A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments.

Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.

Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

The differential diagnosis of lung precursor glandular lesions, micro-invasive adenocarcinoma, and invasive adenocarcinoma using low dose spectral computed tomography perfusion imaging.

Background: Few studies about the association between computed tomography (CT) perfusion imaging parameters and invasiveness in lung adenocarcinoma (LUAD) have been conducted using low dose spectral CT perfusion imaging. The purpose of this study was to investigate application of spectral revolution CT low-dose perfusion imaging in the differential diagnosis of different pathological subtypes of LUAD. Methods: This was a cross-sectional study based on historical data from January 2018 to May 2019 in Peking University Cancer Hospital & Institute. A total of 62 cases were enrolled, including 2 cases of atypical adenomatous hyperplasia (AAH), 3 cases of adenocarcinoma in situ (AIS), 4 cases of minimally invasive adenocarcinoma (MIA), and 53 cases of invasive adenocarcinoma (IAC), all confirmed with pathology. The inclusion and exclusion criteria were regulated. Using Revolution low-dose CT perfusion imaging (GE, USA), the CT perfusion parameters of hemodynamics were obtained: blood flow (BF), blood volume (BV), impulse residue function time of arrival (IRF TO), maximum slope of increase (MSI), mean transit time (MTT), permeability surface area product (PS), positive enhancement integral (PEI), and maximum enhancement time (Tmax). Univariate analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare the differences of CT perfusion quantitative parameters among AAH, AIS, MIA, and IAC. Mann-Whitney test was used to compare the difference of CT perfusion imaging parameters between preinvasive lesions (AAH and AIS) and invasive lung cancer (MIA and IAC). Results: Statistically significant differences in IRF TO were observed in LUAD with different invasiveness, namely, among AIS, MIA, and IAC groups (0.56±0.74 vs. 0.54±1.08 vs. 4.39±2.19, P=0.004). Statistically significant differences in IRF TO were also observed between pre-invasive lesions group (AAH and AIS) and invasive lung cancer group (MIA and IAC) (1.12±1.27 vs. 3.75±2.79, P=0.031), and between AAH + AIS + MIA groups and IAC group (0.83±1.13 vs. 4.12±2.69, P<0.001). There were no statistically significant differences in other CT perfusion parameters of hemodynamics among different pathological subtypes of LUAD (P>0.05). Conclusions: The low-dose perfusion parameter IRF TO of revolution CT has the potential to be employed in the differential diagnosis of different pathological subtypes of LUAD.

Assessing treatment outcomes of chemoimmunotherapy in extensive-stage small cell lung cancer: an integrated clinical and radiomics approach.

BACKGROUND: Small cell lung cancer (SCLC) is a highly malignant cancer characterized by metastasis and an extremely poor prognosis. Although combined chemoimmunotherapy improves the prognosis of extensive-stage (ES)-SCLC, the survival benefits remain limited. Furthermore, no reliable biomarker is available so far to predict the treatment outcomes for chemoimmunotherapy. METHODS: This retrospective study included patients with ES-SCLC treated with first-line combined atezolizumab or durvalumab with standard chemotherapy between Janauray 1, 2019 and October 1, 2022 at five medical centers in China as the chemoimmunotherapy group. The patients were divided into one training cohort and two independent external validation cohorts. Additionally, we created a control group of ES-SCLC who was treated with first-line standard chemotherapy alone. The Radiomics Score was derived using machine learning algorithms based on the radiomics features extracted in the regions of interest delineated on the chest CT obtained before treatment. Cox proportional hazards regression analysis was performed to identify clinical features associated with therapeutic efficacy. The log-rank test, time-dependent receiver operating characteristic curve, and Concordance Index (C-index) were used to assess the effectiveness of the models. RESULTS: A total of 341 patients (mean age, 62±8.7 years) were included in our study. After a median follow-up time of 12.1 months, the median progression-free survival (mPFS) was 7.1 (95% CI 6.6 to 7.7) months, whereas the median overall survival (mOS) was not reached. The TNM stage, Eastern Cooperative Oncology Group performance status, and Lung Immune Prognostic Index showed significant correlations with PFS. We proposed a predictive model based on eight radiomics features to determine the risk of chemoimmunotherapy resistance among patients with SCLC (validation set 1: mPFS, 12.0 m vs 5.0 m, C-index=0.634; validation set 2: mPFS, 10.8 m vs 6.1 m, C-index=0.617). By incorporating the clinical features associated with PFS into the radiomics model, the predictive efficacy was substantially improved. Consequently, the low-progression-risk group exhibited a significantly longer mPFS than the high-progression-risk group in both validation set 1 (mPFS, 12.8 m vs 4.5 m, HR=0.40, p=0.028) and validation set 2 (mPFS, 9.2 m vs 4.6 m, HR=0.30, p=0.012). External validation set 1 and set 2 yielded the highest 6-month area under the curve and C-index of 0.852 and 0.820, respectively. Importantly, the integrated prediction model also exhibited considerable differentiation power for survival outcomes. The HR for OS derived from the low-progression-risk and high-progression-risk groups was 0.28 (95% CI 0.17 to 0.48) in all patients and 0.20 (95% CI 0.08 to 0.54) in validation set. By contrast, no significant differences were observed in PFS and OS, between high-progression-risk patients receiving chemoimmunotherapy and the chemotherapy cohort (mPFS, 5.5 m vs 5.9 m, HR=0.90, p=0.547; mOS, 14.5 m vs 13.7 m, HR=0.97, p=0.910). CONCLUSIONS: The integrated clinical and radiomics model can predict the treatment outcomes in patients with ES-SCLC receiving chemoimmunotherapy, rendering a convenient and low-cost prognostic model for decision-making regarding patient management.

