Initial Radioiodine Therapy Research Articles

Predictive factors determining incomplete response to initial radioiodine therapy in patients with papillary thyroid microcarcinoma

Predictive factors determining incomplete response to initial radioiodine therapy in patients with papillary thyroid microcarcinoma

Influencing Factors of Urinary Iodine Concentration Before and After Radioiodine Therapy for Differentiated Thyroid Cancer: An Initial Exploration of the Relationship With Therapeutic Efficacy.

To investigate the impact of urinary iodine concentration (UIC) and post-stimulatory thyroglobulin (ps-Tg) levels on the therapeutic efficacy of differentiated thyroid cancer (DTC) patients after initial radioiodine therapy, and to analyze the validity of these indicators as prognostic factors. A total of 213 DTC patients received initial radioiodine therapy from June 2022 to September 2023. Demographic data and UIC were collected before and after therapy. Thyrotropin, thyroglobulin (Tg), and thyroglobulin antibody levels were assessed. Iodine uptake rate was measured, and therapeutic efficacy was evaluated 6months post-therapy. Statistical tests were used for data comparison, and logistic regression analysis for response factors. Post-therapy UIC and pre-post UIC difference were significantly correlated with Tg levels but not with reaching excellent response (ER) indicated by suppression of Tg levels below 0.2ug/L. Ps-Tg levels related to therapeutic efficacy, while UIC did not correlate with outcomes. ROC curve analysis found optimal ps-Tg cut-off points for the low-intermediate and high-risk groups classified by primary tumor size, invasion, metastasis, and pathological type. Post-treatment UIC and pre-post UIC difference correlate with ps-Tg levels. Ps-Tg levels are an associated factor for DTC, but UIC changes, despite correlation with ps-Tg, are not significantly related to outcomes and cannot be used as a prognostic factor.

Long-term prognostic analysis of children and adolescents with differentiated thyroid carcinoma based on therapeutic response to initial radioiodine therapy.

The clinical features and prognosis of children and adolescents with differentiated thyroid carcinoma (caDTC) are different from that of adults. Postoperative radioiodine therapy (RIT) was recommended for some intermediate and high risk caDTC patients. The objective of this study was to evaluate the long-term prognosis of pediatric caDTC patients with different responses to initial RIT and to explore the related influencing factors. All subjects were assigned to no clinical evidence of disease (NED) group, biochemical persistent disease (BPD) group, or structural/functional persistent disease (S/FPD) group based on the therapeutic response to initial RIT. Then, disease status was evaluated in all three groups at the last follow-up using ATA guidelines. Meanwhile, disease-free survival (DFS) for NED group and the progression-free survival (PFS) for the BPD and S/FPD groups were also assessed. 117 subjects were divided into NED group (n=29), BPD group (n=48) and S/FPD group (n=34) after initial RIT. At the last follow-up, excellent response (ER), indeterminate response (IDR), biochemically incomplete response (BIR) and structurally incomplete response (SIR) rates were 93.10%, 6.90%, 0% and 0% in NED group; 29.17%, 25.00%, 43.75% and 2.08% in BPD group; and 11.77%, 2.94%, 0%, and 85.29% in S/FPD group. The 5-year DFS rate in NED group was 95.5%. The 5-year PFS rates in BPD and S/FPD groups were 79.2% and 48.6%, respectively. For children with structural or functional lesions, longer PFS were found in male children with 131I-avid lesions, and post-operative stimulated serum thyroglobulin (sti-Tg) < 149.80 ng/ml. The response to initial RIT could be helpful for defining subsequent treatment and follow-up strategies for caDTC patients. Post-operative sti-Tg and 131I-avidity of lesions are correlated with PFS.

Long-term outcomes and prognostic factors of patients with lung metastases from differentiated thyroid cancer after radioiodine therapy in Japan.

