Low-risk Differentiated Thyroid Cancer Patients Research Articles

Association of Radioactive Iodine Administration With Outcome Among Patients With Low-Risk Differentiated Thyroid Cancer: A Real-World Data Analysis.

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.

Clinical inertia in thyrotropin suppressive therapy for low-risk differentiated thyroid cancer: A real-world experience at an endocrine center in Bangkok.

The management of low-risk differentiated thyroid cancer (DTC) has evolved over time toward treatment de-escalation. However, overtreatment with supraphysiological dose of levothyroxine (LT4) continues to be observed despite current clinical guideline. This study aimed to assess the actual thyrotropin suppressive therapy for low-risk DTC patients at an endocrine center in Bangkok. This retrospective study included patients with low-risk DTC who were regularly follow-up for at least 18 months at Theptarin Hospital between 2016 and 2022. The serum thyroid stimulating hormone (TSH) levels were stratified as TSH < 0.1 mIU/L; TSH 0.1 to 0.5 mIU/L; TSH 0.5 to 2.0 mIU/L; and TSH > 2.0 mIU/L. The initial risk stratification (IRS) and dynamic risk stratification were determined at 12 months of follow-up after completing the initial treatment and at the last visit. The clinical factors associated with overtreatment with LT4 were analyzed. A total of 102 patients (83.3% female, age at diagnosis 41.8 ± 13.6 years, mean tumor size 1.6 ± 1.0 cm) were evaluated with a mean follow-up of 5.9 years. The IRS classified 92.2% of patients after the initial treatment and 93.1% of patients at the last follow-up visit into the excellent response category. The mean LT4 daily dosage at the last follow-up was 121.3 ± 44.8 µg/day. Serum TSH levels were in an appropriate target range according to IRS in only 8.8% (9/102) of the patients and then improved to 19.6% (20/102) at the last follow-up visit. Further analysis showed that treating physicians with ≥10 years of practice was associated with severe TSH suppression therapy (TSH < 0.1 mIU/L). Despite the current clinical guideline recommendations and scientific evidences, less than one-fifth of low-risk DTC patients achieved the appropriate serum TSH target. While the proportion of an optimum LT4 suppressive had improved during the study period, further efforts are needed to overcome this clinical inertia.

The effect of COVID-19 pandemic restrictions on the management of differentiated thyroid cancer in Turkey: a single tertiary centre experience.

Many countries have implemented unprecedented health measures since the World Health Organisation declared the novel coronavirus disease 2019 (COVID-19) a global pandemic. These measures have resulted in delays in the diagnosis of differentiated thyroid cancer (DTC). However, there is limited data on the impact of restrictions imposed during the pandemic on DTC management. Thus, the aim of this study is to analyse the clinicopathological and follow-up data of DTC patients diagnosed before and during the COVID-19 outbreak. This retrospective study included 191 DTC patients that were diagnosed between December 2018 and June 2021. The patients were divided into two groups: patients diagnosed before (December 2018 to February 2020) and during (March 2020 to June 2021) the COVID-19 pandemic. The clinicopathological and follow-up data between the two groups were compared. Similar preoperative cytology results were obtained from the two groups. No difference with regard to tumour size, lymphovascular invasion and extrathyroidal invasion was observed between the two groups. While the American Thyroid Association risk stratification was similar between the two groups, radioactive iodine (RAI) therapy was applied less during the COVID-19 period. Although RAI therapy was administered at a lower rate during the COVID-19 period, the recurrence rates among patients after two years of follow-up were similar to those during the pre-COVID-19 period. Although the COVID-19 pandemic restrictions during the pandemic period caused difficulties in the management of DTC patients, this did not negatively affect their prognosis. These findings can confirm the applicability of active surveillance in DTC patients and may help change the real-life treatment practices in selected low-risk DTC patients.

2212MO Major secondary outcomes in the multicentre noninferiority randomised trial IoN: Is ablative radioiodine necessary for low-risk differentiated thyroid cancer patients?

2212MO Major secondary outcomes in the multicentre noninferiority randomised trial IoN: Is ablative radioiodine necessary for low-risk differentiated thyroid cancer patients?

Propensity Score Matched Outcome Analysis of Lobar Ablation Versus Completion Thyroidectomy in Low-Risk Differentiated Thyroid Cancer Patients: Median Follow-Up of 11 Years.

