Initial Management and Follow-up of Differentiated Thyroid Cancer in Children

2010 ◽  
Vol 8 (11) ◽  
pp. 1289-1300 ◽  
Author(s):  
Steven G. Waguespack ◽  
Gary Francis
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
High Risk ◽  
Differentiated Thyroid Cancer ◽  
Residual Disease ◽  
Distant Metastases ◽  
High Volume ◽  
Increased Risk ◽  
Initial Care

Children with differentiated thyroid cancer (DTC) often present with metastatic disease and have a high risk for recurrence, but rarely die of the disease. This article reviews DTC in children and discusses current approaches to their initial care and follow-up. These recommendations take into account the greater risk for recurrence and lower disease-specific mortality in these patients. Total thyroidectomy and central compartment lymph node dissection are appropriate for most children, but should be performed by a high-volume thyroid surgeon. Radioactive iodine (RAI) should generally be prescribed for those at very high risk for recurrence or known to have microscopic residual disease, and those with iodine-avid distant metastases. RAI should be considered in other patients only after carefully weighing the relative risks and benefits and the aggressiveness of the clinical presentation, because RAI may be associated with an increased risk for second malignancies and an increase in overall morbidity and mortality. All patients should be treated with thyroid hormone suppression, and follow-up should be lifelong. However, the degree of thyroid hormone suppression and frequency of disease surveillance usually decrease over time as patients are determined to be disease-free.

scholarly journals Thyroid Hormone Supplementation Therapy for Differentiated Thyroid Cancer After Lobectomy: 5 Years of Follow-Up

2020 ◽  
Vol 11 ◽  
Author(s):  
Soo Young Kim ◽  
Hee Jun Kim ◽  
Seok-Mo Kim ◽  
Hojin Chang ◽  
Yong Sang Lee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Differentiated Thyroid Cancer

scholarly journals Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines

2016 ◽  
Vol 130 (S2) ◽  
pp. S150-S160 ◽  
Author(s):  
A L Mitchell ◽  
A Gandhi ◽  
D Scott-Coombes ◽  
P Perros
Keyword(s):  
Thyroid Cancer ◽  
Total Thyroidectomy ◽  
Neck Dissection ◽  
Differentiated Thyroid Cancer ◽  
Distant Metastases ◽  
Central Compartment ◽  
Extrathyroidal Extension ◽  
Papillary Thyroid ◽  
Ultrasound Scanning

