Prediction of high-grade patterns of stage IA lung invasive adenocarcinoma based on high-resolution CT features: a bicentric study.

OBJECTIVES: This study aims to predict the high-grade pattern (HGP) of stage IA lung invasive adenocarcinoma (IAC) based on the high-resolution CT (HRCT) features. METHODS: The clinical, pathological, and HRCT imaging data of 457 patients (from bicentric) with pathologically confirmed stage IA IAC (459 lesions in total) were retrospectively analyzed. The 459 lesions were classified into high-grade pattern (HGP) (n = 101) and non-high-grade pattern (n-HGP) (n = 358) groups depending on the presence of HGP (micropapillary and solid) in pathological results. The clinical and pathological data contained age, gender, smoking history, tumor stage, pathological type, and presence or absence of tumor spread through air spaces (STAS). CT features consisted of lesion location, size, density, shape, spiculation, lobulation, vacuole, air bronchogram, and pleural indentation. The independent predictors for HGP were screened by univariable and multivariable logistic regression analyses. The clinical, CT, and clinical-CT models were constructed according to the multivariable analysis results. RESULTS: The multivariate analysis suggested the independent predictors of HGP, encompassing tumor size (p = 0.001; OR = 1.090, 95% CI 1.035-1.148), density (p < 0.001; OR = 9.454, 95% CI 4.911-18.199), and lobulation (p = 0.002; OR = 2.722, 95% CI 1.438-5.154). The AUC values of clinical, CT, and clinical-CT models for predicting HGP were 0.641 (95% CI 0.583-0.699) (sensitivity = 69.3%, specificity = 79.2%), 0.851 (95% CI 0.806-0.896) (sensitivity = 79.2%, specificity = 79.6%), and 0.852 (95% CI 0.808-0.896) (sensitivity = 74.3%, specificity = 85.8%). CONCLUSION: The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade pattern of stage IA IAC. KEY POINTS: • The AUC values of clinical, CT, and clinical-CT models for predicting high-grade patterns were 0.641 (95% CI 0.583-0.699), 0.851 (95% CI 0.806-0.896), and 0.852 (95% CI 0.808-0.896). • Tumor size, density, and lobulation were independent predictive markers for high-grade patterns. • The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade patterns of invasive adenocarcinoma.

Computed tomography versus frozen sections for distinguishing lung adenocarcinoma: A cohort study of concordance rate.

BACKGROUND: Computed tomography (CT) imaging can help to predict the pathological invasiveness of early-stage lung adenocarcinoma and guide surgical resection. This retrospective study investigated whether CT imaging could distinguish pre-invasive lung adenocarcinoma from IAC. It also compared final pathology prediction accuracy between CT imaging and intraoperative frozen section analysis. METHODS: This study included 2093 patients with early-stage peripheral lung adenocarcinoma who underwent CT imaging and intraoperative frozen section analysis between March 2013 and November 2014. Nodules were classified as ground-glass (GGNs), part-solid (PSNs), and solid nodules according to CT findings; they were classified as pre-IAC and IAC according to final pathology. Univariate, multivariate, and receiver operating characteristic (ROC) curve analyses were performed to evaluate whether CT imaging could distinguish pre-IAC from IAC. The concordance rates of CT imaging and intraoperative frozen section analyses with final pathology were also compared to determine their accuracies. RESULTS: Multivariate analysis identified tumor size as an independent distinguishing factor. ROC curve analyses showed that the optimal cut-off sizes for distinguishing pre-IAC from IAC for GGNs, PSNs, and solid nodules were 10.79, 11.48, and 11.45 mm, respectively. The concordance rate of CT imaging with final pathology was significantly greater than the concordance rate of intraoperative frozen section analysis with final pathology (P = 0.041). CONCLUSION: CT imaging could distinguish pre-IAC from IAC in patients with early-stage lung adenocarcinoma. Because of its accuracy in predicting final pathology, CT imaging could contribute to decisions associated with surgical extent. Multicenter standardized trials are needed to confirm the findings in this study.

Use of diffusion-weighted magnetic resonance imaging (DW-MRI) to predict early response to anti-tumor therapy in advanced non-small cell lung cancer (NSCLC): a comparison of intravoxel incoherent motion-derived parameters and apparent diffusion coefficient.

