Clinical Outcomes of Radioactive Iodine Redifferentiation Therapy in Previously Iodine Refractory Differentiated Thyroid Cancers.

Objective: Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage 131I therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients who underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT. Methods: This is a retrospective case series of 33 patients with response evaluation criteria in solid tumors (RECIST)-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic (Rochester, MN). All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone, or combination BRAF-MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high-dose 131I therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTCs), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared with 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at 3 weeks on drug(s) alone. The redifferentiated subgroup, following high-dose 131I therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy, and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer, 15.1% (5/33) died, and all had redifferentiated following RDT and received 131I therapy. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following 131I therapy in select patients with RAIR-DTC, particularly those with RAS-driven "follicular" phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation.

Analysis of the Influencing Factors of Tumor Volume, Body Immunity, and Poor Prognosis after 125I Particle Therapy for Differentiated Thyroid Cancer.

Objective: To analyze the influencing factors of tumor volume, body immunity, and poor prognosis after 125I particle therapy for differentiated thyroid cancer. Methods: A total of 104 patients with differentiated TC who were treated with 125I particles during January 2020 to January 2021 was picked. These subjects were graded as low-dose group (80Gy-110Gy) and high-dose group (110Gy-140Gy) according to the minimum dose received by 90% of the target volume (D90) after surgery. The tumor volume before and after treatment was compared, and fasting venous blood was collected before and after treatment. The content of thyroglobulin (Tg) was detected by electrochemiluminescence immunoassay. The levels of absolute lymphocyte count (ALC), lymphocytes, neutrophils, and monocytes were detected on automatic blood cell analyzer. The lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) were calculated. The changes in the condition of patients were closely observed, and the occurrence of adverse reactions in the two groups were compared. The risk factors influencing the efficacy of 125I particle therapy for differentiated TC were analyzed through multivariate logistic regression analysis. Results: The total effective rate of patients in the low- and high-dose groups was 78.85% and 82.69%, respectively (P > 0.05). Compared with the pretreatment period, the tumor volume and Tg level in both groups were much lower (P < 0.05), and the differences in tumor volume and Tg level had no statistically significant difference between the two groups before and after treatment (P > 0.05). At 1 week of the treatment, the total incidence of adverse reactions such as nausea, radiation gastritis, radiation parotitis, and neck discomfort was obviously higher in the high-dose group than in the low-dose group (P < 0.05). At 1 month of treatment, the incidence of adverse reactions such as nausea was markedly higher in the high-dose group than in the low-dose group (P < 0.05). After treatment, serum NLR and PLR contents were memorably elevated and LMR level was sharply decreased in both groups, and serum NLR and PLR contents were higher and LMR content was lower in the high-dose group than in the low-dose group (P < 0.05). Multivariate logistic regression analysis showed that the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage of III~IV, distant metastasis, and high TSH level before 125I particle treatment were all risk factors related to the efficacy of 125I particle treatment of TC (P < 0.05). Conclusion: The efficacy of low-dose and high-dose 125I particles in the treatment of differentiated thyroid cancer is comparable, among which low-dose 125I particles have fewer adverse effects and have less impact on the immunity of the body, which is well tolerated by patients and can be widely used in clinical practice. In addition, the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage III~IV, distant metastasis, and high TSH level before 125I particle treatment are all risk factors that affect the poor effect of 125I particles on thyroid cancer treatment, and early monitoring of the above index changes can help evaluate the prognosis.

The Prognostic Impact of Extent of Vascular Invasion in Follicular Thyroid Carcinoma.