Background: Radioactive iodine lobar ablation (RAILA) of the contralateral thyroid lobe has been suggested as an alternative to completion thyroidectomy in patients of differentiated thyroid cancer (DTC) who underwent initial hemithyroidectomy. However, data on long-term outcomes are scarce. In this study, we intended to describe the long-term outcomes of RAILA versus completion thyroidectomy in a cohort of low-risk DTC patients. Methods: Data of patients with low-risk DTC who underwent initial hemithyroidectomy, and were subsequently treated with either completion thyroidectomy or RAILA between 1996 and 2015, were collected and analyzed. The treatment outcomes included ablation rate, recurrence rate, recurrence-free survival (RFS), and adverse events, and were validated by propensity score matching analysis. Results: Of the 1243 patients (median age: 34 years, range: 5-78) with low-risk DTC, 514 patients underwent upfront RAILA while 729 patients underwent completion thyroidectomy followed by remnant ablation. The ablation rate following the first radioactive iodine (131I) cycle was 75.3% [95% confidence interval (CI) 71.3-78.9] in the RAILA group versus 84.1% [CI 81.2-86.6] in the completion thyroidectomy group (p < 0.001). Over median follow-up of 11.4 years (interquartile range: 8.3-15.8), the recurrence rates between the two groups were not significantly different (1.6% [CI 0.7-3.2] vs. 1.0% [CI 0.4-2.1], respectively, p = 0.343). The product limit estimate of RFS at 10 years was 98.6% [CI 97.6-99.6%] in the RAILA group versus 99.1% [CI 98.3-99.9%] in the completion thyroidectomy group (p = 0.391). The outcomes in 497 matched pairs generated through propensity score analysis were similar. None of the patients in the RAILA group experienced permanent hypocalcemia or recurrent laryngeal nerve palsy, while the corresponding rates in the completion thyroidectomy group were 10/729 (1.4%) (p = 0.006) and 5/729 (0.7%) (p = 0.080), respectively. Radiation thyroiditis was seen in 25/514 (4.9%) patients in the RAILA group versus 3/729 (0.4%) in the completion thyroidectomy group (p < 0.001). Conclusions: Upfront RAILA is seen to be a noninvasive, safe, and effective alternative to surgical completion thyroidectomy in low-risk DTC patients in the absence of macroscopic malignancy in the remaining thyroid lobe.

Retrospective analysis of low-risk differentiated thyroid tumours: is lobectomy the adequate approach?

Introduction: According to the recommendation of the American Thyroid Association 2015 guideline, the treatment of 1-4 cm (T1b-2) low-risk differentiated thyroid cancer (DTC) is lobectomy without radioiodine therapy. Objective: Retrospective analysis of multifocality in surgical and histological data of T1-2 patients living on moderate iodine intake. Methods: Analysis of the pathological characterisation of 81 low-risk (T1-2) DTC patients who underwent total thy-roidectomy. Patients were treated at Flor Ferenc Hospital, Kistarcsa, Hungary, between 2013 and 2019. Results: 64 patients had T1, while 17 patients had T2 status. 65/81 (80.2%) patients had papillary, and 16/81 (19.8%) had follicular subtype. Lymph node metastasis was detected up to 18.4% in papillary and 18% in follicular patients. Multifocal tumours were detected in 25% (16/64) of T1 patients, of these 10.9% (7/64) was unilateral and 14.1% (9/64) was bilateral. Multifocal tumours were detected in 11.7% (2/17) of T2 patients; both were bilateral. Distribution of T1-2 bilateral multifocal patients (11/81; 13.5%) was n = 3 T1a-, n = 6 T1b and n = 2 T2 stadium, from these 10 patients received radioiodine treatment. The sizes of contralateral tumours were <5 mm in 9 patients, and >5 mm in 2 patients. Conclusions: Due to the frequent (13.5%) bilateral multifocality in T1-2 DTC patients, we suggest total thyroidec-tomy instead of lobectomy. After lobectomy, the follow-up of the contralateral tumours is almost impossible by ul-trasonography due to the small tumour size (on average 2.8 mm) and frequently detected benign nodules; therefore the multifocality might remain undetected, which can distort the plan for adjuvant treatment.

A New Dynamic Response to Therapy Assessment in Postoperative Patients With Low-Risk Differentiated Thyroid Cancer Treated Without Radioactive Iodine.

