ABSTRACT The incidence of differentiated thyroid carcinoma (DTC) has increased in recent decades with early stage, low risk papillary thyroid cancer (PTC) being detected and diagnosed. As a result, the psychological, financial, and clinical ramifications of overdiagnosis and excessively aggressive therapy are being increasingly recognized with many authorities calling for a re-evaluation of the traditional “one size fits all” management approaches. To address these critical issues, most thyroid cancer guidelines endorse a more risk adapted management strategy where the intensity of therapy and follow up is matched to the anticipated risk of recurrence and death from DTC for each patient. This “less is more” strategy provides for a minimalistic management approach for properly selected patients with low-risk DTC. This has re-kindled the long-standing debate regarding the routine use of radioactive iodine therapy (RIT) in DTC. Although recent guidelines have moved toward a more selective use of RIT, particular in patients with low-intermediate risk DTC, the proper selection of patients, the expected benefit, and the potential risks continue to be a source of ongoing controversy and debate. In this manuscript, we will review the wide range of clinical, imaging, medical team, and patient factors that must be considered when evaluating individual patients for RIT. Through a review of the current literature evaluating the potential benefits and risks of RIT, we will present a risk adapted approach to proper patient selection for RIT which emphasizes peri-operative risk stratification as the primary tool that clinicians should use to guide initial RIT management recommendations. (DTC stage PTC (PTC diagnosed result psychological financial reevaluation re evaluation one all approaches issues less lowrisk rekindled kindled longstanding long standing (RIT lowintermediate intermediate benefit manuscript imaging team perioperative peri operative recommendations

ABSTRACT Objective: Although thyroid microcarcinoma (TMC) usually has a favorable prognosis, some patients present a higher risk of disease recurrence or persistence. Thus, we aimed at identifying possible risk factors associated with an incomplete response to therapy in TMC. Subjects and methods: This was a retrospective study of 517 patients with TMC treated with total thyroidectomy, with or without radioactive iodine (RAI) therapy, reclassified after 1.1 ± 0.4 years according to the response to treatment into “favorable” (excellent/indeterminate) or “unfavorable” (biochemical/structural incomplete) responses. We evaluated participants' age, sex, tumor size, histological variants, multifocality, presence of vascular/lymphatic/perineural invasion, extrathyroidal extension, metastatic lymph nodes (LN), and distant metastasis. The effect of RAI therapy on the response range was analyzed in a given subgroup. Results: The mean age observed was 46.4 ± 12.0 years, and 89.7% were female. We noted 97.5% with papillary carcinoma, 27.8% with multifocality and 11.2% with LN metastasis. Although the majority of patients had a low risk of recurrence/persistence (78%), 75% were submitted to RAI therapy. Incomplete response (20.7%) was associated with multifocality (p=0.041; OR=1.619) and metastatic LN (p=0.041; OR=1.868). These variables were strongly correlated (p=0.000; OR=3.283). No cut-off of tumor size was identified as a predictor of incomplete response by the receiver operating curve analysis. RAI treatment did not influence the response of patients with multifocality or LN metastasis. Conclusion: Multifocality and LN metastasis are independent risk factors for incomplete response in TMC patients and are strongly correlated. Additional RAI therapy was not associated with a more favorable response in these subgroups.

ABSTRACT Objective: The intermediate-risk (IR) category includes tumors with different degrees of aggression. We aimed to identify the risk factors associated with unfavorable response to initial treatment and compare the effect of low/high radioactive iodine (RAI) therapy. Subjects and methods: A total of 614 IR patients were selected from a database, during 1972-2015. All patients underwent total thyroidectomy and RAI therapy and were reclassified after 12-18 months into the favorable (complete/indeterminate) response group and the unfavorable (biochemical/incomplete structural) response group. A total of 92 patients were assessed for late response (mean: 9.19 ± 5.73 years). Age, gender, tumor size, histology, multifocality, vascular invasion, extrathyroidal extension, presence and number of lymph node metastasis, and stimulated thyroglobulin at ablation (sTg) were evaluated. Results: Mean age at diagnosis was 41.47 ± 15.81 years, and 83.6% of the patients were female. Within 12-18 months after initial therapy, unfavorable response was detected in 41.2% of the patients and was associated, in multivariate analysis, with lymph node metastasis (p = 0.041; odds ratio [OR] = 1.9), presence of more than five metastatic lymph nodes (p = 0,017; OR = 2.6), and sTg > 10 ng/mL (p = 0.005; OR = 10.0). For patients with a longer follow-up, sTg >10 ng/mL was associated with unfavorable response (p = 0.002; OR = 6.8). A higher RAI dose was not related to better prognosis at the end of the follow-up. Conclusion: A sTg level of >10 ng/mL and lymph node metastasis were associated with an unfavorable response 12-18 months after initial treatment. A RAI dose below 150 mCi was proven sufficient to treat IR patients.

ABSTRACT Objective We aimed to evaluate the impact of minimal extrathyroidal extension (mETE) alone on the risk of recurrence of papillary thyroid carcinoma (PTC). The impact of other factors, including multifocality, age, tumor size, and stimulated thyroglobulin (sTg) values was also assessed. Subjects and methods We retrospectively analyzed 1,108 PTC patients from a medical institution, who presented tumors ≤ 4 cm without any adverse characteristics other than mETE. Patients were classified according to their response to initial treatment 12 to 24 months after surgery as proposed by the 2015 American Thyroid Association (ATA) guideline. Statistical analysis was performed using multivariate logistic regression and receiver operating characteristic (ROC) curve. Results In the multivariate logistic regression analysis, mETE did not have an impact on the response to initial treatment (p = 0.44), similar to multifocality, age, and tumor size. Initial Tg value was the only variable associated with a poor response (p < 0.01, odds ratio = 1.303, 95% confidence interval 1.25-1.36). The ROC analysis revealed that Tg was significant (area under curve = 0.8750); the cutoff value of sTg as a predictor of poor response was 10 ng/mL (sensitivity = 72.2%, specificity = 98.5%). Conclusion For low-risk PTC presenting mETE as the only aggressive feature, the initial sTg value is essential to identify patients who may have a poor response after initial treatment and benefit from further treatment. Arch Endocrinol Metab. 2020;64(3):251-6

ABSTRACT Objectives: We sought to assess the relationship between stimulated thyroglobulin (sTg) before radioactive iodine therapy (RIT), and the dynamic risk stratification 1 year after treatment, and to establish the utility of the sTg as a predictor of response to therapy in these patients. A retrospective chart review of patients with differentiated thyroid cancer (DTC) who underwent RIT after surgery and were followed for at least 1 year, was carried out. Subjects and methods: Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The sTg values before RIT were compared among the groups. ROC curve analysis was performed. Results: Fifty-six patients were enrolled (mean age 44.7 ± 14.4 years, 80.7% had papillary carcinoma). Patients with excellent response had sTg = 2.1 ± 3.3 ng/mL, those with indeterminate response had sTg = 8.2 ± 9.2 ng/mL and those with incomplete response had sTg = 22.4 ± 28.3 ng/mL before RIT (p = 0.01). There was a difference in sTg between excellent and incomplete response groups (p = 0.009) while no difference was found between indeterminate and either excellent or incomplete groups. The ROC curve showed an area under the curve of 0.779 assuming a sTg value of 3.75 ng/mL. Conclusion: Our study results suggest that the higher the sTg before RIT, the greater the likelihood of an incomplete response to initial treatment. A sTg cut-off of 3.75 ng/mL was found to be a good predictor of response to initial treatment in patients with DTC.