BACKGROUND: Encapsulated angioinvasive follicular thyroid carcinoma (EAFTC) is associated with an increased risk of distant metastasis and reduced survival compared to minimally invasive follicular thyroid carcinoma (MIFTC). There is controversy regarding the extent of surgery and adjuvant radioactive iodine therapy for angioinvasive follicular thyroid carcinoma when stratified by number of foci of angioinvasion. METHODS: All follicular thyroid carcinoma cases from 1990-2018 were identified from a thyroid cancer database. Primary outcomes were distant metastasis-free survival (DMFS) and disease-specific survival (DSS) with factors of interest being age, gender, tumour size, treatment, foci of angioinvasion and histological subtype. RESULTS: A total of 292 cases were identified; 139 MIFTC, 141 EAFTC and 12 widely invasive follicular thyroid carcinoma (WIFTC). Over a follow-up period of 6.25 years, DMFS was significantly reduced (p < 0.001) with 14.2% (EAFTC) and 50% of WIFTC developing metastasis. The risk of metastasis in EAFTC with ≥ 4 foci of angioinvasion was 31.7% (HR = 5.89, p = 0.004), 6.3% for EAFTC with < 4 foci of angioinvasion (HR = 1.74, p = 0.47), compared to 3.6% MIFTC. Age ≥ 50 years (HR = 4.24, p = 0.005) and tumour size (HR = 1.27, p = 0.014) were significantly associated with increased risk of distant metastasis. DSS was reduced significantly (p < 0.001), with 7.8% EAFTC patients dying of disease. For EAFTC patients, DSS was 96.8% for < 4 foci and 82.6% for ≥ 4 foci of angioinvasion (p = 0.003). CONCLUSION: EAFTC is at increased risk of distant metastasis related to the extent of angioinvasion. Tumours with < 4 foci of angioinvasion should be considered for a total thyroidectomy, particularly in older patients.

Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC).

PURPOSE: Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC. METHODS: Five patients (all female, mean age 62 ± 8 years, ranged from 51 to 69 years) with distant metastatic DTC (dmDTC) after total thyroidectomy (TTE) and neck lymph node dissection were treated with apatinib at a dose 500 mg per day after 18F-Fluorodeoxyglucose (18F-FDG) PET/CT. The effects of apatinib on DTC were evaluated at 4 ± 1 months after treatment with apatinib. RAI therapy was then initiated. The response to apatinib and the combination therapy with RAI treatment was evaluated by Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1) and metabolic activity using serum thyroglobulin (Tg) and 18F-FDG PET/CT. RESULTS: Positive 18F-FDG PET/CT results were found in all patients before apatinib therapy. The immunohistochemical analysis of primary tumour tissues showed high expression of vascular endothelial growth factor receptor-2 (VEGFR-2). Four patients with follicular thyroid carcinoma (FTC) showed partial response (PR) with significant decrease in tumour size and maximum standardized uptake value (SUVmax) after 4 ± 1 month's treatment with apatinib. Further significant reduction of tumour size and SUVmax were observed in three patients after combination therapy with apatinib and RAI. Only one patient with both FTC and papillary thyroid cancer (PTC) demonstrated progressive disease (PD) after treatment with apatinib alone, however, a decrease in tumour size and SUVmax as well as serum Tg levels was achieved after the combination with RAI therapy and apatinib. CONCLUSIONS: Apatinib had significant antitumour effects on progressive distant metastatic DTC. Moreover, beneficial synergistic and complementary effects were shown when apatinib combined with RAI therapy. CLINICAL TRIAL REGISTRATION: NCT04180007, Registered November 26, 2019.

Advanced RAI-refractory thyroid cancer: an update on treatment perspectives.

During the last decades, the knowledge on follicular cell-derived thyroid cancer molecular biology has led to the evolution of a number of novel therapies for these tumors, mainly tyrosine kinase inhibitors. Lenvantinib, sorafenib and recently cabozantinib have been approved for differentiated thyroid cancer (DTC), while larotrectinib and entrectinib for neurotrophic-tropomyosin receptor kinase-fusion thyroid cancer. For radioiodine (RAI) refractory DTCs ongoing research aims to identify agents that may restore RAI-avidity via redifferentiation protocols (vemurafenib or dabrafenib and trametinib) or combination treatments. These treatments are based on the tumor molecular signature. The treatment with targeted therapies has changed the therapeutic strategies and the disease prognosis, however drug resistance remains the main reason for treatment failure. Thus, the understanding of both molecular pathways implicated in tumorigenesis, and tumoral escape mechanisms, are of paramount significance for the development of new therapies for DTC. The present review focuses on the molecular landscape of DTC, the approved targeted therapies as well as the mechanisms of drug resistance. Furthermore, it points to the ongoing research and the future perspectives for the development of more efficient drugs for DTC.

Thyroid cancer incidence and trends by demographic and tumor characteristics in Oran, Algeria: 1993-2013, a population-based analysis.