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.

Estimabl2: Is There a Need for Radioiodine Ablation in Low Risk Differentiated Thyroid Cancer (DTC) Patients?: Results From the French Randomized Phase III Prospective Trial on 776 Patients (NCT 01837745)

Background: The benefits of post-operative radioactive iodine (RAI) administration have not been demonstrated in patients with low risk differentiated thyroid cancer (DTC). The objective of this randomized phase III trial is to assess in low risk DTC patients the non-inferiority of a follow-up strategy as compared to a systematic adjuvant post-operative RAI administration. Methods: ESTIMABL2 is a French multicentric randomized phase III trial in patients with low-risk DTC treated with total thyroidectomy with or without prophylactic neck lymph node dissection (pT1am N0 or Nx with a sum of the diameters of tumor lesions ≥ 10mm, pT1b N0 or Nx). Two to five months after surgery, in the absence of suspicious lateral neck lymph node on ultrasonography (US), patients were randomized either to the follow-up group (FU, no RAI administration) or to the ablation group and received post-operative RAI (1.1 GBq following rhTSH stimulation). Yearly controls under levothyroxine treatment consisted in thyroglobulin (Tg) and Tg antibodies (TgAb) determinations and neck-US. The primary objective was to assess at 3 years after randomization the non-inferiority of the proportion of patients without tumor-related event in the FU group as compared to the ablation group. Non-inferiority is demonstrated if the rate of patients without event at 3 years does not differ by more than ΔL=-5%. A tumor-related event was defined by the occurrence of subsequent treatment (RAI administration or surgery) for abnormal RAI uptake on the post-therapeutic WBS or by elevated Tg or TgAb levels and/or abnormal neck US during controls. Tg levels on levothyroxine treatment were considered elevated if > 2ng/mL in the FU group and > 1ng/mL in the ablation group. TgAb were considered elevated if > the upper limit range with an increase above 50% on 2 consecutive determinations performed 6 months apart. Results: 776 low-risk DTC patients were included between 2013 and 2017 in 35 French centers within the TUTHYREF network; 83% females, mean age: 52 years, papillary TC: 96%, pT1bNx: 43.6%, pT1bN0: 37.5%, pT1amNx: 12.6%, pT1amN0: 6.3%. Among the 729 patients evaluable at 3 years after randomization, tumor-related events occurred in 18/367 patients (4.9% IC95%=[2.9; 7.6]) in the FU group and in 15/362 patients (4.1% IC95%=[2.3; 6.7]) in the ablation group. Thus, 95.1% of patients in the FU group had no event at 3 years and this percentage is not inferior from the 95.9% of patients observed in the ablation group (difference = -0.8% [95% CI:-3.3%; 1.8%]. The number of subsequent surgery and/or RAI administration was 6 (1.6% IC95%=[0.6; 3.5]) in the FU group and 9 (2.5% IC95%=[1.1; 4.7]) in the ablation group. Conclusion: this phase III trial demonstrates the non-inferiority of a follow-up strategy compared to a systematic adjuvant post-operative administration of RAI (1.1GBq following rhTSH) in low risk DTC patients (PHRC 2012; NCT01837745).

Comparison of radioiodine ablation rates between low versus high dose, and according to the surgeon's expertise in the low-risk group of differentiated thyroid cancer.

Radioiodine ablation following surgery is the accepted treatment for patients with differentiated thyroid cancer (DTC). Since that surgical volume and radioiodine dose can have impact on treatment outcome, we aimed to evaluate them on the treatment outcome of low-risk DTC patients. Low-risk DTC patients were classified into four groups, including (1) thyroidectomy was performed by thyroid surgeon and low-dose (1850 MBq [30 mCi]) radioiodine was administered (n = 17), (2) thyroidectomy was performed by thyroid surgeon and high-dose (3700 MBq [100 mCi]) radioiodine was administered (n = 10), (3) thyroidectomy was performed by general surgeon and low-dose radioiodine was administered (n = 22), and (4) thyroidectomy was performed by general surgeon and high-dose radioiodine was administered (n = 29). All patients were followed at least for 6 months and also for evaluation of treatment success, neck sonography, thyroid-stimulating hormone-off, thyroglobulin (Tg)-off, and anti-Tg-off tests were performed. Furthermore, two common radioiodine treatment-associated side effects, including dry mouth, and nausea/vomiting were assessed for all patients. Seventy-eight low-risk DTC patients (female: 70 [89.7%]; male: 8 [10.3%]) aged from 18 to 78 years old with mean of 41.96 ± 13.42 years were enrolled in this study. In total, the treatment was successful in 96.2% of patients. There was no significant difference in treatment success among groups (P > 0.05), while there was a significant association among administered activity and side effects. In low dose patients, only one patient complained from dry mouth; however, 11/39 patients who received high dose of iodine complained from dry mouth (P = 0.002). In addition, 9/39 high dose patients suffered from vomiting/nausea, while none of low-dose patients suffered from vomiting/nausea (P = 0.001). In low-risk DTC patients, surgical volume and amounts of radioiodine had no significant impact on treatment results; therefore, low dose radioiodine following thyroidectomy may be preferable to low-risk DTC patients to avoid side effects.

