatzer vascular plug. To our knowledge, only six such cases treated with transarterial embolization have been reported previously in adult patients.

CHFR promoter hypermethylation and reduced CHFR mRNA expression in ovarian cancer.

BACKGROUND: Ovarian cancer is one of the most common cancers and can be treated with microtubule-targeting drugs. Checkpoint with forkhead and ring finger domains (CHFR) is a protein implicated in cancer sensitivity to microtubule-targeting drugs. Whereas CHFR downregulation, often with CHFR promoter hypermethylation, has been identified in a large number of tumor types, it has not been in ovarian cancer. We therefore searched for CHFR downregulation in primary ovarian tumors. METHODS: Fresh ovarian cancer tissues from 53 patients (test) and normal ovarian tissues from 21 patients (control) were tested for CHFR promoter hypermethylation and CHFR mRNA levels. RESULTS: The CHFR promoter was hypermethylated in 20.75% (11/53) of the ovarian cancers and none (0/21) of the normal controls. The normal controls had a mean mRNA level of 1.89 relative fluorescence units (RFU) with a range of 0.04-24.78 RFU. The cancer tissues had a mean mRNA level of 0.77 RFU with a range of 0.00-68.75 RFU. The median value of the cancer group was significantly lower than that of the control group (p=0.0067). Those cancer samples that had hypermethylated CHFR promoters also had low (n=3) or undetectable (n=8) CHFR mRNA levels. CONCLUSIONS: In contrast to previous reports, we found that alterations in CHFR mRNA and CHFR methylation can be frequently found in ovarian cancers. CHFR hypermethylation was strongly associated with the loss of CHFR mRNA expression. CHFR downregulation in ovarian tumors may be clinically relevant as a staging biomarker, as an indicator of sensitivity to microtubule-targeting drugs, and as a future drug target.

[Pulmonary sarcoidosis: CT features and the changes after glucocorticoid therapy].

OBJECTIVE: To investigate the CT features of pulmonary sarcoidosis and to follow the changes after glucocorticoid therapy. METHODS: CT scans and clinical data of 90 patients with histologically confirmed pulmonary sarcoidosis were retrospectively reviewed. CT follow-up was carried out 5-30 d following therapy in 43 cases. The follow-up lasted 3-48 months. RESULTS: The main CT finding of pulmonary sarcoidosis was nodules which were present in 69 cases (77%), mostly distributed around bronchovascular bundles (n = 37, 41%). Other abnormalities included consolidation (n = 31, 34%), ground-grass ( n = 39, 43%), thickening of bronchovascular bundles (n = 30, 33%) interlobular septal lines (n = 58, 64%), fibrosis (n = 17, 19%), air-trapping (n = 3, 3%) bronchial narrowing (n = 8, 9%), pleural thickening (n = 42, 47%), hilar and mediastinal adenopathy (n =76, 84%). Two or more radiological patterns were present in 83 cases. Twenty-five cases of nodules (25/30), 9 cases of consolidation (9/15), 11 cases of ground-grass (11/16), 10 cases of thickening of bronchovascular bundles (10/12) were improved after therapy. Ten cases of interlobular septa (10/22), 1 case of diffuse linear changes (1/3), but no bronchial distortion (0/4) and honeycombing (0/2), were improved. CONCLUSIONS: The CT manifestations of pulmonary sarcoidosis are varied, with some specific radiographic features. The radiological diagnosis and the effect of glucocorticoid therapy can be evaluated by repeated CT scanning. Nodules, consolidation, ground-grass, and thickening of bronchovascular bundles can be improved markedly after glucocorticoid therapy, but bronchial distortion, linear changes and honeycombing can not.