OBJECTIVES: Incidence rates of thyroid cancer have dramatically increased over recent decades in many countries, particularly the papillary histotype and microcarcinomas. We examined thyroid cancer incidence and trends by demographic and tumor characteristics based on 1443 patients with thyroid cancer diagnosed between 1993 and 2013 in Oran district, in Northwest Algeria. METHODS: All thyroid cancer cases were abstracted from medical records and pathology reports and classified according to the International Classification for Diseases in Oncology, third edition. Age-specific, age-standardized incidence rates per 100 000 person-years, and annual percent changes (APC) in the incidence were calculated. RESULTS: Age-standardized incidence was 11.7 per 100 000 for women and 2.0 per 100 000 for men. Thyroid cancer incidence increased over time significantly in women (APC: +3.72%; P < 0.05), mostly due to an increased incidence of the papillary histotype (APC: +5.48%; P < 0.05), and microcarcinomas (APC: +17.34%; P < 0.05). During the same time period, the incidence of follicular thyroid carcinomas decreased (APC: -3.74%; P < 0.05). CONCLUSIONS: The results of our study showing an upward trend of thyroid cancer incidence driven largely by increases in the papillary histotype are consistent with previous studies. The higher increase has coincided with the introduction of fine needle aspiration and thyroid ultrasound in the 1990s, and may have led to overdiagnosis. However, the increased papillary-to-follicular ratio observed over time is possibly a late effect of iodine supplementation implemented in Algeria in 1967 to combat endemic goiter. Further larger-scale population-based research is needed to gain insight into thyroid cancer etiology.

The diagnostic challenge of coexistent sarcoidosis and thyroid cancer - a retrospective study.

BACKGROUND: Sarcoid lesions may mimic metastatic disease or recurrence in thyroid cancer (TC) patients as both diseases may affect the lungs and lymph nodes. We present the first study to systematically evaluate the clinical course of patients with (TC) after adjuvant radioactive iodine therapy (RIT) and concomitant sarcoidosis of the lung or the lymph nodes. METHODS: We screened 3285 patients and retrospectively identified 16 patients with TC (11 papillary thyroid cancer (PTC), 3 follicular thyroid cancer (FTC), 1 oncocytic PTC, 1 oncocytic FTC) and coexisting sarcoidosis of the lung and/or the lymph nodes treated at our institute. All patients had undergone thyroidectomy and initial adjuvant RIT. Challenges in diagnosing and the management of these patients were evaluated during long term follow-up (median 4.9 years (0.8-15.0 years)). RESULTS: Median age at first diagnosis of TC was 50.1 years (33.0-71.5 years) and of sarcoidosis 39.4 years (18.0-63.9 years). During follow-up, physicians were able to differentiate between SA and persistent or recurrent TC in 10 of 16 patients (63%). Diagnosis was complicated by initial negative thyroglobulin (Tg), positive Tg antibodies and non-specific imaging findings. Histopathology can reliably distinguish between SA and TC in patients with one suspicious lesion. CONCLUSION: Physicians should be aware of the rare coexistence of sarcoidosis and TC. Lymphadenopathy and pulmonary lesions could be metastases, sarcoidosis or even a mix of both. Therefore, this rare patient group should receive a thorough work up including histopathological clarification and, if necessary, separately for each lesion.

Nutritional status and follicular-derived thyroid cancer: An update.

The incidence of differentiated thyroid cancer has been increasing in the last decades all over the world. Such a steady growth cannot be entirely attributable to more intensive thyroid nodule screening and more sensitive diagnostic procedures. Several environmental factors have changed with sufficient rapidity in the same time frame and may represent credible candidates for this increase. They include modified iodine intake, lifestyle-associated risk factors, exposure to various toxic compounds, pollutants and xenobiotics, nutritional deficiencies, eating habits and comorbidities. Foremost, nutritional patterns have gained high interest as possible promoters and modifiable risk factors for thyroid cancer in recent years. The aim of this narrative review is to focus on the relationship between thyroid cancer and nutritional factors, dietary habits and obesity. Low iodine intake has been associated to increased risk of thyroid cancer, favoring the development of more aggressive histotypes. Moreover, correction of iodine deficiency can shift thyroid cancer subtypes toward less aggressive forms, without affecting the overall risk for cancer. Actually, evidence regarding the association between selenium and vitamin D deficiency and thyroid cancer is very limited, despite their well-known anti-cancer potentials, and the clinical usefulness of their supplementation is still uncertain in this setting. Albeit the relationship between single foods and thyroid cancer is difficult to examine, fish and iodine-rich foods, vegetables, and fruits might exert protective effects on thyroid cancer risk. Conversely, no clear association has been found for other foods to date. Lastly, a clear association between obesity and the risk of thyroid cancer, with more aggressive behavior, seems to emerge from most studies, likely involving variations in thyroid function and chronic inflammation mediated by cytokines, insulin, leptin and adiponectins. Although no definite association between dietary factors and thyroid cancer has been firmly established so far, some nutritional patterns, together with excessive weight, seem to play a relevant role in thyroid cancer carcinogenesis as well as in its severity and aggressiveness. These effects may play an additive role to the well-established one exerted by environmental carcinogens, such as pollutants and radiation exposure.