&lt;p&gt;Risk Factors That Influence Surgical Decision-Making for Patients with Low-Risk Differentiated Thyroid Cancer with Tumor Diameters of 1–4 cm&lt;/p&gt;

BackgroundThere are several controversies between thyroid lobectomy and total thyroidectomy for surgical management of low-risk differentiated thyroid cancer (DTC) with a tumor diameter of 1–4 cm.Patients and MethodsIn this study, we explore the factors related to selection of type of surgical procedure for 103 low-risk DTC patients with a tumor diameter of 1–4 cm.ResultsAmong 103 low-risk DTC patients with tumor diameters of 1–4 cm, 43 patients underwent total thyroidectomy and 60 patients underwent thyroid lobectomy based on postoperative pathology. A ROC curve showed that the optimal diagnostic threshold for selecting surgical modality was a tumor diameter of 2.15 cm. For these low-risk DTC patients, the sensitivity and specificity for predicting thyroid lobectomy when tumor diameter <2.15 cm while total thyroidectomy when tumor diameter ≥2.15 cm are 46.5% and 78.3%, respectively. There were significant differences between the selection of type of surgical procedure in patient groups with 1) tumors with multiple foci group vs a single focus (P<0.05), and 2) tumor diameter of ≥2.15 cm vs <2.15 cm (P<0.05). There was no significant difference between gender and age groups (P>0.05). Multivariate analysis confirmed that tumors with multiple foci and diameter ≥2.15 cm were the primary risk factors for implementation of total thyroidectomy (P<0.05).ConclusionThe diameter and multifocal nature of low-risk DTC tumors are the primary factors related to preferred surgical modality. This study revealed that thyroid lobectomy is more applicable to patients with tumor diameter <2.15 cm and a single focus, whereas, total thyroidectomy was preferred in patients with tumor diameter ≥2.15 cm and/or multiple foci.

Thyroglobulin Changes are Highly Dependent on TSH in Low-risk DTC Patients not Treated with Radioiodine

Low-risk differentiated thyroid cancer (DTC) is currently rarely treated with radioiodine (131I) to ablate the postoperative remnant. Therefore, the interpretation of the serum thyroglobulin (Tg) values should be reconsidered. The aim of our study was to evaluate the changes in Tg values during follow-up with regard to the changing values in thyroid stimulating hormone (TSH). We evaluated 271 low-risk DTC patients, treated with total thyroidectomy but not 131I. To be included, patients had to be negative for Tg antibodies and have at least 3 evaluations in our department. All patients were on levothyroxine (L-T4) therapy. After a median follow-up of 73 months, the overall Tg values were stable, while TSH values slightly increased. Therefore, we pooled data of Tg and TSH from all evaluations and a significant positive correlation was demonstrated (R = 0.2; P < 0.01), and was also demonstrated when we performed the analysis using time-weighted values (R = 0.14; P = 0.02). Moreover, when dividing patients into 3 groups according to first postoperative Tg (Group A [Tg < 0.2 ng/ml], Group B [Tg 0.2-1 ng/ml], and Group C [Tg > 1 ng/ml]) most patients showed stable values of Tg at the end of follow-up but TSH variations had a clear impact on the changes in Tg among the groups. We demonstrated that in low-risk DTC not treated with 131I, serum Tg remains substantially stable over time, and the variations observed were correlated with the concomitant variations of TSH levels, mainly due to the modification of LT-4 therapy performed according to the ongoing risk stratification.