Long-term survival in patients with differentiated thyroid cancer (DTC) and lung metastasis remains unexplored in Japan. This study aimed to investigate the long-term survival and prognostic factors of radioiodine therapy (RIT) in a University Hospital setting. This retrospective study included 62 patients with lung metastases from DTC who received RIT between March 2005 and December 2016. According to the 131I whole-body scan and chest computed tomography results, lung metastases were classified as 131I-avid or non-131I-avid, and miliary, micronodular, or macronodular metastases. The 5- and 10-year overall survival (OS) rates from the initial RIT were calculated by the Kaplan-Meier method, and a proportional hazard fit analysis was performed to determine prognostic factors. With a median follow-up of 7.9 years, the 5- and 10-year OS rates from the initial RIT were 93% and 72%, respectively. Univariable and multivariable analyses of patient subgroups revealed that macronodular lung metastases (defined as nodules >1 cm), older age at initial RIT, and high thyroglobulin values (>400 ng/mL) at initial RIT predicted low OS. The 5- and 10-year OS rates of DTC patients with lung metastases were similar to those in previous Japanese reports, which included a smaller sample size compared with ours. Patients with ≤1 cm lung metastases, aged ≤55 years, and a thyroglobulin level of ≤400 ng/mL at the initial RIT had favorable outcomes.

Utility of FDG PET at the Initial Radioiodine Therapy in Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) has a good prognosis, except in the case of patients with radioiodine therapy (RIT)-refractory cancer. However, since DTC is essentially a slowly progressing cancer, it is usually judged to be a DTC with a poor prognosis after multiple RITs and yearly follow-up with echo, computed tomography (CT), and serum thyroglobulin values. This study investigated whether fluorodeoxyglucose-positron emission tomography/CT (FDG PET/CT) combined with initial RIT could identify early-stage patients with poor prognosis. We evaluated 100 patients with high-risk DTC who underwent total thyroidectomy and received RIT at our institution. We analyzed the clinical outcomes of patients and 18F-FDG accumulation using univariate and multivariate Cox proportional hazards regression models. The 10-year overall survival (OS) was 87.9%, with no significant difference in OS between 18F-FDG accumulation at pre-total or near-total thyroidectomy (NTT) (p=0.180) and 131I accumulation at initial RIT (p=0.577). However, 18F-FDG positive patients had a significantly worse prognosis than negative patients (p=0.005) at initial RIT. 18F-FDG PET/CT plays an important role in both the diagnosis and prognostic prediction of RIT refractory disease in DTC patients. 18F-FDG PET/CT can be a useful tool particularly at the time of initial RIT since the 18F-FDG accumulation enables the screening of high-risk DTC with poor prognosis at a very early time stage.

The influence of stimulated thyroglobulin and lymphocyte subsets before radioiodine therapy on the therapeutic response in patients with intermediate- and high-risk papillary thyroid carcinoma.

The aim of the present study was to investigate the factors influencing the short-term response to the initial radioiodine therapy (RT) course in patients with intermediate- and high-risk papillary thyroid carcinoma (PTC). A total of 182 patients with intermediate- and high-risk PTC who underwent RT in our hospital from March 2018 to October 2020 were retrospectively enrolled. The patients were divided into incomplete response (IR) and nonincomplete response (Non-IR) groups according to the response observed in clinical follow-up within 6-12months after RT. Univariate and multivariate logistic regression analyses were used to investigate the effects of 15 observed factors on the response to RT. Receiver operating characteristic (ROC) curve analysis was used to determine the value of factors found to be significant in multivariate analyses for predicting an IR. A total of 182 patients with intermediate- and high-risk PTC were analyzed; the percentage of patients with a Non-IR was 61.54% (112/182), and the percentage of patients with an IR was 38.46% (70/182). The CD4+ T-cell percentage (t = 4.757, P = 0.000), CD4/CD8 (z = - 2.632, P = 0.008), stimulated thyroglobulin (sTg) level (z = - 8.273, P = 0.000) and M stage (χ2 = 17.823, P = 0.000) of the two groups were significantly different. Multivariate analysis showed that only the sTg level (OR: 1.116, 95% CI 1.068-1.165, P < 0.001) and CD4+ T-cell percentage (OR: 0.909, 95% CI 0.854-0.968, P = 0.003) were independent factors associated with the therapeutic response to RT. The cutoff sTg level and CD4+ T-cell percentage for predicting an IR were 7.62μg/L and 40.95%, respectively. The sTg level and CD4+ T-cell percentage were verified to be independent predictive factors of RT response. Higher sTg levels and lower CD4+ T-cell percentages were related to an IR in patients with intermediate- and high-risk PTC.

Course of Disease and Clinical Management of Patients with Poorly Differentiated Thyroid Carcinoma.

