The effect of surveillance for differentiated thyroid carcinoma in childhood cancer survivors on survival rates: a decision-tree-based analysis.

Background: Childhood cancer survivors (CCS) who received radiation therapy exposing the thyroid gland are at increased risk of developing differentiated thyroid cancer (DTC). Therefore, the International Guideline Harmonization Group (IGHG) on late effects of childhood cancer therefore recommends surveillance. It is unclear whether surveillance reduces mortality. Aim: The aim of this study was to compare four strategies for DTC surveillance in CCS with the aim of reducing mortality: Strategy-1, no surveillance; Strategy-2, ultrasound alone; Strategy-3, ultrasound followed by fine-needle biopsy (FNB); Strategy-4, palpation followed by ultrasound and FNB. Materials and methods: A decision tree was formulated with 10-year thyroid cancer-specific survival as the endpoint, based on data extracted from literature. Results: It was calculated that 12.6% of CCS will develop DTC. Using Strategy-1, all CCS with DTC would erroneously not be operated upon, but no CCS would have unnecessary surgery. With Strategy-2, all CCS with and 55.6% of CCS without DTC would be operated. Using Strategy-3, 11.1% of CCS with DTC would be correctly operated upon, 11.2% without DTC would be operated upon and 1.5% with DTC would not be operated upon. With Strategy-4, these percentages would be 6.8, 3.9 and 5.8%, respectively. Median 10-year survival rates would be equal across strategies (0.997). Conclusion: Different surveillance strategies for DTC in CCS all result in the same high DTC survival. Therefore, the indication for surveillance may lie in a reduction of surgery-related morbidity rather than DTC-related mortality. In accordance with the IGHG guidelines, the precise strategy should be decided upon in a process of shared decision-making.

Evaluation of SPECT/CT in the assessment of inflammatory jaw pathologies.

PURPOSE: Since accurate diagnosis of inflammatory jaw diseases is still challenging, this study investigated the performance of three phase bone scintigraphy including SPECT/CT in the assessment of correct diagnosis and size of the affected bone tissue. METHOD: This retrospective study contained 31 patients with suspected jaw-related osteoradionecrosis, osteomyelitis or medication-related osteonecrosis of the jaw, which underwent 3-phase bone scintigraphy including SPECT/CT. Results were reviewed by two nuclear medicine physicians. Positive cases received surgery; negative ones were followed-up for six months. Both served as reference standard. Inflamed bone length was measured in the SPECT/CT images and postoperatively by a pathologist. RESULTS: 19 out of 20 positive cases and 10 out of 11 negative ones were classified correctly by SPECT/CT (sensitivity 95 %, specificity 91 %, accuracy 94 %, positive predictive value 95 %, negative predictive value 91 %). Regarding the length of affected bone, no significant difference (p = 0.23) could be observed between SPECT/CT and postoperative obtained values. Both correlated significantly (r = 0.86, p = 0.0001). CONCLUSION: SPECT/CT can safely detect different kinds of inflammatory jaw pathologies compared to other conventional imaging modalities. Lack of specificity of conventional scintigraphy ranging from 17 % to 71 % in earlier studies could be improved by adding CT-analysis. Additionally, SPECT/CT assists the surgeon in determining the expansion of the process (with focus on the length) preoperatively and thereby optimizing surgery planning.

Correction to: Evaluation of 167 Gene Expression Classifier (GEC) and ThyroSeq v2 Diagnostic Accuracy in the Preoperative Assessment of Indeterminate Thyroid Nodules: Bivariate/HROC Meta-analysis.

The original version of the article unfortunately contained an error.

Evaluation of 167 Gene Expression Classifier (GEC) and ThyroSeq v2 Diagnostic Accuracy in the Preoperative Assessment of Indeterminate Thyroid Nodules: Bivariate/HROC Meta-analysis.