Differences in long-term quality of life between hemithyroidectomy and total thyroidectomy in patients treated for low-risk differentiated thyroid carcinoma

BackgroundThe long-term health-related quality-of-life implications of treating low-risk differentiated thyroid cancer with total thyroidectomy or hemithyroidectomy is important to patients but remains poorly understood. MethodsUsing a cross-sectional mailed survey, we compared long-term health-related quality-of-life in low-risk differentiated thyroid cancer survivors treated with hemithyroidectomy to those treated with total thyroidectomy between 2005 and 2016 at a university hospital. European Organisation for Research and Treatment of Cancer Quality of Life core Questionnaire version 3.0, the supplementary Thyroid Cancer specific questionnaire module version 2.0, and the Assessment of Survivor Concerns (ASC) questionnaires were used. Our primary outcome was the global scale of quality of life. Exploratory outcomes included differences among other health-related quality-of-life items corrected for potential confounders in multivariable regression analyses. ResultsThe response rate was 51.0% (270 of 529), of which 59 patients (21.9%) were treated with hemithyroidectomy. Main outcome score global quality of life did not differ between groups (76.9 hemithyroidectomy vs 77.7 total thyroidectomy, P = .450). Exploratory analyses showed hemithyroidectomy to be associated with more worry about recurrence on the Assessment of Survivor Concerns questionnaire (2.4 hemithyroidectomy vs 2.1 total thyroidectomy, P = .021). ConclusionLong-term quality of life was not significantly different between low-risk differentiated thyroid cancer patients treated with total thyroidectomy compared with hemithyroidectomy. In secondary analyses, worry about recurrence appeared to be higher in individuals treated with hemithyroidectomy. These data highlight previously unreported impact of surgical regimen to the health-related quality-of-life for low-risk differentiated thyroid cancer patients.

Prognostic value of somatic mutation testing and different methods of treatment of low-risk differentiated thyroid cancer

Background: Using molecular testing for prediction the course of the disease could possibly help doctors in making therapeutic decisions about the management of patients, because it remains controversial issues in low-risk differentiated thyroid cancer patients. The experts opinions are different on the volume of treatment of these patients: the adequacy of hemitireoidectomy, the need to remove the lymph nodes of the central zone (level VI) and the need for radioiodine therapy.&#x0D; Aims: to evaluate the frequency of recurrences in different complex treatment options of low-risk differentiated thyroid cancer; to evaluate the frequency of somatic mutations in the hot spots of BRAF, KRAS, KRAS, EIF1AX and TERT genes in histological material and to evaluate their prognostic value.&#x0D; Materials and methods: A prospective, observational, cohort, sample, single-center, open-label, controlled, nonrandomized clinical trial was performed, which included patients with the thyroid neoplasms, recruited in the period from 2012 to 2014. Samples of histological material were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX. After the treatment, the low-risk differentiated thyroid cancer patients group were observed for 4368 months.&#x0D; Results: The study included 90 patients with low-risk well differentiated thyroid cancer. Mutations in the hot spots of the BRAF gene (exon 15, codon area 600-601) were found in 53 patients, mutations in the hot spots of the NRAS gene (exon 3, codon 61) in 3 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. The median follow-up in the well differentiated thyroid cancer group was 56 months. Recurrence diagnosed in 12 patients (13.3%), significant differences in the frequency of recurrence depending on the surgical treatment option was not revealed, significant differences in the frequency of recurrence between the groups BRAF+/BRAF was not revealed.&#x0D; Conclusions: Low-risk well differentiated thyroid cancer patients have characterized a very favorable the course of disease and prognosis, even in the case of recurrence. In this study, complex treatment has not shown significant advantages over thyroidectomy in treating patients with thyroid microcarcinomas. Mutation testing of histological material in hot spots of genes BRAF, KRAS, NRAS, EIF1AX and TERT cant be used as an additional marker in low-risk well differentiated thyroid cancer patients to predict the course of the disease, although the lack of detection of aggressive genes of the disease may indicate a favorable prognosis in these patients.

Preoperative Computed Tomography Changes Surgical Management for Clinically Low-Risk Well-Differentiated Thyroid Cancer.