Simple SummaryPoorly differentiated thyroid carcinoma (PDTC) represents a rare but aggressive variant of thyroid carcinoma and contributes to a significant proportion of thyroid carcinoma-associated deaths. Studies on PDTC are rare; therefore, we aim to assess the clinical course of these patients, evaluate the prognostic value of response to initial radioiodine therapy and identify risk factors for poor prognosis to optimize the clinical management of patients with PDCT.Background: In patients with poorly differentiated thyroid carcinoma, the clinical course and prognostic value of response to initial radioiodine therapy is evaluated. Methods: In 47 patients, clinical and imaging features were analyzed. Patients were stratified in no (NED), biochemical (B-ED) and structural evidence of disease (S-ED) assessed at the first diagnostic control and its impact on survival was evaluated. Further, possible risk factors for a shorter disease-specific survival rate (DSS) were analyzed. Results: In total, 17/47 patients consisted of NED, 10/47 were B-ED and 20/47 S-ED patients. At the last follow-up, 18/47 patients were NED, 2/47 patients B-ED and 27/47 patients S-ED. The median survival time was only reached for the S-ED group (median 3.9 years, 95%CI 2.8–5.1 years) and was not reached in the B-ED and NED groups. Metastases were diagnosed by a 18F-FDG-PET/CT scan in all cases and a multivariate analysis showed that the PET-positivity of metastases was the only significant predictor of DSS (p = 0.036). Conclusion: The response to initial surgery and radioiodine therapy in PDTC patients can achieve an excellent outcome and a further follow-up should be refined based on findings at the first diagnostic control. However, patients with an incomplete response and metastatic patients who become mostly radioiodine refractory show a significantly shorter survival, which makes accurate staging by 18F-FDG-PET/CT imaging crucial.

Clinical predictors of I-131 therapy failure in differentiated thyroid cancer by machine learning: A single-center experience.

Well-differentiated thyroid carcinoma is predominantly a slow-growing malignancy, amendable to treatment, and has an excellent prognosis following thyroidectomy and radioiodine (RAI) therapy. However, patients who fail the initial RAI treatment attempt may require repeated RAI or other treatments and with this, comes an associated impact on patient quality of life. Therefore, the anticipation of patients in whom there is a higher risk of RAI failure may help in patient risk stratification and subsequent management. We conducted a retrospective review to determine the factors associated with initial RAI therapy failure in well-differentiated thyroid cancer patients. Using scikit-learn from Python, we implemented a machine-learning algorithm to determine the clinical patient factors associated with a higher likelihood of treatment resistance. We found that clinical factors such as tumor focality (P = 0.026) and lymph node invasion at surgical resection (P = 0.0135) were significantly associated with initial treatment failure following RAI. Elevated serum thyroglobulin (Tg) and Tg antibody levels following surgery but before RAI were also associated with treatment resistance (P < 0.0001 and P = 0.011 respectively). Less expected factors such as decreased time from surgery to RAI were also associated with treatment failure, however not to a statistically significant degree (P > 0.064). Clinical outcomes following RAI can be stratified by identifying factors that are associated with initial treatment failure. These findings can help restratify patients for RAI treatment and change patient management in certain cases. Such stratification will ultimately help to optimize successful treatment outcomes and improve patient quality of life.

Clinical significance of extra-thyroid 99mTc-pertechnetate uptake before initial radioiodine therapy for differentiated thyroid carcinoma.

ObjectiveTo analyse the clinical characteristics of extra-thyroid 99mTc-pertechnetate uptake in order to explore the effect of the phenomenon on radioactive iodine (RAI) therapy for differentiated thyroid carcinoma (DTC) and its clinical significance.MethodsThis study retrospectively selected patients with DTC and extra-thyroid 99mTc-pertechnetate uptake. The clinical features, location, location count and extra-thyroid 99mTc-pertechnetate uptake distribution were analysed, combined with the uptake rate, stimulated thyroglobulin (sTg) level, post-therapy whole-body scan and curative effect.ResultsA total of 38 patients were enrolled in the study and 65 extra-thyroid 99mTc-pertechnetate foci were detected. Thirty-four patients showed abnormal 99mTc-pertechnetate uptake in the lymph nodes (26 of 38; 68.4%), lungs (four of 38; 10.5%) and bones (four of 38; 10.5%). The corresponding uptake rates were 0.2%, 0.2% and 0.8%, respectively. The uptake rate and sTg were significantly positively correlated (r = 0.36). 131I uptake was found in 36 patients at the 99mTc-pertechnetate uptake site. The number of iodine uptake foci was significantly higher than that of 99mTc-pertechnetate uptake foci. The sTg value and pathological staging significantly differed between the excellent and nonexcellent response groups (Z = –2.947 and Z = –2.348, respectively).ConclusionExtra-thyroid 99mTc-pertechnetate uptake mostly indicated metastases with specific clinical features, which may have prognostic value for the judgment of iodine uptake function and the RAI therapy plan.