Clinical impact of follicular oncocytic (Hürthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma.

PURPOSE: There are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT). METHODS: We retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival. RESULTS: Before and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0-19.8) vs. 20.1 years (95% CI 19.0-21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309-0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years). CONCLUSIONS: Our study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Epidemiology and Long-Term Outcomes in a Strictly Defined Cohort.

Background: A subset of encapsulated/circumscribed follicular variant of papillary thyroid carcinoma (FVPTC) was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reduce overtreatment of a low-risk tumor. Study objectives were to describe the epidemiology and long-term outcomes of NIFTP in a high-volume, urban, tertiary referral center. Methods: Among patients enrolled in the Boston Medical Center (BMC) Thyroid Cancer Registry, 110 cases of FVPTC underwent index thyroid surgery at BMC between 2000 and 2016. Historically, BMC pathologists assess all malignant nodules using sections ≤0.3 cm with evaluation of the entire nodule and capsule. After review of pathology reports to identify potential NIFTPs, slides were rereviewed using criteria established by the NIFTP Working Group in 2016 and 2018. We evaluated interobserver reliability using Cohen's Kappa coefficient. Results: Among 110 FVPTCs, 15 (13%) met NIFTP criteria; 11 women and 4 men, age range 31-64 (mean 47.5) years. Mean tumor diameter was 1.7 cm (compared with 2.2 cm for FVPTC). Among NIFTP cases, there were no lymph node metastases, distant metastases, or tumor recurrences. All NIFTP cases were American Thyroid Association (ATA) low risk compared with only 68% of FVPTC (p = 0.011). Among FVPTCs, 14% had positive lymph nodes at index operation. Four patients (4%) had distant metastases. Mean follow-up time was 46 and 69 months for FVPTC and NIFTP, respectively. Among FVPTCs with an excellent response to therapy (2015 ATA guidelines), there were no recurrences. Just over half (n = 8) of patients with NIFTP received postoperative radioactive iodine (RAI) therapy. Concordance between pathologists was high for ruling out NIFTP (75%), but only 36% for ruling in NIFTP. Overall, for NIFTP designation, Cohen's Kappa was 0.39, which is considered fair. Conclusions: Although this is a relatively small cohort, all NIFTP specimens underwent updated pathology review consistent with current guidelines; mean follow-up was nearly 6 years. NIFTP represents a small fraction of the total papillary neoplasia diagnosed at this tertiary referral center (2.3%). None of the NIFTP cohort experienced an adverse oncologic event, and there were no regional or distant metastases. Over 50% of patients with NIFTP received RAI. Thus, the NIFTP reclassification may substantially reduce the number of patients who require adjuvant therapies, such as completion surgery or RAI.

[From thyroid nodules to thyroid cancer]. / Vom Schilddrüsenknoten zum Schilddrüsenkarzinom.

From thyroid nodules to thyroid cancer Abstract. The prevalence of thyroid nodules is around 1 % per life year, whereas 5 % of the nodules are malignant. Primary diagnostics consist of examination of TSH and cervical ultrasound. Depending on the findings, additional laboratory investigations, a scintigraphy or a biopsy are indicated. In case of thyroid cancer, the primary treatment is usually surgery. There are at least nine different clinical guidelines worldwide to provide a standardized perioperative management, whereas the guidelines of the German Association of Endocrine Surgeons (CAEK) and the American Thyroid Association (ATA) are most frequently used in the German speaking part of Europe. Individual therapy concepts are determined at the interdisciplinary endocrinological tumour boards. The indication for postoperative radioiodine treatment or thyroid hormone supplementation in TSH suppression dose in case of differentiated (papillary or follicular) thyroid cancer is evaluated according to the American Thyroid Association (ATA) risk stratification.

[Indications and results of radioiodine treatment of differentiated thyroid cancer]. / Indikationen und Ergebnisse der Radiojodtherapie beim differenzierten Schilddrüsenkarzinom.

