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The initial treatment for differentiated thyroid cancer includes appropriate surgery and radioactive iodine (RAI) therapy, followed by thyroid-stimulating hormone (TSH) suppression therapy as long-term management to prevent recurrence. RAI therapy following thyroidectomy has the three main purposes: remnant ablation, adjuvant therapy, and therapy for known disease. To optimize the goals and targets of RAI therapy, postoperative disease assessment, determination of recurrence risk, and consideration of various individual factors are necessary. The objectives of RAI therapy are determined based on the individual’s recurrence risk, and the administered activity of RAI is then determined according to these treatment objectives. Adequate stimulation of serum TSH is necessary before RAI therapy, and recombinant human TSH is widely used because of its advantage in reducing the risk of exacerbation of comorbidities associated with levothyroxine discontinuation and improving patients’ quality of life. Additionally, reducing iodine intake through appropriate low-iodine diet is necessary. Whole-body scans are conducted to assess the disease status after RAI therapy. If planar whole-body scans are inconclusive, additional single-photon emission computed tomography (SPECT)/CT imaging is recommended. Over the past decade, prospective randomized or retrospective clinical studies on the selection of candidates for RAI therapy, administered activity, methods of TSH stimulation, and advantages of SPECT/CT have been published. Based on these latest clinical research findings and recommendations from relevant overseas medical societies, this clinical practice guideline presents the indications and methods for administering RAI therapy after thyroidectomy.
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Based on the clinical, histopathological, and perioperative data of a patient with differentiated thyroid cancer (DTC), risk stratification based on their initial recurrence risk is a crucial follow-up (FU) strategy during the first 1–2 years after initial therapy. However, restratifiying the recurrence risk on the basis of current clinical data that becomes available after considering the response to treatment (ongoing risk stratification, ORS) provides a more accurate prediction of the status at the final FU and a more tailored management approach. Since the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and DTC, the latest guidelines that include the National Comprehensive Cancer Network clinical practice and European Association for Medical Oncology guidelines have been updated to reflect several recent evidence in ORS and thyroid-stimulating hormone (TSH) suppression of DTC. The current clinical practice guideline was developed by extracting FU surveillance after the initial treatment section from the previous version of guidelines and updating it to reflect recent evidence. The current revised guideline includes recommendations for recent ORS, TSH target level based on risk stratification, FU tools for detection of recurrence and assessment of disease status, and long-term FU strategy for consideration of the disease status. These evidence-based recommendations are expected to avoid overtreatment and intensive FU of the majority of patients who will have a very good prognosis after the initial treatment of DTC patients, thereby ensuring that patients receive the most appropriate and effective treatment and FU options.
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Radioactive iodine (RAI) therapy can effectively eliminate persistent or recurrent disease in patients with advanced differentiated thyroid cancer (DTC), potentially improving progression-free, disease-specific, and overall survival rates. Repeated administration of RAI along with thyroid-stimulating hormone (TSH) suppression is the mainstay of treatment for patients with distant metastases. Remarkably, one in three patients with distant metastases can be cured using RAI therapy and experience a near-normal life expectancy. Patients with elevated serum thyroglobulin and a negative post-RAI scan may be considered for empiric RAI therapy in the absence of structurally evident disease. However, in some patients, the iodine uptake capacity of advanced lesions decreases over time, potentially resulting in RAI-refractory disease. RAI-administered dose can be either empirically fixed high activities or dosimetry-based individualized activities for treatment of known diseases. The preparation method (levothyroxine withdrawal vs. recombinant human TSH administration) should be individualized for each patient.RAI therapy is a reasonable and safe treatment for patients with advanced DTC. Despite the risk of radiation exposure, administration of low-activity RAI has not been associated with an increased risk of a secondary primary cancer (SPM), leukemia, infertility, adverse pregnancy outcomes, etc. However, depending on the cumulative dose, there is a risk of acute or delayed-onset adverse effects including salivary gland damage, dental caries, nasolacrimal duct obstruction, and SPM. Therefore, as with any treatment, the expected benefit must justify the use of RAI in patients with advanced DTC.