Predictive Factors for RAI-Refractory Disease and Short Overall Survival in PDTC.

Simple SummaryPoorly differentiated thyroid cancer is a rare subtype of thyroid cancer. The course of this disease can vary substantially. Treatment options consist of surgery and radioactive iodine therapy, if possible, and in tyrosine kinase inhibitors for patients where this is not possible. The aim of this study was to identify risk factors for the development of disease that does not respond to radioactive iodine therapy and for premature death, in order to better identify patients in need of more extensive tumor staging and treatment. We identified primary tumor size and infiltration of the tissue surrounding the thyroid gland as risk factors for the development of disease that does not respond to radioactive iodine therapy and tumor volume as a risk factor for early death.Background: The clinical phenotype of poorly differentiated thyroid cancer (PDTC) can vary substantially. We aim to evaluate risk factors for radioiodine refractory (RAI-R) disease and reduced overall survival (OS). Methods: We retrospectively screened our institutional database for PDTC patients. For the assessment of RAI-R disease, we included patients who underwent dual imaging with 18F-FDG-PET and 124I-PET/131I scintigraphy that met the internal standard of care. We tested primary size, extrathyroidal extension (ETE), and age >55 years as risk factors for RAI-R disease at initial diagnosis and during the disease course using uni- and multivariate analyses. We tested metabolic tumor volume (MTV), total lesion glycolysis (TLG) on 18F-FDG-PET, and the progression of stimulated thyroglobulin within 4–6 months of initial radioiodine therapy as prognostic markers for OS. Results: Size of primary >40 mm and ETE were significant predictors of RAI-R disease in the course of disease in univariate (81% vs. 27%, p = 0.001; 89% vs. 33%, p < 0.001) and multivariate analyses. Primary tumor size was an excellent predictor of RAI-R disease (AUC = 0.90). TLG/MTV > upper quartile and early thyroglobulin progression were significantly associated with shorter median OS (29.0 months vs. 56.9 months, p < 0.05; 57.8 months vs. not reached p < 0.005, respectively). Discussion: PDTC patients, especially those with additional risk factors, should be assessed for RAI-R disease at initial diagnosis and in the course of disease, allowing for early implementation of multimodal treatment. Primary tumor size >40 mm, ETE, and age >55 are significant risk factors for RAI-R disease. High MTV/TLG is a significant risk factor for premature death and can help identify patients requiring intervention.

Utility of outpatient fractionated radioiodine therapy for Graves disease involving a large goiter measuring more than 100 mL in volume.

Contrary to large multinodular goiters, reports on 131I radioiodine therapy (RIT) for Graves disease (GD) involving a large goiter are scarce. We retrospectively reviewed a total of 71 consecutive patients (25 males, 46 females) with GD involving a large goiter (>100 mL) who had received RIT in our clinic. Patients with a history of thyroid surgery or with large thyroid nodules and those who had dropped out less than one year after the initial RIT session were excluded. A fixed 131I activity of 481 MBq was administered in most cases. RIT was repeated at intervals of 1-47 months, typically 3-6 months. The follow-up duration after the initial RIT session was 13-233 (median: 81) months. The thyroid volume was estimated using ultrasound. The number of 131I doses were 1 dose in 13 patients, 2 doses in 29, 3 doses in 17, 4 doses in 5, 5 doses in 5, 6 doses in 1, and 8 doses in 1. Sixty-six patients had remission from overt hyperthyroidism after RIT: overt hypothyroidism in 45 patients, subclinical hypothyroidism or euthyroidism in 13, and subclinical hyperthyroidism in 8. Their thyroid volume decreased from 101-481 (median: 126) mL to 1.4-37 (8.2) mL. Three patients still had overt hyperthyroidism under treatment with methimazole after one to three doses, and two dropped out less than six months after the third or sixth dose. Even in GD patients with a large goiter (>100 mL), repeated RIT with an activity of 481 MBq could sufficiently shrink goiters and remit overt hyperthyroidism.

