Low-risk Differentiated Thyroid Cancer Research Articles

Adoption of Active Surveillance for Very Low-Risk Differentiated Thyroid Cancer in the United States: A National Survey.

Active surveillance (AS) of thyroid cancer with serial ultrasounds is a newer management option in the United States. This work aimed to understand factors associated with the adoption of AS. We surveyed endocrinologists and surgeons in the American Medical Association Masterfile. To estimate adoption, respondents recommended treatment for 2 hypothetical cases appropriate for AS. Established models of guideline implementation guided questionnaire development. Outcome measures included adoption of AS (nonadopters vs adopters, who respectively did not recommend or recommended AS at least once; and partial vs full adopters, who respectively recommended AS for one or both cases). The 464 respondents (33.3% response) demographically represented specialties that treat thyroid cancer. Nonadopters (45.7%) were significantly (P < .001) less likely than adopters to practice in academic settings, see more than 25 thyroid cancer patients/year, be aware of AS, use applicable guidelines (P = .04), know how to determine whether a patient is appropriate for AS, have resources to perform AS, or be motivated to use AS. Nonadopters were also significantly more likely to be anxious or have reservations about AS, be concerned about poor outcomes, or believe AS places a psychological burden on patients. Among adopters, partial and full adopters were similar except partial adopters were less likely to discuss AS with patients (P = .03) and more likely to be anxious (P = .04), have reservations (P = .03), and have concerns about the psychological burden (P = .009) of AS. Few respondents (3.2%) believed patients were aware of AS. Widespread adoption of AS will require increased patient and physician awareness, interest, and evaluation of outcomes.

Current practice in patients with differentiated thyroid cancer.

Considerable changes have occurred in the management of differentiated thyroid cancer (DTC) during the past four decades, based on improved knowledge of the biology of DTC and on advances in therapy, including surgery, the use of radioactive iodine (radioiodine), thyroid hormone treatment and availability of recombinant human TSH. Improved diagnostic tools are available, including determining serum levels of thyroglobulin, neck ultrasonography, imaging (CT, MRI, SPECT-CT and PET-CT), and prognostic classifications have been improved. Patients with low-risk DTC, in whom the risk of thyroid cancer death is <1% and most recurrences can be cured, currently represent the majority of patients. By contrast, patients with high-risk DTC represent 5-10% of all patients. Most thyroid cancer-related deaths occur in this group of patients and recurrences are frequent. Patients with high-risk DTC require more aggressive treatment and follow-up than patients with low-risk DTC. Finally, the strategy for treating patients with intermediate-risk DTC is frequently defined on a case-by-case basis. Prospective trials are needed in well-selected patients with DTC to demonstrate the extent to which treatment and follow-up can be limited without increasing the risk of recurrence and thyroid cancer-related death.

The Ongoing Debate Regarding Completion Thyroidectomy Versus Primary Thyroid Surgery for Low and Intermediate Differentiated Thyroid Carcinoma: A Meta-Analysis.

Lobectomy is increasingly performed for low-risk differentiated thyroid cancer (DTC) and papillary thyroid microcarcinoma (PTMC). However, there is a continuous controversy about completion thyroidectomy (CT) following lobectomy. The current meta-analysis aimed to assess the outcomes of the initial surgical procedure versus CT performed for low/intermediate-risk thyroid carcinoma. Six hundred and sixty-one articles were retrieved, and only 15 full texts fulfilled the inclusion and exclusion criteria. There were 15 studies, including 17,143 patients; twelve were retrospective, two prospective studies, and a controlled trial. Seven articles were from Asia, four from the USA, two from Europe, while two were published in Canada. The studies showed no difference between lobectomy and primary thyroid surgery regarding post-surgery complications. CT was not different from the initial surgical procedure in terms of complications for DTC. The study was limited by the retrospective studies included, the outcomes assessed were not uniform, and significant heterogeneity was observed. Further, well-controlled, more specific trials are needed.

&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.

Thyroid remnant ablation with radioiodine activity of 30, 60, and 100 mCi in patients with differentiated thyroid cancer - a prospective comparison of long-term outcomes.

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.

Management and follow-up of differentiated thyroid cancer not submitted to radioiodine treatment: a systematic review.