The objective of this meta-analysis was to evaluate the performance of the Gene Expression Classifier (GEC) and ThyroSeq v2 (ThyroSeq) in the preoperative diagnosis of thyroid nodules with indeterminate fine-needle aspiration biopsy results. We searched literature databases from January 2001 to April 2018. The bivariate model analysis was performed to estimate pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV). Pooled data from 1086 nodules with histopathologic confirmation from 16 GEC studies enabled calculation of diagnostic parameters (95% confidence interval): sensitivity 98% (96-99%), specificity 12% (8-20%), PPV 45% (37-53%), and NPV 91% (85-96%). Pooled data from five ThyroSeq studies assessing 459 nodules showed sensitivity of 84% (74-91%), specificity 78% (50-92%), PPV 58% (31-81%), and NPV 93% (89-97%). When both tools were compared, GEC had a significantly higher sensitivity (p = 0.003), while ThyroSeq had a significantly higher specificity (p < 0.001) and accuracy (p = 0.015). Pooled LR+ was higher for ThyroSeq: 3.79 (1.40-10.27) vs. 1.12 (1.05-1.20). Pooled LR- was higher for GEC, 0.20 (0.10-0.39) vs. 0.13 (0.05-0.31). The bivariate summary estimates of sensitivity and specificity for GEC and ThyroSeq and their pooled accuracy showed a superiority of the ThyroSeq test. The GEC with a high sensitivity and NPV may be helpful in ruling out malignancy in cases of indeterminate thyroid nodule cytology. ThyroSeq has a significantly higher specificity and accuracy with an acceptable sensitivity so that it has the potential for use as an all-round test of malignancy of thyroid nodules.

Thyroid nodules with indeterminate cytology: molecular imaging with 99mTc-methoxyisobutylisonitrile (MIBI) is more cost-effective than the Afirma gene expression classifier.

PURPOSE: To compare the cost-effectiveness of (99m)Tc-methoxyisobutylisonitrile (MIBI) thyroid scintigraphy and the Afirma gene expression classifier for the assessment of cytologically indeterminate thyroid nodules. METHODS: A decision tree model was used. Costs were calculated from the perspective of the German health insurance system. The robustness of the results was assessed with probabilistic sensitivity analyses using a Monte Carlo simulation. RESULTS: Life expectancy was 34.3 years (estimated costs per patient €1,459 - €2,224) for the MIBI scan and 34.1 years (estimated costs €3,560 - €4,071) for the molecular test. These results were confirmed by the Monte Carlo simulation. CONCLUSION: MIBI thyroid scintigraphy is more cost-effective than the gene expression classifier.

Body surface area adapted iopromide 300 mg/ml versus 370 mg/ml contrast medium injection protocol: influence on quantitative and clinical assessment in combined PET/CT.

PURPOSE: To investigate the quantitative and qualitative differences between combined positron emission tomography and computed X-ray tomography (PET/CT) enhanced with contrast medium with either an iodine concentration 300 mg/ml or 370 mg/ml. MATERIALS AND METHODS: 120 consecutive patients scheduled for F-18-Fluorodeoxyglucose (FDG) PET/CT were included. The first (second) 60 patients received contrast medium with 300 (370) mg iodine/ml. Intravenous injection protocols were adapted for an identical iodine delivery rate (1.3mg/s) and body surface area (BSA) adapted iodine dose (22.26 gI/m(2)). Maximum and mean standardized uptake values (SUV(max); SUV(mean)) and contrast enhancement (HU) were determined in the ascending aorta, the abdominal aorta, the inferior vena cava, the portal vein, the liver and the right kidney in the venous contrast medium phase. PET data were evaluated visually for the presence of malignancy and image quality. RESULTS: Both media caused significantly higher values for HU, SUV(mean) and SUV(max) for the enhanced PET/CT than the non-enhanced one (all p<0.01). There were no significant differences in the degree of increase of HU, SUV(mean) and SUV(max) between the two contrast media at any anatomic site (all p>0.05). Visual evaluation of lesions showed no differences between contrast and non-contrast PET/CT or between the two different contrast media (p=0.77). CONCLUSION: When using a constant iodine delivery rate and total iodine dose in a BSA adapted injection protocol, there are no quantitative or qualitative differences in either CT or PET between contrast media with an iodine concentration of 300 mg/ml and 370 mg/ml, respectively.

