Radiomics-based Management of Indeterminate Lung Nodules? Are We There Yet?
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ABSTRACT:
SUBMITTER: Peikert T
PROVIDER: S-EPMC7365373 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeAs ~25% of cytologically indeterminate thyroid nodules harbour malignancy, diagnostic lobectomy is still performed in many cases. 18FDG PET/CT rules out malignancy in visually negative nodules; however, none of the currently available interpretation criteria differentiates malignant from benign 18FDG-avid nodules. We evaluated the ability of PET metrics and radiomics features (RFs) to predict final diagnosis of 18FDG-avid cytologically indeterminate thyroid nodules.MethodsSeventy-eight patients were retrospectively included. After volumetric segmentation of each thyroid lesion, 4 PET metrics and 107 RFs were extracted. A logistic regression was performed including thyroid stimulating hormone, PET metrics, and RFs to assess their predictive performance. A linear combination of the resulting parameters generated a radiomics score (RS) that was matched with cytology classes (Bethesda III and IV) and compared with final diagnosis.ResultsTwo RFs (shape_Sphericity and glcm_Autocorrelation) differentiated malignant from benign lesions. A predictive model integrating RS and cytology classes effectively stratified the risk of malignancy. The prevalence of thyroid cancer increased from 5 to 37% and 79% in accordance with the number (score 0, 1 or 2, respectively) of positive biomarkers.ConclusionsOur multiparametric model may be useful for reducing the number of diagnostic lobectomies with advantages in terms of costs and quality of life for patients.
| S-EPMC8763930 | biostudies-literature
Project description:Evaluation of indeterminate pulmonary nodules is a complex challenge. Most are benign but frequently undergo invasive and costly procedures to rule out malignancy. A plasma protein classifier was developed that identifies likely benign nodules that can be triaged to CT surveillance to avoid unnecessary invasive procedures. The clinical utility of this classifier was assessed in a prospective-retrospective analysis of a study enrolling 475 patients with nodules 8-30 mm in diameter who had an invasive procedure to confirm diagnosis at 12 sites. Using this classifier, 32.0 % (CI 19.5-46.7) of surgeries and 31.8 % (CI 20.9-44.4) of invasive procedures (biopsy and/or surgery) on benign nodules could have been avoided. Patients with malignancy triaged to CT surveillance by the classifier would have been 24.0 % (CI 19.2-29.4). This rate is similar to that described in clinical practices (24.5 % CI 16.2-34.4). This study demonstrates the clinical utility of a non-invasive blood test for pulmonary nodules.
| S-EPMC4651976 | biostudies-literature
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.
| S-EPMC5300187 | biostudies-literature
Project description:BackgroundThe impact of oncogene panel results on the surgical management of indeterminate thyroid nodules (ITNs) is currently unknown.MethodsSurgical management of 649 patients consecutively evaluated from October 2008 to April 2016 with a single nodule biopsied and indeterminate cytology (193 evaluated with and 456 without oncogene panels) was assessed and compared. Histological features of 629 consecutively resected ITNs (164 evaluated with and 465 without oncogene panels) were also characterized and compared.ResultsOncogene panel evaluation was associated with higher rates of total thyroidectomy (45% vs 28%; P = .006), and central lymph node dissection (19% vs 12%; P = .03) without increasing the yield of malignancy or decreasing the rate of completion thyroidectomy. Most malignancies (64%), including 83% of those with driver mutation identified, were low-risk cancers for which a lobectomy could have been sufficient initial treatment.ConclusionCurrent oncogene panel results seem insufficient to guide the surgical extent of solitary ITNs.
