Remnant Ablation Research Articles

A Rare Case of Isolated Pericardial Effusion Detected by SPECT/CT on a Post-Therapeutic Radioiodine Whole-Body Scan.

We reported a rare finding of isolated pericardial uptake detected by SPECT/CT on posttherapeutic radioiodine whole body scan. This case highlights the usefulness of hybrid SPECT/CT, with subsequent correlation with biochemical results, in ruling out metastatic pericardial effusion in the postsurgical radioiodine remnant ablation setting. The effusion was resolved after reinstituted thyroid replacement therapy. Recombinant thyrotropin is recommended to avoid such rare but life-threatening complication.

Recombinant TSH stimulated remnant ablation therapy in thyroid cancer: the success rate depends on the definition of ablation success--an observational study.

IntroductionPatients with differentiated thyroid cancer (DTC) are treated with (near)-total thyroidectomy followed by remnant ablation. Optimal radioiodine-131 (131I) uptake is achieved by withholding thyroid hormone (THW), pretreatment with recombinant human Thyrotropin Stimulating Hormone (rhTSH) is an alternative. Six randomized trials have been published comparing THW and rhTSH, however comparison is difficult because an uniform definition of ablation success is lacking. Using a strict definition, we performed an observational study aiming to determine the efficacy of rhTSH as preparation for remnant ablation.Patients and MethodsAdult DTC patients with, tumor stage T1b to T3, Nx, N0 and N1, M0 were included in a prospective multicenter observational study with a fully sequential design, using a stopping rule. All patients received remnant ablation with 131I using rhTSH. Ablation success was defined as no visible uptake in the original thyroid bed on a rhTSH stimulated 150 MBq 131I whole body scan (WBS) 9 months after remnant ablation, or no visible uptake in the original thyroid bed on a post therapeutic WBS when a second high dose was necessary.ResultsAfter interim analysis of the first 8 patients, the failure rate was estimated to be 69% (90% confidence interval (CI) 20-86%) and the inclusion of new patients had to be stopped. Final analysis resulted in an ablation success in 11 out of 17 patients (65%, 95% CI 38-86%).ConclusionAccording to this study, the efficacy of rhTSH in the preparation of 131I ablation therapy is inferior, when using a strict definition of ablation success. The current lack of agreement as to the definition of successful remnant ablation, makes comparison between different ablation strategies difficult. Our results point to the need for an international consensus on the definition of ablation success, not only in routine patient’s care but also for scientific reasons.Trial RegistrationDutch Trial Registration NTR2395

New therapies for dedifferentiated papillary thyroid cancer.

The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, which fails to respond to RAI, exhibiting a more aggressive behavior. The lack of specific, effective and well-tolerated drugs, the scarcity of data about the association of multi-targeting drugs, and the limited role of radioiodine for dedifferentiated thyroid cancer, call for further efforts in the field of new drugs development. Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF proto-oncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways playing a crucial role in the development of thyroid cancer. Targeted novel compounds have been demonstrated to induce clinical responses and stabilization of disease. Sorafenib has been approved for differentiated thyroid cancer refractory to RAI.

Persistent quality of life impairments in differentiated thyroid cancer patients: results from a monitoring programme.

PurposeHealth-related quality of life (HRQOL) in differentiated thyroid cancer (DTC) research has so far received little attention and available results are conflicting. We studied the HRQOL of radioiodine-naive DTC patients in comparison with the general population (GP), investigated the course of HRQOL up to 30 months after radioiodine remnant ablation (RAA) and sought to identify patient characteristics associated with HRQOL.MethodsWe analysed data from routine HRQOL monitoring at a nuclear medicine department. Between 2005 and 2013, a total of 439 thyroid cancer patients (all histologies) completed the EORTC Quality of Life Questionnaire Core-30 (QLQ-C30) at least once during their treatment at the department. We compared patients’ baseline HRQOL scores before RAA with scores from age-matched and sex-matched controls from the Austrian GP. We then determined the course of HRQOL over the 30 months after RAA and assessed the impact of the following clinical variables on HRQOL: method of thyroid-stimulating hormone (TSH) stimulation, histology (papillary vs. follicular) and disease stage.ResultsA total of 284 patients (mean age 48.3 years, SD 15.0 years; 71.6 % women; 80.7 % papillary type) with a baseline HRQOL assessment before RAA were available. We found clinically meaningful differences in the detriment in patients on almost all domains. These were largest for fatigue (23 points) and role functioning (25 points). Data from 241 patients (mean age 48.6 years, SD 15.9 years; 68.9 % women; 76.3 % papillary type) were included in the longitudinal analysis. Investigating the course of HRQOL, a significant improvement over time was found for role and emotional functioning, fatigue, pain, and dyspnoea. A range of HRQOL scores were improved in patients with exogenous TSH stimulation, but some scores both in patients with exogenous TSH stimulation and in those followed for 30 months, especially fatigue and role functioning, did not reach levels in the GP sample.ConclusionOur results show that the favourable prognosis of DTC does not directly translate into good HRQOL in these patients. Persistent restrictions in regaining their normal daily life in terms of work and leisure highlight the importance of more detailed investigation of DTC patients’ wellbeing, support needs, and disease experience.