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Pediatric differentiated thyroid cancers (DTCs), mostly papillary thyroid cancer (PTC, 80-90%), are diagnosed at more advanced stages with larger tumor sizes and higher rates of locoregional and/or lung metastasis. Despite the higher recurrence rates of pediatric cancers than of adult thyroid cancers, pediatric patients demonstrate a lower mortality rate and more favorable prognosis. Considering the more advanced stage at diagnosis in pediatric patients, preoperative evaluation is crucial to determine the extent of surgery required. Furthermore, if hereditary tumor syndrome is suspected, genetic testing is required. Recommendations for pediatric DTCs focus on the surgical principles, radioiodine therapy according to the postoperative risk level, treatment and follow-up of recurrent or persistent diseases, and treatment of patients with radioiodine-refractory PTCs on the basis of genetic drivers that are unique to pediatric patients.
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Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
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Radioiodine has been effectively applied for the management of hyperthyroidism and differentiated thyroid cancers in most countries of the world. The majority of thyroid cancers are differentiated thyroid cancer that has an overall excellent prognosis, which attributed to appropriate treatment of the disease including administration of radioiodine, I-131. I-131 therapy has usually been undertaken for the ablation of remnant tissue or adjuvant treatment after surgical resection of the thyroid. I-131 therapy was routinely recommended for patients with high-risk disease, and should be considered for intermediate-risk disease as an adjuvant purpose. Several latest studies refute worries of increase cancer risk with I-131 treatment for thyroid cancer. Thus, recent ATA guidelines have shifted toward a more individual and stratified approach, because of benign nature of the differentiated thyroid cancer as well as awareness of side effects including potential increasing incidence of second primary malignancy after I-131 treatment. While some retrospective studies also pointed out that potential increases in cancer development after I-131 treatment for hyperthyroidism recently. Treatment decisions regarding the use of radioiodine therapy should consider the balance of risks and benefits for individual patients with low risk differentiated thyroid cancer and hyperthyroidism, if it is true. Thus, we will review current understanding for the association of increased secondary malignancy and I-131 treatment of thyroid diseases.
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Background@#Positron emission tomography (PET) viability scan is used to determine whether patients with a myocardial scar on single-photon emission computed tomography (SPECT) may need revascularization. However, the clinical utility of revascularization decision-making guided by PET viability imaging has not been proven yet. The purpose of this study was to investigate the impact of PET to determine revascularization on clinical outcomes. @*Methods@#Between September 2012 and May 2021, 53 patients (37 males; mean age = 64 ± 11 years) with a myocardial scar on MIBI SPECT who underwent PET viability test were analyzed in this study. The primary outcome was a temporal change in echocardiographic findings.The secondary outcome was all-cause mortality. @*Results@#Viable myocardium was presented by PET imaging in 29 (54.7%) patients.Revascularization was performed in 26 (49.1%) patients, including 18 (34.0%) with percutaneous coronary intervention (PCI) and 8 (15.1%) with coronary artery bypass grafting.There were significant improvements in echocardiographic findings in the revascularization group and the viable myocardium group. All-cause mortality was significantly lower in the revascularization group than in the medical therapy-alone group (19.2% vs. 44.4%, log-rank P = 0.002) irrespective of viable (21.4% vs. 46.7%, log-rank P = 0.025) or non-viable myocardium (16.7% vs. 41.7%, log-rank P = 0.046). All-cause mortality was significantly lower in the PCI group than in the medical therapy-alone group (11.1% vs. 44.4%, log-rank P < 0.001). @*Conclusion@#Revascularization improved left ventricular systolic function and survival of patients with a myocardial scar on SPECT scans, irrespective of myocardial viability on PET scans.
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Background and Objectives@#The aim of this study was to determine the clinical effectiveness of parotid gland (PG) massage for the prevention of PG dysfunction after administration of radioiodine (I-131) therapy for treatment of differentiated thyroid cancer (DTC). @*Materials and Methods@#One hundred patients with DTC with planned high-dose I-131 therapy were enrolled in the clinical trial and randomized into two groups (massage and non-massage group). Serum amylase values were obtained before and 24 h after I-131 therapy, and salivary gland scintigraphy (SGS) were taken before and at eight months after the I-131 therapy. Additional SGS (addSGS) were taken when the patients complained symptoms related to salivary gland dysfunction. Questionnaire surveys were performed before and until two years after I-131 therapy. @*Results@#Ninety-five of 100 patients finished the study protocol. Changes in survey scores tended to be higher in the non-massage group. The non-massage group had more severe symptoms related to salivary gland dysfunction. Among 32 patients who underwent addSGS, 27 had normal 8-month SGS. Of these 27 patients, 18 (66.7%) had salivary gland dysfunction on the addSGS. Amylase values were significantly increased in patients with normal 8-month SGS but abnormal addSGS, as compared to patients who were normal on both 8-month SGS and addSGS (p=0.046). Amylase difference values were a significant predictor of abnormal addSGS (p=0.002). Conclusion: PG massage reduced symptoms related to salivary gland dysfunction. The PG massage may be helpful in preventing damage to salivary glands caused by I-131 therapy.