The influence of different contrast medium concentrations and injection protocols on quantitative and clinical assessment of FDG-PET/CT in lung cancer.

OBJECTIVES: To compare the effects of two different contrast medium concentrations for use in computed X-ray tomography (CT) employing two different injection protocols on positron emission tomography (PET) reconstruction in combined 2-(18)F-desoxyglucose (FDG) PET/CT in patients with a suspicion of lung cancer. METHODS: 120 patients with a suspicion of lung cancer were enrolled prospectively. PET images were reconstructed with the non-enhanced and venous phase contrast CT obtained after injection of iopromide 300 mg/ml or 370 mg/ml using either a fixed-dose or a body surface area adapted injection protocol. Maximum and mean standardized uptake values (SUV(max) and SUV(mean)) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and in the suspicious lung lesion. PET data were evaluated visually for the presence of malignancy and image quality. RESULTS: At none of the sites a significant difference in the extent of the contrast enhancement between the four different protocols was found. However, the variability of the contrast enhancement at several anatomical sites was significantly greater in the fixed dose groups than in the BSA groups for both contrast medium concentrations. At none of the sites a significant difference was found in the extent of the SUV(max) and SUV(mean) increase as a result of the use of the venous phase contrast enhanced CT for attenuation. Visual clinical evaluation of lesions showed no differences between contrast and non-contrast PET/CT (P=0.32). CONCLUSIONS: Contrast enhanced CT for attenuation correction in combined PET/CT in lung cancer affects neither the clinical assessment nor image quality of the PET-images. A body surface adapted contrast medium protocol reduces the interpatient variability in contrast enhancement.

Thyroglobulin levels and thyroglobulin doubling time independently predict a positive 18F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma.

PURPOSE: To assess the relationship between serum thyroglobulin (Tg) levels, Tg doubling time (Tg-DT) and the diagnostic performance of (18)F-FDG PET/CT in detecting recurrences of (131)I-negative differentiated thyroid carcinoma (DTC). METHODS: Included in the present study were 102 patients with DTC. All patients were treated by thyroid ablation (e.g. thyroidectomy and (131)I), and underwent (18)F-FDG PET/CT due to detectable Tg levels and negative conventional imaging. Consecutive serum Tg measurements performed before the (18)F-FDG PET/CT examination were used for Tg-DT calculation. The (18)F-FDG PET/CT results were assessed as true or false after histological and/or clinical follow-up. RESULTS: Serum Tg levels were higher in patients with a positive (18)F-FDG PET/CT scan (median 6.7 ng/mL, range 0.7-73.6 ng/mL) than in patients with a negative scan (median 1.8 ng/mL, range 0.5-4.9 ng/mL; P < 0.001). In 43 (88 %) of 49 patients with a true-positive (18)F-FDG PET/CT scan, the Tg levels were >5.5 ng/mL, and in 31 (74 %) of 42 patients with a true-negative (18)F-FDG PET/CT scan, the Tg levels were ≤5.5 ng/mL. A Tg-DT of <1 year was found in 46 of 49 patients (94 %) with a true-positive (18)F-FDG PET/CT scan, and 40 of 42 patients (95 %) with a true-negative scan had a stable or increased Tg-DT. Moreover, combining Tg levels and Tg-DT as selection criteria correctly distinguished between patients with a positive and a negative scan (P<0.0001). CONCLUSION: The accuracy of (18)F-FDG PET/CT significantly improves when the serum Tg level is above 5.5 ng/mL during levothyroxine treatment or when the Tg-DT is less than 1 year, independent of the absolute value.

Different intravenous contrast media concentrations do not affect clinical assessment of 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans in an intraindividual comparison.