An Effective Malignancy Prediction Model for Incidentally Detected Pulmonary Subsolid Nodules Based on Current and Prior CT Scans.

INTRODUCTION: It is challenging to diagnose and manage incidentally detected pulmonary subsolid nodules due to their indolent nature and heterogeneity. The objective of this study is to construct a decision tree-based model to predict malignancy of a subsolid nodule based on radiomics features and evolution over time. MATERIALS AND METHODS: We derived a training set (2947 subsolid nodules), a test set (280 subsolid nodules) from a cohort of outpatient CT scans, and a second test set (5171 subsolid nodules) from the National Lung Cancer Screening Trial (NLST). A Computer-Aided Diagnosis system (CADs) automatically extracted 28 preselected radiomics features, and we calculated the feature change rates as the change of the quantitative measure per time unit between the prior and current CT scans. We built classification models based on XGBoost and employed 5-fold cross validation to optimize the parameters. RESULTS: The model that combined radiomics features with their change rates performed the best. The Areas Under Curve (AUCs) on the outpatient test set and on the NLST test set were 0.977 (95% CI, 0.958-0.996) and 0.955 (95% CI, 0.930-0.980), respectively. The model performed consistently well on subgroups stratified by nodule diameters, solid components, and CT scan intervals. CONCLUSION: This decision tree-based model trained with the outpatient dataset gives promising predictive performance on the malignancy of pulmonary subsolid nodules. Additionally, it can assist clinicians to deliver more accurate diagnoses and formulate more in-depth follow-up strategies.

Procedure-related pain during CT-guided percutaneous transthoracic needle biopsies of lung lesions: a prospective study.