The effects of radioiodine therapy on parathyroid function among patients with papillary thyroid cancer: a retrospective cohort study.

To explore the effects of initial radioiodine therapy on parathyroid function among postoperative papillary thyroid cancer (PTC) patients. Postoperative PTC patients who were admitted in our department from April 2018 to April 2019 were recruited. Patients were divided into two groups: Group A, who underwent surgery and initial radioiodine therapy in our hospital, and Group B, who did not receive radioiodine therapy after surgery. The levels of serum calcium, magnesium, phosphorus, parathyroid hormone (PTH), and 25 hydroxyvitamin D3 were collected. Data were analyzed by SPSS 25.0. A total of 252 patients were included. Between the two groups, no significant difference of PTH in 6th, 9th, and 12th month was found during postoperative follow-up (p = 0.493, p = 0.202, p = 0.814). No significant difference of PTH was found after stratifying Group A according to 131I dosage (p = 0.751 for 6th month after operation, p = 0.130 for 9th month after operation, p = 0.683 for 12th month after operation), interval time between surgery and radioiodine therapy (p = 0.522 for 3rd day after 131I therapy, p = 0.184 for 9th month after operation, p = 0.311 for 12th month after operation), and ratio of parathyroid autotransplantation (p = 0.545 for 3rd day after 131I therapy, p = 0.485 for 6th month after operation, p = 0.201 for 9th month after operation, p = 0.146 for 12th month after operation). Initial radioiodine therapy following PTC surgery had no significant adverse effect on parathyroid function in the short term. However, physicians should inform patients of possible risks of abnormal parathyroid function prior to RAI therapy, and parathyroid function was periodically reviewed after RAI therapy.

Long-Term Outcomes of Radioiodine Therapy for Juvenile Graves Disease with Emphasis on Subsequently Detected Thyroid Nodules: A Single Institution Experience from Japan

To investigate the long-term outcomes of radioiodine therapy (RIT) for juvenile Graves disease (GD) and the ultrasonographic changes of the thyroid gland. All of 117 juvenile patients (25 males and 92 females, aged 10 to 18 &lsqb;median 16] years) who had undergone RIT for GD at our clinic between 1999 and 2018 were retrospectively reviewed. Each RIT session was delivered on an outpatient basis. The maximum 131I dose per treatment was 13.0 mCi, and the total 131I dose per patient was 3.6 to 29.8 mCi (median, 13.0 mCi). 131I administration was performed once in 89 patients, twice in 26, and three times in 2 patients. Ultrasonography of the thyroid gland was regularly performed after RIT. The duration of follow-up after the initial RIT ranged from 4 to 226 (median 95) months. At the latest follow-up more than 12 months after RIT (n = 111), the patients' thyroid functions were overt hypothyroidism (91%), subclinical hypothyroidism (2%), normal (5%), or subclinical hyperthyroidism (2%). New thyroid nodules were detected in 9 patients, 4 to 17 years after initial RIT. Patients with newly detected thyroid nodules underwent RIT with lower doses of 131I and had larger residual thyroid volumes than those without nodules. None of the patients were diagnosed with thyroid cancer or other malignancies during the follow-up period. Over a median follow-up period of 95 months (range, 4 to 226 months), RIT was found to be effective and safe in juvenile GD. However, cumulative evidence from further studies is required to confirm the long-term safety of RIT for juvenile GD. ATD = antithyroid drug; GD = Graves disease; KI = potassium iodide; LT4 = levothyroxine; MMI = methimazole; PTU = propylthiouracil; RAIU = radio-active iodine uptake; RIT = radioiodine therapy; 99mTc = technetium-99m; TSH = thyrotropin.

Long-term outcome of rare oncocytic papillary (Hürthle cell) thyroid carcinoma following (adjuvant) initial radioiodine therapy.

