CT findings as predictive factors for treatment failure in Mycobacterium abscessus complex lung disease: a retrospective cohort study.

PURPOSE: Mycobacterium abscessus complex (MABC) commonly causes lung disease (LD) and has a high treatment failure rate of around 50%. In this study, our objective is to investigate specific CT patterns for predicting treatment prognosis and monitoring treatment response, thus providing valuable insights for clinical physicians in the management of MABC-LD treatment. METHODS: We retrospectively assessed 34 patients with MABC-LD treated between January 2015 and December 2020. CT scores for bronchiectasis, cellular bronchiolitis, consolidation, cavities, and nodules were measured at initiation and after treatment. The ability of the CT scores to predict treatment outcomes was analyzed in logistic regression analyses. RESULTS: The CT scoring system had excellent inter-reader agreement (all intraclass correlation coefficients, > 0.82). The treatment failure (TF) group (17/34; 50%) had higher cavitation diameter (p = 0.049) and extension (p = 0.041) at initial CT and higher cavitation diameter (p = 0.049) and extension (p =0 .045), consolidation (p = 0.022), and total (p = 0.013) scores at follow-up CT than the treatment success (TS) group. The changes of total score and consolidation score (p = 0.049 and 0.024, respectively) increased in the TF group more than the TS group between the initial and follow-up CT. Multivariable logistic regression analysis showed initial cavitation extension, follow-up consolidation extension, and change in consolidation extension (adjusted odds ratio: 2.512, 2.495, and 9.094, respectively, per 1-point increase; all p < 0.05) were significant predictors of treatment failure. CONCLUSIONS: A high pre-treatment cavitation extension score and an increase in the consolidation extension score during treatment on CT could be alarm signs of treatment failure requiring tailor the treatment of MABC-LD carefully.

Clinical Variables and Radiomics Features for Predicting Pneumothorax in Patients Undergoing CT-guided Transthoracic Core Needle Biopsy.

Purpose To develop a prediction model combining both clinical and CT texture analysis radiomics features for predicting pneumothorax complications in patients undergoing CT-guided core needle biopsy. Materials and Methods A total of 424 patients (mean age, 65.6 years ± 12.7 [SD]; 232 male, 192 female) who underwent CT-guided core needle biopsy between January 2021 and October 2022 were retrospectively included as the training data set. Clinical and procedure-related characteristics were documented. Texture analysis radiomics features were extracted from the subpleural lung parenchyma traversed by needle. Moderate pneumothorax was defined as a postprocedure air rim of 2 cm or greater. The prediction model was developed using logistic regression with backward elimination, presented by linear fusion of the selected features weighted by their coefficients. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Validation was conducted in an external cohort (n = 45; mean age, 58.2 years ± 12.7; 19 male, 26 female) from a different hospital. Results Moderate pneumothorax occurred in 12.0% (51 of 424) of the training cohort and 8.9% (four of 45) of the external test cohort. Patients with emphysema (P < .001) or a longer needle path length (P = .01) exhibited a higher incidence of moderate pneumothorax in the training cohort. Texture analysis features, including gray-level co-occurrence matrix cluster shade (P < .001), gray-level run-length matrix low gray-level run emphasis (P = .049), gray-level run-length matrix run entropy (P = .003), gray-level size-zone matrix gray-level variance (P < .001), and neighboring gray-tone difference matrix complexity (P < .001), showed higher values in patients with moderate pneumothorax. The combined clinical-radiomics model demonstrated satisfactory performance in both the training (AUC 0.78, accuracy = 71.9%) and external test cohorts (AUC 0.86, accuracy 73.3%). Conclusion The model integrating both clinical and radiomics features offered practical diagnostic performance and accuracy for predicting moderate pneumothorax in patients undergoing CT-guided core needle biopsy. Keywords: Biopsy/Needle Aspiration, Thorax, CT, Pneumothorax, Core Needle Biopsy, Texture Analysis, Radiomics, CT Supplemental material is available for this article. © RSNA, 2024.

Hemorrhage risk prediction after computed tomography-guided lung biopsy: Clinical parameters and quantitative pulmonary vascular analysis.