AbstractThis is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides recommendations on the management of thyroid cancer in adults and is based on the 2014 British Thyroid Association guidelines.Recommendations• Ultrasound scanning (USS) of the nodule or goitre is a crucial investigation in guiding the need for fine needle aspiration cytology (FNAC). (R)• FNAC should be considered for all nodules with suspicious ultrasound features (U3–U5). If a nodule is smaller than 10 mm in diameter, USS guided FNAC is not recommended unless clinically suspicious lymph nodes on USS are also present. (R)• Cytological analysis and categorisation should be reported according to the current British Thyroid Association Guidance. (R)• Ultrasound scanning assessment of cervical nodes should be done in FNAC-proven cancer. (R)• Magnetic resonance imaging (MRI) or computed tomography (CT) should be done in suspected cases of retrosternal extension, fixed tumours (local invasion with or without vocal cord paralysis) or when haemoptysis is reported. When CT with contrast is used pre-operatively, there should be a two-month delay between the use of iodinated contrast media and subsequent radioactive iodine (I131) therapy. (R)• Fluoro-deoxy-glucose positron emission tomography imaging is not recommended for routine evaluation. (G)• In patients with thyroid cancer, assessment of extrathyroidal extension and lymph node disease in the central and lateral neck compartments should be undertaken pre-operatively by USS and cross-sectional imaging (CT or MRI) if indicated. (R)• For patients with Thy 3f or Thy 4 FNAC a diagnostic hemithyroidectomy is recommended. (R)• Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter or tumours of any size in association with any of the following characteristics: multifocal disease, bilateral disease, extrathyroidal spread (pT3 and pT4a), familial disease and those with clinically or radiologically involved nodes and/or distant metastases. (R)• Subtotal thyroidectomy should not be used in the management of thyroid cancer. (G)• Central compartment neck dissection is not routinely recommended for patients with papillary thyroid cancer without clinical or radiological evidence of lymph node involvement, provided they meet all of the following criteria: classical type papillary thyroid cancer, patient less than 45 years old, unifocal tumour, less than 4 cm, no extrathyroidal extension on ultrasound. (R)• Patients with metastases in the lateral compartment should undergo therapeutic lateral and central compartment neck dissection. (R)• Patients with follicular cancer with greater than 4 cm tumours should be treated with total thyroidectomy. (R)• I131 ablation should be carried out only in centres with appropriate facilities. (R)• Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid cancer (DTC), but not sooner than six weeks after surgery. (R)• Patients who have undergone total or near total thyroidectomy should be started on levothyroxine 2 µg per kg or liothyronine 20 mcg tds after surgery. (R)• The majority of patients with a tumour more than 1 cm in diameter, who have undergone total or near-total thyroidectomy, should have I131 ablation. (R)• A post-ablation scan should be performed 3–10 days after I131 ablation. (R)• Post-therapy dynamic risk stratification at 9–12 months is used to guide further management. (G)• Potentially resectable recurrent or persistent disease should be managed with surgery whenever possible. (R)• Distant metastases and sites not amenable to surgery which are iodine avid should be treated with I131 therapy. (R)• Long-term follow-up for patients with differentiated thyroid cancer (DTC) is recommended. (G)• Follow-up should be based on clinical examination, serum Tg and thyroid-stimulating hormone assessments. (R)• Patients with suspected medullary thyroid cancer (MTC) should be investigated with calcitonin and carcino-embryonic antigen levels (CEA), 24 hour catecholamine and nor metanephrine urine estimation (or plasma free nor metanephrine estimation), serum calcium and parathyroid hormone. (R)• Relevant imaging studies are advisable to guide the extent of surgery. (R)• RET (Proto-oncogene tyrosine-protein kinase receptor) proto-oncogene analysis should be performed after surgery. (R)• All patients with known or suspected MTC should have serum calcitonin and biochemical screening for phaeochromocytoma pre-operatively. (R)• All patients with proven MTC greater than 5 mm should undergo total thyroidectomy and central compartment neck dissection. (R)• Patients with MTC with lateral nodal involvement should undergo selective neck dissection (IIa–Vb). (R)• Patients with MTC with central node metastases should undergo ipsilateral prophylactic lateral node dissection. (R)• Prophylactic thyroidectomy should be offered to RET-positive family members. (R)• All patients with proven MTC should have genetic screening. (R)• Radiotherapy may be useful in controlling local symptoms in patients with inoperable disease. (R)• Chemotherapy with tyrosine kinase inhibitors may help in controlling local symptoms. (R)• For individuals with anaplastic thyroid carcinoma, initial assessment should focus on identifying the small proportion of patients with localised disease and good performance status, which may benefit from surgical resection and other adjuvant therapies. (G)• The surgical intent should be gross tumour resection and not merely an attempt at debulking. (G)

High-Risk Patients with Differentiated Thyroid Cancer T4 Primary Tumors Achieve Remnant Ablation Equally Well Using rhTSH or Thyroid Hormone Withdrawal

Thyroid ◽  
2014 ◽  
Vol 24 (3) ◽  
pp. 480-487 ◽  
Author(s):  
Peter Bartenstein ◽  
Elisa Caballero Calabuig ◽  
Carlo Ludovico Maini ◽  
Renzo Mazzarotto ◽  
M. Angustias Muros de Fuentes ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
High Risk ◽  
Differentiated Thyroid Cancer ◽  
Primary Tumors ◽  
Remnant Ablation ◽  
Thyroid Hormone Withdrawal ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients

2011 ◽  
Vol 165 (3) ◽  
pp. 441-446 ◽  
Author(s):  
Maria Grazia Castagna ◽  
Fabio Maino ◽  
Claudia Cipri ◽  
Valentina Belardini ◽  
Alexandra Theodoropoulou ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Risk Stratification ◽  
Initial Treatment ◽  
Differentiated Thyroid Cancer ◽  
Low Risk ◽  
Risk Category ◽  
Radioiodine Ablation ◽  
Risk Patients

IntroductionAfter initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed.ObjectiveTo evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8–12 months after initial treatment).MethodsWe reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8–12 months after initial treatment, patients were re-stratified according to their clinical status: DRS.ResultsUsing DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively,P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS.ConclusionsDelaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

scholarly journals Serum thyroglobulin and 131I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer

