Radioactive iodine for differentiated thyroid carcinoma.

The goal was to determine if there was a relation between the introduction of evidence-based radioactive iodine (RAI) treatment guidelines for differentiated thyroid cancer (DTC) at Cedars-Sinai Medical Center (CSMC) and subsequent RAI use. In addition, we compared RAI treatment rates for DTC at CSMC to data from the National Cancer Database (NCDB) to see if the trends in RAI use at CSMC differed from the national trends. RAI data from the CSMC Thyroid Cancer Center were reviewed to determine if RAI treatment was given appropriately. Kaplan-Meier curves were used to estimate disease-free survival for patients who received or did not receive treatment. RAI data from the NCDB were also used to compare how CSMC treatment rates compare nationally. There were 444 CSMC patients identified with DTC between 2009 and 2012. Approximately 95% of the patients had papillary thyroid cancer (n=423) with 65% in the stage I risk group (n=290). Kaplan-Meier curves for stages I-III show that those who did not receive RAI treatment had 100% disease-free survival, which was better than those who had received RAI. However, given that the total population in both stages II and III is quite small, having received RAI ablation was not found to be statistically significant. Stage I patients who received RAI had a significantly increased incidence of recurrent disease. The NCDB RAI rates for all DTC stages in each year have consistently been over 50% with an overall treatment rate of 57%. There were significant differences in the treatment rates between CSMC and NCDB, with a decrease in the use of RAI in low-risk patients with stage I tumors at CSMC following institution of the guidelines. Prudent use of RAI treatment should be considered for low-risk patients. Ablation rates have been decreasing steadily at CSMC, particularly among low-risk patients, with the adoption of more stringent RAI treatment guidelines. It is apparent from our data that physician practices can change with the implementation and dissemination of evidence-based guidelines for the treatment of DTC with RAI.

The study aimed to assess the impact of postoperative radioactive iodine (RAI) therapy on parathyroid function in patients who underwent total or subtotal thyroidectomy for differentiated thyroid cancer (DTC). Data from 150 patients treated with RAI for DTC and 76 patients with low-risk DTC not receiving RAI were retrospectively analyzed. Clinical characteristics, preoperative and 1-month postoperative biochemical parameters, and adjusted calcium, phosphorus, parathyroid hormone (PTH), and 25-hydroxyvitamin D3 (25-OH-D) levels at 3months, 1year, 3years, and 5years post-RAI (or in the low-risk group) were recorded. A total of 226 DTC patients were included in the study (80.5% female, mean age 42.7 ± 13.2years). Total thyroidectomy was performed in 97.3% (n = 220) of patients, with central lymph node dissection (CLND) in 41.6% (n = 94). No significant preoperative differences in PTH, aCa, P, Mg, or 25-hydroxyvitamin D3 levels were observed. However, patients receiving ≥ 3.7GBq (or 100mCi) RAI (n = 70) had lower calcium and PTH levels at the end of the first year following RAI treatment (p = 0.048, p = 0.032). The non-RAI group showed significantly higher calcium levels at one month postoperatively (p = 0.031) and lower rates of CLND and neck dissection. No significant differences in biochemical parameters were found at the five-year follow-up, except for one patient who developed normocalcemic hyperparathyroidism after RAI. High-dose RAI therapy may lead to transient decreases in calcium and PTH levels in the early post-treatment period. However, long-term parathyroid function appears to remain unaffected in DTC patients, regardless of the RAI dose administered. Nonetheless, close monitoring of calcium and PTH levels is recommended, particularly in the early post-treatment period, to promptly manage any potential transient hypoparathyroidism.

Despite the generally favourable long-term prognosis of low-risk differentiated thyroid cancer (DTC), questions remain about disease-free survival (DFS) after initial treatment, particularly regarding the use of radioactive iodine (RAI). Although there are RCT trial confirming that RAI ablation therapy is not superior to follow-up in terms of the 3-year DFS rate in low-risk thyroid cancer, its longer-term prognosis remains to be established. The objective of this study was to assess the impact of RAI ablation on the presence of structural persistent/recurrent disease in patients with low-risk DTC. We retrospectively identified 720 low-risk DTC patients who had undergone total or near-total thyroidectomy (TT) at a tertiary medical centre between January 2008 and July 2018. Propensity scores were calculated using a multivariable logistic regression model that accounted for age, sex, tumour size, neck dissection, multifocality, capsular invasion and lymph node (LN) metastasis. We compared DFS between patients who received RAI and those who did not using log-rank tests and multivariate Cox analyses. Subgroup analyses were also conducted. Of the total cohort, 180 (25.0%) patients received RAI, while 540 (75.0%) did not before matching. The median follow-up duration was 59.5 months. After matching, the RAI group comprised 135 (39.8%) patients and the non-RAI group comprised 204 (60.2%) patients. In the entire cohort, the 5-year DFS rate was 97.6% for patients receiving RAI compared to 96.8% for those not receiving RAI (p = 0.704). In the matched cohort, the rates were 98.5% and 95.6%, respectively (p = 0.090). Matched multivariate Cox analysis demonstrated that RAI was neither significantly nor independently associated with DFS (hazard ratio [HR] = 0.29; 95% CI 0.06-1.37; p = 0.118). Further subgroup analyses reaffirmed that RAI ablation did not significantly reduce the risk of developing structural persistent/recurrent disease. Administering RAI ablation following TT did not result in improved DFS for low-risk DTC patients. Our findings suggest that decisions regarding RAI should be made judiciously to avoid overtreatment in this clinical scenario.