In the current guidelines for differentiated thyroid cancer (DTC), computed tomography (CT) of the neck has a limited role. The authors hypothesized that adding CT to the workup of clinically low-risk DTC size 4cm or smaller changes the surgical management for a portion of patients due to detection of clinically significant lymph node metastases not located by ultrasound of the neck. A prospective cohort of DTC patients at an academic referral center between 2012 and 2016 was reviewed. All the patients with fine-needle aspiration cytopathology results suspicious for malignancy or malignant tumor (Bethesda category 5 or 6, respectively) underwent CT before surgery. Clinically low-risk DTC patients were selected if they had a tumor diameter of 4cm or less and no evidence for local invasion or suspicious lymph nodes seen on ultrasound. Outcomes focused on alteration of the surgical plan based on CT and correlation with pathology. The CT findings for 25 (22.5%) of 111 patients with clinically low-risk DTC led to a change in surgical management. Of these 25 patients, 16 (14.4% of the entire cohort) benefited due to the removal of clinically significant lymph node disease not seen on ultrasound. Categorization of the group that had a change in management showed that 6 (85.7%) of 7 lateral neck dissections and 10 (55.6%) of 18 central neck dissections (CND) harbored metastatic nodes larger than 2mm. In the group with clinically low-risk DTC, CT changed surgical management for a substantial number of the patients with clinically significant nodal disease not detected by ultrasound. This highlights the fact that in certain practice settings, adding CT to the preoperative staging may be favorable for the detection of nodal metastasis.

Can We Discharge Dynamically Risk-Stratified Low-Risk (Excellent Response to Treatment) Thyroid Cancer Patients After 5 Years of Follow-Up?

AimsThe 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of thyroid cancer patients. This is probably unnecessary, can cause patient anxiety, is time consuming and places significant demand on National Health Service resources. It has been suggested that low-risk differentiated thyroid cancer (DTC) patients could be discharged to primary care once they are 5 years from diagnosis and treatment. The aim of this study was to investigate the potential safety of this practice. Materials and methodsIn total, 756 patients with dynamically risk-stratified (DRS) low-risk/excellent response to treatment DTC treated over 2001–2013 in the Leeds region were followed after diagnostic surgery and the recurrence rate calculated. ResultsThe median follow-up time was nearly 10 years (5–17 years). Radiological recurrence occurred in 13/756 (1.7%) patients and was always preceded by raised thyroglobulin/ thyroglobulin antibody levels. In all 13 patients elevation of thyroglobulin occurred within 5 years of diagnosis. Two additional patients were found to have rising thyroglobulin at almost 9 and 10.5 years from diagnosis, although to date radiological recurrence has not been detected. Assuming these two patients developed recurrence with longer duration of follow-up, then 0.26% (2/756) of patients would not have their recurrence discovered within 5 years of diagnosis. To detect 100% of patients with a putative recurrence in our cohort would require 10.5 years of follow-up. Four patients had transiently raised thyroglobulin, which became undetectable within 2 years (in three patients), without any treatment and radiological recurrence was not discovered. ConclusionDischarge of DRS low-risk DTC patients to primary care after 5 years of secondary care follow-up is reasonable, accepting that late recurrence may occur in a very small minority of individuals (0.26%, ∼1:400). A more cautious approach would be to continue monitoring for 10 years, although the frequency of assessments could be reduced with increasing duration of follow-up.

Fractionated dosage of radioiodine for the ablation of low-risk differentiated thyroid cancer has no impact on survival.

Due to a limited number of hospital beds dedicated to radioiodine therapy (RIT) in some countries, a fractionated dose of radioiodine may be considered as the ablation therapy of differentiated thyroid cancer (DTC). The aim of the study was to compare the late effects of ablation therapy with single and fractionated dose of radioiodine in patients with DTC. Patients with low-risk DTC referred to our institution 5-16 weeks after thyroidectomy, treated with 2.2 GBq of 131I, either in a single dose (2.2 GBq, group 1) or in two fractions (1.1 GBq+1.1 GBq administered with a 24 h interval, group 2) were retrospectively included. Clinical outcome of the treatment and overall survival (OS) was evaluated. 83 patients treated with single dose and 186 patients treated with fractionated dose of radioiodine were included. Mean duration of follow-up was 8.0 vs.7.8 years, respectively (p=ns). There were no significant differences between the groups in male to female ratio, age at the time of the first RIT, proportion of papillary thyroid cancers, volume of the thyroid tissue, thyroid-stimulating hormone and thyroglobulin levels before first RIT. RIT was repeated in 55.4% and 54.8% of patients from group 1 and 2 respectively (p=ns). There were no significant differences including the course and outcomes of the treatment between the groups, measured by: cumulative dose of 131I, mean number of 131I administrations and mean thyreoglobulin concentration at the follow-up. Also the overall survival did not differ significantly between the groups. Probability of 5-year OS was 98.6% for patients treated with single and 99.5% with fractionated dose of 131-I, 10 year OS - 98.6 and 97.1% respectively, 15 year OS - 95.5 and 92.9% respectively (p=ns). In the long-term follow-up, radioiodine ablation therapy with fractionated doses in low-risk DTC patients is equally effective as with single dose. < p > < /p >.