The treatment of differentiated thyroid cancer (DTC) has been changing. In low (LR) and intermediate (IR) risk DTC, surgery is becoming more conservative and the usefulness of radioiodine (131I) has been questioned. An increasing number of patients are treated with lobectomy or total thyroidectomy (TTx), but without 131I. Consequently, the management and the follow-up of these patients need to be revised. We reviewed the available data about the management of these growing categories of patients. We focused on the emerging roles of the conventional tools in the follow-up [thyroglobulin (Tg), thyroglobulin antibodies (TgAb) and neck ultrasound (US)]. Moreover, we evaluated the changes in the use of levothyroxine (L-T4) therapy, and the role of the ongoing risk re-stratification. Tg, TgAb and neck US continue to represent the cornerstone of the follow-up, however, a change in their interpretation is needed. In particular, the absolute value of Tg and TgAb lost their clinical meaning, while their trend over time acquired a greater value. At variance, the diagnostic role of neck US is becoming very relevant for the early identification of the local recurrences. In addition, L-T4 therapy should be personalized according with the type of surgery, the age of patients and their comorbidities. Management of DTC treated with lobectomy or TTx but without 131I is worldwide changing. The evidences suggest that in this setting of patients with LR or IR of recurrences, a relaxed surveillance could represent the most reasonable choice.

Completion Thyroidectomy is Less Common Following Updated 2015 American Thyroid Association Guidelines.

The 2015 American Thyroid Association (ATA) guidelines recommended that low-risk, differentiated thyroid cancers (DTC) between 1 and 4cm may be treated with thyroid lobectomy alone. We sought to determine the effect of these guideline changes on the rate of completion thyroidectomy (CT) for low-risk DTC and factors influencing surgical decision-making. All patients from 2014 to 2018 who received an initial thyroid lobectomy at our institution with final pathology demonstrating DTC were included. Patients were divided into "pre" and "post" guideline cohorts (2014-2015 and 2016-2018, respectively). The rate of CT was compared between the two cohorts. Patient demographics and tumor characteristics were examined for association with CT. A total of 163 patients met study criteria: 63 patients in the 2014-2015 ("pre") and 100 in the 2016-2018 ("post") group. In the "pre" period, 41 (65.1%) patients received CT compared with 43 (43.0%) in the "post" period (p < 0.01)-a 34% decrease in the rate of completion surgery (p < 0.01). Of low-risk patients with DTC between 1 and 4cm in size, 17 of 35 (48.6%) received CT in the "pre" period compared with 15 of 60 (25.0%) in the post period-a 48.6% decrease in the rate of completion surgery (p = 0.02). Greater tumor size, capsular invasion, and multifocality were associated with CT in low-risk "post" guideline patients (p < 0.05 for all). The rate of CT decreased significantly by 48.6% for low-risk patients with DTC between 1 and 4cm, demonstrating recognition of the 2015 ATA guidelines. However, 25% of these patients underwent CT, suggesting additional factors influencing the decision for further treatment.

Risk of structural persistent disease in pediatric patients with low or intermediate risk differentiated thyroid cancer.

In pediatric patients with differentiated thyroid cancer (DTC), the risk of recurrence is high and the indication for postoperative 131I administration is still debated. The aim of this study was to assess the outcome in low and intermediate risk pediatric DTC patients. We retrospectively evaluated 45 pediatric patients with low or intermediate risk DTC, treated with surgery and 131I between 1992 and 2002 and with no detectable antithyroglobulin (Tg) antibodies. Follow-up was performed every 6-12 months with Tg blood level determination and imaging procedures. During follow-up (64 ± 53 months), 15 events occurred (33% cumulative event rate, with an annual event rate of 5% person years). Five of these patients were submitted to additional surgery and all these 15 patients underwent a second 131I treatment course. All patients were alive at the end of the follow-up. Structural persistent disease occurred more frequently in patients at intermediate risk (p < 0.01) and in those with Tg values after thyroid hormone withdrawal >10 ng/ml before 131I therapy (p < 0.01). At multivariate analysis, only a postoperative thyroid stimulating hormone-stimulated Tg level >10 ng/ml was an independent predictor of persistent disease. In pediatric patients with DTC, postoperative high stimulated Tg values (>10 ng/ml) should be taken into account for deciding the extent of both initial treatment and follow-up.

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.