BACKGROUND: The existing data on the degree of pain in patients during CT-guided percutaneous transthoracic needle biopsy (PTNB) of lung lesions are limited and the factors related to pain are unclear. In this study, we aimed to evaluate the prevalence and severity of pain reported during PTNB and to identify factors associated with increased reported pain. METHODS: Patients who underwent PTNB from April 2022 to November 2022 were prospectively evaluated using the numeric rating scale, which assesses subjective pain based on a 0-10 scoring system (0 = no pain; 10 = the worst pain imaginable). The scale divides the scores into three categories: mild pain (1-3 points), moderate pain (4-6 points), and severe pain (7-10 points). Pain scores from 4 to 10 were considered significant pain. Demographic data of patients, lesion characteristics, biopsy variables, complications, the patient's subjective feelings, and pathological result data were analyzed by multivariable logistic regression analysis to identify variables associated with significant pain. RESULTS: We enrolled 215 participants who underwent 215 biopsy procedures (mean age: 64.5 ± 9.3 years, 123 were men). The mean procedure-related pain score was 2 ± 2. Overall, 20% (43/215) of participants reported no pain (score of 0), 67.9% (146/215) reported pain scores of 1-3, 11.2% (24/215) reported scores of 4-6, and 0.9% (2/215) reported scores of 7 or higher. Furthermore, non-significant pain (scores of 0-3) was reported during 87.9% (189/215) of the procedures. In the adjusted model, significant pain was positively associated with lesions ≥ 34 mm (p = 0.001, odds ratio [OR] = 6.90; 95% confidence interval [CI]: 2.18, 21.85), a needle-pleural angle ≥ 77° (p = 0.047, OR = 2.44; 95% CI: 1.01, 5.89), and a procedure time ≥ 26.5 min (p = 0.031, OR = 3.11; 95% CI: 1.11, 8.73). CONCLUSIONS: Most participants reported no pain or mild pain from CT-guided percutaneous transthoracic needle biopsies of lung lesions. However, those with a larger lesion, a greater needle-pleural angle, and a longer procedure time reported greater pain.

Prediction of the lymphatic, microvascular, and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging.

BACKGROUND: Significant correlation between lymphatic, microvascular, and perineural invasion (LMPI) and the prognosis of pancreatic neuroendocrine tumors (PENTs) was confirmed by previous studies. There was no previous study reported the relationship between magnetic resonance imaging (MRI) parameters and LMPI. AIM: To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs (NFPNETs). METHODS: A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study. The patients were divided into group 1 (n = 34, LMPI negative) and group 2 (n = 27, LMPI positive). The clinical characteristics and qualitative MRI features were collected. In order to predict LMPI status in NF-PNETs, a multivariate logistic regression model was constructed. Diagnostic performance was evaluated by calculating the receiver operator characteristic (ROC) curve with area under ROC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. RESULTS: There were significant differences in the lymph node metastasis stage, tumor grade, neuron-specific enolase levels, tumor margin, main pancreatic ductal dilatation, common bile duct dilatation, enhancement pattern, vascular and adjacent tissue involvement, synchronous liver metastases, the long axis of the largest lymph node, the short axis of the largest lymph node, number of the lymph nodes with short axis > 5 or 10 mm, and tumor volume between two groups (P < 0.05). Multivariate analysis showed that tumor margin (odds ratio = 11.523, P < 0.001) was a predictive factor for LMPI of NF-PNETs. The area under the receiver value for the predictive performance of combined predictive factors was 0.855. The sensitivity, specificity, PPV, NPV and accuracy of the model were 48.1% (14/27), 97.1% (33/34), 97.1% (13/14), 70.2% (33/47) and 0.754, respectively. CONCLUSION: Using preoperative MRI, ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

Among Multiple Needle Core Biopsy Samples, the One with the Highest Tumor Proportion Score Best Represents the PD-L1 Status of the Whole Surgical Specimen in Non-Small Cell Lung Cancer.

The heterogeneity of programmed death-ligand 1 (PD-L1) status between core needle biopsies (CNBs) from one tumor has not been well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. Random CNB was performed in surgical specimens from 170 consecutive non-small cell lung cancer samples. Fifty-one cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. Heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56% of PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cut-off of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3%, and 86.3%; At a cut-off of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4%, and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen. The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cut-offs.

Hypofractionated Volumetric-Modulated Arc Radiotherapy for Patients With Non-Small-Cell Lung Cancer Not Suitable for Surgery or Conventional Chemoradiotherapy or SBRT.