Incidence of Nonthyroidal Primary Malignancy and the Association with (131)I Treatment in Patients with Differentiated Thyroid Cancer.

The occurrence of nonthyroidal primary malignancy (NTPM) and the potential association of with radioiodine (RAI) treatment are important concerns in patients with differentiated thyroid cancer (DTC), but incidence data are conflicting. The aims of the present study were to investigate the incidence of NTPM and its association with RAI treatment in a cohort of DTC patients treated at a single tertiary medical center. The data of 1943 patients with DTC recorded in the Rabin Medical Center Thyroid Cancer Registry were cross-matched with data from the Israeli National Cancer Registry to identify those diagnosed with an NTPM. Patient medical files were reviewed. Second primary malignancy (SPM) was defined as new malignancy diagnosed at least two years after DTC diagnosis. For 1434 of the 1943 patients (73.8%), the American Joint Committee on Cancer TNM stage was 1-2. The mean follow-up was 9.3 years. Of the 1943 patients, 1574 (81%) were treated with RAI, and 1467 were followed for at least 2 years, and of these, 1145 patients (78%) received a cumulative dose of ≤200 mCi. A total of 409 NTPMs were diagnosed in 368/1943 patients with DTC (18.9%; 265 female, mean age 53.9 ± 15 years), including 173 SPMs (42.3%) in 166/368 patients. The most common NTPM and SPM was breast cancer followed by hematologic malignancies. In patients followed for ≥2 years, SPMs were diagnosed in 9% of RAI-treated patients and 10.5% of non-RAI-treated patients. SPM rates were 10.2% and 7.8% for a cumulative RAI dose of ≤100 mCi and >100 mCi respectively. Hazard ratios for SPM in patients that received/did not receive RAI treatment was 1.27 (95% confidence interval 0.88-1.82; p = 0.1). There was no correlation between first or cumulative RAI dose and diagnosis of SPM. NTPMs are not uncommon in patients with DTC and usually antecede the DTC. In a population of mostly low-risk DTC patients, in whom limited activities of RAI are usually administered, this treatment is apparently not associated with an overall increased risk of SPMs compared with subjects not receiving RAI treatment.

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.

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.

Thyroglobulin Test at 3 Weeks after Surgery in Well-Differentiated Thyroid Cancer and its Predictive Value: The Role of Endocrine–Metabolic Status

Aim &amp; methods: The present pilot study included 50 differentiated thyroid cancer (DTC) patients (mean age: 45.8 ± 1.8 years, range: 18–73 years) who were followed after surgery for in average 30.0 ± 2.6 months. All patients were subdivided into two groups as having either &lt;2 ng/ml or ≥2 ng/ml blood thyroglobulin level 3 weeks after the operation (3-WTT). Results: Subsequent tumor progression was revealed more often in patients with higher thyroglobulinemia (≥2 ng/ml) in both low- and high-risk DTC groups. Patients with high-risk DTC and 3-week thyroglobulin levels ≥2 ng/ml were more likely to have a higher pre-surgical thyrotropin (TSH) levels. On the contrary, patients with low-risk DTC and 3-week thyroglobulin level ≥2 ng/ml demonstrated tendency to higher preoperative serum insulin levels and higher BMI. Conclusion: These differential findings could suggest that, whereas maximal suppression of TSH is reasonable in high-risk DTC patients, in low-risk DTC patients, for whom this is not justified, a moderate TSH suppression supplemented by multivalent drugs, such as antidiabetic biguanide metformin, could be advised.