Contemporary considerations in adjuvant radioiodine treatment of adults with differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a growing incidence worldwide. The initial conventional management is surgery, followed by consideration of 131 I treatment that includes three options. These are termed remnant ablation (targeting benign thyroid remnant), adjuvant (targeting presumed microscopic DTC) and known disease (targeting macroscopic DTC) treatments. Some experts mostly rely on clinicopathologic assessment for recurrence risk to select patients for the 131 I treatment. Others, in addition, apply radioiodine imaging to guide their treatment planning, termed theranostics (aka theragnostics or radiotheragnostics). In patients with low-risk DTC, remnant ablation rather than adjuvant treatment is generally recommended and, in this setting, the ATA recommends a low 131 I activity. 131 I adjuvant treatment is universally recommended in patients with high-risk DTC (a primary tumor of any size with gross extrathyroidal extension) and is generally recommended in intermediate-risk DTC (primary tumor >4 cm in diameter, locoregional metastases, microscopic extrathyroidal extension, aggressive histology or vascular invasion). The optimal amount of 131 I activity for adjuvant treatment is controversial, but experts reached a consensus that the 131 I activity should be greater than that for remnant ablation. The main obstacles to establishing timely evidence through randomized clinical trials for 131 I therapy include years-to-decades delay in recurrence and low disease-specific mortality. This mini-review is intended to update oncologists on the most recent clinical, pathologic, laboratory and imaging variables, as well as on the current 131 I therapy-related definitions and management paradigms, which should optimally equip them for individualized patient guidance and treatment.

Microscopic Positive Tumor Margin Increases Risk for Disease Persistence but Not Recurrence in Patients with Stage T1-T2 Differentiated Thyroid Cancer.

Introduction Differentiated thyroid cancer (DTC) has an overall excellent prognosis. Patients who develop recurrent disease have a more unfavorable disease course than those with no recurrence. Higher recurrence rates are seen with incomplete surgical resection and gross positive margins. It is unclear whether microscopic positive margin affects disease recurrence rates as much as grossly positive margin. Aim of the Study. To assess whether microscopic positive margin is an independent predictor of disease recurrence in patients with overall low-risk DTC. Patients and Methods. We conducted a retrospective single-center institutional review of 1,583 consecutive patients' charts from 1995–2013 using the Canadian Thyroid Cancer Consortium Registry. We included adult patients with nonmetastasizing T1 and T2 DTC with a minimum of three years follow-up. Univariate and multivariate analyses were used to study factors that may influence the risk of persistent/recurrent disease. Strict definitions of persistent versus recurrent disease were applied. Results 963 patients (152 men and 811 women) were included in the study with a mean age of 46 years. Microscopic positive margins were present in 12% of the specimens and were associated with an increased rate of persistent disease (8% versus 2% in the controls) but not with an increased risk of recurrent disease (1% in both groups). T2 tumors had a significantly higher incidence of positive margins than T1 tumors (48% versus 36%) and significantly higher nodal staging. Conclusions Microscopic positive margin in the histopathology report in patients with low-risk DTC was associated with a higher rate of persistent disease but did not increase the risk of disease recurrence. A close follow-up of biomarkers and occult residual cancerous lesions is needed, especially in the first year. Further studies are needed to determine whether additional therapeutic measures to prevent recurrence are indicated in T1 and T2 DTC with positive microscopic surgical margins.

Efficacy of low radioiodine activity versus intermediate-high activity in the ablation of low-risk differentiated thyroid cancer.

The aim of our study was to compare the efficacy of thyroid remnant ablation using low (1.1 GBq) and intermediate-high radioiodine (RAI) activity (1.85-3.7 GBq) in low-risk differentiated thyroid carcinoma (DTC) and to evaluate the staging role of the whole body scan (WBS) in detection extrathyroidal disease. We retrospectively included 277 patients who underwent total thyroidectomy and RAI for low-risk DTC and divided them in two groups according to RAI activity at ablation: group 1 (n = 174) treated with low activity (1.1 GBq), and group 2 (n = 103) with intermediate-high activity (1.85-3.7 GBq). To evaluate the successful ablation rate, the WBS 1 year after RAI was visually interpreted using a three-point scale: score 0 in case of absence of visible RAI uptake in thyroid bed; score 1 in presence of faint uptake in the thyroid bed; and score 2 in case of significant RAI uptake in thyroid bed. The success ablation rate was significantly higher in group 2 than group 1 (p < 0.001) with the presence of a positive WBS (score 1-2) in 65% low-activity group and 33% in intermediate-high group. Considering response to therapy categories, excellent response rate was significantly higher in group 2 (p = 0.020), while indeterminate response was higher in group 1 (p value = 0.005). Post RAI imaging revealed extrathyroidal uptake in 27 cases: 17 laterocervical nodal and 10 distant metastases. In both groups similar detection rate of nodal and distant metastases were recognized without any statistical difference. The ablation rate with intermediate-high RAI activity (1.85-3.7 GBq) was better than with a low activity (1.1 GBq). First WBS may help to recognize nodal and distant metastases in about 10% of cases changing clinical stage and subsequent management.