BACKGROUND: Hypofractionated radiotherapy (HypoRT) has been used to pursue an alternative treatment regimen for patients with non-small-cell lung cancer (NSCLC) who are not eligible for stereotactic ablative radiotherapy (SABR), surgery or concurrent chemoradiotherapy (CCRT) and has shown good local control and safety. We analyzed the feasibility of using volumetric-modulated arc radiotherapy (VMAT) with the simultaneous integrated boost (SIB) technique to achieve high local control with few treatment-related toxicities. PATIENTS AND METHODS: A total of 55 patients with stage I-IV NSCLC who were not candidates for SABR, surgery or CCRT were included in the present study. All patients received a prescribed dose of 60 to 66 Gy in 15 fractions. Local progression-free survival (LPFS), PFS, overall survival (OS), and toxicities were retrospectively analyzed. RESULTS: Thirty-three patients (60.0%) had stage IV or recurrent disease in this study. The median follow-up time was 8 months (interquartile range: 5.0-16.3 months). The 1-year and 2-year OS rates were 84.3% and 69.9%, and the 1-year and 2-year LPFS rates were 91.0% and 63.0%. The median OS (mOS) and median LPFS (mLPFS) were not reached, and median PFS (mPFS) was 15 months. Twenty-eight (51.9%) patients had disease progression at the time of analysis. Of these, 7 (13.0%), 7 (13.0%) and 21 (38.9%) had local recurrence, locoregional failure and distant metastasis, respectively. All cases of local recurrence were found within the SIB region. Four patients had grade 2-3 pneumonitis, and 8 patients had grade 2-3 esophagitis. Patients with grade 2-3 esophagitis had significantly higher maximum dose and dose to 5 cm3 volume to esophagus than those with grade 0-1 esophagitis. No grade 4 or higher toxicity was observed. CONCLUSION: The 60 to 66 Gy in 15 fractions RT regimen provides favorable local control and survival with well-tolerated toxicities. Hypofractionated VMAT+SIB is an alternative treatment option for patients with NSCLC who cannot tolerate standard definitive therapy.

Major pathologic response assessment and clinical significance of metastatic lymph nodes after neoadjuvant therapy for non-small cell lung cancer.

For neoadjuvant therapy in patients with non-small cell lung cancer, the major pathologic response of primary tumors may be an assessable and reliable surrogate measure of survival. Few studies have examined the pathologic evaluation of metastatic lymph node responses and their prognostic significance. This retrospective study enrolled 336 patients with non-small cell lung cancer (squamous cell carcinoma, n = 216; adenocarcinoma, n = 120) treated with neoadjuvant therapy including chemotherapy (n = 316) and targeted therapy (adenocarcinoma, n = 20). The treatment response of the primary tumor and lymph node metastases (LNM) were pathologically assessed according to the multidisciplinary recommendations of the International Association for the Study of Lung Cancer. The relationship of overall survival (OS) and disease-free survival (DFS) with the responses of the primary tumor or LNM was analyzed. The optimal cutoff value of the residual viable tumor (%RVT) of the primary tumor was 12% for both OS (P < 0.001) and DFS (P < 0.001). The pathologic assessment identified LNM in 208 patients. The optimal %RVT cutoff value in LNM was 8% for both OS (P = 0.003) and DFS (P < 0.001). The Spearman's rank correlation coefficient between primary tumors and corresponding LNM was 0.487 for %RVT (P < 0.001), which indicated a positive correlation. On multivariable analysis, an RVT of the primary tumor ≤12% was an independent prognostic factor for improved OS (P = 0.024), whereas an RVT of LNM ≤ 8% was an independent prognostic factor for increased DFS (P = 0.018). Furthermore, in the neoadjuvant chemotherapy group, the optimal %RVT cutoff values for OS in patients with squamous cell carcinoma and adenocarcinoma in the primary tumor were 12% and 58%, respectively. Considering its convenience and operability in clinical application, a 10% threshold RVT value can be used for prognostic evaluation of LNM and primary tumors of squamous cell carcinoma histology; further studies are needed to confirm the optimal cutoff value for primary tumors of adenocarcinoma.

Low-dose spectral CT perfusion imaging of lung cancer quantitative analysis in different pathological subtypes.