| S-EPMC7771319 | biostudies-literature
Project description:Background:Up to 30% of thyroid nodules undergoing fine needle aspiration (FNA) yield an indeterminate result. Recent research efforts have suggested that nuclear morphometry and morphology may enhance the diagnostic accuracy of FNA as an objective adjunct. We applied nuclear morphometric analysis on a diverse cohort of patients to evaluate the association between nuclear morphometry and malignancy. Methods:Forty-five randomly selected patients, who underwent thyroid surgery after an indeterminate FNA result (Bethesda III & IV) between 2012-2015, were reviewed. One hundred representative nuclei per FNA of a thyroid nodule were analyzed using ImageJ. Seven validated morphometric parameters were collected: nuclear area, perimeter, circularity, aspect ratio, roundness, and maximum/minimum Feret's diameter. L/S ratio was subsequently calculated. All 8 nuclear parameters were reported as averages with standard errors of the mean (SEM). A Student's t-test was used to assess the association of nuclear parameters with final surgical pathology. Results:The mean age of all patients was 56.31±15.39 years, with female patients comprising 68.9% of the cohort. Twenty-two patients had malignant thyroid nodules. The mean perimeter of nuclei for the cohort was 18.48±0.45 µm, the mean area was 22.19±0.93 µm, and the mean maximum Feret's diameter was 6.67±0.13 µm. No significant differences in the 8 nuclear parameters were observed between the malignant and non-malignant groups. Conclusions:In the population examined, our results suggest that nuclear morphometry is not yet a tool of reliable diagnostic value in accessing malignant and non-malignant thyroid nodules. Further investigation is necessary to identify objective parameters that will enhance diagnostic accuracy of indeterminate FNA cytology to minimize the number of diagnostic thyroid surgery.
| S-EPMC7225500 | biostudies-literature
Project description:ObjectivesTo investigate the value of radiomics based on CT imaging in predicting invasive adenocarcinoma manifesting as pure ground-glass nodules (pGGNs).MethodsThis study enrolled 395 pGGNs with histopathology-confirmed benign nodules or adenocarcinoma. A total of 396 radiomic features were extracted from each labeled nodule. A Rad-score was constructed with the least absolute shrinkage and selection operator (LASSO) in the training set. Multivariate logistic regression analysis was conducted to establish the radiographic model and the combined radiographic-radiomics model. The predictive performance was validated by receiver operating characteristic (ROC) curve. Based on the multivariate logistic regression analysis, an individual prediction nomogram was developed and the clinical utility was assessed.ResultsFive radiomic features and four radiographic features were selected for predicting the invasive lesions. The combined radiographic-radiomics model (AUC 0.77; 95% CI, 0.69-0.86) performed better than the radiographic model (AUC 0.71; 95% CI, 0.62-0.81) and Rad-score (AUC 0.72; 95% CI, 0.63-0.81) in the validation set. The clinical utility of the individualized prediction nomogram developed using the Rad-score, margin, spiculation, and size was confirmed in the validation set. The decision curve analysis (DCA) indicated that using a model with Rad-score to predict the invasive lesion would be more beneficial than that without Rad-score and the clinical model.ConclusionsThe proposed radiomics-based nomogram that incorporated the Rad-score, margin, spiculation, and size may be utilized as a noninvasive biomarker for the assessment of invasive prediction in patients with pGGNs.Key points• CT-based radiomics analysis helps invasive prediction manifested as pGGNs. • The combined radiographic-radiomics model may be utilized as a noninvasive biomarker for predicting invasive lesion for pGGNs. • Radiomics-based individual nomogram may serve as a vital decision support tool to identify invasive pGGNs, obviating further workup and blind follow-up.
| S-EPMC7305264 | biostudies-literature
Project description:BackgroundIndeterminate pulmonary nodules in patients diagnosed with osteosarcoma present a challenge for accurate staging and prognosis. The aim of this study was to explore the significance of this finding.MethodsA retrospective cohort study of 120 patients with osteosarcoma was performed in the North East of England. Chest computed tomographies (CTs) at presentation were reviewed and the incidence of 'indeterminate' nodules recorded. Follow-up scans were reviewed and survival as well as prognostic features were analysed.Results25% of our cohort presented with indeterminate nodules. Of these, 33% were subsequently confirmed as metastases, the majority within a year. Kaplan-Meier survival analysis showed that patients with indeterminate nodules fared better than those with frank metastatic disease, and similar to those who presented with a normal chest CT. We found no radiographic features that predicted survival.ConclusionsIndeterminate nodules remain a clinical and diagnostic dilemma. Close monitoring of patients is advised during the first year from presentation, and there is potential for indeterminate nodules to develop into frank metastases later than five years from presentation.