An update on the management of low-risk differentiated thyroid cancer.

Low-risk papillary cancers, which represent the vast majority of thyroid cancers diagnosed today, do not require aggressive treatment or follow-up. Initial treatment consists of a total thyroidectomy without prophylactic lymph node dissection. A hemithyroidectomy is an alternative in some patients with an intrathyroidal tumor and with a normal contralateral lobe at pre-operative neck ultrasonography. The use of post-operative radioiodine should be restricted to selected patients. Follow-up at 6-18 months is based on serum thyroglobulin (Tg), Tg-antibody determination and neck ultrasonography. In the absence of any abnormality (excellent response to treatment), the risk of recurrence is extremely low and follow-up may consist of serum TSH monitoring that is maintained in the normal range, and a Tg and Tg-antibody titer determination every year. There is no need for referral to a specialized center. In patients with detectable serum Tg or detectable Tg antibodies, the trend over time of these markers on levothyroxine treatment will dictate subsequent follow-up: a decreasing trend is reassuring, but an increasing trend should lead to imaging, starting with neck ultrasonography.

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.

Extent of Surgery for Low-Risk Differentiated Thyroid Cancer.

Although the incidence of thyroid cancer is increasing, survival remains unchanged. Due to concern for overtreatment, surgical management of thyroid cancer has evolved. Papillary thyroid microcarcinoma measuring 1cm or smaller are considered very low risk and can be managed with either thyroid lobectomy or active surveillance. Total thyroidectomy is no longer recommended for these cancers unless there is evidence of metastasis, local invasion, or aggressive disease. Recommendations for low-risk differentiated thyroid cancer measuring 1 cm to 4cm remain controversial. This article explores the controversies over the extent of surgery for patients with very low-risk and low-risk differentiated thyroid cancer.

SUN-623 Markedly Elevated Thyroglobulin Levels in a Patient with Papillary Thyroid Carcinoma in the Setting of Hashimoto’s Thyroiditis and Negative Imaging: A Case Report

Background: Despite the high survival rate of differentiated thyroid cancer (DTC), recurrence may occur. After tumor resection, radioactive iodine (RAI) can be considered if necessary, and serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels as well as neck ultrasound (US) are the main tools used for surveillance. Discrepancies between laboratory testing and imaging findings may present. This can occur due to assay interference or less commonly in the setting of Hashimoto’s thyroiditis (HT). We present the case of a patient with low risk DTC and chronic markedly elevated Tg levels in the setting of no evidence of structural disease and a history of HT. Clinical Case: A 72-year-old woman with a history of primary hypothyroidism and non-toxic multinodular goiter underwent left hemithyroidectomy in 2012. Pathology revealed incidentally discovered papillary thyroid microcarcinoma, 0.2 cm with negative margins and negative lymphovascular invasion in a background of chronic lymphocytic thyroiditis. Due to the low risk of recurrence, she did not undergo completion thyroidectomy nor RAI. Post operatively, she was noted to have a serum Tg level of 752 ng/mL (no reference range), TgAb <20 IU/mL (reference range < or =1 IU/mL), with a TSH of 4.3 mIU/L (reference range 0.4-4.5 mIU/L). Since then she has remained with elevated Tg levels ranging from 236 to 786 ng/mL, including Tg levels by liquid chromatography mass spectrometry (LC/MS) and negative TgAb. She did have a thyroid peroxidase antibody measured at > 1000 IU/mL (reference range < 35 IU/mL). Imaging included multiple serial neck US negative for right hemi-thyroid nodules and no suspicious lymph nodes. CT scan of the chest was negative. PET/CT showed FDG uptake in the right thyroid lobe (SUV max 8.6) without any evidence of FDG avid tumor in the rest of the body. She is otherwise clinically stable on levothyroxine therapy to maintain her TSH between 0.5 to 2 mIU/L. Discussion: This patient presents persistently elevated serum Tg levels significantly above what is expected for a patient status post hemithyroidectomy. We suspect the most likely explanation for this finding is her underlying HT causing autoimmune thyroid tissue destruction. Moving forward, we suggest measuring heterophilic antibodies and remeasuring Tg level with serial dilutions to rule out the possibility of assay interference. This case is especially challenging as she has an intact hemi-thyroid, which limits some of the imaging diagnostic modalities available. HT has been shown to result in a diffuse distribution of FDG uptake in the thyroid gland on PET/CT as seen in this case. Conclusion: Even though in most cases with DTC Tg levels serve as a sensitive and reliable tumor marker, in the setting of elevated thyroglobulin levels and no clear structural evidence of disease, it is important to consider other possible etiologies and not only disease recurrence.