Thyroid remnant volume and Radioiodine ablation in Differentiated thyroid carcinoma

Aims: The aims of the study were to determine the thyroid remnant volume and to see the effect of radioiodine ablation on thyroid remnant volume. Methods: A retrospective analysis of seventy-one differentiated thyroid carcinoma patients treated with high dose radioiodine (I-131) for post surgical ablation of thyroid remnants were done in Institute of Nuclear Medicine & Allied Sciences, Comilla of Bangladesh Atomic Energy Commission. Female were 60 and male were 11 with female-male ration of 5.5:1. All patients enrolled during the period from January 2001 to December 2011. The age range of the patients was 15 years to 90 years. The thyroid remnant volumes were determined by SPECT scintigraphy. High dose radioiodine (I-131) ablations were done with doses ranged from 2.77 GBq (75mCi) to 5.55 GBq (175 mCi). A successful ablation was defined as the absence of activity in the thyroid bed on subsequent imaging studies. Results: Fifty-nine patients (83.1%) showed complete ablation and twelve (16.9%) showed partial ablation of thyroid remnants after radioiodine therapy. The remnant thyroid volume as determined from scintigraphic images was significantly different (p = 0.048) between them who were completely ablated and them who were partially ablated. It was also observed that in complete ablation, 52.5% had thyroid remnant volume <1.0 gm, 40.7% had 1.1 to 2.0 gm, 5.1% had 2.1 to 3.0 gm and 1.7% had > 3.0 gm. i.e., The smaller the volume of thyroid remnant, better the response and larger the volume, the poorer the response to radioiodine. Conclusions: Successful ablation of thyroid remnants significantly depends on their volume and the successful ablation is inversely related with thyroid remnant volume. DOI: http://dx.doi.org/10.3329/bjnm.v17i1.22492 Bangladesh J. Nuclear Med. 17(1): 55-60, January 2014

Radioiodine remnant ablation in low-risk differentiated thyroid cancer patients who had R0 dissection is an over treatment.

Low-risk (LR) differentiated thyroid cancer (DTC) patients should be ablated or not, albeit, with small dose of radioiodine is highly controversial. We hypothesized that those LR DTC patients who were surgically ablated need no radioiodine remnant ablation (RRA). This study aims to evaluate the long-term outcome in these two groups of patients. Retrospective cohort study conducted from January 1991 to December 2012. Based on extent of surgical resection and histopathology, LR DTC patients were classified as Gr-1: 169 patients, who were surgically ablated; Gr-2: 153 patients, who had significant remnant in thyroid bed. Basal parameters were comparable between two groups except pretherapy 24 h radioiodine uptake (0.16 ± 0.01% vs. 5.64 ± 0.46%; P < 0.001). No patient received RRA in Gr-1; Gr-2 patients were administered 30 mCi 131I. Total number of events (recurrence, persistent, and progression of disease), with median follow up of 10.3 years, was observed in 10/322 (3.1%) of LR DTC patients. Only one patient had disease recurrence from Gr-1, who became disease-free after radioiodine therapy. Similarly, one patient from 126, who was ablated with single dose of RRA, had recurrence from Gr-2. However, 8/27 (29.7%) patients from Gr-2 had persistent disease; even two of them subsequently developed disease progression, who failed first-dose of RRA. The event-free survival rates were 99.4% and 94.1% (P = 0.006) in Gr-1 and Gr-2, respectively. RRA is an overtreatment in surgically ablated LR DTC patients. Successfully ablated RRA patients also had similar long-term outcome, however, those who failed, should be re-stratified as intermediate-risk category, and managed aggressively.

