Surgical approach and radioactive iodine therapy for small well-differentiated thyroid cancer.

BACKGROUND: Management of small well-differentiated thyroid cancer (DTC) has generated much debate regarding the surgical approach and radioactive iodine treatment (RAI). AIM: The aim of the study was to evaluate the impact of surgical extension and RAI on the outcome of DTC ≤2 cm. METHODS: A retrospective analysis of 176 cases of DTC ≤2 cm was performed. RESULTS: At diagnosis, tumor size was 1.38 ± 0.55 cm, age 40.2 ± 13.6 years. After a mean follow-up period of 14.1 ± 4.5 years, 15.9 % patients had recurrent/persistent structural disease, with cervical neck disease (thyroid gland area and/or cervical lymph nodes) in 11.9 % cases and distant metastasis in 5.1 %. Disease specific mortality was of 1.1 %. No difference in outcome was observed between patients submitted to total or subtotal thyroidectomy. After total and subtotal thyroidectomy, the rate of recurrent/persistent structural disease was 19.1 and 10.6 % (p = 1.00), respectively. Using the multivariate cox proportion hazards analysis, no difference in the clinical outcome was observed after total or subtotal thyroidectomy (p = 0.703) neither after RAI (p = 0.807). Similar results were observed after stratification by tumor size. Multifocal disease (p = 0.007), extra-thyroid extension (p = 0.007) and presence of lymph node metastasis (p = 0.000) were associated with unfavorable outcome. CONCLUSIONS: Total thyroidectomy and RAI did not improve clinical outcomes of DTC ≤2.0 cm when compared with less extensive surgery and no RAI in selected patients. Therefore, in carefully selected patients with DTC ≤2.0 cm and no unfavorable risk factors (multifocal disease, extra-thyroid extension, lymph node and/or distant metastasis), less extensive surgery and no RAI may be acceptable treatment options.

How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study.

BACKGROUND: Studies from every continent have shown that only around 50% of the patients subjected to thyroid hormone replacement have TSH in the normal range. However, to date, there are no consistent data about Brazil. OBJECTIVES: To evaluate levothyroxine (LT4) replacement treatment in patients with primary hypothyroidism followed in referral centers in Brazil. METHODS: Patients with primary hypothyroidism followed in referral centers (University Hospitals from Universidade Federal do Rio de Janeiro - UFRJ, Unicamp, Universidade Federal do Paraná - UFPR and Universidade Federal do Ceará-UFC) answered a questionnaire that inquired about clinical and biochemical conditions, social- economic status, life quality and clinicians' orientations as well as their understanding about the information given. Serum TSH was checked close to the interview. RESULTS: 2292 consecutive patients met the inclusion criteria. Mean age 51.2 yr and TSH values between 0.4 and 4.0 mUI/l were considered to be within the reference range. Among all patients taking thyroid medication, 42.7% had an abnormal serum TSH (28.3% were undertreated and 14.4% were overtreated). Approximately all patients (99%) took LT4 in the morning but less than 30 min before breakfast (85.4%). Regarding the clinicians' orientations: 97.5% of the patients were instructed to take the medication daily, and 92.6% to take 30 min before breakfast (92.6%). However, only 52.1% were told not to take LT4 along with other medication. CONCLUSIONS: Our study found that a significant number of patients taking thyroid hormones were not in the therapeutic range. Clinicians should, therefore, consider monitoring patients on thyroid replacement more frequently and being more precise on giving recommendations about the correct use of LT4.

Initial therapy with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural disease recurrence in properly selected patients with differentiated thyroid cancer.