MON-558 Radioiodine Is Not Associated with Quality of Life Outcomes in Early Stage Thyroid Cancer Survivors, a Matched-Pair Analysis.

Background: Radioiodine ablation (RAI) is often given as adjuvant therapy following thyroidectomy for differentiated thyroid cancer (DTC). The benefits of RAI are unclear in low-risk DTC, and the effects of RAI on health-related quality of life (HRQoL) are not well described. We hypothesized RAI would be associated with lower HRQoL in survivors of DTC. Methods: A matched-pair analysis was performed using DTC survivors >18 years of age recruited from a thyroid cancer support group. Demographics, clinical features, treatments and surgical complications were self-reported via online survey. Postoperative dysphonia and dysphagia, and post-RAI xerostomia and dysphagia were assessed using Likert scale. HRQoL was evaluated using PROMIS-29 domains of anxiety, depression, fatigue, pain, physical function, sleep disturbance, and social role function. Stage I respondents who received RAI were matched for age, sex, race, and years since diagnosis against those who did not receive RAI. PROMIS T-scores were compared between RAI and no RAI groups by univariate analysis and Wilcoxon rank-sum test. A mean T-score difference of 3 or more was considered clinically significant. Categorical outcomes were assessed via Fisher’s exact test, alpha set at 0.05. Results: 138 pairs were matched for extent of surgery, stage, age, sex, race, and years since diagnosis. Mean age was 43.7+/-11.6 and 44.8+/-10.9 years, and mean time since surgery was 2.6+/-2.6 and 2.7+/-2.5 years for RAI and no RAI groups, respectively. There was no difference in incidence of the surgical complications of hypocalcemia (p=0.76), infection (p=0.61), dysphonia (p=0.87), or dysphagia (p=0.74) between the RAI and no RAI groups. There was no significant difference between mean PROMIS T-scores in any PROMIS domains. In those respondents reporting normal preoperative voice and swallowing (86 pairs), the mean T-score in the pain domain in the RAI group (53.9+/-10.3 vs 49.8+/-10.5; p=0.009) was clinically and statistically significantly higher than the no RAI group. 9.3% reported chronic xerostomia and dysphagia that developed after RAI. Conclusions: This is the first study to use PROMIS measures to evaluate the association between RAI and HRQoL in early stage DTC. In a matched-pair analysis of DTC survivors with stage 1 disease, no statistically significant difference was identified in HRQoL between groups that did or did not receive RAI. In subset analysis of respondents who reported normal preoperative voice and swallowing, RAI was associated solely with worse scores in the PROMIS pain domain.​ Further investigation is needed to describe why patients treated with RAI experience more pain.

Is hemi-thyroidectomy adequate in low risk differentiated thyroid cancer?

In low-risk differentiated thyroid carcinoma (LRDTC), appropriate surgical procedure in terms of hemi/total thyroidectomy (TT) has been an area of debate. The aim was to determine whether in LRDTC patients, hemithyroidectomy would be an adequate treatment, determine incidence of disease in contralateral lobe and evaluate the effect of radioactive iodine ablation (RAIA). Retrospective study was done from 2008 to 2014 at a single institution. Preoperative ultrasound (USG) and histopathology reports of all LRDTC patients following total/completion thyroidectomy were recorded. Details of postthyroidectomy, thyroid whole body scan, and stimulated serum thyroglobulin (sTg) levels were also documented and results analyzed. A total of 114/562 patients met inclusion criteria. Of these, 25/114 (22%) underwent hemithyroidectomy followed by a completion thyroidectomy while remaining 89/114 (78%) underwent TT initially. Preoperative USG detected single-lobe involvement in 44 patients; however, among them, histopathology revealed bilateral lobe disease in 17 (38.6%). There was a significant fall of sTg level following RAIA as compared to that before RAIA in T1b-T2 (P = 0.009 and 0.012, respectively). Median follow-up was 2 years (range: 1–7 years) with no distant metastasis or deaths recorded till 2017, except for one local recurrence 4 years after RAIA. In conclusion, the role of TT in LRDTC patients is important as 46% of patients were found to have tumor in contralateral lobe as well. Significant fall in sTg levels following RAIA justifies RAIA of remnant lobe even in LRDTC (T > 1a). It facilitates early detection of recurrence when sTg alone is used for follow-up.