The HiLo Trial: a Multicentre Randomised Trial of High- versus Low-dose Radioiodine, with or without Recombinant Human Thyroid Stimulating Hormone, for Remnant Ablation after Surgery for Differentiated Thyroid Cancer

Radioiodine therapy in advanced differentiated thyroid cancer: Resistance and overcoming strategy

Modern use of post-operative radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) should be implemented in line with patients’ risk stratification. Although beneficial effects of radioiodine are undisputed in high-risk patients, controversy remains in intermediate-risk and some low-risk patients. Since the last consensus on post-surgical use of RAI in DTC patients, new retrospective data and results of prospective randomized trials have been published, which have allowed the development of a new European Thyroid Association (ETA) statement for the indications of post-surgical RAI therapy in DTC. Questions about which patients are candidates for RAI therapy, which activities of RAI can be used, and which modalities of pre-treatment patient preparation should be used are addressed in the present guidelines.

Review of the management decisions that must be made by the endocrinologist during the use of radioactive iodine (RAI) therapy of hyperthyroidism and differentiated thyroid cancer. Since the 1940s radioactive (131)I (RAI) therapy has been a major component of the treatment of hyperthyroidism and differentiated thyroid cancer. RAI is the most common definitive treatment of hyperthyroidism. Pretherapy decisions including use of antithyroid medication and low-iodine diet will be discussed with the relevant supportive literature. The method of semi-quantitative calculation used for RAI treatment of hyperthyroidism will be described. Evidence-based guideline for the management of differentiated thyroid cancer by the American Thyroid Association, new drug development and recent randomized controlled trials have changed current practice of how RAI is used for remnant ablation and adjuvant therapy of differentiated thyroid cancer. RAI is a common tool for the endocrinologist in the management of hyperthyroidism and differentiated thyroid cancer. Review of the management decisions and practice of RAI therapy will educate the endocrinologist of the literature supporting current RAI use in hyperthyroidism and new developments in limiting the radiation exposure to the patients with differentiated thyroid cancer.

Low-risk differentiated thyroid cancer (DTC) is overdiagnosed, but true incidence has increased as well. Owing to its excellent prognosis with low morbidity and mortality, balancing treatment risks with risks of disease progression can be challenging, leading to several areas of controversy. This mini-review is an overview of controversies and difficult decisions around the management of all stages of low-risk DTC, from diagnosis through treatment and follow-up. In particular, overdiagnosis, active surveillance vs surgery, extent of surgery, radioactive iodine (RAI) treatment, thyrotropin suppression, and postoperative surveillance are discussed. Recommendations regarding the diagnosis of DTC, the extent of treatment for low-risk DTC patients, and the intensity of posttreatment follow-up have all changed substantially in the past decade. While overdiagnosis remains a problem, there has been a true increase in incidence as well. Treatment options range from active surveillance of small tumors to total thyroidectomy followed by RAI in select cases. Recommendations for long-term surveillance frequency and duration are similarly broad. Clinicians and patients must approach each case in a personalized and nuanced fashion to select the appropriate extent of treatment on an individual basis. In areas of evidential equipoise, data regarding patient-centered outcomes may help guide decision-making.

BackgroundTotal thyroidectomy (TT) or lobectomy without radioactive iodine (RAI) is becoming a common management for patients with low-risk differentiated thyroid cancer (DTC). However, the assessment of response to therapy for these patients remains controversial. The aim of this study was to propose and validate a new dynamic evaluation strategy to assess the response to therapy in patients with low-risk DTC treated with TT or lobectomy but without RAI.MethodsWe performed a retrospective analysis of 543 adult patients with low-risk DTC who underwent TT or lobectomy without RAI therapy. Follow-up consisted of trends of serum thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb) levels and neck ultrasonography (US) were conducted every 6–24 months. Response to therapy assessments were defined as excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response according to the follow-up findings.ResultsAt a median follow-up of 51 months (range 33–66 months), 517 (95%) had excellent response, while the other 26 had either biochemical incomplete response (an increasing trend of suppressed serum Tg levels, n=9; an increasing trend of TgAb levels, n=3) or indeterminate response (a stable or decreasing trend of suppressed serum Tg levels, but a stable positive trend of TgAb levels, n=14). No patients had structural incomplete response or no deaths related to thyroid cancer. The risk of incomplete response was significantly higher in lobectomy than in TT (p<0.001).ConclusionOur study proposed and validated a new dynamic response to therapy assessment depending on trends of suppressed serum Tg, TgAb levels, and neck US findings which could be an appropriate tool for postoperative follow-up in low-risk DTC patients without RAI therapy. Our findings provided further evidence to support no routine recommendation of RAI after surgery in low-risk DTC.