OBJECTIVE: The purpose of this study was to perform an intraindividual comparison of the influences of different iodine contrast media on tracer uptake, contrast enhancement, and image quality in combined positron emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: Fifty-one patients underwent baseline and follow-up combined PET/CT consisting of low-dose unenhanced and venous contrast-enhanced CT with contrast media containing a high concentration of iodine (iopromide, 370 mg/mL) and a standard iodine concentration (iopromide, 300 mg/mL). The total iodine load (44.4 g) and the iodine delivery rate (1.29 g/s) were identical for the 2 protocols. The mean and maximum standard uptake values, as measures of tracer uptake and contrast enhancement for unenhanced and contrast-enhanced PET/CT, were quantified at 10 different anatomical sites, and images were analyzed for clinically relevant differences. RESULTS: The mean and maximum standard uptake values were significantly increased in contrast-enhanced PET/CT compared with unenhanced PET/CT at each anatomical site (P < 0.05). Comparison of tracer uptake between the 300- and 370-mg iodine contrast media showed no significant differences (all P > 0.05). Comparison of contrast enhancement between the 300- and 370-mg iodine contrast media showed no significant difference at any anatomical site (all P > 0.05). Analysis of image quality revealed no clinically relevant differences between the 2 different iodine contrast media (P = 0.739). CONCLUSION: The use of contrast-enhanced CT scans for attenuation correction in PET/CT does not cause clinically relevant artifacts in PET scan reconstruction, regardless of the iodine concentration used. Standard- and high-iodine contrast media can be used equivalently.

PET/CT in lung cancer: Influence of contrast medium on quantitative and clinical assessment.

OBJECTIVES: To evaluate the influence of intravenous contrast medium and different contrast medium phases on attenuation correction, PET image quality and clinical staging in combined PET/CT in patients with a suspicion of lung cancer. METHODS: Sixty patients with a suspicion of lung cancer were prospectively enrolled for combined (18)F-FDG-PET/CT examination. PET images were reconstructed with non-enhanced and arterial and venous phase contrast CT. Maximum and mean standardised uptake values (SUVmax and SUVmean) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and lung tumour. PET data were evaluated visually for clinical staging and image quality. RESULTS: SUVmax was significantly increased between contrast and non-contrast PET/CT at all anatomic sites (all P < 0.001). SUVmax was significantly increased for arterial PET/CT compared to venous PET/CT in the arteries (all P < 0.001). Venous PET/CT resulted in significantly higher SUVmax values compared to arterial PET/CT in the parenchymatous organs (all P < 0.05). Visual clinical evaluation of malignant lesions showed no differences between contrast and non-contrast PET/CT (P = 1.0). CONCLUSIONS: Contrast enhanced CT is suitable for attenuation correction in combined PET/CT in lung cancer; it affects neither the clinical assessment nor image quality of the PET images. KEY POINTS : • Positron emission tomography combined with computed tomography is now a mainstream investigation • There has been debate about whether CT contrast agents affect PET results • Contrast-enhanced CT is satisfactory for attenuation correction in lung cancer PET/CT • Multiphase CT does not affect PET; additional unenhanced CT is unnecessary • For quantitative follow-up PET analysis, an identical PET/CT protocol is required.

Multiphase CT scanning and different intravenous contrast media concentrations in combined F-18-FDG PET/CT: Effect on quantitative and clinical assessment.