BACKGROUND: The intravoxel incoherent motion (IVIM) method of magnetic resonance imaging (MRI) analysis can provide information regarding many physiological and pathological processes. This study aimed to investigate whether IVIM-derived parameters and the apparent diffusion coefficient (ADC) can act as imaging biomarkers for predicting non-small cell lung cancer (NSCLC) response to anti-tumor therapy and compare their performances. METHODS: This prospective study included 45 patients with NSCLC treated with chemotherapy (29 men and 16 women, mean age 57.9±9.7 years). Diffusion-weighted imaging was performed with 13 b-values before and 2-4 weeks after treatment. The IVIM parameter pseudo-diffusion coefficient (D*), perfusion fraction (f), diffusion coefficient (D), and ADC from a mono-exponential model were obtained. Responses 2 months after chemotherapy were assessed. The diagnostic performance was evaluated, and optimal cut-off values were determined by receiver operating characteristic (ROC) curve analysis, and the differences of progression-free survival (PFS) in groups of responders and non-responders were tested by Cox regression and Kaplan-Meier survival analyses. RESULTS: Of 45 patients, 30 (66.7%) were categorized as responders, and 15 as non-responders. Differences in the diffusion coefficient D and ADC between responders and non-responders were statistically significant (all P<0.05). Conversely, differences in f and D* between responders and non-responders were both not statistically significance (all P>0.05). The ROC analyses showed the change in D value (ΔD) was the best predictor of early response to anti-tumor therapy [area under the ROC curve (AUC), 0.764]. The Cox-regression model showed that all ADC and D parameters were independent predictors of PFS, with a range of reduction in risk from 56.2% to 82.7%, and ΔD criteria responders had the highest reduction (82.7%). CONCLUSIONS: ADC and D derived from IVIM are potentially useful for the prediction of NSCLC treatment response to anti-tumor therapy. Although ΔD is best at predicting response to treatment, ΔADC measurement may simplify manual efforts and reduce the workload.

Radiomics Signature Facilitates Organ-Saving Strategy in Patients With Esophageal Squamous Cell Cancer Receiving Neoadjuvant Chemoradiotherapy.

After neoadjuvant chemoradiotherapy (NCRT) in locally advanced esophageal squamous cell cancer (ESCC), roughly 40% of the patients may achieve pathologic complete response (pCR). Those patients may benefit from organ-saving strategy if the probability of pCR could be correctly identified before esophagectomy. A reliable approach to predict pathological response allows future studies to investigate individualized treatment plans. METHOD: All eligible patients treated in our center from June 2012 to June 2019 were retrospectively collected. Radiomics features extracted from pre-/post-NCRT CT images were selected by univariate logistic and LASSO regression. A radiomics signature (RS) developed with selected features was combined with clinical variables to construct RS+clinical model with multivariate logistic regression, which was internally validated by bootstrapping. Performance and clinical usefulness of RS+clinical model were assessed by receiver operating characteristic (ROC) curves and decision curve analysis, respectively. RESULTS: Among the 121 eligible patients, 51 achieved pCR (42.1%) after NCRT. Eighteen radiomics features were selected and incorporated into RS. The RS+clinical model has improved prediction performance for pCR compared with the clinical model (corrected area under the ROC curve, 0.84 vs. 0.70). At the 60% probability threshold cutoff (i.e., the patient would opt for observation if his probability of pCR was >60%), net 13% surgeries could be avoided by RS+clinical model, equivalent to implementing organ-saving strategy in 31.37% of the 51 true-pCR cases. CONCLUSION: The model built with CT radiomics features and clinical variables shows the potential of predicting pCR after NCRT; it provides significant clinical benefit in identifying qualified patients to receive individualized organ-saving treatment plans.

Correlation between CT based radiomics features and gene expression data in non-small cell lung cancer.

OBJECTIVE: Radiogenomics investigates radiographic imaging phenotypes associated with gene expression patterns. This study aims to explore relationships between CT imaging radiomics features and gene expression data in non-small cell lung cancer (NSCLC). METHODS: Eighty-nine NSCLC patients are included in the study. Radiomics features are extracted and selected to quantify the phenotype of tumors on CT-scans. Co-expressed genes are also clustered and the first principal component of the cluster is represented, which is defined as a metagene. Then, statistical analysis was performed to assess association of CT radiomics features with metagenes. In addition, predictive models are built and metagene enrichment are conducted to further evaluate performance of NSCLC radiogenomics statistically and biologically. RESULTS: There are 187 significant pairwise correlations between a CT radiomics feature and a metagene of NSCLC, where eighteen metagenes are annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms. Metagenes are predicted in terms of radiomics features with an accuracy of 41.89% -89.93%. CONCLUSIONS: This study reveals the associations between CT imaging radiomics features and NSCLC co-expressed gene sets. The findings suggest that CT radiomics features can reflect important biological information of NSCLC patients, which may have a significant clinical impact as CT is routinely used in clinical practice, assisting in improving medical decision-support at low cost.