2003 ◽  
pp. 19-24 ◽  
Author(s):  
M Torlontano ◽  
U Crocetti ◽  
L D'Aloiso ◽  
N Bonfitto ◽  
A Di Giorgio ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Thyroid Hormone ◽  
Differentiated Thyroid Cancer ◽  
Whole Body ◽  
Whole Body Scan ◽  
Serum Thyroglobulin ◽  
Risk Patients ◽  
Node Metastases

OBJECTIVE: The 'standard' postoperative follow-up of patients with differentiated thyroid cancer (DTC) has been based upon serum thyroglobulin (Tg) measurement and (131)I whole body scan ((131)I-WBS) after thyroid hormone (T(4)) treatment withdrawal. However, (131)I-WBS sensitivity has been reported to be low. Thyroid hormone withdrawal, often associated with hypothyroidism-related side effects, may now be replaced by recombinant human thyroid stimulating hormone (rhTSH). The aim of our study was to evaluate the diagnostic accuracy of (131)I-WBS and serum Tg measurement obtained after rhTSH stimulation and of neck ultrasonography in the first follow-up of DTC patients. DESIGN: Ninety-nine consecutive patients previously treated with total thyroidectomy and (131)I ablation, with no uptake outside the thyroid bed on the post-ablative (131)I-WBS (low-risk patients) were enrolled. METHODS: Measurement of serum Tg and (131)I-WBS after rhTSH stimulation, and ultrasound examination (US) of the neck. RESULTS: rhTSH-stimulated Tg was <or=1 ng/ml in 78 patients (Tg-) and >1 ng/ml (Tg+) in 21 patients, including 6 patients with Tg levels >5 ng/ml. (131)I-WBS was negative for persistent or recurrent disease in all patients (i.e. sensitivity = 0%). US identified lymph-node metastases (confirmed at surgery) in 4/6 (67%) patients with stimulated Tg levels >5 ng/ml, in 2/15 (13%) with Tg>1<5 ng/ml, and in 2/78 (3%) who were Tg-negative. CONCLUSIONS: (i) diagnostic (131)I-WBS performed after rhTSH stimulation is useless in the first follow-up of DTC patients; (ii) US may identify lymph node metastases even in patients with low or undetectable serum Tg levels.

scholarly journals Dynamic Risk Stratification for Predicting Treatment Response in Differentiated Thyroid Cancer

2020 ◽  
Vol 9 (9) ◽  
pp. 2708
Author(s):  
Evanthia Giannoula ◽  
Christos Melidis ◽  
Nikitas Papadopoulos ◽  
Panagiotis Bamidis ◽  
Vasilios Raftopoulos ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Treatment Response ◽  
Differentiated Thyroid Cancer ◽  
Early Stage ◽  
Distant Metastases ◽  
Significant Degree ◽  
Whole Body ◽  
Size Grade

Prognosis in Differentiated Thyroid Cancer (DTC) patients is excellent, but a significant degree of overtreatment still exists because of the inability to accurately identify small patient cohorts who experience a more aggressive form of the disease, often associated with certain poor prognostic factors. Identifying these cohorts at an early stage would allow patients at high risk to receive more aggressive treatment while avoiding unnecessary and invasive treatments in those at low risk. Most risk stratification systems include age, tumor size, grade, presence of local invasion, and regional or distant metastases. Here we discuss these common factors as well as their association with treatment response, but also other upcoming markers including histology and multifocality of primary tumor, dose administered and preparation method for Radioiodine Therapy (RAI), Thyroglobulin (Tg), Anti-thyroglobulin Antibodies (Tg-Ab) levels both at initial management and during follow-up, and the presence of previously existing benign thyroid disease. In addition, we examine the role of remnant size and avidity as well as surgeons’ experience in performing thyroidectomies with recurrence rate, discussing its impact on disease prognosis. Our results reveal that treatment response has a statistically significant association with histology, T and M stages, surgeons’ experience, Tg levels and remnant score both during RAI and follow up and Tg-Ab levels during follow-up whole body scan (WBS).

scholarly journals Long-Term Prognostic Value of the Response to Therapy Assessed by Laboratory and Imaging Findings in Patients with Differentiated Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4338
Author(s):  
Michele Klain ◽  
Emilia Zampella ◽  
Leandra Piscopo ◽  
Fabio Volpe ◽  
Mariarosaria Manganelli ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
High Risk ◽  
Differentiated Thyroid Cancer ◽  
Response To Therapy ◽  
Whole Body ◽  
American Thyroid Association ◽  
Neck Ultrasound ◽  
Risk Of Recurrence