Differences in Physicians' and Patients' Perception of Acute Hypothyroid Symptoms Induced by Thyroid Hormone Withdrawal in Thyroid Cancer Patients: A Multicenter Survey in Korea

Background: Acute short-term hypothyroidism induced by thyroid hormone withdrawal (THW) for follow-up surveillance or therapeutic radioiodine causes patients with differentiated thyroid cancer to suffer from a myriad of deleterious symptoms. Objectives: To know how patient recognition of hypothyroid symptoms compares to physician perception of patient symptoms. Methods: The survey was performed in 10 referral hospitals throughout Korea from December 2010 to May 2011 and targeted patients with total thyroidectomy and remnant ablation. The survey consisted of questions regarding the effect of THW on patient symptoms, the duration of symptoms, impact on social life, and patient complaints. The physicians treating thyroid cancer patients also responded to the survey and provided their perceptions of patient symptoms and treatment decisions. Results: About 70% of the patients responded that they experienced a negative physical or psychological impact on their life and work due to hypothyroid symptoms. However, 76% of doctors thought hypothyroidism could negatively impact a patient's daily life but would be endurable. Two thirds of physicians do not routinely recommend recombinant human TSH (rhTSH) to their patients. Multivariate analysis showed patients with female sex, stronger educational background, emotionally negative experiences of hypothyroidism, and younger age were more willing to pay for therapy that could prevent hypothyroidism symptoms. Conclusions: There was a substantial gap in the perception of hypothyroid symptoms during THW between physicians and patients. Physicians who are aware of the seriousness of hypothyroidism in their patients were more likely to recommend the use of rhTSH for their patients.

Low-risk differentiated thyroid cancer and radioiodine remnant ablation: a systematic review of the literature.

Radioiodine remnant ablation (RRA) has traditionally been one of the cornerstones of differentiated thyroid cancer (DTC) treatment. The decision to use RRA in low-risk (LR) and intermediate-risk (IR) patients is controversial. The aim of this review is to examine the evidence of RRA benefit in the staging, follow-up, and recurrence prevention in LR and IR DTC patients. From a PubMed search, we selected original papers (OPs) using the following inclusion criteria: 1) DTC; 2) LR and IR patients; 3) non-RRA-treated patients or RRA-treated vs non-RRA-treated groups; 4) a report of the outcome of cancer recurrence; and 5) publication since 2008. Neck ultrasonography is superior to whole-body scan for disease detection in the neck. A rising or declining serum thyroglobulin level over time provides an excellent positive or negative predictive value, respectively, even in non-RRA-treated patients. No OP demonstrating RRA benefit on recurrence in LR patients was found; two OPs found no evidence of benefit. We found 11 OPs that observed some benefit in reducing recurrence rates with RRA in IR patients and 13 OPs that failed to show benefit from RRA in this group. Neck ultrasonography and serum thyroglobulin measurement are equivalent or superior in detecting and localizing residual disease compared to post-therapy whole-body scan. There is no evidence of RRA benefit in recurrence prevention for LR patients. There are conflicting data on IR patients and only a few studies with homogenous and properly stratified populations. A careful evaluation of tumor pathological features and patient characteristics and preferences should guide RRA decision making.

Prothrombotic changes due to an increase in thyroid hormone levels.

With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 μg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.

Radioiodine remnant ablation in low-risk differentiated thyroid cancer: the "con" point of view.

A growing body of evidence is challenging the indiscriminate use of postoperative radioiodine for remnant ablation (RRA) in low-risk (LR) differentiated thyroid cancer patients. We critically reviewed the current evidence on which the rationale for RRA is based for LR patients and analyzed the new evidence-based recommendations for LR patients from the draft of the 2015 American Thyroid Association (ATA) guidelines. Cost-effective tools for staging and follow-up, such as neck ultrasonography and serial thyroglobulin testing, are useful for monitoring non-RRA-treated patients. Recurrence rates are very low in non-RRA-treated LR patient cohorts. Most RRA side effects are mild and transient, but can impair a patient's quality of life. RRA is appropriately not routinely recommended in LR patients according to the draft 2015 ATA guidelines and should be reserved for higher-risk patients.