Radiological biomarkers for assessing response to locoregional therapies in hepatocellular carcinoma: From morphological to functional imaging (Review).

Many hepatocellular carcinoma (HCC) patients do not qualify for curative surgical intervention and are instead treated with locoregional therapies (LRTs) including ablative and endovascular therapies. Assessment of imaging response is essential in the management of HCC for determining efficacy of therapy and as a surrogate marker for improved survival. The established morphological image biomarkers for tumor burden measurement continue to be applied, as size measurement can easily be used in clinical practice. However, in the setting of liver-directed LRTs for HCC, simple tumor morphological changes can be less informative and usually appear later than biologic changes. Functional imaging (such as perfusion and diffusion imaging, PET-CT/MR and MR spectroscopy) has the potential to be a promising technique for assessment of HCC response to LRTs. Although promising, none of these functional imaging biomarkers have gone through all the required steps of standardization and validation and established accepted criteria for clinical practice.

Diffusion-Weighted MR Imaging of Hepatocellular Carcinoma: Current Value in Clinical Evaluation of Tumor Response to Locoregional Treatment.

The established size-based image biomarkers for tumor burden measurement continue to be applied to solid tumors, as size measurement can easily be used in clinical practice. However, in the setting of novel targeted therapies and liver-directed locoregional treatments for hepatocellular carcinoma (HCC), simple tumor anatomic changes can be less informative and usually appear later than biologic changes. Functional magnetic resonance (MR) imaging has the potential to be a promising technique for assessment of HCC response to therapy. Diffusion-weighted MR imaging is now widely used as a standard imaging modality to evaluate the liver. This review discusses the current clinical value of diffusion-weighted MR imaging in the evaluation of tumor response after nonsurgical locoregional treatment of HCC.

Utility of diffusion-weighted imaging to assess hepatocellular carcinoma viability following transarterial chemoembolization.

The purpose of the present study was to evaluate whether diffusion-weighted imaging (DWI) can be used to assess hepatocellular carcinoma (HCC) viability following transarterial chemoembolization (TACE). A total of 41 consecutive patients were treated according to chemoembolization protocols. The follow-up was performed between six and eight weeks post-chemoembolization by multidetector computed tomography [or enhanced magnetic resonance imaging (MRI)] and DW-MRI on the same day. The presence of any residual tumor and the extent of tumor necrosis were evaluated according to the European Association for the Study of the Liver. The apparent diffusion coefficient (ADC) values of the entire area of the treated mass and the vital and necrotic tumor tissues were recorded. Correlation coefficients were also calculated to compare the percentage of necrosis with ADC values. The mean ADC values of the necrotic and vital tumor tissues were 2.22±0.31×10-3 mm2/sec and 1.42±0.25×10-3 mm2/sec, respectively (Mann-Whitney U test, P<0.001). The results from the receiver operating characteristic analysis showed that the threshold ADC value was 1.84×10-3 mm2/sec with 92.3% sensitivity and 100% specificity for identifying the necrotic tumor tissues. A significant linear regression correlation was identified between the ADC value of the entire area of the treated mass and the extent of tumor necrosis (r=0.58; P<0.001). In conclusion, DWI can be used to assess HCC viability following TACE.

High resolution CT in differentiating minimally invasive component in early lung adenocarcinoma.

OBJECTIVES: To analyze high-resolution computed tomography (HRCT) appearances of early lung adenocarcinoma and evaluate HRCT in the differentiation of minimally invasive component in early lung adenocarcinoma. MATERIALS AND METHODS: HRCT appearances of 140 nodules (less than 2 cm in diameter) of early lung adenocarcinoma were reviewed retrospectively. All these nodules were proven by surgery and pathology including 60 nodules of minimally invasive adenocarcinoma (MIA) and 80 nodules of preinvasive lesion (PL). HRCT features of two groups of lung nodules, including shape, margin, pattern, diameter, diameter of solid component, vascular changes, air bronchogram, vacuole, pleural indentation and multiplicity were analyzed and compared using univariate logistic regression analysis. Attenuation values of pure ground-glass nodule, pure ground-glass component and solid component of mixed ground-glass nodule were compared by using unpaired t-test or Wilcoxon rank-sum test. RESULTS: The statistically significant differences were found in shape, margin, pattern, diameter, diameter of solid component, pulmonary vein changes, air bronchogram and pleural indentation (Odds ratio [OR] = 3.115 [P = 0.001], OR = 3.754 [P = 0.011], OR = 9.815 [P = 0.000], OR = 1.306 [P = 0.000], OR = 1.361 [P = 0.031], OR= 6.971 [P = 0.000], OR = 6.167 [P=0.000], OR = 2.296 [P = 0.027], respectively). The statistically significant difference was also found in attenuation value of solid component (t = 3.702, P = 0.000). By multivariate logistic analysis, attenuation value of solid component was significantly associated with MIA (OR = 1.005, P = 0.032). MIA was more often a larger, lobulated or irregular, mixed ground-glass nodule with a solid component larger than 5 mm, and higher attenuation values. In addition, MIA often had an abnormality in pulmonary vein, air bronchogram and pleural indentation. CONCLUSIONS: HRCT can demonstrate the morphological features of early lung adenocarcinoma and identify minimally invasive component.