BACKGROUND/PURPOSE: We evaluated the utility of combining quantitative pulmonary vasculature measures with clinical factors for predicting pulmonary hemorrhage after computed tomography (CT)-guided lung biopsy. METHODS: Patients who underwent CT-guided lung biopsy were retrospectively included in this study. Clinical and radiographic vasculature variables were evaluated as predictors of pulmonary hemorrhage. The radiographic pulmonary vascular analysis included vessel count, density, diameter, and area, and also blood volume in small vessels with a cross-sectional area ≤5 mm2 (BV5) and total blood vessel volume (TBV) in the lungs. Univariate and multivariate logistic regressions were used to identify the independent risk factors of higher-grade pulmonary hemorrhage and establish the prediction model presented as a nomogram. RESULTS: The study included 126 patients; discovery cohort n = 103, and validation cohort n = 23. All pulmonary hemorrhage, higher-grade (grade ≥2) pulmonary hemorrhage, and hemoptysis occurred in 42.9%, 15.9%, and 3.2% of patients who underwent CT-guided lung biopsies. In the discovery cohort, patients with larger lesion depth (p = 0.013), higher vessel density (p = 0.033), and higher BV5 (p = 0.039) were more likely to experience higher-grade hemorrhage. The nomogram prediction model for higher-grade hemorrhage built by the discovery cohort showed similar performance in the validation cohort. CONCLUSIONS: Higher-grade pulmonary hemorrhage may occur after CT-guided lung biopsy. Lesion depth, vessel density, and BV5 are independent risk factors for higher-grade pulmonary hemorrhage. Nomograms integrating clinical parameters and radiographic pulmonary vasculature measures offer enhanced capability for assessing hemorrhage risk following CT-guided lung biopsy, thereby facilitating improved patient clinical care.

Dual-energy computed tomography for evaluating nodal staging in lung adenocarcinoma: correlation with surgical pathology.

PURPOSE: To ascertain the performance of dual-energy CT (DECT) with iodine quantification in differentiating malignant mediastinal and hilar lymph nodes (LNs) from benign ones, focusing on patients with lung adenocarcinoma. MATERIALS AND METHODS: In this study, patients with suspected lung cancer received a preoperative contrast-enhanced DECT scan from Jun 2018 to Dec 2020. Quantitative DECT parameters and the size were compared between metastatic and benign LNs. Their diagnostic performances were analyzed by the ROC curves and compared by using the two-sample t test. RESULTS: 72 patients (23 men, 49 women; mean age 62.5 ± 10.1 years) fulfilled the inclusion criteria. A total of 98 LNs (67 benign, 31 metastatic) were analyzed. The iodine concentration normalized by muscle (NICmuscle) was significantly higher (P < 0.001) in metastatic LNs (4.79 ± 1.70) than in benign ones (3.00 ± 1.45). The optimal threshold of NICmuscle was 3.44, which yielded AUC: 0.798, sensitivity: 83.9%, specificity: 73.1%, accuracy: 76.5%, respectively. Applying the established size parameters with 10 mm as the threshold yielded AUC: 0.600, sensitivity: 29.0%, specificity: 91.0%, accuracy: 71.4%, respectively. The diagnostic performance of NICmuscle was significantly better (P = 0.007) than the performance obtained using the established size parameters. CONCLUSIONS: For lung adenocarcinoma, the quantitative measurement of NICmuscle derived from DECT is useful for differentiating benign and metastatic mediastinal and hilar LNs before surgical intervention.

CT findings of 144 in-hospital patients with influenza pneumonia: A retrospective analysis.

