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A Low-Dose CT-Based Radiomic Model to Improve Characterization and Screening Recall Intervals of Indeterminate Prevalent Pulmonary Nodules.

ABSTRACT: Lung cancer (LC) is currently one of the main causes of cancer-related deaths worldwide. Low-dose computed tomography (LDCT) of the chest has been proven effective in secondary prevention (i.e., early detection) of LC by several trials. In this work, we investigated the potential impact of radiomics on indeterminate prevalent pulmonary nodule (PN) characterization and risk stratification in subjects undergoing LDCT-based LC screening. As a proof-of-concept for radiomic analyses, the first aim of our study was to assess whether indeterminate PNs could be automatically classified by an LDCT radiomic classifier as solid or sub-solid (first-level classification), and in particular for sub-solid lesions, as non-solid versus part-solid (second-level classification). The second aim of the study was to assess whether an LCDT radiomic classifier could automatically predict PN risk of malignancy, and thus optimize LDCT recall timing in screening programs. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. The experimental results showed that an LDCT radiomic machine learning classifier can achieve excellent performance for characterization of screen-detected PNs (mean AUC of 0.89 ± 0.02 and 0.80 ± 0.18 on the blinded test dataset for the first-level and second-level classifiers, respectively), providing quantitative information to support clinical management. Our study showed that a radiomic classifier could be used to optimize LDCT recall for indeterminate PNs. According to the performance of such a classifier on the blinded test dataset, within the first 6 months, 46% of the malignant PNs and 38% of the benign ones were identified, improving early detection of LC by doubling the current detection rate of malignant nodules from 23% to 46% at a low cost of false positives. In conclusion, we showed the high potential of LDCT-based radiomics for improving the characterization and optimizing screening recall intervals of indeterminate PNs.

SUBMITTER: Rundo L

PROVIDER: S-EPMC8471292 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose18F-FDG PET/CT is widely used to evaluate indeterminate pulmonary nodules (IPNs). False positive results occur, especially from active granulomatous nodules. A PET-based imaging agent with superior specificity to 18F-FDG for IPNs, is badly needed, especially in areas of endemic granulomatous nodules. Somatostatin receptors (SSTR) are expressed in many malignant cells including small cell and non-small cell lung cancers (NSCLCs). 68Ga-DOTATATE, a positron emitter labeled somatostatin analog, combined with PET/CT imaging, may improve the diagnosis of IPNs over 18F-FDG by reducing false positives. Our study purpose was to test this hypothesis in our region with high endemic granulomatous IPNs.MethodsWe prospectively performed 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT scans in the same 30 patients with newly diagnosed, treatment-naïve lung cancer (N = 14) or IPNs (N = 15) and one metastatic nodule. 68Ga-DOTATATE SUVmax levels at or above 1.5 were considered likely malignant. We analyzed the scan results, correlating with ultimate diagnosis via biopsy or 2-year chest CT follow-up. We also correlated 68Ga-DOTATATE uptake with immunohistochemical (IHC) staining for SSTR subtype 2A (SSTR2A) in pathological specimens.ResultsWe analyzed 31 lesions in 30 individuals, with 14 (45%) being non-neuroendocrine lung cancers and 1 (3%) being metastatic disease. McNemar's result comparing the two radiopharmaceuticals (p = 0.65) indicates that their accuracy of diagnosis in this indication are equivalent. 68Ga-DOTATATE was more specific (94% compared to 81%) and less sensitive 73% compared to 93%) than 18F-FDG. 68Ga-DOTATATE uptake correlated with SSTR2A expression in tumor stroma determined by immunohistochemical (IHC) staining in 5 of 9 (55%) NSCLCs.Conclusion68Ga-DOTATATE and 18F-FDG PET/CT had equivalent accuracy in the diagnosis of non-neuroendocrine lung cancer and 68Ga-DOTATATE was more specific than 18F-FDG for the diagnosis of IPNs. IHC staining for SSTR2A receptor expression correlated with tumor stroma but not tumor cells.

Project description:ObjectivesThis study aimed to develop radiomic models based on low-dose CT (LDCT) and standard-dose CT to distinguish adenocarcinomas from benign lesions in patients with solid solitary pulmonary nodules and compare the performance among these radiomic models and Lung CT Screening Reporting and Data System (Lung-RADS). The reproducibility of radiomic features between LDCT and standard-dose CT were also evaluated.MethodsA total of 141 consecutive pathologically confirmed solid solitary pulmonary nodules were enrolled including 50 adenocarcinomas and 48 benign nodules in primary cohort and 22 adenocarcinomas and 21 benign nodules in validation cohort. LDCT and standard-dose CT scans were conducted using same acquisition parameters and reconstruction method except for radiation dose. All nodules were automatically segmented and 104 original radiomic features were extracted. The concordance correlation coefficient was used to quantify reproducibility of radiomic features between LDCT and standard-dose CT. Radiomic features were selected to build radiomic signature, and clinical characteristics and radiomic signature were combined to develop radiomic nomogram for LDCT and standard-dose CT, respectively. The performance of radiomic models and Lung-RADS was assessed by area under curve (AUC) of receiver operating characteristic curve, sensitivity, and specificity.ResultsShape and first order features, and neighboring gray tone difference matrix features were highly reproducible between LDCT and standard-dose CT. No significant differences of AUCs were found among radiomic signature and nomogram of LDCT and standard-dose CT in both primary and validation cohort (0.915 vs. 0.919 vs. 0.898 vs. 0.909 and 0.976 vs. 0.976 vs. 0.985 vs. 0.987, respectively). These radiomic models had higher specificity than Lung-RADS (all correct P < 0.05), while there were no significant differences of sensitivity between Lung-RADS and radiomic models.ConclusionsThe diagnostic performance of LDCT-based radiomic models to differentiate adenocarcinomas from benign lesions in solid pulmonary nodules were equivalent to that of standard-dose CT. The LDCT-based radiomic model with higher specificity and lower false-positive rate than Lung-RADS might help reduce overdiagnosis and overtreatment of solid pulmonary nodules in lung cancer screening.