BACKGROUND: To explore the value of the quantitative parameters of low-dose computed tomography (CT) perfusion in the diagnosis of lung cancers of different pathological types. METHODS: Eighty-five patients with lung cancer confirmed by pathology underwent enhanced spectral CT imaging with a General Electric (GE) Revolution Xtream CT scanner, including 7 patients with lung squamous cell carcinoma, 8 patients with small cell carcinoma, 67 patients with lung adenocarcinoma, and 3 patients with other pathologies. The low-dose CT perfusion parameters [blood flow (BF), blood volume (BV), time of arrival (IRF TO), maximum slope of increase (MSI), mean transit time (MTT), positive enhancement integral (PEI), time to peak (TTP) and time to maximum (Tmax)] were calculated and compared among the first three groups. One-way analysis of variance (ANOVA) or the Kruskal-Wallis test was used to compare the quantitative parameters among the three groups, and the Bonferroni method was used to correct for multiple comparisons. RESULTS: Among the quantitative parameters, MSI was significantly different among the three lung cancers (adenocarcinoma vs. squamous cell carcinoma vs. small cell carcinoma: 11.37±8.74 vs. 2.35±0.88 vs. 1.40±0.26, respectively; P=0.016). The MSI of lung adenocarcinoma was lower than that of non-adenocarcinoma (P=0.001), and the MSI of small cell carcinoma was lower than that of non-small cell carcinoma (P=0.014). There were no significant differences in the other parameters among these three groups (P>0.05). CONCLUSIONS: Low-dose CT perfusion parameters may have a certain value in classifying the pathological type of lung cancer.

CircACC1 Promotes NSCLC Proliferation via miR-29c-3p/MCL-1 Signaling Pathway.

Non-small cell lung cancer remains the leading cause of cancer-related deaths worldwide with high morbidity and mortality. There is an urgent need to reveal new molecular mechanisms that contribute to NSCLC progression to facilitate drug development and to improve overall survival. Much attention has been paid to the role of circRNAs in NSCLC development. However, the knowledge of circRNAs in NSCLC is still limited, and need to be further explored. The dysregulation of circACC1 was evaluated by qRT-PCR in NSCLC samples and cell lines. The oncogenic role of circACC1 in NSCLC progression was analyzed by CCK8 and colony formation assays. The interaction between the circACC1 and miR-29c-3p, as well as MCL-1, was verified by qRT-PCR, Western blot, luciferase reporter assay, and RIP experiment. Elevated levels of circACC1 were found in NSCLC patients and were negatively correlated with OS. Ectopic expression of circACC1 promoted the capacity of cell growth and clonogenicity, while the inhibition of circACC1 decreased the proliferation and clonogenicity potential. Mechanism studies elucidated that circACC1 contributes to cell growth via directly binding to miR-29c-3p. Transfection of miR-29c-3p mimic blocked circACC1 mediated NSCLC cell proliferation. MCL-1 is a downstream target of miR-29c-3p in NSCLC cells. The circACC1/miR-29c-3p/MCL-1 axis is important in NSCLS proliferation.

Virtual bronchoscopic navigation without fluoroscopy guidance for peripheral pulmonary lesions in inexperienced pulmonologist.

OBJECTIVE: Fluoroscopy guidance is generally required for endobronchial ultrasonography with guide sheath (EBUS-GS) in peripheral pulmonary lesions (PPLs). Virtual bronchoscopic navigation (VBN) can guide the bronchoscope by creating virtual images of the bronchial route to the lesion. The diagnostic yield and safety profiles of VBN without fluoroscopy for PPLs have not been evaluated in inexperienced pulmonologist performing EBUS-GS. METHODS: Between January 2016 and June 2017, consecutive patients with PPLs referred for EBUS-GS at a single cancer center were enrolled. The diagnostic yield as well as safety profiles was retrospectively analyzed, and our preliminary experience was shared. RESULTS: A total of 109 patients with 109 lesions were included, 99 (90.8%) lesions were visible on EBUS imaging. According to the procedure time needed to locate the lesion on EBUS, 24.8% (27/109) were deemed technically difficult procedures; however, no significant relationships were identified between candidate parameters and technically difficult procedures. The overall diagnosis yield was 74.3% (81/109), and the diagnostic yield of malignancy was 83.7% (77/92). Lesions larger than 20 mm [odds ratio (OR), 2.758; 95% confidence interval (95% CI), 1.077-7.062; P=0.034] and probe of within type (OR, 3.174; 95% CI, 1.151-8.757, P=0.026) were independent factors leading to a better diagnostic yield in multivariate analysis. About 30 practice procedures were needed to achieve a stable diagnostic yield, and the proportion of technically difficult procedures decreased and stabilized after 70 practice procedures. Regarding complications, one patient (0.9%) had intraoperative hemorrhage (100 mL) which was managed under endoscopy. CONCLUSIONS: VBN without fluoroscopy guidance is still useful and safe for PPLs diagnosis, especially for malignant diseases when performed by pulmonologist without previous experience of EBUS-GS. VBN may simplify the process of lesion positioning and further multi-center randomized studies are warranted.

