Health Technology Assessment (Aug 2024)
Real-time ultrasound elastography in the diagnosis of newly identified thyroid nodules in adults: the ElaTION RCT
Abstract
Background Strain and shear wave elastography which is commonly used with concurrent real-time imaging known as real-time ultrasound shear/strain wave elastography is a new diagnostic technique that has been reported to be useful in the diagnosis of nodules in several organs. There is conflicting evidence regarding its benefit over ultrasound-guided fine-needle aspiration cytology alone in thyroid nodules. Objectives To determine if ultrasound strain and shear wave elastography in conjunction with fine-needle aspiration cytology will reduce the number of patients who have a non-diagnostic first fine-needle aspiration cytology results as compared to conventional ultrasound-only guided fine-needle aspiration cytology. Design A pragmatic, unblinded, multicentre randomised controlled trial. Setting Eighteen centres with a radiology department across England. Participants Adults who had not undergone previous fine-needle aspiration cytology with single or multiple nodules undergoing investigation. Interventions Ultrasound shear/strain wave elastography-ultrasound guided fine-needle aspiration cytology (intervention arm) – strain or shear wave elastography-guided fine-needle aspiration cytology. Ultrasound-only guided fine-needle aspiration cytology (control arm) – routine ultrasound-only guided fine-needle aspiration cytology (the current standard recommended by the British Thyroid Association guidelines). Main outcome measure The proportion of patients who have a non-diagnostic cytology (Thy 1) result following the first fine-needle aspiration cytology. Randomisation Patients were randomised at a 1 : 1 ratio to the interventional or control arms. Results A total of 982 participants (80% female) were randomised: 493 were randomised to ultrasound shear/strain wave elastography-ultrasound guided fine-needle aspiration cytology and 489 were randomised to ultrasound-only guided fine-needle aspiration cytology. There was no evidence of a difference between ultrasound shear/strain wave elastography and ultrasound in non-diagnostic cytology (Thy 1) rate following the first fine-needle aspiration cytology (19% vs. 16% respectively; risk difference: 0.030; 95% confidence interval −0.007 to 0.066; p = 0.11), the number of fine-needle aspiration cytologies needed (odds ratio: 1.10; 95% confidence interval 0.82 to 1.49; p = 0.53) or in the time to reach a definitive diagnosis (hazard ratio: 0.94; 95% confidence interval 0.81 to 1.10; p = 0.45). There was a small, non-significant reduction in the number of thyroid operations undertaken when ultrasound shear/strain wave elastography was used (37% vs. 40% respectively; risk difference: −0.02; 95% confidence interval −0.06 to 0.009; p = 0.15), but no difference in the number of operations yielding benign histology – 23% versus 24% respectively, p = 0.70 (i.e. no increase in identification of malignant cases) – or in the number of serious adverse events (2% vs. 1%). There was no difference in anxiety and depression, pain or quality of life between the two arms. Limitations The study was not powered to detect differences in malignancy. Conclusions Ultrasound shear/strain wave elastography does not appear to have additional benefit over ultrasound-guided fine-needle aspiration cytology in the diagnosis of thyroid nodules. Future work The findings of the ElaTION trial suggest that further research into the use of shear wave elastography in the diagnostic setting of thyroid nodules is unlikely to be warranted unless there are improvements in the technology. The diagnostic difficulty in distinguishing between benign and malignant lesions still persists. Future studies might examine the role of genomic testing on fine-needle aspiration samples. There is growing use of targeted panels of molecular markers, particularly aimed at improving the diagnostic accuracy of indeterminate (i.e. Thy3) cytology results. The application of these tests is not uniform, and their cost effectiveness has not been assessed in large-scale trials. Study registration This study is registered as ISRCTN (ISRCTN18261857). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/19/04) and is published in full in Health Technology Assessment; Vol. 28, No. 46. See the NIHR Funding and Awards website for further award information. Plain language summary About half the population will have lumps in their thyroid if examined by an ultrasound scan but may not know they have one. About one in twenty people will feel a thyroid lump in their neck at some time in their life, with about one in twenty of those being malignant. Currently, the recommended way of getting a diagnosis of thyroid nodules is by using ultrasound to guide a needle to get cells from the lump, called ultrasound-guided fine-needle aspiration cytology. These cells are examined to determine the cause of the lump. If there are enough cells, Doctors can then make a diagnosis of whether the lump is benign or malignant. If not, patients will undergo another ultrasound-guided fine-needle aspiration