OBJECTIVE: To describe the risk of structural disease recurrence in a cohort of patients with differentiated thyroid cancer selected for treatment with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation (RRA). DESIGN: Retrospective review. PATIENTS: A total of 289 patients were selected for either thyroid lobectomy (n = 72) or total thyroidectomy (n = 217) without RRA and followed with modern disease detection tools in a tertiary referral centre. Most patients had papillary thyroid cancer (89%) without clinically evident lymph node metastases (91%). However, 55% (156/289) of patients had primary tumours that were >1 cm and 10% (28/289) had minor extrathyroidal extension. MEASUREMENTS: The primary endpoint was detection of recurrent/persistent structural disease. RESULTS: After a 5-year median follow-up, structural disease recurrence was detected in 2·3% (5/217) of patients treated with total thyroidectomy without RRA, and in 4·2% (3/72) of patients treated with thyroid lobectomy. Size of the primary tumour, the presence of cervical lymph node metastases and American Thyroid Association risk category were all statistically significant predictors of recurrence. Changes in serum thyroglobulin were not helpful in identifying the presence of persistent/recurrent structural disease. Importantly, 88% (7/8) of the patients that had recurrent disease were rendered clinically disease free with additional therapies. CONCLUSIONS: Initial risk stratification is able to identify a cohort of patients with differentiated thyroid cancer with a very low risk of structural disease recurrence following treatment with either thyroid lobectomy or total thyroidectomy without RRA. Our data strongly support a selective approach to the initial management of thyroid cancer.

Clinical presentation and clinical outcomes in Chernobyl-related paediatric thyroid cancers: what do we know now? What can we expect in the future?

Over the last 20 years, nearly 5000 cases of differentiated thyroid cancer have been diagnosed and treated in the regions of Russia, Ukraine and Belarus in young people previously exposed to the Chernobyl radioactive fallout during childhood. At diagnosis, 60-70% of the Chernobyl-related paediatric thyroid cancers had clinically evident cervical lymph node metastases (N1) and 10-15% had distant metastases (M1). Despite early reports suggesting that the paediatric thyroid cancer cases that developed after exposure to Chernobyl fallout were particularly aggressive, it now seems that the initial presentation and early clinical course of most of these cases are very similar to both non-radiation-associated paediatric thyroid cancers and thyroid cancers that arise after exposure to external beam irradiation. Over an average clinical follow-up period of about 10 years, the disease-specific mortality rate in these paediatric thyroid cancer cases that developed after the Chernobyl accident is quite low (1% or less). As would be expected in paediatric thyroid cancer, short-term recurrence rates range from 7 to 28% in published reports (mean 17%). However, long-term studies of paediatric thyroid cancer suggest that although the 30 year disease-specific mortality rate should be about 1%, the risk of developing structural disease recurrence is nearly 30% (of which 80% are expected to be locoregional recurrences and 20% are probably new distant metastases). Projected over 30 years of follow-up, a 1% disease-specific mortality in this cohort of 5000 patients would equate to about 50 deaths directly attributable to thyroid cancer. However, a 30% recurrence rate would also mean that about 1500 patients may develop a clinically meaningful recurrence that would need to be diagnosed and treated. It is imperative that we continue to work with our colleagues in Belarus, Ukraine and Russia to ensure that this large volume of patients destined to develop clinically significant recurrences are diagnosed and treated in a timely manner. Ready access to modern disease detection tools (serum thyroglobulin, postoperative neck ultrasonography, cytology/pathology support, and radioactive iodine scanning) and treatments (surgery for recurrent disease, radioactive iodine therapy) in their major academic centres are mandatory if we expect to achieve the excellent clinical outcomes that should be seen when paediatric thyroid cancer recurrence is diagnosed early and treated appropriately.

Follow-up of patients treated with retinoic acid for the control of radioiodine non-responsive advanced thyroid carcinoma

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40 percent of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (131I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg-1·day-1 for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8 percent, a stable disease rate in 25 percent and a progression disease rate in 56.2 percent. Five patients died (62.5 percent) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.

Follow-up of patients treated with retinoic acid for the control of radioiodine non-responsive advanced thyroid carcinoma.

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40% of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (¹³¹I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg⁻¹·day⁻¹ for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8%, a stable disease rate in 25% and a progression disease rate in 56.2%. Five patients died (62.5%) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.