FDG-PET/CT in indeterminate thyroid nodules: cost-utility analysis alongside a randomised controlled trial.
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ABSTRACT: Purpose
To evaluate cost-effectiveness of an [18F]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [18F]FDG-PET/CT avoids 40% of futile diagnostic surgeries for benign Bethesda III/IV nodules.Methods
Lifelong societal costs and quality-adjusted life years (QALYs) were assessed for 132 patients participating in a randomised controlled multicentre trial comparing [18F]FDG-PET/CT to diagnostic surgery. The observed 1-year trial results were extrapolated using a Markov model. The probability of cost-effectiveness was estimated using cost-effectiveness acceptability curves, taking uncertainty about sampling, imputation, and parameters into account.Results
The observed 1-year cost difference of [18F]FDG-PET/CT as compared to diagnostic surgery was - €1000 (95% CI: - €2100 to €0) for thyroid nodule-related care (p = 0.06). From the broader societal perspective, the 1-year difference in total societal costs was - €4500 (- €9200 to €150) (p = 0.06). Over the modelled lifelong period, the cost difference was - €9900 (- €23,100 to €3200) (p = 0.14). The difference in QALYs was 0.019 (- 0.045 to 0.083) at 1 year (p = 0.57) and 0.402 (- 0.581 to 1.385) over the lifelong period (p = 0.42). For a willingness to pay of €50,000 per QALY, an [18F]FDG-PET/CT-driven work-up was the cost-effective strategy with 84% certainty.Conclusion
Following the observed reduction in diagnostic surgery, an [18F]FDG-PET/CT-driven diagnostic workup reduced the 1-year thyroid nodule-related and societal costs while sustaining quality of life. It is very likely cost-effective as compared to diagnostic surgery for Bethesda III/IV nodules.Trial registration number
This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .
SUBMITTER: de Koster EJ
PROVIDER: S-EPMC9308600 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThis study assessed the health-related quality of life (HRQoL) in patients undergoing 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT for an indeterminate (Bethesda III/IV) thyroid nodule. FDG-PET/CT accurately rules out malignancy and prevents 40% of futile diagnostic surgeries in these nodules.DesignSecondary analyses of HRQoL data from a randomised controlled multicentre trial (NCT02208544) in 126 patients from 15 hospitals in the Netherlands were done.MethodsLongitudinal HRQoL assessment was performed using the EuroQol 5-dimension 5-level (EQ-5D-5L), the RAND 36-item Health Survey v2.0 (RAND-36), and the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire on baseline, 3, 6, and 12 months, relative to the date of the FDG-PET/CT scan.ResultsPatients who were randomised to active surveillance following an FDG-negative nodule instead of diagnostic surgery reported stable HRQoL scores throughout the year. Univariate analysis indicated better HRQoL for patients undergoing surveillance than surgical patients with benign histopathology on multiple physical and psychosocial domains. Univariate within-group analysis suggested both temporary and continued HRQoL deteriorations in patients with benign histopathology over time. Multivariate within-group analysis demonstrated no significant longitudinal HRQoL changes in patients undergoing active surveillance. In contrast, in patients with benign histopathology, worse HRQoL was observed with regard to ThyPRO cognitive impairment (P = 0.01) and cosmetic complaints (P = 0.02), whereas goitre symptoms (P < 0.001) and anxiety (P = 0.04) improved over time. In patients with malignant histopathology, anxiety also decreased (P = 0.05).ConclusionsThe reassurance of a negative FDG-PET/CT resulted in sustained HRQoL throughout the first year of active surveillance. Diagnostic surgery for a nodule with benign histopathology resulted in more cognitive impairment and physical problems including cosmetic complaints, but improved goitre symptoms and anxiety. Anxiety was also reduced in patients with malignant histopathology.