Spectral CT imaging parameters and Ki-67 labeling index in lung adenocarcinoma.

OBJECTIVE: To explore the correlation between the spectral computed tomography (CT) imaging parameters and the Ki-67 labeling index in lung adenocarcinoma. METHODS: Spectral CT imaging parameters [iodine concentrations of lesions (ICLs) in the arterial phase (ICLa) and venous phase (ICLv), normalized IC in the aorta (NICa/NICv), slope of the spectral HU curve (λHUa/λHUv) and monochromatic CT number enhancement on 40 keV and 70 keV images (CT40keVa/v, CT70keVa/v)] in 34 lung adenocarcinomas were analyzed, and common molecular markers, including the Ki-67 labeling index, were detected with immunohistochemistry. Different Ki-67 labeling indexes were measured and grouped into four grades according to the number of positive-stained cells (grade 0, ≤1%; 1%30%). One-way analysis of variance (ANOVA) was used to compare the four different grades, and the Bonferroni method was used to correct the P value for multiple comparisons. A Spearman correlation analysis was performed to further research a quantitative correlation between the Ki-67 labeling index and spectral CT imaging parameters. RESULTS: CT40keVa, CT40keVv, CT70keVa and CT70keVv increased as the grade increased, and CT70keVa and CT70keVv were statistically significant (P<0.05). These four parameters and the Ki-67 labeling index showed a moderate positive correlation with lung adenocarcinoma nodules. ICL, NIC and λHU in the arterial and venous phases were not significantly different among the four grades. CONCLUSIONS: The spectral CT imaging parameters CT40keVa, CT40keVv, CT70keVa and CT70keVv gradually increased with Ki-67 expression and showed a moderate positive correlation with lung adenocarcinomas. Therefore, spectral CT imaging parameter-enhanced monochromatic CT numbers at 70 keV may indicate the extent of proliferation of lung adenocarcinomas.

Is there any correlation between spectral CT imaging parameters and PD-L1 expression of lung adenocarcinoma?

BACKGROUND: The aim of this study was to explore whether spectral computed tomography (CT) imaging parameters are associated with PD-L1 expression of lung adenocarcinoma. METHODS: Spectral CT imaging parameters (iodine concentrations [IC] of lesion in arterial phase [ICLa] and venous phase [ICLv], normalized IC [NICa/NICv]-normalized to the IC in the aorta, slope of the spectral HU curve [λHUa/λHUv] and enhanced monochromatic CT number [CT40keVa/v, CT70keVa/v] on 40 and 70 keV images) were analyzed in 34 prospectively enrolled lung adenocarcinoma patients with common molecular pathological markers including PD-L1 expression detected with immunohistochemistry. Patients were divided into two groups: positive PD-L1 expression and negative PD-L1 expression groups. Two-sample Mann-Whitney U test was used to test the difference of spectral CT imaging parameters between the two groups. RESULTS: The CT40keVa (127.03 ± 37.92 vs. -54.69 ± 262.04), CT40keVv (124.39 ± 34.71 vs. -45.73 ± 238.97), CT70keVa (49.56 ± 11.76 vs. -136.51 ± 237.08) and CT70keVv (46.13 ± 15.81 vs. -133.10 ± 230.72) parameters in the positive PD-L1 expression group of lung adenocarcinoma were significantly higher than the negative PD-L1 expression group (all P < 0.05). There was no difference detected in IC, NIC and λHU of the arterial and venous phases between both groups (all P > 0.05). CONCLUSION: CT40keVa, CT40keVv, CT70keVa and CT70keVv were increased in positive PD-L1 expression. These parameters may be used to distinguish the PD-L1 expression state of lung adenocarcinoma.

[Diagnostic Utility of Virtual Bronchoscopic Navigation Assisted Endobronchial 
Ultrasonography with Guide Sheath for Peripheral Pulmonary Lesions].