Economic Evaluation of Recombinant Human Thyroid Stimulating Hormone Stimulation vs. Thyroid Hormone Withdrawal Prior to Radioiodine Ablation for Thyroid Cancer: The Korean Perspective.

BackgroundPrevious studies have suggested that recombinant human thyroid stimulating hormone (rhTSH) stimulation is an acceptable alternative to thyroid hormone withdrawal (THW) when radioiodine remnant ablation is planned for thyroid cancer treatment, based on superior short-term quality of life with non-inferior remnant ablation efficacy. This study evaluated the cost-effectiveness of radioiodine remnant ablation using rhTSH, compared with the traditional preparation method which renders patients hypothyroid by THW, in Korean perspective.MethodsThis economic evaluation considered the costs and benefits to the Korean public healthcare system. Clinical experts were surveyed regarding the current practice of radioiodine ablation in Korea and their responses helped inform assumptions used in a cost effectiveness model. Markov modelling with 17 weekly cycles was used to assess the incremental costs per quality-adjusted life year (QALY) associated with rhTSH. Clinical inputs were based on a multi-center, randomized controlled trial comparing remnant ablation success after rhTSH preparation with THW. The additional costs associated with rhTSH were considered relative to the clinical benefits and cost offsets.ResultsThe additional benefits of rhTSH (0.036 QALY) are achieved with an additional cost of Korean won ₩961,105, equating to cost per QALY of ₩26,697,361. Sensitivity analyses had only a modest impact upon cost-effectiveness, with one-way sensitivity results of approximately ₩33,000,000/QALY.ConclusionThe use of rhTSH is a cost-effective alternative to endogenous hypothyroid stimulation prior to radioiodine ablation for patients who have undergone thyroidectomy in Korea.

Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer.

Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (<1.0 ng/mL). Various factors including age, off-Tg, and histopathology were analyzed to predict ablation success rates. Of 176 patients, 68.8% (n = 121) who achieved successful remnant ablation were classified into Group A, and the remaining 55 were classified into Group B. Group A presented with significantly lower off-Tg at the first radioiodine administration (pre-ablative Tg) than those of Group B (1.2 ± 2.3 ng/mL vs. 6.2 ± 15.2 ng/mL, P = 0.027). Pre-ablative Tg was the only significant factor related with ablation success rates. Diagnostic performances of pre-ablative Tg < 10.0 ng/mL were sensitivity of 99.1%, specificity of 14.0%, positive predictive value of 71.1%, and negative predictive value of 87.5%, respectively. Single administration of low radioiodine activity could be sufficient for remnant thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation.

Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma.

To determine whether postoperative radioiodine (RAI) combined with radiofrequency ablation (RFA) is an effective, safe, and feasible method for elimination of excessive postsurgical thyroid remnant for differentiated thyroid carcinoma (DTC). We took a prospective study and treated 12 DTC patients (4 males, 8 females, age 20-78 years) who underwent thyroidectomy for RFA followed by 131 I ablation. The pretreatment requires iodine-free diet and thyroid hormone withdrawal for 3-4 week. All the patients showed the level of serum thyroid-stimulating hormone (TSH) <30 mU/L, and obvious thyroid remnant in 99m Technetium (99m Tc) imaging. Serum TSH level was determined 1 day before RFA and on days 1, 7, 14 after RFA, and 99m Tc imaging was performed on day 14 after RFA. Subsequently, the patients were given an oral dosage of 3700 MBq 131 I for remnant ablation, and posttreatment whole body scan was performed on day 5 after ablation. Efficacy evaluation was done 4-6 months after treatment. The changes of variants before and after RFA were analyzed using Wilcoxon signed rank sum test. Serum TSH was <30 μIU/ml (mean value 10.27 ± 6.16 μIU/ml) before RFA, and increased to more than 30 μIU/ml (34.73 ± 3.93 μIU/ml) 2 weeks later (P = 0.002, Wilcoxon rank sum test). The 99m Tc uptake ratio on day 14 postRFA was (0.31 ± 0.12)%, which is significantly lower than before RFA (0.80 ± 0.16)% (P = 0.002, Wilcoxon rank sum test). The success rate of thyroid remnant ablation was 91.7% (11/12), which was assessed 4-6 months after treatment. All patients reported neck discomfort and some are self-limiting, with no hoarseness, choking, or radiation thyroiditis symptoms. Five patients had puncture area pain, among which one patient had neck edema, which was relieved after prednisone treatment. Combined use of RAI therapy and radiofrequency ablation in treating excessive postsurgical thyroid remnant of DTC can be an effective approach and avoids re-operation. Long-term efficacy monitoring would further determine its feasibility.