BACKGROUND/PURPOSE: Patients with influenza infection during their period of admission may have worse computed tomography (CT) manifestation according to the clinical status. This study aimed to evaluate the CT findings of in-hospital patients due to clinically significant influenza pneumonia with correlation of clinical presentations. METHODS: In this retrospective, single center case series, 144 patients were included. All in-hospital patients were confirmed influenza infection and underwent CT scan. These patients were divided into three groups according to the clinical status of the most significant management: (1) without endotracheal tube and mechanical ventilator (ETTMV) or extracorporeal membrane oxygenation (ECMO); (2) with ETTMV; (3) with ETTMV and ECMO. Pulmonary opacities were scored according to extent. Spearman rank correlation analysis was used to evaluate the correlation between clinical parameters and CT scores. RESULTS: The predominant CT manifestation of influenza infection was mixed ground-glass opacity (GGO) and consolidation with both lung involvement. The CT scores were all reach significant difference among all three groups (8.73 ± 6.29 vs 12.49 ± 6.69 vs 18.94 ± 4.57, p < 0.05). The chest CT score was correlated with age, mortality, and intensive care unit (ICU) days (all p values were less than 0.05). In addition, the CT score was correlated with peak lactate dehydrogenase (LDH) level and peak C-reactive protein (CRP) level (all p values were less than 0.05). Concomitant bacterial infection had higher CT score than primary influenza pneumonia (13.02 ± 7.27 vs 8.95 ± 5.99, p < 0.05). CONCLUSION: Thin-section chest CT scores correlated with clinical and laboratory parameters in in-hospital patients with influenza pneumonia.

Deep Learning-Based Localization and Detection of Malpositioned Endotracheal Tube on Portable Supine Chest Radiographs in Intensive and Emergency Medicine: A Multicenter Retrospective Study.

OBJECTIVES: We aimed to develop a computer-aided detection (CAD) system to localize and detect the malposition of endotracheal tubes (ETTs) on portable supine chest radiographs (CXRs). DESIGN: This was a retrospective diagnostic study. DeepLabv3+ with ResNeSt50 backbone and DenseNet121 served as the model architecture for segmentation and classification tasks, respectively. SETTING: Multicenter study. PATIENTS: For the training dataset, images meeting the following inclusion criteria were included: 1) patient age greater than or equal to 20 years; 2) portable supine CXR; 3) examination in emergency departments or ICUs; and 4) examination between 2015 and 2019 at National Taiwan University Hospital (NTUH) (NTUH-1519 dataset: 5,767 images). The derived CAD system was tested on images from chronologically (examination during 2020 at NTUH, NTUH-20 dataset: 955 images) or geographically (examination between 2015 and 2020 at NTUH Yunlin Branch [YB], NTUH-YB dataset: 656 images) different datasets. All CXRs were annotated with pixel-level labels of ETT and with image-level labels of ETT presence and malposition. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the segmentation model, the Dice coefficients indicated that ETT would be delineated accurately (NTUH-20: 0.854; 95% CI, 0.824-0.881 and NTUH-YB: 0.839; 95% CI, 0.820-0.857). For the classification model, the presence of ETT could be accurately detected with high accuracy (area under the receiver operating characteristic curve [AUC]: NTUH-20, 1.000; 95% CI, 0.999-1.000 and NTUH-YB: 0.994; 95% CI, 0.984-1.000). Furthermore, among those images with ETT, ETT malposition could be detected with high accuracy (AUC: NTUH-20, 0.847; 95% CI, 0.671-0.980 and NTUH-YB, 0.734; 95% CI, 0.630-0.833), especially for endobronchial intubation (AUC: NTUH-20, 0.991; 95% CI, 0.969-1.000 and NTUH-YB, 0.966; 95% CI, 0.933-0.991). CONCLUSIONS: The derived CAD system could localize ETT and detect ETT malposition with excellent performance, especially for endobronchial intubation, and with favorable potential for external generalizability.

Noninvasive cardiac radioablation for ventricular tachycardia: dosimetric comparison between linear accelerator- and robotic CyberKnife-based radiosurgery systems.