PURPOSESince the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation.METHODSUsing nine US SEER cancer registries (1975-2017), we estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes v no or unknown) using Poisson regression among ≥ 5- and ≥ 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively.RESULTSAmong 27,050 ≥ 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among ≥ 20-year DTC survivors (RRsolid = 1.47; 95% CI, 1.24 to 1.74; RRbreast = 1.46; 95% CI, 1.10 to 1.95). Among 32,171 ≥ 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.CONCLUSIONIn addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

The purpose of this study was to investigate the effect and influencing factors of postsurgical radioactive iodine (RAI) therapy for patients with low- and intermediate-risk differentiated thyroid cancer (DTC). A retrospective analysis of 423 low- and intermediaterisk DTC patients admitted to the Department of Nuclear Medicine, Sichuan Provincial People's Hospital from January 2005 to December 2020 was performed. All patients were treated with surgery, had a postoperative pathological diagnosis, and were treated with RAI, including 89 males and 334 females. Recurrence risk stratification: 143 cases were low-risk, and 280 cases were intermediaterisk. The excellent response (ER) rate for low- and intermediate-risk were 93.7% and 78.2%, respectively (P < 0.05). There were significant differences in age, cumulative dose of [131I], and pretreatment stimulated-Tg (pre-Tg) levels between the low- and intermediate-risk groups (P < 0.05). There were significant differences in the cumulative dose of 131I and pre-Tg levels between ER and the non-ER group (P < 0.05). The area under the curve (AUC) values were 0.799 in the low-risk group, and 0.747 in the intermediate-risk group for the ROC curve by ER status of pre-Tg. The ER rate with RAI treatment decreased with an increase in pre-Tg levels. Pre-Tg was an important factor for RAI treatment decision-making and prognostic evaluation and differed between low-risk and intermediate-risk DTC. Aggressive RAI therapy was recommended for low-risk DTC with pre-Tg ≥ 20.0 ng/mL and in intermediate-risk group with pre-Tg ≥ 10.0 ng/mL.

IntroductionThe aim of this prospective study was to evaluate long-term outcomes in differentiated thyroid cancer (DTC) patients postoperatively treated with distinct RAI activities of 30 mCi, 60 mCi, and 100 mCi.Material and methodsThe analysis involved 277 low-risk and 46 intermediate-risk patients, who underwent radioiodine (RAI) ablation with 30 mCi, 60 mCi or 100 mCi under prospective, randomized clinical trials. Seventy-eight patients from the low-risk group received 30 mCi, whereas 125 and 74 patients received 60 mCi and 100 mCi, respectively. Regarding the intermediate-risk group, 20 patients were given 60 mCi, and 26 subjects were given 100 mCi. The mean time of follow-up was 11 years.ResultsAn excellent treatment response was obtained in 88%, 89% and 90% of low-risk patients treated with 30 mCi, 60 mCi, and 100 mCi, respectively, and in 85% of intermediate-risk patients, who were administered 60 or 100 mCi. An indeterminate response was achieved in 9.4% and 6.5%, whereas an incomplete structural response was obtained in 1.4% and 6.5% of low-risk and intermediate-risk patients, respectively. An incomplete biochemical response was observed only in 2.2% of intermediate-risk patients. The differences in treatment response regarding RAI activity were not significant.ConclusionsRAI activity of 30 mCi demonstrates a comparable efficacy as 60 mCi and 100 mCi in low-risk DTC. RAI activity of 60 mCi seems to be effective in intermediate-risk DTC.