Oncocytic (Hürthle cell) papillary thyroid carcinoma (OPTC) is a rare variant of the papillary thyroid carcinoma (PTC) which comprises approximately 1 to 11% of PTC cases. Its clinical course and prognosis have not been comprehensively documented and the clinical outcome remains a controversial issue. Therefore, we investigated the long-term prognosis after thyroidectomy and (adjuvant) initial radioactive iodine therapy (RIT) of OPTC compared to PTC. A total of 563 patients (47 with OPTC and 516 with PTC) with a median follow-up of 9.9 (0.3; 23.5) years were studied. All patients underwent thyroidectomy followed by (adjuvant) initial RIT. Data on the patients' demographics, pathology, laboratory findings, imaging studies, treatment, and follow-up including recurrence, and disease-specific survival were collected. Cox's multivariate regression model was used to identify independent prognostic factors for survival. OPTC patients were significantly older (55.2 ± 12.3years) than PTC patients (50.3 ± 13.5) at the time of initial diagnosis (p value 0.016). Initial tumor size was larger in the OPTC group (2.8 ± 1.8cm for OPTC patients, 1.5 ± 1.2cm for PTC patients, p value < 0.001). Before matching, OPTC patients presented more often with evidence of disease at the last visit of follow-up (p value 0.046). However, this difference was not observed anymore after matching for risk factors (p value 0.637). Disease-specific survival did not differ significantly. Age (HR, 1.183; 95% CI, 1.097-1.276) was identified as an independent prognostic factor for disease-specific survival. OPTC patients predominantly showed a recurrence of distant metastasis within a shorter time despite being not statistically significant. At initial diagnosis, OPTC shows significant differences in terms of age and initial tumor size compared to PTC. Patients suffering from OPTC present with the same clinical long-term outcome indifferent to PTC after (adjuvant) initial RIT after matching.

Well-differentiated Thyroid Carcinoma of Childhood and Adolescence- A Long Term Experience at a Single Institute

&lt;p&gt;&lt;strong&gt;&lt;em&gt;Background:&lt;/em&gt;&lt;/strong&gt; Thyroid carcinoma is rare in childhood and adolescence. The presentation is more advanced in case of children as compared to adults. However, the prognosis for survival in children is reportedly excellent. The aim of the study was to see the outcome of patients with well differentiated thyroid carcinoma during childhood and adolescence treated at a single institute.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Patients and methods:&lt;/em&gt;&lt;/strong&gt; A retrospective study of 61 children and adolescent patients (age ≤18years) with well differentiated thyroid carcinoma (DTC) enrolled in the National Institute of Nuclear Medicine and Allied Sciences, Dhaka during the period of January1986 up to December 2007 was carried out. To allow for a theoretical follow up of at least 5 years the last inclusion year was 2007 and follow up was carried on up to June 2013. All patients were treated by thyroidectomy followed by radioiodine ablation therapy. Whole body scans, Tg, anti Tg Ab and neck ultrasound findings were recorded six months to one year after initial therapy to classify patients into remission, persistent or recurrent disease. Status on last follow up was noted to estimate the survival rate.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Results:&lt;/em&gt;&lt;/strong&gt; A total of 40 patients had papillary carcinoma, 18 had follicular variant of papillary carcinoma (FVPCT) and three had follicular carcinoma. Age range at diagnosis was nine to 18 years with a mean of 15± 2 years. The number of patients ≤10 years were five and &amp;gt; 10 years were 56. There were 12 males and 49 females giving a M: F ratio of about 1:4. Among the 61 patients 30 patients had lymph node metastases and two had both nodal and lung metastases at initial presentation. After one year follow up from the initial radioiodine therapy, 30 patients were in remission and 31 patients had persistent disease. Eventually recurrence occurred in five patients. Three patients died during the whole observation period and all of them were cancer related giving a cancer specific mortality ratio of 0.049%, 95% CI 0 to 0.105%. Cancer specific survival by Kaplan-Meier curve was 98.2%, 98.2% and 66% at 5, 10 and 15 years respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Conclusion:&lt;/em&gt;&lt;/strong&gt; DTC in children and adolescent has a good prognosis in the presence of neck and distant metastases. Awareness of the patient and regular follow up with life long surveillance is essential to obtain a favorable outcome.&lt;/p&gt;&lt;p&gt;Bangladesh J. Nuclear Med. 20(2): 99-104, July 2017&lt;/p&gt;

Delayed initial radioiodine therapy related to incomplete response in low- to intermediate-risk differentiated thyroid cancer.