| S-EPMC9346328 | biostudies-literature
Project description:PurposeTo evaluate whether quantitative [18F]FDG-PET/CT assessment, including radiomic analysis of [18F]FDG-positive thyroid nodules, improved the preoperative differentiation of indeterminate thyroid nodules of non-Hürthle cell and Hürthle cell cytology.MethodsProspectively included patients with a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT imaging. Receiver operating characteristic (ROC) curve analysis was performed for standardised uptake values (SUV) and SUV-ratios, including assessment of SUV cut-offs at which a malignant/borderline neoplasm was reliably ruled out (≥ 95% sensitivity). [18F]FDG-positive scans were included in radiomic analysis. After segmentation at 50% of SUVpeak, 107 radiomic features were extracted from [18F]FDG-PET and low-dose CT images. Elastic net regression classifiers were trained in a 20-times repeated random split. Dimensionality reduction was incorporated into the splits. Predictive performance of radiomics was presented as mean area under the ROC curve (AUC) across the test sets.ResultsOf 123 included patients, 84 (68%) index nodules were visually [18F]FDG-positive. The malignant/borderline rate was 27% (33/123). SUV-metrices showed AUCs ranging from 0.705 (95% CI, 0.601-0.810) to 0.729 (0.633-0.824), 0.708 (0.580-0.835) to 0.757 (0.650-0.864), and 0.533 (0.320-0.747) to 0.700 (0.502-0.898) in all (n = 123), non-Hürthle (n = 94), and Hürthle cell (n = 29) nodules, respectively. At SUVmax, SUVpeak, SUVmax-ratio, and SUVpeak-ratio cut-offs of 2.1 g/mL, 1.6 g/mL, 1.2, and 0.9, respectively, sensitivity of [18F]FDG-PET/CT was 95.8% (95% CI, 78.9-99.9%) in non-Hürthle cell nodules. In Hürthle cell nodules, cut-offs of 5.2 g/mL, 4.7 g/mL, 3.4, and 2.8, respectively, resulted in 100% sensitivity (95% CI, 66.4-100%). Radiomic analysis of 84 (68%) [18F]FDG-positive nodules showed a mean test set AUC of 0.445 (95% CI, 0.290-0.600) for the PET model.ConclusionQuantitative [18F]FDG-PET/CT assessment ruled out malignancy in indeterminate thyroid nodules. Distinctive, higher SUV cut-offs should be applied in Hürthle cell nodules to optimize rule-out ability. Radiomic analysis did not contribute to the additional differentiation of [18F]FDG-positive nodules.Trial registration numberThis trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .
| S-EPMC9165273 | biostudies-literature
Project description:PurposeTo assess the impact of an [18F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology.MethodsIn this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT and were randomised to an [18F]FDG-PET/CT-driven or diagnostic surgery group. In the [18F]FDG-PET/CT-driven group, management was based on the [18F]FDG-PET/CT result: when the index nodule was visually [18F]FDG-positive, diagnostic surgery was advised; when [18F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules.ResultsPatient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [18F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [18F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2-40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [18F]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively.ConclusionAn [18F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules.Trial registration numberThis trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .
| S-EPMC9016050 | biostudies-literature
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:Background: An accurate preoperative workup of cytologically indeterminate thyroid nodules (ITN) may rule out malignancy and avoid diagnostic surgery for benign nodules. This study assessed the performance of molecular diagnostics (MD) and 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in ITN, including their combined use, and explored whether molecular alterations drive the differences in [18F]FDG uptake among benign nodules. Methods: Adult, euthyroid patients with a Bethesda III or IV thyroid nodule were prospectively included in this multicenter study. They all underwent MD and an [18F]FDG-PET/CT scan of the neck. MD was performed using custom next-generation sequencing panels for somatic mutations, gene fusions, and copy number alterations and loss of heterozygosity. Sensitivity, specificity, negative and positive predictive value (NPV, PPV), and benign call rate (BCR) were assessed for MD and [18F]FDG-PET/CT separately and for a combined approach using both techniques. Results: In 115 of the 132 (87%) included patients, MD yielded a diagnostic result on cytology. Sensitivity, specificity, NPV, PPV, and BCR were 80%, 69%, 91%, 48%, and 57% for MD, and 93%, 41%, 95%, 36%, and 32% for [18F]FDG-PET/CT, respectively. When combined, sensitivity and specificity were 95% and 44% for a double-negative test (i.e., negative MD plus negative [18F]FDG-PET/CT) and 68% and 86% for a double-positive test, respectively. Concordance was 63% (82/130) between MD and [18F]FDG-PET/CT. There were more MD-positive nodules among the [18F]FDG-positive benign nodules (25/59, 42%, including 11 (44%) isolated RAS mutations) than among the [18F]FDG-negative benign nodules (7/30, 19%, p = 0.02). In oncocytic ITN, the BCR of [18F]FDG-PET/CT was mere 3% and MD was the superior technique. Conclusions: MD and [18F]FDG-PET/CT are both accurate rule-out tests when unresected nodules that remain unchanged on ultrasound follow-up are considered benign. It may vary worldwide which test is considered most suitable, depending on local availability of diagnostics, expertise, and cost-effectiveness considerations. Although complementary, the benefits of their combined use may be confined when therapeutic consequences are considered, and should therefore not routinely be recommended. In nononcocytic ITN, sequential testing may be considered in case of a first-step MD negative test to confirm that withholding diagnostic surgery is oncologically safe. In oncocytic ITN, after further validation studies, MD might be considered. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov: NCT02208544 (August 5, 2014), https://clinicaltrials.gov/ct2/show/NCT02208544.