e18095 Background: The use of RAI in the treatment of DTC of various stages and risk levels is widespread. However, its efficacy continues to be a subject of debate, particularly with regard to low-risk patients. Some studies have found significant differences in RAI's ability to decrease recurrence and distant metastasis, while others have not. Thus, we conducted this study to evaluate the effect of RAI on disease-specific survival (DSS) in patients with DTC without distant metastasis. Methods: Data were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between the years 2000 and 2018. Patients who have distant metastatic, tumor size ≥200 mm, receiving chemotherapy or any type of radiation other than RAI were excluded. Only patients with total thyroidectomy as surgical procedure were included. These patients were classified into three groups based on their histology: classical papillary thyroid carcinoma (C-PTC), follicular type variant carcinoma (FV-PTC), and follicular thyroid cancer (FTC). T-tests and chi-square tests were employed to compare variables, while the Cox proportional hazards model was utilized to assess the effect of RAI on DSS, presenting adjusted hazard ratios and confidence intervals. Results: The study population consisted of 96,557 patients, with 59,460 classified as having C-PTC, 31,583 as FV-PTC, and 5,489 as FTC. Most patients were female (78.6%), and the mean age was 45.8 years. 80.5% of the patients were white. The mean tumor size was 19.4 mm, with FTC tumors having a larger mean size of 34.8 mm. About a third of cases had an extrathyroidal extension. FV-PTC had the most favorable survival outcome with a 5-year DSS of 97.9%, followed by C-PTC (97.1%) and then FTC (96.9%). RAI was administered to 61.2% of FTC cases, 53.2% of C-PTC cases, and 52.1% of FV-PTC cases. In both FV-PTC and C-PTC, patients who received RAI had significantly better long-term survival than those who underwent surgery alone. The multivariable analysis confirmed that RAI had a more favorable prognosis in FV-PTC (HR = 0.68, 95%CI: 0.61 to 0.77, p&lt;0.001) and C-PTC (HR = 0.60, 95%CI: 0.54 to 0.67, p&lt;0.001), but did not result in improved DSS in FTC (HR = 0.87, 95%CI: 0.70 to 1.09, p = 0.226). There was a survival difference between the three histological subtypes in the overall cohort (p&lt;0.001), even after matching baseline characteristics (p = 0.019). Conclusions: Our results showed that RAI administration was statistically associated with improved long-term DSS outcomes in FV-PTC and C-PTC histological subtypes, but not in FTC. However, a careful interpretation of these results is needed as the survival benefit was less than 3% in all cohorts, it might be clinically insignificant. This study was the first to examine all histological types of DTC using a large sample size. There is a need for a randomized trial to confirm the efficacy of RAI in FTC treatment.

ESTIMABL2, a multicentre randomised phase 3 trial in patients with low-risk differentiated thyroid cancer (ie, pT1am or pT1b, N0 [no evidence of regional nodal involvement] or Nx [involvement of regional lymph nodes that cannot be assessed in the absence of neck dissection]), showed the non-inferiority of a follow-up strategy without radioactive iodine (131I) administration compared with a postoperative 131I administration at 3 years post-randomisation. Here, we report a pre-specified analysis after 5 years of follow-up. Patients treated with total thyroidectomy with or without prophylactic neck lymph node dissection, without postoperative suspicious findings on neck ultrasonography, were randomly assigned to the no-radioiodine group or to the radioiodine group (1·1 GBq-30 mCi after recombinant human thyrotropin-stimulating hormone). Follow-up consisted of annual thyroglobulin and thyroglobulin antibody determinations during levothyroxine treatment and neck ultrasonography in odd-numbered years. An event was defined as abnormal foci of 131I uptake on the post-treatment whole-body-scan requiring subsequent treatment, abnormal neck ultrasonography, elevated thyroglobulin levels, increasing titres or appearance of thyroglobulin antibody (using the same laboratory assay), or a combination of these definitions. Non-inferiority of the proportion of patients without an event in one group compared with the other at 5 years after randomisation was shown if this proportion and its CI did not differ by more than -5%. This study was registered on ClinicalTrials.gov (NCT01837745) and is completed. Of the 776 patients (n=642 [82·7%] female and n=134 [17·3%] male, median age 52·9 years [IQR 42·6-63·1]) enrolled, 698 were evaluable at 5 years. The proportions of patients without events were 93·2% in the no-radioiodine group and 94·8% in the radioiodine group, for a difference of -1·6% (90% CI -4·5 to 1·4). Events consisted of structural or functional abnormalities (n=11) and biological abnormalities (n=31). The non-inferiority of a follow-up strategy compared with postoperative 131I administration in low risk differentiated thyroid cancer was confirmed at 5 years. There is no loss of opportunity in following these patients without postoperative ablation. Programme de Recherche Hospitalier Clinique.

Differentiated thyroid cancer (DTC) incidence is increasing worldwide in recent decades and is the most common endocrine cancer. Fortunately, most of the increase is in low-risk tumors; however, we are seeing an increase across all sized tumors. Papillary thyroid cancer (PTC) is the most common form accounting for about 85 % of DTC, and prognosis overall is very favorable for patients with DTC. Initial therapy often consists of surgery and then radioactive iodine (RAI) ablation of thyroid remnant in those that are deemed intermediate risk or high risk by the American Thyroid Association (ATA) classification. An additional component of therapy also includes achieving low normal or suppression of thyroid-stimulating hormone (TSH) levels.