BACKGROUND: Virtual bronchoscopic navigation (VBN) assisted endobronchial ultrasonography with guide sheath (EBUS-GS) has reduced the difficulty and even avoiding radiation exposure during performing transbronchus lung biopsy (TBLB). To evaluate the feasibility and safety of virtual bronchoscopic navigation assisted endobronchial ultrasonography with guide sheath for peripheral pulmonary lesions. METHODS: We performed a retrospective analysis of the patients with PPLs who received VBN assisted EBUS-GS-TBLB in Peking University Cancer Hospital from January 2016 to December 2017. Their clinicopathologic data and complications were assessed. RESULTS: A total of 121 patients were enrolled in the study. The patients included 65 men and 56 women, with a mean age of (58.8±10.3) years. A total of 121 PPLs were examined, and 108 lesions of which could be detected by EBUS. The overall diagnostic yield of EBUS-GS was 73.5%. The diagnostic yield of malignancy was 82.5%. The combination of transbronchial lung biopsy, brush smear and bronchoalveolar lavage fluid provided the greatest diagnostic yield (χ²=6.084, P=0.014). Factors that significantly affected and predicted diagnostic success were EBUS probe within the lesions (χ²=20.372, P=0.000) and PPLs located in the central two-thirds of the lung (χ²=10.810, P=0.001). 1 patient (0.8%) suffered from intraoperative bleeding which could be managed under endoscopy. CONCLUSIONS: VBN assisted EBUS-GS-TBLB for PPLs was an effective and safe procedure.

Can spectral computed tomography imaging improve the differentiation between malignant and benign pulmonary lesions manifesting as solitary pure ground glass, mixed ground glass, and solid nodules?

BACKGROUND: This study quantitatively assessed the efficacy of spectral computed tomography (CT) imaging parameters for differentiating the malignancy and benignity of solitary pulmonary nodules (SPNs) manifesting as ground glass nodules (GGNs) and solid nodules (SNs). METHODS: The study included 114 patients with SPNs (61 GGNs, and 53 SNs) who underwent CT plain and enhanced scans in the arterial (a) and venous (v) phases using the spectral imaging mode. The spectral CT imaging parameters included: iodine concentrations (IC) of lesions in the arterial (ICLa) and venous (ICLv) phases; normalized IC (NICa/NICv, normalized to the IC in the aorta); the slope of the spectral Hounsfield unit (HU) curve (λHUa/λHUv); and monochromatic CT number (CT40keVa/v, CT70keVa/v) enhancement on 40 and 70 keV images. The two-sample Mann-Whitney U test was used to compare quantitative parameters between malignant and benign SPNs, SNs, and GGNs. RESULTS: Pathology revealed 75 lung cancer cases, 3 metastatic nodules, 14 benign nodules, and 22 inflammatory nodules. Among the 53 SNs there were 37 malignant and 16 benign nodules. Among the 61 GGNs there were 41 malignant and 20 benign nodules. Overall, the CT40keVa, λHUa, CT40keVv, λHUv, and ICLv of benign SPNs were all greater than those of malignant SPNs (all P < 0.05). For GGNs, CT40keVa/v, CT70keVa/v, λHUa/λHUv, and ICLv of malignant GGNs were all lower than those of benign GGNs. CONCLUSION: Spectral CT imaging is a more promising method for distinguishing malignant from benign nodules, especially in nodules manifesting as GGNs in contrast-enhanced scanning.

Multivariate Analysis of Pleural Invasion of Peripheral Non-Small Cell Lung Cancer-Based Computed Tomography Features.

OBJECTIVE: The aim of this study was to comprehensively analyze computed tomography features to improve the diagnostic accuracy of visceral pleural invasion of peripheral non-small cell lung cancer. METHODS: The computed tomography features of 205 non-small cell lung cancer patients were retrospectively studied. The lesion's relation to the pleura was classified into 5 grades. A multivariate logistic regression analysis was conducted to identify independent factors predicting pleural invasion. RESULTS: The multivariate logistic regression analysis showed that sex (odds ratio [OR], 1.822; P = 0.080), pleural indentation (OR, 4.111; P < 0.001), tumor density (OR, 2.735; P = 0.008), and distance between the lesion and pleura (OR, 1.981; P = 0.048) were independent predictors of pleural invasion. A patient with a score of 10.6 had an 80% risk of pleural invasion, whereas a score lower than 2 was associated with a lower (20%) risk of pleural invasion. CONCLUSIONS: Comprehensive consideration of these factors of pleural indentation, sex, tumor density, and distance between the lesion and pleura might improve the diagnosis of pleural invasion.