This study assessed the long-term predictive value of the response to therapy, evaluated by serum thyroglobulin (Tg) determination and neck ultrasound, and estimated the potential additional impact of diagnostic whole-body scan (WBS) in patients with differentiated thyroid cancer (DTC) treated with surgery and radioactive iodine (RAI) therapy. We retrospectively evaluated 606 DTC patients treated with surgery and RAI. Response to 131I therapy at 12 months was assessed by serum Tg measurement, neck ultrasound, and diagnostic WBS. According to American Thyroid Association (ATA) guidelines, patients were classified as having a low, intermediate or high risk of recurrence and at 12 months as having an excellent response (ER) or no-ER. Follow-up was then performed every 6–12 months with serum Tg determination and imaging procedures. With a median follow-up of 105 months (range 10–384), 42 (7%) events requiring further treatments occurred. Twenty-five patients had additional RAI therapy, 11 with structural disease in the thyroid bed, eight in both thyroid bed and neck lymph nodes, four had lung metastases and two had bone metastases. The other 17 patients had additional surgery for nodal disease followed by RAI therapy. The ATA intermediate and high risk of recurrence, post-operative and pre-RAI therapy Tg ≥ 10 ng/mL, and the absence of ER at 12 months were independent predictors of events. Diagnostic WBS at 12 months permitted the identification of only five recurrences among the 219 ER patients according to serum Tg levels and ultrasound. In DTC patients, the response to therapy at 12 months after RAI therapy could rely on serum Tg measurement and neck ultrasound, while diagnostic WBS was not routinely indicated in patients considered in ER.

Treatment Intensification Improves Outcome in Children with iAMP21 positive ALL

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 656-656
Author(s):  
Anthony V. Moorman ◽  
Hazel M Robinson ◽  
Sue M Richards ◽  
Claire Schwab ◽  
Christopher D Mitchell ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Chromosome 21 ◽  
Differential Outcomes ◽  
Runx1 Gene ◽  
Increased Risk ◽  
Genetic Aberration ◽  
First Remission

Abstract Abstract 656 Chromosomal abnormalities present in the bone marrow cells of children with acute lymphoblastic leukaemia (ALL) are used to assist diagnosis and define risk groups that guide therapy. One such primary genetic aberration is intrachromosomal amplification of chromosome 21 (iAMP21) which is defined as the presence of 3 or more extra copies of the RUNX1 gene on a single abnormal chromosome 21. FISH with probes targeting the RUNX1 gene is the commonly used detection method. Approximately 2–3% children with ALL harbour iAMP21 and it is associated with older age (median 10 years) and a low white cell count (WCC, <20×109/L). Among 28 patients treated on the MRC ALL97 trial between 1997 and 2002, 27 (96%) achieved a complete remission (CR), 22 (81%) relapsed and 13 (46%) died. The event free survival (EFS), relapse rate (RR) and overall survival (OS) rates at 5 years were 29% (14–46%), 70% (53–86%) and 67% (47–82%), respectively. There was no evidence that National Cancer Institute (NCI) high risk (HR) and standard risk (SR) patients had differential outcomes and the RR appeared constant with time (figure). On the basis of this increased risk of relapse, we chose to stratify these patients to the most intensive arm of the ALL2003 protocol (regimen C) which included augmented Berlin-Frankfurt-Munster (BFM) consolidation, two blocks of escalating Capizzi maintenance and a double delayed intensification. First remission transplants were recommended for patients who were slow early responders (SER) or minimal residual disease (MRD) positive (>0.01%) at day 29. Due to a relatively high transplant related mortality, transplants were restricted to patients not in CR by day 29 after June 2008. Prospective FISH screening of 2575 patients treated on ALL2003 between January 2003 and July 2011 identified 53 (2%) with iAMP21. The cohort showed a female predominance (30:23), had a median age of 10 years and 47 (89%) patients had a WCC <20×109/L. Follow-up information was available for 52 (98%) patients with a median follow-up time of 4.9 years. The majority of patients (48/52, 92%) were transferred to regimen C as directed by the protocol. At least 2 of the remaining 4 patients did not transfer to regimen C because of induction toxicity problems. Treatment response was measured at day 15 or day 8 according to whether patients received a 3 (NCI SR) or 4 (NCI HR) drug induction, respectively. Whilst none of the SR patients were SER, 13/28 (46%) HR patients had >25% blasts at day 8. MRD was assessed in 45 patients: 23 (51%) were positive (>0.01%) and 22 (49%) were negative (<0.01%) at day 28. All patients achieved a CR, 6 (12%) have subsequently relapsed whilst 4 (8%) died in first remission following a transplant from infection (n=3) or transplant-related complications (n=1). One patient relapsed and died after receiving a transplant; so in total, 5 (10%) patients have died. Among 20 (38%) patients who received a transplant in first CR, 18 (90%) were either MRD positive at day 28 or a SER. The EFS, RR, OS rates at 5 years were 78% (61–88%), 16% (7–34%) and 89% (76–95%), respectively (figure). There were no significant differences in outcome according to sex, age, WCC, NCI risk status or MRD levels at day 28. Interestingly, among the 5 relapses who had MRD measured at day 28 only 1 was positive (>0.01%); although 2 more had borderline levels (>0.005%). A comparison between the outcome of iAMP21 patients treated on ALL97 and ALL2003 showed a statistically significant decrease in RR (p<0.0001) with significant increases in EFS (p<0.0001) and OS (p<0.01). The key endpoint was the proportion of patients suffering a relapse which decreased nearly seven-fold (81% to 12%) between the two trials. Importantly none of the ALL2003 relapses occurred on treatment and all bar one were classified as late events (>6 months after the end of treatment). The findings presented herein clearly illustrate the benefit of this treatment intervention in improving survival in these patients who otherwise had an extremely poor outcome when given standard therapy. In light of these results, iAMP21 patients treated on our new trial, ALL2011, will continue to be classified in the high risk cytogenetic subgroup and will receive regimen C. They are recommended for transplant only if they fail to achieve a CR by day 29. This study illustrates how the discovery and characterisation of a disease-specific genetic aberration can be used to tailor therapy more precisely. Disclosures: No relevant conflicts of interest to declare.