Prognostic significance of thyroglobulin antibody epitopes in differentiated thyroid cancer.

Thyroglobulin antibodies (TgAbs) are surrogate markers of disease recurrence or persistence in differentiated thyroid cancer (DTC). However, the prognostic significance of TgAb heterogeneity in DTC has not been investigated. To evaluate the relationship between TgAb epitope specificities and clinical outcomes in DTC patients. We studied 61 TgAb-positive patients with DTC, post-thyroidectomy and remnant ablation (7 males, 54 females; age-range 16-80 years, median follow-up duration 8.9 years). TgAb epitope reactivities were mapped using a panel of 10 thyroglobulin (Tg) monoclonal antibodies delineating six antigenic Tg clusters in competitive ELISA studies. Sera from 45 patients with Hashimoto's thyroiditis (HT) and 22 TgAb-positive healthy subjects served as autoimmune and healthy controls. Tg was measured by immunoradiometric assay (IRMA), electrochemiluminescence immunoassay (ECLIA), and RIA, while TgAbs was measured by ELISA and ECLIA methods. Samples from 26 DTC patients showed TgAb epitope restriction similar to HT patients, while 35 patients exhibited nonspecific reactivity comparable to healthy controls. DTC patients with epitope restriction had higher rates of recurrent/persistent disease (81% vs 17%, P < .001), higher median TgAb concentration (887.0 vs 82.0 kIU/L; P < .001), and a higher prevalence of thyroid lymphocytic infiltration (71.4% vs 26.8%; P < .001) compared to patients with nonspecific reactivity. Samples with epitope restriction also had a lower median Tg-IRMA/RIA ratio (3.0% vs 36.0%; P < .001) denoting greater degrees of Tg assay interference. TgAb epitope restriction is associated with a less favorable prognosis than nonspecific reactivity in DTC patients. TgAb epitope specificities may have prognostic value in DTC.

Lowest effective 131I activity for thyroid remnant ablation of differentiated thyroid cancer patients. Dosimetry-based model for estimation.

A theoretical dosimetry-based model was applied to estimate the lowest effective radioiodine activity for thyroid remnant ablation of low-risk differentiated thyroid cancer patients. The model is based on the distribution of the absorbed (radiation) dose per administered radioiodine activity and the absorbed dose threshold of 300 Gy for thyroid remnants, the level believed to destroy most thyroid remnants. For this purpose, ¹²⁴I PET/CT images of 49 thyroidectomised patients were retrospectively analysed to measure the distribution of the (average) absorbed doses to thyroid remnant per administered ¹³¹I activity. The fraction of thyroid remnants that received at least 300 Gy was determined for standard activities between 0.37 and 5.55 GBq. The lower activity was considered to be equally effective to that obtained with higher activity if the (absolute) fraction difference was below 5%. A total of 62 thyroid remnants were included. The medians and ranges (in parentheses) for the absorbed dose per unit 131I activity were 359 Gy/GBq (34 to 1825 Gy/GBq). The fractions of thyroid remnants receiving more than 300 Gy at different therapy activities (within parentheses) were 60% (1.11 GBq), 76% (1.85 GBq), 79% (2.22 GBq), and 81-82% for activities between 2.59 and 3.70 GBq. The therapy activity of 1.11 GBq is considerably less effective than that of 1.85 or 2.22 GBq; therapy activities were equally effective in the range between 2.22 to 3.70 GBq. On the basis of the model and the patients' data included, the lowest effective therapy activity appears to be approximately 2.2 GBq to ablate thyroid remnants. The results of this study may help to guide the design of prospective clinical studies.