Whether the initiating time of radioiodine (RAI) therapy will affect the clinical outcome in differentiated thyroid cancer (DTC) remains controversial. The objective of this study was to evaluate the impact of RAI therapy initiating time on response to initial therapy in low- to intermediate-risk DTC. A total of 235 consecutive patients with low- to intermediate-risk DTC were retrospectively reviewed. According to the time interval between thyroidectomy and RAI therapy, patients were divided into Group 1 (interval<3months, n=187) and Group 2 (interval≥3months, n=48). Response to RAI therapy was evaluated as excellent, indeterminate, biochemical incomplete or structural incomplete response (ER, IDR, BIR or SIR) with a median follow-up of 780days. The univariate and multivariate analyses were further conducted to identify factors associated with incomplete response (IR, including BIR and SIR). Response to initial therapy was significantly different between 2 groups (P<.05), after excluding the impact of other risk factors (age, gender, histological type, status of T and N, RAI dose, thyrotropin, stimulated thyroglobulin and follow-up time). A significantly higher IR rate (18.8% vs 4.3%, P=.001) and a lower ER proportion (62.5% vs 78.1%, P=.027) were observed in Group 2. By univariate analysis, both T status and N status, stimulated thyroglobulin and time interval were significant risk factors for IR (P<.05). Multivariate analysis demonstrated that the time interval was an independent risk factor for IR (P=.008). Delayed initial RAI therapy (≥3months after thyroidectomy) related to incomplete response in low- to intermediate-risk DTC.

Short course of oral lithium therapy as an adjunct in patients with thyrotoxicosis who failed initial radioiodine therapy: should this be worthwhile to consider in the absence of contraindications?

Short course of oral lithium therapy as an adjunct in patients with thyrotoxicosis who failed initial radioiodine therapy: should this be worthwhile to consider in the absence of contraindications?

Clinical outcomes of low-dose and high-dose postoperative radioiodine therapy in patients with intermediate-risk differentiated thyroid cancer.

Recent studies have suggested that a low dose (LD) of radioiodine (RAI) is sufficient to treat differentiated thyroid cancer (DTC) even in patients with intermediate risk. However, these studies evaluated the efficacy of RAI therapy, irrespective of the results of the whole-body scan (WBS). The aim of the present study was to evaluate the response to LD and high-dose (HD) RAI therapy using two different criteria (with and without WBS results) and the reclassification system according to the revised 2015 guidelines of the American Thyroid Association in Korean intermediate-risk DTC patients. In addition, we evaluated the long-term clinical outcomes of treatment with LD and HD RAI. In total, 204 intermediate-risk DTC patients who underwent postoperative RAI therapy at two tertiary referral hospitals from 2003 to 2004 were enrolled in the present retrospective study. One hundred and twenty-four patients were treated with 3.7 and 5.55 GBq (HD) of RAI in one center and 80 patients were treated with 1.11 GBq (LD) in the other center. The success rate of RAI therapy was assessed with or without the inclusion of WBS results in the analysis. In addition, the response to therapy during the first 2 years of follow-up after the initial RAI therapy was categorized according to the reclassification system of 2015 American Thyroid Association guidelines as excellent response, indeterminate response, biochemical incomplete response, or structural incomplete response. Recurrence was defined as a newly detected cytologically or pathologically confirmed lesion. There were no significant differences between the success rates of the HD and LD groups irrespective of the inclusion of WBS results in the analysis (with WBS: 54.84 vs. 45.0%, P=0.23; without WBS: 60.48 vs. 62.5%, P=0.77). The response to HD and LD RAI therapy was excellent in 54.84 and 45.0% of the patients, respectively; indeterminate in 34.68 and 30.0% of the patients, respectively; biochemical incomplete in 4.03 and 13.75% of the patients, respectively; and structural incomplete in 6.45% and in 11.25% of the patients, respectively (P=0.04). In particular, the biochemical or structural incomplete response rate was lower in patients treated with HD than in patients treated with LD (HD, 10.48%; LD, 25.0%, P=0.01). At the last follow-up (HD, median 11 years; LD, median 10 years), patients who achieved an excellent response showed no evidence of disease. After the initial RAI therapy, eight patients in the HD group and 18 patients in the LD group who achieved either indeterminate response or biochemical incomplete response received additional RAI therapy. Seven patients (indeterminate response in five patients; biochemical incomplete response in two patients) in the HD group and seven patients (indeterminate response in five patients; biochemical incomplete response in two patients) in the LD group showed recurrences. LD RAI therapy after thyroidectomy appears to be insufficient in Korean DTC patients with intermediate risk. The patients in the LD group predominantly showed biochemical or structural incomplete response to initial RAI therapy and additional RAI therapy was required.