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Co-existence of subacute thyroiditis and papillary thyroid cancer (PTC) is rarely reported. We have recently experienced interesting cases of subacute thyroiditis, which developed while waiting for elective surgery of thyroid cancer in two patients. Two women, aged 52 and 55 years, suspected or diagnosed as PTC complained of anterior neck pain and febrile sensation several weeks before the scheduled surgery. Both cases showed elevated serum thyroid hormones and erythrocyte sedimentation rate, and decreased thyroid-stimulating hormone. Ill-defined hypoechoic lesions on ultrasonography and decreased uptake on Tc-99m pertechnetate scan were noted in both lobes. Total thyroidectomy for PTC was performed after relief of symptoms either by steroid or non-steroid anti-inflammatory drug treatment. Pathologic evaluation of surgical specimen revealed multinucleated giant cells and mononuclear cell infiltration. Pathognomic findings of subacute thyroiditis in addition to PTC were observed in both cases.
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Background and Objectives@#Even though most of the thyroid cancer shows good prognosis, de-differentiated thyroid cancer is still refractory to conventional treatments. Recently, kinase inhibitors including multi-kinase and BRAF inhibitors are widely used for treatment of de-differentiated thyroid cancers, but resistant to single kinase inhibitor treatment eventually encountered. Therefore, combination therapy may have better therapeutic effect than single therapy for thyroid cancer. In this study, we evaluated therapeutic effect of multi-kinase and BRAF inhibitor combination to anaplastic thyroid cancer cell lines with and without BRAF mutation. @*Materials and Methods@#We used anaplastic thyroid cancer cell lines with BRAF V600E mutation (8505C) and with NRAS mutation (HTh7). Both cell lines were treated with various concentration of multi-kinase inhibitor (lenvatinib) and BRAF inhibitor (vemurafenib). And combination of various concentration of both kinase inhibitors were used to treat both cell lines. Cytotoxic effect was assessed with cell counting kit-8 and therapeutic effect of single kinase inhibitor therapy and the combination therapy was compared. @*Results@#Anti-proliferative effect of vemurafenib on 8505C BRAF V600E -mutated cells was demonstrated from 0.25 μM concentration. However, HTh7 cells with NRAS mutation represented drug resistance up to 4 μM of vemurafenib. In case of lenvatinib treatment as a multi-kinase inhibitor, 8505C and HTh7 cells showed decreased cell viability dose-dependent manner. Combination treatment with vemurafenib and lenvatinib showed synergistic cytotoxic effect in BRAF mutated 8505C cell line, even at lower concentrations. @*Conclusion@#Combination treatment with multi-kinase inhibitor and BRAF inhibitor showed promising therapeutic results in BRAF mutated anaplastic thyroid cancer cell line.
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Background and Objectives@#The aim of this study was to determine the clinical effectiveness of parotid gland (PG) massage for the prevention of PG dysfunction after administration of radioiodine (I-131) therapy for treatment of differentiated thyroid cancer (DTC). @*Materials and Methods@#One hundred patients with DTC with planned high-dose I-131 therapy were enrolled in the clinical trial and randomized into two groups (massage and non-massage group). Serum amylase values were obtained before and 24 h after I-131 therapy, and salivary gland scintigraphy (SGS) were taken before and at eight months after the I-131 therapy. Additional SGS (addSGS) were taken when the patients complained symptoms related to salivary gland dysfunction. Questionnaire surveys were performed before and until two years after I-131 therapy. @*Results@#Ninety-five of 100 patients finished the study protocol. Changes in survey scores tended to be higher in the non-massage group. The non-massage group had more severe symptoms related to salivary gland dysfunction. Among 32 patients who underwent addSGS, 27 had normal 8-month SGS. Of these 27 patients, 18 (66.7%) had salivary gland dysfunction on the addSGS. Amylase values were significantly increased in patients with normal 8-month SGS but abnormal addSGS, as compared to patients who were normal on both 8-month SGS and addSGS (p=0.046). Amylase difference values were a significant predictor of abnormal addSGS (p=0.002). Conclusion: PG massage reduced symptoms related to salivary gland dysfunction. The PG massage may be helpful in preventing damage to salivary glands caused by I-131 therapy.