Indications of radioactive iodine ablation in papillary thyroid cancer

Differentiated thyroid carcinoma (DTC) is a relatively common endocrine malignancy. Of these cancers, papillary cancer comprises about 85% of cases compared to about 10% with follicular histology, and 3% that are Hurthle cell or oxyphil tumours. Papillary thyroid carcinoma (PTC) greater than 1cm in diameter is best managed by total thyroidectomy. Postoperatively, radioactive iodine ablation followed by thyroid stimulating hormone (TSH) suppression is indicated in certain patients to improve locoregional control and reduce recurrence. To decide whether ablation is worthwhile, the TNM classification is recommended which is a system that provides the rationale for therapy and the strength of existing evidence for or against treatment. Several histological subtypes of PTC, the presence of intrathyroidal vascular invasion, or the finding of gross or microscopic multifocal disease may place the patient at higher risk of local recurrence or metastases. Moreover, the size of the tumour, lymph node status, and patient age may increase the risk of recurrence or metastatic spread to a degree that is high enough to ablate these patients. The minimum activity of radioactive iodine necessary to achieve successful remnant ablation is suggested, particularly for low-risk patients.

Prediction of the success of thyroid remnant ablation using preablative 99mTc pertechnetate scintigraphy and postablative dual 131I scintigraphy.

The aim of this study was to predict the success of 131I ablation using preablative 99mTc pertechnetate salivary scintigraphy and a postablative dual 131I scan in differentiated thyroid cancer (DTC). A total of 168 DTC patients who underwent 131I ablation with preablative salivary scintigraphy and a postablative dual (early and delayed) 131I scan were enrolled. For salivary scintigraphy, the thyroid remnant uptake was visually assessed. For the dual 131I scan, the thyroid remnant to background uptake ratios (TBRs) on early and delayed scans were measured and the percentage change in TBR (TBRΔ) was calculated. Thyroid remnant uptake was seen in 69 (41%) patients on salivary scintigraphy and in 162 (96%) patients on the dual 131I scan. The success rate of ablation was higher in patients with negative remnant uptake on salivary scintigraphy (86%) than in patients with positive remnant uptake (58%, P=0.0001). The success rate of ablation was 100% in patients with no remnant uptake on both salivary scintigraphy and the dual 131I scan. The success rate of ablation was higher in patients with TBRΔ 0 or more than in patients with TBRΔ less than 0, irrespective of remnant uptake on salivary scintigraphy (91 vs. 70%, P=0.03, for patients without remnant uptake on salivary scintigraphy; 74 vs. 48%, P=0.05, for patients with remnant uptake on salivary scintigraphy). The success of thyroid remnant ablation in DTC can be predicted by the presence of remnant uptake on preablative 99mTc pertechnetate scintigraphy and change in remnant uptake on the postablative dual 131I scan.

Recombinant Human Thyroid-Stimulating Hormone-Aided Remnant Ablation Achieves a Response to Treatment Comparable to That with Thyroid Hormone Withdrawal in Patients with Clinically Relevant Lymph Node Metastases

It has already been shown that remnant ablation in patients with thyroid cancer and lymph node (LN) metastases has similar results when patients are prepared after recombinant human thyroid-stimulating hormone (rhTSH) therapy or thyroid hormone withdrawal (THW). Due to the current changes in the risk-of-recurrence classifications, we decided to evaluate the initial response to treatment and the outcome at medium-term follow-up in 40 consecutive patients with clinically relevant lymph nodes who received radioiodine remnant ablation after rhTSH therapy (n = 20) or THW (n = 20). Each patient received either 100 or 150 mCi 131-I for ablation based on TNM status, and the mean amounts of 131-I used in the 2 groups were not significantly different. An excellent response to treatment was observed in 45% of the patients prepared after rhTSH therapy compared to 20% of those prepared after THW (p = 0.08). Three patients (2 in the THW group and 1 in the rhTSH group) who had N1a in the initial surgery presented with structural persistence as an initial response to treatment. One patient in the THW group had a follow-up of the persistent disease with no surgical treatment, and 2 others received a lateral LN dissection. When the status at final follow-up was considered (median follow-up 3.3 years, range 3-4.2), 60% of the patients ablated after rhTSH therapy were considered with no evidence of disease, compared to 30% of those who underwent THW. The frequency of structural persistence (metastatic LN) was similar in the 2 groups (15 vs. 25%), and the distribution of the responses at final follow-up was not statistically significantly different (p = 0.12). We conclude that preparation after rhTSH therapy seems to be as effective as after THW for patients with clinically relevant LN metastases.