BACKGROUND: Few dosimetric comparisons have been published between linear accelerator (LA)-based systems and CyberKnife (CK)-based robotic radiosurgery systems for cardiac radio-ablation in ventricular tachycardia. This study aimed to compare the dosimetry of noninvasive cardiac radio-ablation deliverable on LA with that on CK. METHODS: Thirteen patients who underwent noninvasive cardiac radio-ablation by LA were included. The prescribed dose was 25 Gy in 1 fraction, and the average planning target volume was 49.8 ± 31.0 cm3 (range, 14.4-93.7 cm3). CK plans were generated for comparison. RESULTS: Both the CK and LA plans accomplished appropriate dose coverage and normal tissue sparing. Compared with the LA plans, the CK plans achieved significantly lower gradient indices (3.12 ± 0.71 vs. 3.48 ± 0.55, p = 0.031) and gradient measures (1.00 ± 0.29 cm vs. 1.17 ± 0.29 cm, p < 0.001). They had similar equivalent conformity indices (CK vs. LA: 0.84 ± 0.08 vs. 0.87 ± 0.07, p = 0.093) and maximum doses 2 cm from the planning target volume (PTV) in any direction (CK vs. LA: 50.8 ± 9.9% vs. 53.1 ± 5.3%, p = 0.423). The dosimetric advantages of CK were more prominent in patients with a PTV of ≤ 50 cm3 or a spherical PTV. In patients with a PTV of > 50 cm3 or a non-spherical PTV, the LA and CK plans were similar regarding dosimetric parameters. CK plans involved more beams (232.2 ± 110.8 beams vs. 10.0 ± 1.7 arcs) and longer treatment times (119.2 ± 43.3 min vs. 22.4 ± 1.6 min, p = 0.007). CONCLUSIONS: Both CK and LA are ideal modalities for noninvasive cardiac radio-ablation. Upfront treatment should be considered based on clinical intent.

Discrimination of invasive lung adenocarcinoma from Lung-RADS category 2 nonsolid nodules through visual assessment: a retrospective study.

OBJECTIVES: Invasive adenocarcinomas (IADs) have been identified among nonsolid nodules (NSNs) assigned as Lung Imaging Reporting and Data System (Lung-RADS) category 2. This study used visual assessment for differentiating IADs from noninvasive lesions (NILs) in this category. METHODS: This retrospective study included 222 patients with 242 NSNs, which were resected after preoperative computed tomography (CT)-guided dye localization. Visual assessment was performed by using the lung and bone window (BW) settings to classify NSNs into BW-visible (BWV) and BW-invisible (BWI) NSNs. In addition, nodule size, shape, border, CT attenuation, and location were evaluated and correlated with histopathological results. Logistic regression was performed for multivariate analysis. A p value of < 0.05 was considered statistically significant. RESULTS: A total of 242 NSNs (mean diameter, 7.6 ± 2.8 mm), including 166 (68.6%) BWV and 76 (31.4%) BWI NSNs, were included. IADs accounted for 31% (75) of the nodules. Only 4 (5.3%) IADs were identified in the BWI group and belonged to the lepidic-predominant (n = 3) and acinar-predominant (n = 1) subtypes. In univariate analysis for differentiating IADs from NILs, the nodule size, shape, CT attenuation, and visual classification exhibited statistical significance. Nodule size and visual classification were the significant predictors for IAD in multivariate analysis with logistic regression (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of visual classification in IAD prediction were 94.7%, 43.1%, 42.8%, and 94.7%, respectively. CONCLUSIONS: The window-based visual classification of NSNs is a simple and objective method to discriminate IADs from NILs. CLINICAL RELEVANCE STATEMENT: The present study shows that using the bone window to classify nonsolid nodules helps discriminate invasive adenocarcinoma from noninvasive lesions. KEY POINTS: • Evidence has shown the presence of lung adenocarcinoma in Lung-RADS category 2 nonsolid nodules. • Nonsolid nodules are classified into the bone window-visible and the bone window-invisible nonsolid nodules, and this classification differentiates invasive adenocarcinoma from noninvasive lesions. • The Lung-RADS category 2 nonsolid nodules are unlikely invasive adenocarcinoma if they show nonvisualization in the bone window.

Treatment Response Evaluation by Computed Tomography Pulmonary Vasculature Analysis in Patients With Chronic Thromboembolic Pulmonary Hypertension.