BACKGROUND: Malignant tumors of the thyroid gland are the most frequent malignant endocrine neoplasms, comprising approximately 1% of all malignant tumors. In recent years there has been a clear rise in the incidence of differentiated thyroid carcinomas (DTC), especially small papillary carcinomas. OBJECTIVE: Indications for and results of radioiodine treatment (RAI) of DTC. MATERIAL AND METHODS: A review of the current literature and guidelines of RAI in DTC was carried out. RESULTS: The use of RAI is the most important adjuvant treatment option for DTC and is generally well-tolerated. CONCLUSION: Due to the combination of surgery and RAI the DTC has a very good prognosis compared with other cancers, with an average survival rate of more than 90%.

Randomised comparison of 1.1 GBq and 3.7 GBq radioiodine to ablate the thyroid in the treatment of low-risk thyroid cancer: a 13-year follow-up.

Purpose: The optimal activity of radioiodine (I-131) administered for ablation therapy in papillary and follicular thyroid cancer after thyroidectomy remains unknown in a long-term (> 10 year) follow-up. Some, shorter follow-up studies suggest that activities 1.1 GBq and 3.7 GBq are equally effective. We evaluated the long-term outcomes after radioiodine treatment to extend current knowledge about the optimal ablative dose of I-131.Methods: One hundred and sixty consecutive adult patients (129 females, 31 males; mean age 46 ± 14 y, range 18-89 y) diagnosed with histologically confirmed differentiated thyroid cancer, were randomised in a prospective, phase III, open-label, single-centre study, to receive either 1.1 GBq or 3.7 GBq of I-131 after thyroidectomy. At randomisation, patients were stratified according to the histologically verified cervical lymph node status and were prepared for ablation using thyroid hormone withdrawal. No uptake in the whole-body scan with I-131 and serum thyroglobulin concentration less than 1 ng/mL at 4-8 months after treatment was considered successful ablation.Results: Median follow-up time was 13.0 years (mean 11.0 ± 4.8 y; range 0.3-17.1 y). Altogether 81 patients received 1.1 GBq with successful ablation in 45 (56%) patients. In the original study, thirty-six patients (44%) needed one or more extra administrations to replete the ablation. Of these, 4 (8.9%) and 5 (14%) patients relapsed during the follow-up, respectively. Of the 79 patients treated with 3.7 GBq 45 (57%) had successful ablation after one administration of radioiodine and 34 (43%) needed several treatments. Of these, 2 (4.4%) and 9 (26.5%) patients relapsed, respectively. The groups did not differ in the proportion of patients relapsing (p = .591).Conclusion: During follow-up of median 13 years, 3.7 GBq is not superior to 1.1 GBq in the radioiodine treatment after thyroidectomy in papillary and follicular thyroid cancer.

Unexpected radioactive iodine accumulation on whole-body scan after I-131 ablation therapy for differentiated thyroid cancer.

We retrospectively evaluated the frequency of unexpected accumulation of radioactive iodine on the post-therapy whole-body scan (Rx-WBS) after radioactive iodine (RAI) ablation therapy in patients with differentiated thyroid cancer (DTC). We searched our institutional database for Rx-WBSs of DTC patients who underwent RAI ablation or adjuvant therapy between 2012 and 2019. Patients with distant metastasis diagnosed by CT or PET/CT before therapy, and those had previously received RAI therapy were excluded. In total, 293 patients (201 female and 92 male, median age 54 years) were selected. Two nuclear medicine physicians interpreted the Rx-WBS images by determining the visual intensity of radioiodine uptake by the thyroid bed, cervical and mediastinal lymph nodes, lungs, and bone. Clinical features of the patients with and without the metastatic accumulation were compared by chi-square test and median test. Logistic regression analyses were performed to compare the association between the presence of metastatic accumulation and these clinical factors. Eighty-four of 293 patients (28.7%) showed metastatic accumulation. Patients with metastatic RAI accumulation showed a significantly higher frequency of pathological N1 (pN1) and serum thyroglobulin (Tg) > 1.5 ng/ml under TSH stimulation (p = 0.035 and p = 0.031, respectively). Logistic regression analysis indicated that a serum Tg > 1.5 ng/ml was significantly correlated with the presence of metastatic accumulation (odds ratio = 1.985; p = 0.033). In conclusion, Patients with Tg > 1.5 ng/ml were more likely to show metastatic accumulation. In addition, the presence of lymph node metastasis at the initial thyroid surgery was also associated with this unexpected metastatic accumulation.