TERT Promoter Mutation Predicts Radioiodine-Refractory Character in Distant Metastatic Differentiated Thyroid Cancer.

TERT promoter and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in primary tumors of 66 patients with distant metastatic DTC. Stimulated thyroglobulin (sTg) changes, radioiodine uptake status (avid or nonavid), and other imaging evidence were analyzed to evaluate therapy response. After a median follow-up of 46.5 mo (interquartile range, 29.0-70.5 mo), therapy response was classified as either disease control or refractory. The prevalence of TERT mutations was 22.73% (15/66), of which C228T mutation was more prevalent (13/15) than C250T mutation (2/15). Rising sTg was noticed in 93.33% (14/15) of the TERT mutation group. Of cases negative for both mutations, 78.12% (25/32) presented with decreased sTg. TERT mutation closely correlated with a poor response to radioiodine therapy (P < 0.001), and all 15 patients were classified as refractory to radioiodine therapy, with a positive predictive value of 100% at the endpoint of follow-up. TERT mutation was associated with older mean age at diagnosis (P < 0.001), larger mean tumor diameter (P = 0.013), and greater likelihood of both BRAF mutation coexistence (P = 0.044) and radioiodine-refractory character (P < 0.001). In the 36 cases whose imaging results underwent semiquantitative analysis, TERT mutation significantly correlated with non-radioiodine avidity, with a much lower mean tumor-to-background ratio (obtained from postradioiodine whole-body scanning) than in TERT wild-type cases (P < 0.001). In addition, patients with distant metastatic DTC with TERT mutation were more likely to lose radioiodine avidity at the initial radioiodine therapy than were those with only BRAF mutation (8/8 vs. 5/11; Fisher exact test, P = 0.018). TERT mutation closely associates with non-radioiodine avidity in distant metastatic DTC, and when compared with BRAF mutation, TERT mutation manifested a greater negative influence on radioiodine uptake. TERT mutation could also be used as an early predictor of radioiodine-refractory cases.

Timing of Radioactive Iodine Therapy does not Impact Overall Survival in High-Risk Papillary Thyroid Carcinoma

Postthyroidectomy radioiodine (RAI) therapy is indicated for papillary thyroid carcinoma (PTC) with high-risk features. There is variability in the timing of RAI therapy with no consensus. We analyzed the impact of the timing of initial RAI therapy on overall survival (OS) in PTC. The National Cancer Data Base (NCDB) was queried from 2003 to 2006 for patients with PTC undergoing near/subtotal or total thyroidectomy and RAI therapy. High-risk patients had tumors >4 cm in size, lymph node involvement, or grossly positive margins. Early RAI was ≤3 months, whereas delayed was between 3 and 12 months after thyroidectomy. Kaplan-Meier (KM) and Cox survival analyses were performed after adjusting for patient and tumor-related variables. A propensity-matched set of high-risk patients after eliminating bias in RAI timing was also analyzed. There were 9,706 patients in the high-risk group. The median survival was 74.7 months. KM analysis showed a survival benefit for early RAI in high-risk patients (P = .025). However, this difference disappeared (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.98-1.62, P = .07) on adjusted Cox multivariable analysis. Timing of RAI therapy failed to affect OS in propensity-matched high-risk patients (HR 1.09, 95% CI 0.75-1.58, P = .662). The timing of postthyroidectomy initial RAI therapy does not affect OS in patients with high-risk PTC. CI = confidence interval CLNM = cervical lymph node metastasis FVPTC = follicular variant papillary thyroid carcinoma HR = hazard ratio KM = Kaplan-Meier NCDB = National Cancer Data Base OS = overall survival PTC = papillary thyroid carcinoma RAI = radioactive iodine.