| S-EPMC5846065 | biostudies-literature
Project description:BackgroundApproximately 25% of thyroid nodule fine-needle aspirates (FNAs) have cytology that is indeterminate for malignant disease. Accurate risk stratification of these FNAs with ancillary testing would reduce unnecessary thyroid surgery.MethodsWe evaluated the performance of an ancillary multiplatform test (MPTX) that has three diagnostic categories (negative, moderate, and positive). MPTX includes the combination of a mutation panel (ThyGeNEXT®) and a microRNA risk classifier (ThyraMIR®). A blinded, multicenter study was performed using consensus histopathology diagnosis among three pathologists to validate test performance.ResultsUnanimous consensus diagnosis was reached in 197 subjects with indeterminate thyroid nodules; 36% had disease. MPTX had 95% sensitivity (95% CI,86%-99%) and 90% specificity (95% CI,84%-95%) for disease in prevalence adjusted nodules with Bethesda III and IV cytology. Negative MPTX results ruledout disease with 97% negative predictive value (NPV; 95% CI,91%-99%) at a 30% disease prevalence, while positive MPTX results ruledin high risk disease with 75% positive predictive value (PPV; 95% CI,60%-86%). Such results are expected in four out of five Bethesda III and IV nodules tested, including RAS positive nodules in which the microRNA classifier was useful in rulingin disease. 90% of mutation panel false positives were due to analytically verified RAS mutations detected in benign adenomas. Moderate MPTX results had a moderate rate of disease (39%, 95% CI,23%-54%), primarily due to RAS mutations, wherein the possibility of disease could not be excluded.ConclusionsOur results emphasize that decisions for surgery should not solely be based on RAS or RAS-like mutations. MPTX informs management decisions while accounting for these challenges.
| S-EPMC7754490 | biostudies-literature
Project description:BACKGROUND: Following fine needle aspiration, 15-30% of thyroid nodules are not clearly benign or malignant. These cytologically indeterminate nodules are often referred for diagnostic surgery, though most prove benign. A novel diagnostic test measuring the expression of 167 genes has shown promise in improving pre-operative risk assessment. We evaluated this test in a prospective, multicenter study. METHODS: Over 19 months, we performed a prospective study at 49 clinical sites enrolling 3,789 patients and collecting 4,812 samples from thyroid nodules >1cm requiring evaluation. We obtained 577 cytologically indeterminate aspirates with corresponding histopathology of excised lesions on 413. Central blinded histopathologic review served as the reference (“gold”) standard. After applying inclusion criteria, gene expression classifier results were obtained for 265 indeterminate nodules used in this analysis, and performance was calculated. RESULTS: 85 of 265 indeterminate nodules were malignant. The gene expression classifier correctly identified 78 of 85 as ‘suspicious’ (92% sensitivity, [84%-97%] 95% CI). Specificity was 52%, [44%-59%]. The negative predictive value was 95%, 94%, and 85%, respectively, for aspirates with AUS/FLUS, FN/SFN, or ‘suspicious’ cytology. Analysis of 7 false negative cases revealed 6 with a paucity of thyroid follicular cells, suggesting that insufficient sampling of the nodule had occurred. CONCLUSIONS: Though individualized clinical care is recommended, these data support consideration of a conservative approach for most patients with indeterminate FNA cytology and benign gene expression classifier results.
2012-06-25 | GSE34289 | GEO
Project description:RationaleThe workup and longitudinal monitoring for subjects presenting with pulmonary nodules is a pressing clinical problem. A blood-based biomarker panel potentially has utility for identifying subjects at higher risk for harboring a malignant nodule for whom additional workup would be indicated or subjects at reduced risk for whom imaging-based follow-up would be indicated.ObjectivesTo assess whether a previously described four-protein biomarker panel, reported to improve assessment of lung cancer risk compared with a smoking-based lung cancer risk model, can provide discrimination between benign and malignant indeterminate pulmonary nodules.MethodsA previously validated multiplex enzyme-linked immunoassay was performed on matched case and control samples from each cohort.MeasurementsThe biomarker panel was tested in two case-control cohorts of patients presenting with indeterminate pulmonary nodules at the University of Pittsburgh Medical Center and the University of Texas Southwestern.Main resultsIn both cohorts, the biomarker panel resulted in improved prediction of lung cancer risk over a model on the basis of nodule size alone. Of particular note, the addition of the marker panel to nodule size greatly improved sensitivity at a high specificity in both cohorts.ConclusionsA four-marker biomarker panel, previously validated to improve lung cancer risk prediction, was found to also have utility in distinguishing benign from malignant indeterminate pulmonary nodules. Its performance in improving sensitivity at a high specificity indicates potential utility of the marker panel in assessing likelihood of malignancy in otherwise indeterminate nodules.
| S-EPMC8218328 | biostudies-literature