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PURPOSE: Bisphosphonate (BP) is the first-line therapy for the management of osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral fracture (AFF) are increasingly common comorbidities in patients with osteoporosis under long-term BP treatment. The aim of this study was to evaluate the incidence and risk factors for AFF features on bone scintigraphy in patients with BRONJ.METHODS: Among total of 373 BRONJ patients treated between September 2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent three-phase bone scintigraphy were enrolled for this retrospective study. AFF features on bone scintigraphy and the related clinical factors were assessed.RESULTS: Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone scintigraphy. BP medication duration (p = 0.049) correlated significantly with AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of 34 months was the cutoff value for predicting the presence of AFF features on bone scintigraphy. Among the patients with BRONJ, all those with AFF features on bone scintigraphy were female patients with osteoporosis who were on oral BP medication; however, these factors were not significantly different along with AFF features on bone scintigraphy.CONCLUSIONS: The incidence of AFF features on bone scintigraphy was relatively high in patients with BRONJ. A careful observation of patients presenting with the AFF features on bone scintigraphy may be needed, particularly for female BRONJ patients with osteoporosis who have been on BP medication for over 34 months.
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Femenino , Humanos , Masculino , Osteonecrosis de los Maxilares Asociada a Difosfonatos , Comorbilidad , Fracturas del Fémur , Incidencia , Maxilares , Osteonecrosis , Osteoporosis , Prevalencia , Cintigrafía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Radioactive iodine (RAI) therapy for differentiated thyroid cancer has been successfully used for more than 70 years. However, there is still plenty of controversy surrounding the use and doses of radioiodine. There is insufficient evidence to answer the questions. Recent American Thyroid Association (ATA) guidelines seem to favor low-dose RAI, based on recent clinical trials and meta-analyses. However, long-term follow-up data remains limited, and there are additional factors we should consider that might affect the efficacy of RAI therapy. Therefore, until sufficient data are available, it is necessary to remain cautious about determining RAI doses by considering multiple patient-specific variables.
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Estudios de Seguimiento , Yodo , Glándula Tiroides , Neoplasias de la TiroidesRESUMEN
PURPOSE@#Bisphosphonate (BP) is the first-line therapy for the management of osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral fracture (AFF) are increasingly common comorbidities in patients with osteoporosis under long-term BP treatment. The aim of this study was to evaluate the incidence and risk factors for AFF features on bone scintigraphy in patients with BRONJ.@*METHODS@#Among total of 373 BRONJ patients treated between September 2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent three-phase bone scintigraphy were enrolled for this retrospective study. AFF features on bone scintigraphy and the related clinical factors were assessed.@*RESULTS@#Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone scintigraphy. BP medication duration (p = 0.049) correlated significantly with AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of 34 months was the cutoff value for predicting the presence of AFF features on bone scintigraphy. Among the patients with BRONJ, all those with AFF features on bone scintigraphy were female patients with osteoporosis who were on oral BP medication; however, these factors were not significantly different along with AFF features on bone scintigraphy.@*CONCLUSIONS@#The incidence of AFF features on bone scintigraphy was relatively high in patients with BRONJ. A careful observation of patients presenting with the AFF features on bone scintigraphy may be needed, particularly for female BRONJ patients with osteoporosis who have been on BP medication for over 34 months.
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Radioactive iodine (RAI) therapy for differentiated thyroid cancer has been successfully used for more than 70 years. However, there is still plenty of controversy surrounding the use and doses of radioiodine. There is insufficient evidence to answer the questions. Recent American Thyroid Association (ATA) guidelines seem to favor low-dose RAI, based on recent clinical trials and meta-analyses. However, long-term follow-up data remains limited, and there are additional factors we should consider that might affect the efficacy of RAI therapy. Therefore, until sufficient data are available, it is necessary to remain cautious about determining RAI doses by considering multiple patient-specific variables.