Project description:RationalePulmonologists frequently encounter indeterminate pulmonary nodules in practice, but it is unclear what clinical factors they rely on to guide the diagnostic evaluation.ObjectivesTo assess the current approach to the management of indeterminate pulmonary nodules and to determine the extent to which the addition of a hypothetical diagnostic blood test will influence clinical decision making.MethodsSelected pulmonologists practicing in the United States were invited to participate in a conjoint exercise based on 20 randomly generated cases of varying age, smoking history, and nodule size. Some cases included the result of a hypothetical blood test. Each respondent chose from among three diagnostic options for a patient: noninvasive monitoring (i.e., serial CT or positron emission tomography scan), a minor procedure (i.e., biopsy or bronchoscopy), or a major procedure (i.e., video-assisted thorascopic surgery or thoracotomy). Multivariate logistic regression was used to assess the impact of the three risk factors and the diagnostic blood test on decision making.Measurements and main resultsFour hundred nineteen physicians participated (response rate, 10%). One hundred fifty-three physician surveys met predetermined criteria and were analyzed (4% of all invitees). A diagnostic procedure was recommended for 23% of 6-mm nodules, versus 54, 66, 77, and 84% of nodules 10, 14, 18, and 22 mm, respectively (P?<?0.001). Older age limited recommendations for invasive testing: 54% of 80-year-olds versus 61, 64, 63, and 61% of patients 71, 62, 53, and 44 years of age, respectively (P?<?0.001). In multivariate analyses, nodule size, smoking history, age, and the blood test each influenced decision making (P?<?0.001).ConclusionsThe pulmonologists who participated in this survey were more likely to proceed with invasive testing, instead of observation or additional imaging, as the size of the nodule increased. The use of a hypothetical blood test resulted in significant alterations in the decision to pursue invasive testing.

Project description:PurposeTo develop a radiomics prediction model to improve pulmonary nodule (PN) classification in low-dose CT. To compare the model with the American College of Radiology (ACR) Lung CT Screening Reporting and Data System (Lung-RADS) for early detection of lung cancer.MethodsWe examined a set of 72 PNs (31 benign and 41 malignant) from the Lung Image Database Consortium image collection (LIDC-IDRI). One hundred three CT radiomic features were extracted from each PN. Before the model building process, distinctive features were identified using a hierarchical clustering method. We then constructed a prediction model by using a support vector machine (SVM) classifier coupled with a least absolute shrinkage and selection operator (LASSO). A tenfold cross-validation (CV) was repeated ten times (10 × 10-fold CV) to evaluate the accuracy of the SVM-LASSO model. Finally, the best model from the 10 × 10-fold CV was further evaluated using 20 × 5- and 50 × 2-fold CVs.ResultsThe best SVM-LASSO model consisted of only two features: the bounding box anterior-posterior dimension (BB_AP) and the standard deviation of inverse difference moment (SD_IDM). The BB_AP measured the extension of a PN in the anterior-posterior direction and was highly correlated (r = 0.94) with the PN size. The SD_IDM was a texture feature that measured the directional variation of the local homogeneity feature IDM. Univariate analysis showed that both features were statistically significant and discriminative (P = 0.00013 and 0.000038, respectively). PNs with larger BB_AP or smaller SD_IDM were more likely malignant. The 10 × 10-fold CV of the best SVM model using the two features achieved an accuracy of 84.6% and 0.89 AUC. By comparison, Lung-RADS achieved an accuracy of 72.2% and 0.77 AUC using four features (size, type, calcification, and spiculation). The prediction improvement of SVM-LASSO comparing to Lung-RADS was statistically significant (McNemar's test P = 0.026). Lung-RADS misclassified 19 cases because it was mainly based on PN size, whereas the SVM-LASSO model correctly classified 10 of these cases by combining a size (BB_AP) feature and a texture (SD_IDM) feature. The performance of the SVM-LASSO model was stable when leaving more patients out with five- and twofold CVs (accuracy 84.1% and 81.6%, respectively).ConclusionWe developed an SVM-LASSO model to predict malignancy of PNs with two CT radiomic features. We demonstrated that the model achieved an accuracy of 84.6%, which was 12.4% higher than Lung-RADS.

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A Low-Dose CT-Based Radiomic Model to Improve Characterization and Screening Recall Intervals of Indeterminate Prevalent Pulmonary Nodules.

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