Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

Strategies of radioiodine ablation in patients with low-risk thyroid cancer.

BACKGROUND: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

Gated blood pool SPECT: The estimation of right ventricular volume and function is algorithm dependent in a clinical setting.

BACKGROUND: Gated blood pool SPECT (GBPS) requires further validation for the assessment of the right ventricle (RV). This study evaluated three algorithms: BP-SPECT, QBS, and TOMPOOL (results are referred using this order). We compared (1) their "quantitative-accuracy": estimation of RV ejection fraction (EF), end-diastolic volume (EDV), and cardiac output (CO); (2) their "qualitative-accuracy": threshold values allowing diagnosing an impairment of the RV function; (3) their reproducibility: inter-observer relative variability (IOV). METHODS AND RESULTS: Forty-eight consecutive patients underwent GBPS. Recommended reference standards were used: cardiac magnetic resonance imaging (CMR) (EDV, EF, n = 48), catheter measurements from thermodilution (TD) (CO, n = 25). (1) "Quantitative-accuracy": r = 0.42, 0.30, 0.42 for RVEF (CMR); r = 0.69, 0.77, 0.53 for RVEDV (CMR); 0.32, 0.36, 0.52 for RCO (TD). (2) "Qualitative-accuracy": optimal thresholds were 54.7%, 38.5%, 45.2% (AUC: 0.83, 0.80, 0.79) for RVEF; 229, 180, 94 mL (AUC: 0.83, 0.81, 0.81) for RVEDV; 4.1, 4.4, 2.6 L·minute(-1) (AUC: 0.73, 0.77, 0.80) for RCO. (3) Reproducibility: IOV was 5% ± 6%, 8% ± 12%, 17% ± 18% for RVEF; 6% ± 8%, 4% ± 4%, 21% ± 18% for RVEDV; 8% ± 8%, 11% ± 15%, 24% ± 20% for RCO. CONCLUSION: Diagnostic accuracies are similar. A CMR-based calibration is required for a quantitative-analysis (cautious interpretation) or an accurate qualitative analysis (thresholds must be adjusted). Automatic procedures (BP-SPECT, QBS) offer the best compromise accuracy/reproducibility.

Is TOMPOOL (gated blood-pool SPECT processing software) accurate to diagnose right and left ventricular dysfunction in a clinical setting?

BACKGROUND: The assessment of right ventricular function is crucial for management of heart disease. TOMPOOL is a software that processes data acquired with Tomographic Equilibrium Radionuclide Ventriculography. In this report, TOMPOOL's diagnostic accuracy and inter-observer reproducibility were assessed in a cohort of patients with various etiologies of ventricular dysfunction. METHODS AND RESULTS: End-diastolic volume (EDV), ejection fraction (EF), and cardiac output (CO) were calculated for the right ventricle (RV) and the left ventricle (LV) using TOMPOOL in 99 consecutive patients. Thirty-five patients underwent cardiac magnetic resonance imaging (CMR) considered as the reference-standard to measure EDV and EF; the Spearman's rho correlation coefficients were r = 0.73/0.80 and 0.67/0.73 for right/left EF and EDV, respectively. Twenty-one patients had thermodilution measurements of right CO (reference-standard), the correlation was r = 0.57. The best cut-off points (sensitivity/specificity) in order to diagnose a ventricular dysfunction or enlargement were 46% for RVEF (67%/89%), 62% for LVEF (100%/90%), 94 mL for RVEDV (77%/73%), and 84 mL for LVEDV (100%/91%). The areas under the ROC curve were, respectively, 0.79, 0.91, 0.83, and 0.99. Inter-observer reproducibility was r = 0.81/0.94, 0.77/0.90, and 0.78/0.75 for Right/Left EF, EDV, and CO, respectively. CONCLUSION: TOMPOOL is accurate: measurements of EDV, EF, and CO are reproducible and correlate with CMR and thermodilution. However, thresholds must be adjusted.

Prediction of all-cause mortality from gated-SPECT global myocardial wall thickening: comparison with ejection fraction and global longitudinal 2D-strain.