OBJECTIVE: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. MATERIALS AND METHODS: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). RESULTS: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV (P = 0.004) and positively associated with 6MWD (P = 0.013). CONCLUSION: Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Cisplatin and Albumin-Based Gold-Cisplatin Nanoparticles Enhance Ablative Radiation Therapy-Induced Antitumor Immunity in Local and Distant Tumor Microenvironment.

PURPOSE: Ablative radiation therapy (RT) is an important strategy to eliminate primary tumor and can potentially induce the abscopal effect. Human serum albumin nanoparticle (NP) was used for controlled release of cisplatin to decrease cisplatin's systemic toxicity, and gold (Au) was added to increase RT-induced immunogenic cell death and potentiate the abscopal antitumor immunity. METHODS AND MATERIALS: The designed albumin-based cisplatin-conjugated AuNPs were administered concurrently with ablative RT. C57BL/6 mice implanted with syngeneic murine Lewis lung carcinoma or murine MB49 tumor models were treated with ablative RT (12 Gy per fraction for 2 fractions, total 24 Gy), cisplatin, or Au-cisplatin NPs. RESULTS: Combining ablative RT with cisplatin or Au-cisplatin NPs both destroyed the primary tumor effectively and elicited immunogenic cell death accompanied by release of danger-associated molecular patterns. This enhanced recruitment of effector tumor-infiltrating immune cells, including natural killer T cells and CD8+ T cells, and elicited an increased percentage of professional antigen-presenting CD11c+ dendritic cells. Transient weight loss, accompanying hepatotoxicity, nephrotoxicity, and hematopoietic suppression, was observed as a systemic adverse event in the cisplatin but not the Au-cisplatin NPs group. Cisplatin and Au-cisplatin NPs both showed equivalent ability to reduce metastatic potential when combined with ablative RT, confirmed by suppressed unirradiated flank tumor growth and decreased metastatic lung tumor burden, which translated to improved survival. Mobilization and abundance of effector tumor-infiltrating immune cells including CD8+ T cells and dendritic cells were observed in the distant lung tumor microenvironment after ablative RT with cisplatin or Au-cisplatin NPs, demonstrating increased antitumor immunotherapeutic activity as an abscopal effect. CONCLUSIONS: Compared with cisplatin, the albumin-based Au-cisplatin NPs exhibited equivalent but no superior antitumor immunotherapeutic activity while reducing systemic adverse events and can be safely administered concurrently with ablative RT. Alternative NP formulations may be designed to further improve anticancer outcomes.

Therapeutic efficacy of cyclin-dependent kinase inhibition in combination with ionizing radiation for lung cancer.

PURPOSE: To evaluate the therapeutic efficacy of cyclin-dependent kinase (CDK) inhibition in combination with ionizing radiation for lung cancer. MATERIALS AND METHODS: Human lung adenocarcinoma (A549) and squamous cell carcinoma (H520) cells were used to evaluate the therapeutic efficacy of CDK inhibition in combination with ionizing radiation in vitro using colony formation assay, γH2AX immunofluorescence staining, western blotting, and cell cycle phase analysis. We also performed in vivo evaluations of ectopic tumor growth. RESULTS: In vitro pretreatment with the CDK inhibitor, seliciclib, before irradiation significantly decreased the survival of A549 and H520 cells in a dose-dependent manner. Although CDK inhibition alone did not increase the intensity of γH2AX foci, its combination with ionizing radiation increased DNA double-strand breaks, as shown by γH2AX immunofluorescence staining and western blotting. The combination of CDK inhibition and ionizing radiation-induced G2/M arrest and increased apoptosis, as evidenced by the increased proportion of cells in G2/M arrest, subG1 apoptotic population, and expression of apoptotic markers (cleaved PARP-1 and cleaved caspase-3). Mechanistic studies showed reduced expression of cyclin A with combined treatment, indicating cell cycle shifting effects. An in vivo xenograft model showed that the combination of CDK inhibition and ionizing radiation delayed xenograft tumor growth, and increased the proportion of cleaved PARP-1- and cleaved caspase-3-positive cells, compared to either treatment alone. CONCLUSIONS: We provide preclinical tumoricidal evidence that the combination of CDK inhibition and ionizing radiation is an efficacious treatment for lung cancer.