Intra-arterial infusion chemotherapy for advanced non-small-cell lung cancer: preliminary experience on the safety, efficacy, and clinical outcomes.

PURPOSE: To investigate the effectiveness and toxicity of intra-arterial infusion chemotherapy as a therapeutic modality for advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: In a retrospective study, 40 patients with stage III NSCLC received intra-arterial infusion chemotherapy with gemcitabine and cisplatin. Tumor staining was graded based on angiography, and the number of NSCLC feeding arteries detected was recorded. Toxicity was assessed according to National Cancer Institute Common Toxicity Criteria for Adverse Events. The response to treatment was evaluated per Response Evaluation Criteria In Solid Tumors (RECIST). Efficacy was assessed based on time to tumor progression (TTP), and survival was estimated by Kaplan-Meier analysis. Prognostic factors influencing TTP and overall survival rate were evaluated by Cox regression analysis. RESULTS: The most frequent drug-related adverse events were cough (n = 17; 42.5%), anorexia (n = 14; 35%), and pain (n = 9; 22.5%). Evaluated per RECIST, a total of 47.5% of patients (n = 19) exhibited response to therapy after completion of the first three cycles of intra-arterial infusion chemotherapy. The median TTP was 5 months. Patients had a median life expectancy of 9 months. By Cox regression analysis, tumor staining was shown to be an independent prognostic factor for TTP (relative risk, 0.405; 95% confidence interval, 0.216-0.760) and overall survival (relative risk, 0.348; 95% confidence interval, 0.185-0.656). CONCLUSIONS: Intra-arterial infusion chemotherapy for advanced lung cancer has the potential to reduce the size of tumors and has no severe adverse effects.

Assessment of the feeding arteries by three-dimensional computed tomography angiography prior to multi-arterial infusion chemotherapy for lung cancer.

The aim of this study was to evaluate the efficacy of multi-detector row helical computed tomography (MDCT) angiography in the detection of feeding arteries prior to multi-arterial infusion for lung cancer. A total of 59 consecutive patients (44 males and 15 females; age range, 27-86 years; median age, 62 years) with non-small cell lung cancer underwent MDCT angiography of the thorax prior to multi-arterial infusion for lung cancer. Findings on CT angiograms, including CT scans, maximum intensity projections and three-dimensional volume-rendered images, were used to evaluate the depiction of bronchial and non-bronchial systemic arteries. The results of detecting the feeding arteries for lung cancer by MDCT angiography and conventional angiography were compared. Among the 59 patients treated with multi-arterial infusion chemotherapy, a total of 80 feeding arteries (62 bronchial feeding arteries and 18 non-bronchial systemic arteries) were detected by conventional angiography and/or MDCT angiography. In 56 (70%) feeding arteries (including 44 bronchial feeding arteries and 12 non-bronchial systemic arteries) for lung cancers, concordant findings were observed with the two modalities. In 23 (29%) cases, MDCT angiography could not be used to define feeding arteries, but was used to identify the ostia of these feeding arteries. In one (1/80, 1.3%) case, the CT-defined feeding artery was not selectively catheterized. MDCT angiography of the chest is able to provide an overview for successful catheterization in multi-arterial infusion chemotherapy for lung cancer.

Folate receptor-mediated targeted polymeric gadolinium complexes for magnetic resonance imaging in pulmonary tumor xenografts.