Serum thyroglobulin level after radioiodine therapy (Day 3) to predict successful ablation of thyroid remnant in postoperative thyroid cancer.

The utility of serum thyroglobulin (Tg) level, 3 days after radioactive iodine (RAI) therapy, was assessed as a means of predicting successful ablation of thyroid remnant in patients with postoperative thyroid cancer. A total of 152 patients with thyroid cancer (mean age = 44.9 ± 13.7 year) undergoing RAI therapy after total thyroidectomy were included. Levels of TSH-stimulated Tg prior to ablation (stimTg) and serum Tg sampled immediately after RAI therapy (Day 3) were measured (immTg). ImmTg samples were collected during patient hospital visits for scheduled follow-up of radioiodine scans. Successful ablation was determined by the second time stimulated Tg levels (≤1 ng/ml) and negative radioiodine uptake at thyroid bed after 6.1 ± 1.1 months of RAI therapy. Univariate and multivariate analyses were done for immTg, stimTg, change in Tg levels (deltaTg: immTg - stimTg), immTg:stimTg ratio (ratioTg), and other potential clinical and pathologic markers of successful ablation. Of selected laboratory variables, ratioTg was a significant predictor of successful ablation. StimTg, tumor diameter, metastatic lymph node (LN) numbers, lymphatic invasion were possible clinical markers of successful ablation by univariate analysis. By multivariate analysis, ratioTg (odds ratio = 7.851), stimTg (odds ratio = 16.819), metastatic LN numbers (odds ratio with stimTg = 6.732) proved significant results. Furthermore, combining high ratioTg and low stimTg provided added predictive value. High ratioTg (reflecting extensive release of Tg to the blood after RAI therapy) and low stimTg (reflecting small remnant thyroid tissue) constitute the indices of successful ablation after RAI therapy. Immediate Tg level could give an useful information on RAI ablation of postoperative thyroid remnant.

MicroRNA-339-5p modulates Na+/I- symporter-mediated radioiodide uptake.

Na(+)/I(-) symporter (NIS)-mediated radioiodide uptake (RAIU) serves as the basis for targeted ablation of thyroid cancer remnants. However, many patients with thyroid cancer have reduced NIS expression/function and hence do not benefit from radioiodine therapy. microRNA (miR) has emerged as a promising therapeutic target in many diseases; yet, the role of miRs in NIS-mediated RAIU has not been investigated. In silico analysis was used to identify miRs that may bind to the 3'UTR of human NIS (hNIS). The top candidate miR-339-5p directly bound to the 3'UTR of hNIS. miR-339-5p overexpression decreased NIS-mediated RAIU in HEK293 cells expressing exogenous hNIS, decreased the levels of NIS mRNA, and RAIU in transretinoic acid/hydrocortisone (tRA/H)-treated MCF-7 human breast cancer cells as well as thyrotropin-stimulated PCCl3 rat thyroid cells. Nanostring nCounter rat miR expression assay was conducted to identify miRs deregulated by TGFβ, Akti-1/2, or 17-AAG known to modulate RAIU in PCCl3 cells. Among 38 miRs identified, 18 were conserved in humans. One of the 18 miRs, miR-195, was predicted to bind to the 3'UTR of hNIS and its overexpression decreased RAIU in tRA/H-treated MCF-7 cells. miR-339-5p was modestly increased in most papillary thyroid carcinomas (PTCs), yet miR-195 was significantly decreased in PTCs. Interestingly, the expression profiles of 18 miRs could be used to distinguish most PTCs from nonmalignant thyroid tissues. This is the first report, to our knowledge, demonstrating that hNIS-mediated RAIU can be modulated by miRs, and that the same miRs may also play roles in the development or maintenance of thyroid malignancy. Accordingly, miRs may serve as emerging targets to halt the progression of thyroid cancer and to enhance the efficacy of radioiodine therapy.