PURPOSE: To evaluate the influence of multiphase CT scanning and different intravenous contrast media on contrast enhancement, attenuation correction and image quality in combined PET/CT. MATERIAL AND METHODS: 140 patients were prospectively enrolled for F-18-FDG-PET/CT including a low-dose unenhanced, arterial and venous contrast enhanced CT. The first (second) 70 patients, received contrast medium with 370 (300) mg iodine/ml. The iodine delivery rate (1.3mg/s) and total iodine load (44.4g) were identical for both groups. Contrast enhancement and maximum and mean standardized FDG uptake values (SUVmax and SUVmean) were determined for the un-enhanced, arterial and venous PET/CT at multiple anatomic sites and PET reconstructions were visually evaluated. RESULTS: Arterial contrast enhancement was significantly higher for the 300mg/ml contrast medium compared to 370mgI/ml at all anatomic sites. Venous enhancement was not different between the two contrast media. SUVmean and SUVmax were significantly higher for the contrast enhanced compared to the non-enhanced PET/CT at all anatomic sites (all P<0.001). Tracer uptake was significantly higher in the arterial than in the venous PET/CT in the arteries using both contrast media (all P<0.001). No differences in tracer uptake were found between the contrast media (all P>0.05). Visual assessment revealed no relevant differences between the different PET reconstructions. CONCLUSIONS: There is no relevant qualitative influence on the PET scan from the use of different intravenous contrast media in its various phases in combined multiphase PET/CT. For quantitative analysis of tracer uptake it is required to use an identical PET/CT protocol.

A phantom assessment of portable imaging and radio-guided surgery systems with technetium-99m and fluorine-18.

AIM: To perform a detailed analysis of the performance of mobile intraoperative imaging systems and gamma probes in a phantom set-up, and compare this with a conventional gamma camera. METHODS: Two separate experiments were performed. In the first, a modified Jaszczak phantom equipped with five (99m)Tc-filled hot spheres (0.5-20 ml) was analyzed using Sentinella, declipseSPECT and a conventional gamma camera under three conditions: no background, spheres on the surface of the background activity, and totally immersed spheres (contrast level in both 1: 8). In the second experiment, two phantom spheres (0.5 and 2 ml) filled with (99m)Tc and (18)F (infinite contrast, 1: 4 and 1: 8) were measured using the hand-held probes Navigator and GammaLocator DXI. Data analysis consisted of signal-to-background ratios and determination of the full-width at half-maximum (FWHM). A visual scoring was performed by three nuclear medicine physicians. RESULTS: At infinite contrast, (99m)Tc-filled spheres with volumes of at least 2 ml could be detected adequately with all systems (e.g. 2 ml sphere, FWHM: ECAM 11 mm, declipseSPECT 9 mm, Navigator 13 mm, GammaLocator 12 mm). Under decreased contrast conditions, the results for all systems were impaired and the 0.5 ml phantom sphere filled with either (99m)Tc or (18)F was only detected accurately by the GammaLocator (FWHM range: 13-17 mm). CONCLUSION: All systems are suitable for intraoperative sentinel node detection with nearly infinite signal-to-background contrast. At a lower contrast, the GammaLocator performed best for the detection of small volumes at low-contrast ratios regardless of the radionuclide.

A phantom assessment of cold stomach-related artifacts in myocardial perfusion imaging.

AIM: To study the effect of a 'cold stomach', caused by either air or water, on Tl-201 and Tc-99m myocardial perfusion single-photon emission computed tomography (MPS). MATERIALS AND METHODS: A stomach insert was created in a thorax phantom. MPS was performed with Tl-201 or Tc-99m. MPS was recorded with an empty stomach, a stomach filled with 0.5 or 1 l of water, or with 0.5 or 1 l of air. For Tc-99m, transmission scans for attenuation correction (AC) were also obtained. RESULTS: In Tl-201 MPS, filling the stomach with air caused an increase of activity in the infero-lateral wall, whereas filling the stomach with 1 l of water resulted in a slight decrease of activity in the infero-lateral wall. In Tc-99m MPS, filling the stomach with air also resulted in a higher activity in the infero-lateral wall, which normalized when AC was applied. Filling the stomach with water caused no marked differences in Tc-99m MPS with or without AC. CONCLUSION: A stomach filled with large amounts of water causes (mild) infero-lateral wall defects in Tl-201 MPS; a stomach filled with air causes a strong scintigraphic overexpression of the infero-lateral wall in both Tl-201 and Tc-99m MPS which can be compensated with AC.