Xenon-Enhanced Ventilation Computed Tomography for Functional Lung Avoidance Radiation Therapy in Patients With Lung Cancer.

PURPOSE: This phase 2 trial aimed to determine whether xenon-enhanced ventilation computed tomography (XeCT)-guided functional-lung-avoidance radiation therapy could reduce the radiation pneumonitis (RP) rate in patients with lung cancer undergoing definitive chemoradiation therapy. METHODS AND MATERIALS: Functional lung ventilation was measured via pulmonary function testing (PFT) and XeCT. A standard plan (SP) without reference to XeCT and a functional-lung-avoidance plan (fAP) optimized for lowering the radiation dose to the functional lung at the guidance of XeCT were designed. Dosimetric parameters and predicted RP risks modeled by biological evaluation were compared between the 2 plans in a treatment planning system (TPS). All patients received the approved fAP. The primary endpoint was the rate of grade ≥2 RP, and the secondary endpoints were the survival outcomes. The study hypothesis was that fAP could reduce the rate of grade ≥2 RP to 12% compared with a 30% historical rate. RESULTS: Thirty-six patients were evaluated. Xenon-enhanced total functional lung volumes positively correlated with PFT ventilation parameters (forced vital capacity, P = .012; forced expiratory volume in 1 second, P = .035), whereas they were not correlated with the diffusion capacity parameter. We observed a 17% rate of grade ≥2 RP (6 of 36 patients), which was significantly different (P = .040) compared with the historical control. Compared with the SP, the fAP significantly spared the total ventilated lung, leading to a reduction in predicted grade ≥2 RP (P = .001) by TPS biological evaluation. The median follow-up was 15.2 months. The 1-year local control (LC), disseminated failure-free survival (DFFS), and overall survival (OS) rates were 88%, 66%, and 91%, respectively. The median LC and OS were not reached, and the median DFFS was 24.0 months (95% confidence interval, 15.7-32.3 months). CONCLUSIONS: This report of XeCT-guided functional-lung-avoidance radiation therapy provided evidence showing its feasibility in clinical practice. Its benefit should be assessed in a broader multicenter trial setting.

Multi-energy level fusion for nodal metastasis classification of primary lung tumor on dual energy CT using deep learning.

Lymph node metastasis also called nodal metastasis (Nmet), is a clinically primary task for physicians. The survival and recurrence of lung cancer are related to the Nmet staging from Tumor-Node-Metastasis (TNM) reports. Furthermore, preoperative Nmet prediction is still a challenge for the patient in managing the surgical plan and making treatment decisions. We proposed a multi-energy level fusion model with a principal feature enhancement (PFE) block incorporating radiologist and computer science knowledge for Nmet prediction. The proposed model is custom-designed by gemstone spectral imaging (GSI) with different energy levels on dual-energy computer tomography (CT) from a primary tumor of lung cancer. In the experiment, we take three different energy level fusion datasets: lower energy level fusion (40, 50, 60, 70 keV), higher energy level fusion (110, 120, 130, 140 keV), and average energy level fusion (40, 70, 100, 140 keV). The proposed model is trained by lower energy level fusion that is 93% accurate and the value of Kappa is 86%. When we used the lower energy level images to train the fusion model, there has been a significant difference to other energy level fusion models. Hence, we apply 5-fold cross-validation, which is used to validate the performance result of the multi-keV model with different fusion datasets of energy level images in the pathology report. The cross-validation result also demonstrates that the model with the lower energy level dataset is more robust and suitable in predicting the Nmet of the primary tumor. The lower energy level shows more information of tumor angiogenesis or heterogeneity provided the proposed fusion model with a PFE block and channel attention blocks to predict Nmet from primary tumors.

Preclinical evaluation of PEGylated liposomal doxorubicin as an effective radiosensitizer in chemoradiotherapy for lung cancer.