| S-EPMC10818054 | biostudies-literature
Project description:Thyroid nodules with indeterminate fine-needle aspiration cytology (FNA) represent a major challenge in clinical practice. We conducted a systematic review and meta-analysis evaluating the ability of hybrid imaging using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to appropriately select these nodules for surgery. PubMed, CENTRAL, Scopus, and Web of Science were searched until July 2019. Original articles reporting data on the performance of 18F-FDG PET/CT in thyroid nodules with indeterminate FNA were included. Summary operating points including 95% confidence interval values (95% CI) were estimated using a random-effects model. Out of 786 retrieved papers, eight studies evaluating 104 malignant and 327 benign thyroid nodules were included. The pooled positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR) of 18F-FDG PET/CT were 1.7 (95% CI: 1.4-2.0), 0.4 (95% CI: 0.2-0.7), and 3.5 (95% CI: 1.7-7.1), respectively. No heterogeneity was found for LR+ and DOR. In patients with thyroid nodules with indeterminate FNA, 18F-FDG PET/CT has a moderate ability to correctly discriminate malignant from benign lesions and could represent a reliable option to reduce unnecessary diagnostic surgeries. However, further studies using standardized criteria for interpretation are needed to confirm the reproducibility of these findings.
| S-EPMC6780221 | biostudies-literature
Project description:BACKGROUND:Many clinical guidelines recommend FDG PET/CT for the evaluation of pulmonary nodules ?8?mm detected during low dose computed tomography (LDCT) lung cancer screening. However, its added value in this setting requires confirmation. We evaluated the clinical utility of FDG PET/CT, including incidental findings, during the evaluation of lung nodules detected on LDCT screening. METHODS:A retrospective cohort study was performed among 75 patients who completed FDG PET/CT between January 2010 and December 2017, after lung nodules >?8?mm had been detected on LDCT lung cancer screening. We report demographic variables, characteristics of the initial nodules on LDCT and FDG PET/CT, incidental findings on FDG PET/CT, as well as further work up performed and the influence of FDG PET/CT findings on management. RESULTS:Nodules were reported to be benign on FDG PET/CT in 38/75 (50.6%) patients. Physicians chose either radiological follow-up or no further work up in all 38. FDG PET/CT was indeterminate or suggested malignancy in 37 (49.3%) patients. Biopsy was performed in 32 (86%) of these patients. Incidental findings on FDG PET/CT were reported in 37/75 (49%) patients. Further work-up of incidental findings was performed in 21/75 (28%) of patients. CONCLUSIONS:In this study, for majority of individuals with lung nodules identified during LDCT lung cancer screening, FDG PET/CT results were able to guide physicians in choosing between routine follow up or invasive biopsies. Conversely, 28% of these patients required additional investigations to address incidental findings.
| S-EPMC7309986 | 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:PurposeTo develop a methodology for the quantification of gastrointestinal (GI) inflammation as indicated by 2-deoxy-2-(18F)fluoro-D-glucose (FDG) uptake on positron-emissions tomography/computed tomography (PET/CT) imaging. This is intended to investigate the feasibility of using standard uptake value (SUV) levels to assess levels of GI inflammation in humans.Methods131 participants were injected with a weight-controlled dose of FDG 180 minutes prior to PET/CT scanning. Operator-guided software was used to segment the GI tract and perform (SUV) calculations. Regions of interest (ROIs) were created using CT images and stacked to create three dimensional volumes of interest (VOIs). These VOIs defined 6 sections of the GI tract: esophagus, stomach, descending colon, ascending and transverse colon, bowel below the ilium and small bowel above the ilium.ResultsThis study found a significant correlation between age and average FDG uptake (avg-SUV) of the GI tract (P=.0003) with the esophagus showing the highest significance. Correlations were found between avg-SUV of the sigmoid segment and the group average (P<.0001), and between the descending colon VOI and the group (P<.0001). Intra-operator reproducibility over 3 trials showed a coefficient of variation (CV) of .63%. Inter-operator CV over 5 randomly selected patients was 5.6% over the entire GI tract.ConclusionThis study shows that FDG-PET/CT imaging is a promising technique for quantifying bowel inflammation, despite the fact that age related inflammation may not be of clinical utility. The fact that we were able to detect these subtle changes indicates this as an avenue for potential future investigation.
| S-EPMC8414397 | 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