BACKGROUND: The aim of this study was to assess the correlation between global wall thickening (GWT) obtained by gated-single photon emission computed tomography (SPECT) and echocardiographic measures [ejection fraction (EF), global longitudinal strain (GLS), and strain rate (GLSR)] and to compare their prognostic value for all-cause mortality. METHODS AND RESULTS: Seventy-four patients with referral for dipyridamole myocardial perfusion SPECT were prospectively included and underwent transthoracic echocardiography to measure left ventricular EF, GLS, and GLSR. The strongest correlation with GWT was for EF (R = 0.63, P < .001), followed by GLSR (R = -0.57, P < .001) and GLS (R = -0.53, P < .001). There were ten deaths over a period of 14.6 ± 5.7 months. Using the multivariate Cox analysis, summed stress score (HR 1.108; P = .023), EF (HR 1.01, P = .031), GLS (HR 1.593, P = .001), and GWT (HR 0.898, P = .034) remained independent predictors of mortality. Mean survival rate evaluated by Kaplan-Meier analysis was longer in patients with GWT ≥ 24% (21.9 ± 0.6 months) than those with GWT < 24% (13.6 ± 2.7 months; P < .001). CONCLUSIONS: GWT assessed is a highly sensitive tool to detect early myocardial systolic dysfunction and may bring additional prognostic information.

New concept of myocardial longitudinal strain reserve assessed by a dipyridamole infusion using 2D-strain echocardiography: the impact of diabetes and age, and the prognostic value.

AIMS: Although dipyridamole is a widely used pharmacological stress agent, the direct effects on myocardium are not entirely known. Diabetic cardiomyopathy can be investigated by 2D-strain echocardiography. The aim of this study was to assess myocardial functional reserve after dipyridamole infusion using speckle-tracking echocardiography. METHODS: Seventy-five patients referred for dipyridamole stress myocardial perfusion gated SPECT (MPGS) were examined by echocardiography to assess a new concept of longitudinal strain reserve (LSR) and longitudinal strain rate reserve (LSRR) respectively defined by the differences of global longitudinal strain (GLS) and longitudinal strain rate between peak stress after dipyridamole and rest. Twelve patients with myocardial ischemia were excluded on the basis of MPGS as gold standard. RESULTS: Mean LSR was -2.28±2.19% and was more important in the 28 (44%) diabetic patients (-3.27±1.93%; p=0.001). After multivariate analyses, only diabetes improved LSR (p=0.011) after dipyridamole infusion and was not associated with glycaemic control (p=0.21), insulin therapy (p=0.46) or duration of the disease (p=0.80). Conversely, age (p=0.002) remained associated with a decrease in LSR. LSSR was also correlated to age (p=0.005). Patients with a LSR<0% have a better survival after 15 months (log-rank p=0.0012). CONCLUSION: LSR explored by 2D speckle-tracking echocardiography after dipyridamole infusion is a simple and new concept that provides new insights into the impact of diabetes and age on the myocardium with a potential prognostic value.

Clinical outcomes 1 year after empiric 131I therapy for hyperthyroid disorders: real life experience and predictive factors of functional response.

Radioiodine is a therapeutic option in Europe for Graves' disease (GD) and toxic multinodular goiter (MNG). PURPOSE: To compare empiric and calculated I activities using 2013 EANM recommendations. To look for predictive factors of therapeutic response to an empiric activity of I. To assess clinical situations favoring calculated treatment modalities. PATIENTS AND METHODS: Prospective monocentric study of clinical outcomes at 1 year follow-up in 86 patients with GD and MNG who received empiric I therapeutic activities (348-939 MBq). Differences between empiric and calculated activities were confronted to clinical outcomes. Physicians were not aware of the calculated activity at the time of prescription. RESULTS: One year after treatment, 9% (5/57) of GD patients and 7% (2/29) of MNG patients were still in a hyperthyroid state. Thyroid volume was reduced by 67% for GD and by 50% for MNG. In GD, empiric I activities were higher than calculated ones (564±131 vs. 316±319 MBq, P<0.001) in 93% (53/57) of patients. Pretherapeutic thyroid volume (>26 ml for GD; >40 ml for MNG) was associated with persistent hyperthyroidism. CONCLUSION: Empirically administered I for GD and MNG was associated with very high efficacy in thyroid function control and no side effects. Thyroid volume reduction did not preclude treatment efficacy. Activity calculation could be a useful method for treating patients with GD and thyroid volumes higher than 26 ml or patients with MNG and thyroid volumes higher than 40 ml. A selective approach based on pretherapeutic thyroid volume and radioiodine biokinetics might improve treatment success.

Quality of Life and Cost-Effectiveness Assessment of Radioiodine Ablation Strategies in Patients With Thyroid Cancer: Results From the Randomized Phase III ESTIMABL Trial.

PURPOSE: In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 ((131)I) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial. PATIENTS AND METHODS: HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 ± 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for (131)I administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and (131)I activities. Sensitivity analyses of the costs of rhTSH were performed. RESULTS: At (131)I administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+€474/patient). The probability that rhTSH would be cost effective at a €50,000/QALY threshold was 47% in France. The use of 1.1 GBq of (131)I instead of 3.7 GBq reduced per-patient costs by €955 (US$1,018) but with slightly decreased efficacy (-0.007 QALY/patient). CONCLUSION: rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price.