PURPOSE: Development of a safe and effective systemic chemotherapeutic agent for concurrent administration with definitive thoracic radiotherapy remains a major goal of lung cancer management. The synergistic effect of PEGylated liposomal doxorubicin and irradiation was evaluated in lung cancer cell lines both in vitro and in vivo. METHODS: In vitro radiosensitization of A549 and LLC cell lines was evaluated by colony formation assay, γH2AX fluorescent staining and western blot assay, and annexin V staining. A radiosensitization study with healthy human lung-derived cell line BEAS-2B was performed for comparative purposes. In vivo radiosensitization was evaluated by tumor ectopic growth, cell survival, pharmacokinetics, and biodistribution analyses. Cleaved caspase­3, the marker for apoptosis, was assessed immunohistochemically in A549 xenograft tumors. RESULTS: Treatment with PEGylated liposomal doxorubicin decreased A549 and LLC cell proliferation in a dose-dependent manner. In vitro studies revealed comparable radiosensitizer advantages of PEGylated liposomal doxorubicin and free doxorubicin, showing equivalent DNA double-strand breaks according to γH2AX fluorescent staining and western blot assays, similar numbers of apoptotic cells in the annexin­V staining assay, and moderately decreased clonogenic survival. In vivo studies demonstrated markedly slow ectopic tumor growth with prolonged survival following treatment with PEGylated liposomal doxorubicin plus irradiation in both A549 and LLC mouse models, suggesting that PEGylated liposomal doxorubicin is more effective as a radiosensitizer than free doxorubicin in vivo. Pharmacokinetics evaluation showed a longer half-life of approximately 40 h for PEGylated liposomal doxorubicin, confirming that the liposomal carrier achieved controlled release. Biodistribution evaluation of PEGylated liposomal doxorubicin confirmed high accumulation of doxorubicin in tumors, indicating the promising drug delivery attributes of PEGylated liposomal doxorubicin. Although free doxorubicin caused histopathologic myocarditis with the cardiac muscle fibers showing varying degrees of damage, PEGylated liposomal doxorubicin caused no such effects. The immunohistochemical expression of cleaved caspase-3-positive cells was greatest expressed in the irradiation and PEGylated liposomal doxorubicin combined treatment group, indicating prolonged tumoricidal effects. CONCLUSIONS: Our study provides preclinical in vitro and in vivo evidence of the effectiveness of PEGylated liposomal doxorubicin as a radiosensitizer, supporting its potential clinical development as a component of chemoradiotherapy.

Dual energy CT image prediction on primary tumor of lung cancer for nodal metastasis using deep learning.

Lymph node metastasis (LNM) identification is the most clinically important tasks related to survival and recurrence from lung cancer. However, the preoperative prediction of nodal metastasis remains a challenge to determine surgical plans and pretreatment decisions in patients with cancers. We proposed a novel deep prediction method with a size-related damper block for nodal metastasis (Nmet) identification from the primary tumor in lung cancer generated by gemstone spectral imaging (GSI) dual-energy computer tomography (CT). The best model is the proposed method trained by the 40 keV dataset achieves an accuracy of 86 % and a Kappa value of 72 % for Nmet prediction. In the experiment, we have 11 different monochromatic images from 40∼140 keV (the interval is 10 keV) for each patient. When we used the model of 40 keV dataset, there has significant difference in other energy levels (unit of keV). Therefore, we apply in 5-fold cross-validation to explain the lower keV is more efficient to predict Nmet of the primary tumor. The result shows that tumor heterogeneity and size contributed to the proposed model to estimate whether absence or presence of nodal metastasis from the primary tumor.

Real-World Evaluation of Modern Adjuvant Radiotherapy in Women with Stage IB Endometrial Cancer.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI); low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS); patients with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

Assessing tumor angiogenesis using dynamic contrast-enhanced integrated magnetic resonance-positron emission tomography in patients with non-small-cell lung cancer.

BACKGROUND: Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC. METHODS: This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), reverse reflux rate constant (kep), volume transfer constant (Ktrans), blood plasma volume fraction (vp), extracellular extravascular volume fraction (ve), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously. RESULTS: Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p <  0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, Ktrans, and kep, showed strong linear correlations (p <  0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations (p = 0.004), MTV values (p <  0.001), and kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10- 3/min (p = 0.069), and kep > 900 10- 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. CONCLUSIONS: The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.