Targeted delivery is a highly desirable strategy for diagnostic imaging due to enhanced efficacy and reduced dosage/toxicity. The need to develop target-specific magnetic resonance imaging (MRI) contrast agents to aid in disease characterization is highly essential. In this study, a specific contrast agent, Gd-DTPA-poly-L-lysine (PL-Gd-DTPA)-folate, was synthesized and evaluated for its efficacy as a targeted agent for the imaging of tumors that overexpress the folate receptor. Folic acid was conjugated to PL-Gd-DTPA via the ε-amino groups. The receptor binding properties of folate-PL-Gd-DTPA were studied in cultured tumor cells that overexpressed the folate receptor. The tumor-selecting properties of folate-PL-Gd-DTPA were then evaluated in BALB/c mice bearing subcutaneously implanted folate receptor-positive tumors. Tissue MR signal intensities were measured at six different time-points. In the in vitro study, the folate-PL-Gd-DTPA was able to bind to these cells, which overexpressed the folate receptor, as with free folic acid. Excellent tumor selectivity was also shown in the animal model; after the success of injection of folate-PL-Gd-DTPA, a maximum intensity increase of 125.4% was observed from pre-injection compared to post-injection images of the tumor at the 48 h time-point. The liver enhancement was non-specific and the muscle signal intensity at any time-point after injection showed no statistical difference with that observed before injection. Folate-PL-Gd-DTPA is a promising, novel receptor-specific MRI contrast agent with potential applications in the imaging of human folate receptor-positive tumors.

Characterization of solitary pulmonary nodules: Use of washout characteristics at contrast-enhanced computed tomography.

The purpose of this study was to determine whether computed tomographic scans and attenuation measurements on contrast material-enhanced and non-enhanced computed tomographic scans could be used to characterize solitary pulmonary nodules and, in particular, to characterize these lesions using washout characteristics on contrast-enhanced computed tomography. A total of 63 patients (38 males, 25 females; age range, 21-80 years; mean age, 58±13.2 years) with pulmonary nodules revealed on contrast-enhanced computed tomography underwent 20-min delayed enhanced scans. The mean diameter of the pulmonary nodules was 1.8±0.6 cm (range, 0.8-2.9). Region-of-interest measurements were obtained at non-enhanced, dynamic enhanced and delayed enhanced computed tomography and were used to calculate a relative percentage washout as follows: 1 - (Hounsfield unit measurement on delayed image/Hounsfield unit measurement on dynamic image) × 100%. There was a mean relative washout of 33% on the delayed computed tomographic scans (range, 12-46) in benign solitary pulmonary nodules; and a mean relative washout of 7% (range, -36-51) in malignant solitary pulmonary nodules (Mann-Whitney U test, p<0.001). Results of the receiver operating curve analysis revealed that a threshold relative washout of 14.5% had 74.3% sensitivity and 92.9% specificity for identifying malignant nodules. Calculation of the relative percentage washout on dynamic and delayed enhanced computed tomographic scans may lead to a highly specific test for solitary pulmonary nodule characterization and reduce the need for, and possibly obviate, follow-up imaging or biopsy.

Relationship of apparent diffusion coefficient to survival for patients with unresectable primary hepatocellular carcinoma after chemoembolization.

OBJECTIVES: to evaluate the prognostic value of apparent diffusion coefficient (ADC) values from MR diffusion-weighted imaging of unresectable hepatocellular carcinoma after chemoembolization. METHODS: our study was proved by our institute and informed consent was obtained from all patients before commencement of the study. Twenty-three patients with unresectable hepatocellular carcinoma were scanned immediately before and after chemoembolization within 24h using conventional anatomical MR imaging and diffusion-weighted imaging, from which ADC values in the lesions were measured. The changes in ADC values after chemoembolization were calculated. The relationship between the lesion ADC and the survival time was analyzed by correlation analysis. The overall cumulative survival was analyzed by the Kaplan-Meier method, and survival curves were compared by the log-rank test. RESULTS: the mean overall survival period was (25.0±8.7) months. The pre-chemoembolization lesion ADC value was (1.36±0.249)×10(-3) mm2/s; the change in ADC values post-chemoembolization was (0.377±0.332)×10(-3) mm2/s. There were significant linear regression relation between the survival time and pre-chemoembolization lesion ADC values (r=-0.698, P<0.001) or the changes in ADC value post-chemoembolization (r=0.702, P<0.001). And Log-rank test showed that pre-chemoembolization ADC values (χ2=7.339, P=0.007) or the changes in ADC value post-chemoembolization (χ2=9.820, P=0.002) significantly influenced the overall cumulative survival. CONCLUSION: Pre-treatment ADC values as well as changes in ADC values after treatment may provide useful information for predicting survival for patients with unresectable hepatocellular carcinoma.