cytology. One in five ultrasound-guided fine-needle aspiration cytologies are non-diagnostic with an overall false-positive rate of approximately 24%. This means one in five patients, with benign disease, may undergo unnecessary diagnostic operations. Thyroid surgery carries risks of complications, which could be avoided if we had better ways to diagnose which patients actually need an operation. We conducted a randomised trial, ElaTION, to determine if a new technology called strain and shear wave elastography, commonly known as real-time elastography, would be better at helping the radiologist take a sufficient sample of cells and reduce the number of non-diagnostic results, reducing the number of fine-needle aspiration cytologies required to make a definitive diagnosis. Nine hundred eighty-two patients were recruited between 2015 and 2018 and followed up until the end of the trial. Patients were randomised into two groups: 489 patients received the standard ultrasound-guided fine-needle aspiration cytology alone, and 493 patients received ultrasound-guided fine-needle aspiration cytology + shear wave elastography. Ultrasound shear/strain wave elastography did not reduce non-diagnostic cytology at first fine-needle aspiration cytology or improve the likelihood of determining whether the lump is benign or malignant. The results of ElaTION do not support the use of shear wave elastography-fine-needle aspiration cytology in the diagnosis of thyroid nodules. Scientific summary Background Strain elastography (STE) which is commonly used with concurrent real-time imaging known as real-time elastography (RTE) and shear wave elastography (SWE) are new diagnostic techniques that have been reported to be useful in the diagnosis of nodules in several organs. There is conflicting evidence regarding its benefit over ultrasound-guided fine-needle aspiration cytology (US-FNAC) alone in thyroid nodules. Objectives The primary objective was to determine if strain/shear wave ultrasound elastography (USE) in conjunction with FNAC will reduce the number of patients with thyroid nodules who have a non-diagnostic first FNAC result as compared to conventional ultrasound (US)-only guided FNAC. Design ElaTION was a pragmatic, multicentre randomised controlled trial. Setting Eighteen centres with a radiology department across England. Participants Adults with thyroid nodules who had not undergone previous FNAC with single or multiple nodules undergoing investigation. Interventions Ultrasound shear/strain wave elastography-US guided FNAC (intervention arm) – strain or shear wave elastography (USE)-guided FNAC. US-only guided FNAC (control arm) – routine US-only guided FNAC (the current standard recommended by the British Thyroid Association guidelines). Main outcome measures Primary outcome The proportion of patients who have a non-diagnostic cytology (Thy 1) result following the first FNAC. Secondary outcomes The number of FNACs required to obtain a definitive diagnosis; time from first FNAC to a definitive diagnosis; the false-positive rate of nodules; the number of patients who have a non-diagnostic cytology result following any FNAC; the proportion of patients undergoing thyroidectomy; accuracy of US alone (overall); accuracy of first FNAC; accuracy of USE or US without FNAC compared to accuracy of USE or US with FNAC; and patient reported anxiety, pain and quality of life [by the Hospital Anxiety and Depression Scale (HADS), Visual Analogue Pain Scale (VAPS) and EuroQol (EQ)-5D questionnaire at baseline, 3, 6 and 12 months post randomisation]. Results A total of 982 participants were randomised: 493 were randomised to USE-US guided FNAC and 489 were randomised to US-only guided FNAC. There was no evidence of a difference between USE and US in non-diagnostic (Thy 1) rate following the first FNAC [19% vs. 16% respectively; risk difference (RD): 0.030; 95% confidence interval (CI), −0.007 to 0.066; p = 0.11], the number of FNACs needed [odds ratio (OR): 1.10; 95% CI, 0.82 to 1.49; p = 0.53] or in the time to reach a definitive diagnosis [hazard ratio (HR): 0.94; 95% CI, 0.81 to 1.10; p = 0.45]. There was a small, non-significant reduction in the number of thyroid operations undertaken when USE was used (37% vs. 40% respectively; RD: −0.02; 95% CI, −0.06 to 0.009; p = 0.15), but no difference in the number of operations yielding benign histology – 23% versus 24% respectively, p = 0.70 (i.e. no increase in identification of malignant cases) – or in the number of serious adverse events (2% vs. 1%). There was no difference in anxiety and depression, pain or quality of life between the two arms. Limitations The study was not powered to detect differences in malignancy. Conclusions Ultrasound shear/strain wave elastography does not appear to have additional benefit over US-FNAC in the diagnosis of thyroid nodules. Study registration This study is registered as ISRCTN (ISRCTN18261857). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/19/04) and is published in full in Health Technology Assessment; Vol. 28, No. 46. See the NIHR Funding and Awards website for further award information.
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