Detecting small pulmonary nodules with spiral ultrashort echo time sequences in 1.5 T MRI.

OBJECTIVE: This study investigated ultrashort echo time (UTE) sequences in 1.5 T magnetic resonance imaging (MRI) for small lung nodule detection. MATERIALS AND METHODS: A total of 120 patients with 165 small lung nodules before video-associated thoracoscopic resection were enrolled. MRI sequences included conventional volumetric interpolated breath-hold examination (VIBE, scan time 16 s), spiral UTE (TE 0.05 ms) with free-breathing (scan time 3.5-5 min), and breath-hold sequences (scan time 20 s). Chest CT provided a standard reference for nodule size and morphology. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis. RESULTS: The nodule detection rate was significantly higher in spiral UTE free-breathing (> 78%, p < 0.05) and breath-hold sequences (> 75%, p < 0.05) compared with conventional VIBE (> 55%), reaching 100% when nodule size was > 16 mm, and reaching 95% when nodules were in solid morphology, regardless of size. The inter-sequence reliability between free-breathing and breath-hold spiral UTE was good (κ > 0.80). Inter-reader agreement was also high (κ > 0.77) for spiral UTE sequences. Nodule size measurements were consistent between CT and spiral UTE MRI, with a minimal bias up to 0.2 mm. DISCUSSION: Spiral UTE sequences detect small lung nodules that warrant surgery, offers realistic scan times for clinical work, and could be implemented as part of routine lung MRI.

Applying Compressed Sensing Volumetric Interpolated Breath-Hold Examination and Spiral Ultrashort Echo Time Sequences for Lung Nodule Detection in MRI.

This prospective study aimed to investigate the ability of spiral ultrashort echo time (UTE) and compressed sensing volumetric interpolated breath-hold examination (CS-VIBE) sequences in magnetic resonance imaging (MRI) compared to conventional VIBE and chest computed tomography (CT) in terms of image quality and small nodule detection. Patients with small lung nodules scheduled for video-assisted thoracoscopic surgery (VATS) for lung wedge resection were prospectively enrolled. Each patient underwent non-contrast chest CT and non-contrast MRI on the same day prior to thoracic surgery. The chest CT was performed to obtain a standard reference for nodule size, location, and morphology. The chest MRI included breath-hold conventional VIBE and CS-VIBE with scanning durations of 11 and 13 s, respectively, and free-breathing spiral UTE for 3.5-5 min. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and normal structure visualizations were measured to evaluate MRI quality. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis. Inter-reader and inter-modality reliability analyses were performed using the Cohen κ statistic and the nodule size comparison was performed using Bland-Altman plots. Among 96 pulmonary nodules requiring surgery, the average nodule diameter was 7.7 ± 3.9 mm (range: 4-20 mm); of the 73 resected nodules, most were invasive cancer (74%) or pre-invasive carcinoma in situ (15%). Both spiral UTE and CS-VIBE images achieved significantly higher overall image quality scores, SNRs, and CNRs than conventional VIBE. Spiral UTE (81%) and CS-VIBE (83%) achieved a higher lung nodule detection rate than conventional VIBE (53%). Specifically, the nodule detection rate for spiral UTE and CS-VIBE reached 95% and 100% for nodules >8 and >10 mm, respectively. A 90% detection rate was achieved for nodules of all sizes with a part-solid or solid morphology. Spiral UTE and CS-VIBE under-estimated the nodule size by 0.2 ± 1.4 mm with 95% limits of agreement from -2.6 to 2.9 mm and by 0.2 ± 1.7 mm with 95% limits of agreement from -3.3 to 3.5 mm, respectively, compared to the reference CT. In conclusion, chest CT remains the gold standard for lung nodule detection due to its high image resolutions. Both spiral UTE and CS-VIBE MRI could detect small lung nodules requiring surgery and could be considered a potential alternative to chest CT; however, their clinical application requires further investigation.