Diffusion-weighted images (DWI) without ADC values in assessment of small focal nodules in cirrhotic liver.

OBJECTIVE: To assess if diffusion-weighted magnetic resonance (MR) imaging without apparent diffusion coefficient (ADC) values provides added diagnostic value in combination with conventional MR imaging in the detection and characterization of small nodules in cirrhotic liver. METHODS: Two observers retrospectively and independently analyzed 86 nodules (≤3 cm) certified pathologically in 33 patients with liver cirrhosis, including 48 hepatocellular carcinoma (HCC) nodules, 13 high-grade dysplastic nodules (HDN), 10 low-grade dysplastic nodules (LDNs) and 15 other benign nodules. All these focal nodules were evaluated with conventional MR images (T1-weighted, T2-weighted and dynamic gadolinium-enhanced images) and breath-hold diffusion-weighted images (DWI) (b=500 s/mm(2)). The nodules were classified by using a scale of 1-3 (1, not seen; 3, well seen) on DWI for qualitative assessment. These small nodules were characterized by two radiologists. ADC values weren't measured. The diagnostic performance of the combined DWI-conventional images and the conventional images alone was evaluated using receiver operating characteristic (ROC) curves. The area under the curves (Az), sensitivity and specificity values for characterizing different small nodules were also calculated. RESULTS: Among 48 HCC nodules, 33 (68.8%) were graded as 3 (well seen), 6 (12.5%) were graded as 2 (partially obscured), and 9 weren't seen on DWI. Among 13 HDNs, there were 3 (23.1%) and 4 (30.8%) graded as 3 and 2 respectively. Five (50%) of 10 benign nodules were partially obscured and slightly hyperintense. For 86 nodules, the average diagnostic accuracy of combined DWI-conventional images was 82.56%, which was increased significantly compared with conventional MR images with 76.17%. For HCC and HDN, the diagnostic accuracy of combined DWI-conventional images increased from 78.69% to 86.07%. CONCLUSIONS: Diffusion-weighted MR imaging does provide added diagnostic value in the detection and characterization of HDN and HCC, and it may not be helpful for LDN and regenerative nodule (RN) in cirrhotic liver.

Assessment of the hepatic microvascular changes in liver cirrhosis by perfusion computed tomography.

AIM: To assess the hepatic microvascular parameters in patients with liver cirrhosis by perfusion computed tomography (CT). METHODS: Perfusion CT was performed in 29 patients without liver disease (control subjects) and 39 patients with liver cirrhosis, including 22 patients with compensated cirrhosis and 17 patients with decompensated cirrhosis, proved by clinical and laboratory parameters. CT cine-scans were obtained over 50 s beginning with the injection of 50 mL of contrast agent. Hepatic microvascular parameters, mean transit time (MTT) and permeability surface area product (PS) were obtained with the Perfusion 3 software (General Electric, ADW 4.2). RESULTS: The overall differences of MTT and PS between control subjects, patients with compensated cirrhosis and those with decompensated cirrhosis were statistically significant (P = 0.010 and P = 0.002, respectively). MTT values were 15.613 +/- 4.1746 s, 12.592 +/- 4.7518 s, and 11.721 +/- 4.5681 s for the three groups, respectively, while PS were 18.945 +/- 7.2347 mL/min per 100 mL, 22.767 +/- 8.3936 mL/min per 100 mL, and 28.735 +/- 13.0654 mL/min per 100 mL. MTT in decompensated cirrhotic patients were significantly decreased compared to controls (P = 0.017), whereas PS values were remarkably increased (P = 0.001). CONCLUSION: The hepatic microvascular changes in patients with liver cirrhosis can be quantitatively assessed by perfusion CT. Hepatic microvascular parameters (MTT and PS), as measured by perfusion CT, were significantly altered in decompensated cirrhosis.