scholarly journals PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Martina Sollini ◽  
Luca di Tommaso ◽  
Margarita Kirienko ◽  
Chiara Piombo ◽  
Marco Erreni ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Distant Metastases ◽  
Cox Models ◽  
Cumulative Score ◽  
Cancer Aggressiveness ◽  
Positive Score ◽  
Psma Expression

Abstract Background Prostate-specific membrane antigen (PSMA) is overexpressed on the endothelial cells of tumor neo-vessels of several solid malignancies, including differentiated thyroid cancer (DTC). We aimed to test the potential role of PSMA as a biomarker for DTC aggressiveness and outcome prediction. We retrospectively screened all patients who underwent thyroidectomy between 1 January 2010 and 31 December 2017 in our institution. Applying the inclusion (histological diagnosis of thyroid cancer and tissue availability) and exclusion criteria (no clinical or follow-up data or diagnosis of medullary thyroid cancer), a cohort of 59 patients was selected. The monoclonal mouse anti-human PSMA antibody was used to stain tissue sections. A 3-point scale was used to score PSMA positivity: 0–5% expression was considered as negative (score 0), 6–50% as moderately positive (score 1), and 51–100% as highly positive (score 2). A cumulative score (0–10%, 11–79%, and 80–100%) was also explored. Univariate and multivariate logistic regression analyses were performed to predict the presence of distant metastases, chosen as endpoint of aggressiveness. The area under the curve (AUC) was calculated. Cox models were built to predict patient outcome in terms of recurrence, iodine refractoriness, and status at last follow-up, which were calculated using the Kaplan-Meier failure function. Results At immunostaining, 12, 25, and 22 patients had scores of 0, 1, and 2, respectively. According to the cumulative score, PSMA expression was ≤ 10% in 17 cases, 11–79% in 31 cases, and ≥ 80% in 11 cases. At multivariate analysis, age, sex, histotype, vascular invasion, T and N parameters, and PSMA positivity were significant predictors of distant metastases. The AUC was 0.92. Recurrence or progression occurred in 19/59 patients. Twelve patients developed radioiodine (RAI) refractoriness, after a median time of 17 months (range 2–32). One patient died of DTC; 46 of the 58 patients alive at last follow-up were disease free. Median DFS was 23 months (range 3–82). The final multivariate model to predict RAI refractoriness included as covariates the stage, high PSMA expression (≥ 80%), and the interaction between moderate PSMA expression (11–79%) and stage. Conclusions PSMA, a marker of neovasculature formation expressed by DTC, contributes in the prediction of tumor aggressiveness and patient outcome.

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