Preoperative Vitamin D Supplementation in Patients With Vitamin D Deficiency Undergoing Total Thyroidectomy.

BACKGROUND: Transient hypocalcemia due to parathyroid gland or vessel manipulation is a common complication following thyroidectomy. Considering the role of 25-hydroxyvitamin D (25(OH)D) in calcium hemostasis, this study aimed to evaluate the effect of preoperative vitamin D supplementation on hypocalcemia incidence in thyroidectomy patients. METHODS: In this randomized clinical trial, 100 patients scheduled for total thyroidectomy and suffering from preoperative moderate or severe vitamin D deficiency were enrolled. Patients were randomly allocated to either study or control groups using the sealed envelope method. Patients in the study group received vitamin D3 50,000-unit pearl weekly for 4 weeks prior to the operation. The control group received placebo. Total and ionized serum calcium levels were checked before surgery, the day after surgery, and 2 weeks postoperatively. RESULTS: No significant difference was observed in terms of demographic data. During serial total calcium checks (5 episodes), total calcium levels changed significantly in patients who had received vitamin D supplements compared to the control group (P = 0.043). Symptomatic hypocalcemia incidence was significantly lower in patients supplemented with 25-hydroxyvitamin D (25(OH)D) (P = 0.04). Also, the requirement for intravenous calcium administration in order to treat the hypocalcemia symptoms was significantly lower in the study in comparison to the control group (P = 0.03). CONCLUSIONS: Vitamin D supplementation in patients with vitamin D deficiency might lead to a lower incidence of early-onset symptomatic hypocalcemia; hence, requiring less calcium supplementation for the management of hypocalcemia.

[Implementation of the Bethesda system for reporting the thyroid cytopathology: study on 5 729 cases from a cancer center].

Objective: To analyze the data of the Bethesda system for reporting thyroid cytopathology applied in a comprehensive cancer center and to evaluate the diagnostic ability of fine needle aspiration (FNA). Methods: We retrospectively reviewed the medical records of 5 729 cases applying this reporting system at Cancer Hospital, Chinese Academy of Medical Sciences. The series were from 5 011 patients including 1 174 men and 3 837 women, and their median age was 45 years (range, 7-88 years). FNA results were correlated with final histological diagnosis after surgery and the accuracy of FNA diagnosis and the malignancy rates for each of categories were also analyzed. Results: Among 5 729 thyroid aspirates, aside from 456 (8.0%) cases with nondiagnostic or unsatisfactory (ND/UNS) outcomes, 1 055 (18.4%) cases were benign, 409 (7.1%) cases showed atypical of undetermined significance or follicular lesions with undetermined significance (AUS/FLUS), 80 (1.4%) cases were follicular neoplasm or suspicious for follicular neoplasm (FN/SFN), 982 (17.1%) cases were suspicious for malignancy (SUS), and 2 747 cases were malignant (47.9%). Of 5 729 cases, 3 239 had received thyroidectomies after FNA, 95.99% of them were proven histologically to be malignant, with following malignancy rates in individual FNA categories: ND/UNS 75.00%; benign 40.91%; AUS/FLUS 77.67%; FN/SFN 41.67%; SUS 96.86%; and malignant 99.96%. FNA predicted malignancy with sensitivity, specificity, accuracy, positive predictive value and negative predictive values of 98.8%, 60.5%, 97.7%, 98.9% and 59.1%, respectively. Conclusions: The data of the Bethesda reporting system indicates high proportion of malignant diagnosis and high risk of malignancy at all FNA diagnostic categories. FNA offers high diagnostic accuracy and positive predictive value for the diagnosis of thyroid diseases.

Ultrasound and cytological characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features compared to papillary carcinomas.

INTRODUCTION: NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features, formerly non-invasive encapsulated follicular variant of papillary thyroid carcinoma) has been removed from the carcinoma category because of its indolent character and good prognosis. This change impacts clinical and surgical management, since these tumors no longer require total thyroidectomy, or complementary radioactive iodine therapy for <4cm tumor. The aim of the present study was to identify preoperative ultrasound and cytological differences between NIFTP and papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A retrospective study included 81 patients who underwent total thyroidectomy or thyroid lobectomy with histologic diagnosis of PTC, NIFTP or invasive follicular variant of PTC (IFVPTC) between January 1st, 2016 and May 31st, 2018. Ultrasound and cytological data were analyzed and compared between NIFTP and non-NIFTP (PTC and invasive follicular variant of PTC). RESULTS: Fourteen NIFTPs, 67 PTCs, including 20 IFVPTCs, were included. In comparison with non-NIFTP PTC, nodules in NIFTP were more often isoechoic (69.2% vs. 17.4%; P=0.0007), with smooth borders (92.3% vs. 31.1%; P=0.0001) and TI-RADS score 2, 3 or 4a. Cytologically, NIFTPs were mainly in categories AUS/FLUS, FN and SusM of the Bethesda System for Reporting Thyroid Cytopathology. Only nuclear pseudo-inclusions were significantly associated with non-NIFTP (P=0.0031). CONCLUSION: NIFTP appears non-suspect on preoperative ultrasound and indeterminate on cytology. These differences with respect to PTC can guide diagnosis and surgical treatment.

The role of radioactive iodine in the management of patients with differentiated thyroid cancer - An oncologic surgical perspective.

With improved understanding of the biology of differentiated thyroid carcinoma its management is evolving. The approach to surgery for the primary tumour and elective nodal surgery is moving from a "one-size-fits-all" recommendation to a more personalised approach based on risk group stratification. With this selective approach to initial surgery, the indications for adjuvant radioactive iodine (RAI) therapy are also changing. This selective approach to adjuvant therapy requires understanding by the entire treatment team of the rationale for RAI, the potential for benefit, the limitations of the evidence, and the potential for side-effects. This review considers the evidence base for the benefits of using RAI in the primary and recurrent setting as well as the side-effects and risks from RAI treatment. By considering the pros and cons of adjuvant therapy we present an oncologic surgical perspective on selection of treatment for patients, both following pre-operative diagnostic biopsy and in the setting of a post-operative diagnosis of malignancy.

Evaluation of the 2015 ATA Guidelines in Patients With Distant Metastatic Differentiated Thyroid Cancer.

CONTEXT: Current American Thyroid Association (ATA) Management Guidelines for the treatment of differentiated thyroid cancer (DTC) stratify patients to decide on additional radioiodine (RAI) therapy after surgery, and to predict recurring/persisting disease. However, studies evaluating the detection of distant metastases and how these guidelines perform in patients with distant metastases are scarce. OBJECTIVE: To evaluate the 2015 ATA Guidelines in DTC patients with respect to 1) the detection of distant metastases, and 2) the accuracy of its Risk Stratification System in patients with distant metastases. PATIENTS AND MAIN OUTCOME MEASURES: We retrospectively included 83 DTC patients who were diagnosed with distant metastases around the time of initial therapy, and a control population of 472 patients (312 low-risk, 160 intermediate-risk) who did not have a routine indication for RAI therapy. We used the control group to assess the percentage of distant metastases that would have been missed if no RAI therapy was given. RESULTS: Two hundred forty-six patients had no routine indication for RAI therapy of which 4 (1.6%) had distant metastases. Furthermore, among the 83 patients with distant metastases, 14 patients (17%) had excellent response, while 55 (67%) had structural disease after a median follow-up of 62 months. None of the 14 patients that achieved an excellent response had a recurrence. CONCLUSIONS: In patients without a routine indication for RAI therapy according to the 2015 ATA Guidelines, distant metastases would initially have been missed in 1.6% of the patients. Furthermore, in patients with distant metastases upon diagnosis, the 2015 ATA Guidelines are an excellent predictor of both persistent disease and recurrence.

Multifocal recurrence on the transaxillary robotic thyroidectomy incision.

INTRODUCTION: Robotic thyroidectomy (RT) has been reported to achieve satisfactory results. However, its long-term oncological results have not been validated. The use of RT to treat thyroid cancer comprises specific risks that are not encountered with open thyroidectomy (OT). CASE SUMMARY: We report the case of a patient operated by two-stage RT for stage pT3a follicular carcinoma, followed by tumour seeding along the incision despite adjuvant Iodine-131 therapy and external beam radiotherapy. DISCUSSION: This case illustrates the limitations and insufficient perspective of RT for thyroid cancer, with the recent discovery of a risk of tumour seeding along the incision. Rigorous patient selection should help to avoid this risk of tumour seeding.