Lobectomy in patients with differentiated thyroid cancer: experience of a Chilean tertiary center.

PURPOSE: Thyroid lobectomy (TL) is an appropriate treatment for up to 4 cm intrathyroidal differentiated thyroid cancer (DTC). There is scarce data regarding TL outside first-world centers. Our aim is to report a cohort of patients with DTC treated with TL in Chile. METHODS: We included DTC patients treated with TL, followed for at least 6 months, characterized their clinicopathological features and classified their risk of recurrence and response to treatment. RESULTS: Eighty-two patients followed for a median of 2.3 years (0.5-7.0). Seventy-three (89%) patients had papillary, 8 (9.8%) follicular and 1 (1.2%) high-grade DTC. The risk of recurrence was low in 56 (68.3%) and intermediate in 26 (31.7%). Eight (9.8%) patients required early completion thyroidectomy and radioiodine. At last follow-up, 52 (70.3%) had excellent, 19 (25.7%) had indeterminate, and 1 (1.4%) had structural incomplete response. CONCLUSION: In a developing country, TL is an adequate option for appropriately selected DTC patients.

Efficacy of radioiodine therapy for treating 20 patients with pulmonary metastases from differentiated thyroid cancer and a meta-analysis of the current literature.

BACKGROUND: Radioiodine therapy (RAI) after total or near-total thyroidectomy is a recommended treatment for patients with pulmonary metastasis from differentiated thyroid cancer (DTC). However, the total effective rate of iodine-131 therapy remains controversial. This study aimed to determine the efficacy of RAI for treating patients with pulmonary metastasis from DTC, and to identify independent predictors of its efficacy. METHODS: We conducted a retrospective study to evaluate 20 patients with pulmonary metastasis from DTC who underwent RAI at our center at first and performed a meta-analysis to evaluate relevant literature regarding the overall efficacy of RAI and subgroup-specific efficacies subsequently. RESULTS: The efficacy rate at our center was 40%, and no significant differences were observed according to sex, age, pathological type, metastasis state, or interval between the initial RAI and final surgery. The meta-analysis revealed that the pooled overall efficacy rate was 58%, and significant differences were observed when we compared pulmonary metastasis versus pulmonary and other distant metastasis, age of < 40 years versus age of ≥ 40 years, papillary thyroid cancer versus follicular thyroid cancer and male patients versus female patients. CONCLUSIONS: These results suggest that RAI is an effective treatment for patients with pulmonary metastasis from DTC after surgical treatment. The efficacy of RAI was significantly predicted by the presence of papillary thyroid cancer, age of < 40 years, the absence of non-lung distant metastasis and female patients.

Thyroglobulin levels before radioactive iodine therapy and dynamic risk stratification after 1 year in patients with differentiated thyroid cancer

ABSTRACT Objectives: We sought to assess the relationship between stimulated thyroglobulin (sTg) before radioactive iodine therapy (RIT), and the dynamic risk stratification 1 year after treatment, and to establish the utility of the sTg as a predictor of response to therapy in these patients. A retrospective chart review of patients with differentiated thyroid cancer (DTC) who underwent RIT after surgery and were followed for at least 1 year, was carried out. Subjects and methods: Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The sTg values before RIT were compared among the groups. ROC curve analysis was performed. Results: Fifty-six patients were enrolled (mean age 44.7 ± 14.4 years, 80.7% had papillary carcinoma). Patients with excellent response had sTg = 2.1 ± 3.3 ng/mL, those with indeterminate response had sTg = 8.2 ± 9.2 ng/mL and those with incomplete response had sTg = 22.4 ± 28.3 ng/mL before RIT (p = 0.01). There was a difference in sTg between excellent and incomplete response groups (p = 0.009) while no difference was found between indeterminate and either excellent or incomplete groups. The ROC curve showed an area under the curve of 0.779 assuming a sTg value of 3.75 ng/mL. Conclusion: Our study results suggest that the higher the sTg before RIT, the greater the likelihood of an incomplete response to initial treatment. A sTg cut-off of 3.75 ng/mL was found to be a good predictor of response to initial treatment in patients with DTC.

Correlation among ocular surface disease, xerostomia, and nasal symptoms in patients with differentiated thyroid carcinoma subjected to radioiodine therapy: A prospective comparative study.

BACKGROUND: Some complications of radioiodine therapy have been reported, but the involvement of the eyes and adnexa is rarely discussed. The purpose of this study was to determine the correlation among ocular surface changes, xerostomia, and changes in the nasal mucosa associated with radioiodine therapy. METHODS: Patients subjected to radioiodine therapy (group 1) or not subjected (group 2) were prospectively evaluated by examinations of the ocular surface and tear film, saliva production, and nasal endoscopy. Ocular and nasal symptoms and xerostomia were evaluated using questionnaires. RESULTS: Evaluation of the ocular surface did not indicate significant differences between the groups. Nasal endoscopy revealed higher mucosal pallor in group 1 and worsening of the endoscopic appearance. Worsening of ocular symptoms and nasal symptoms, xerostomia, and a significant decrease in salivary production was also observed in group 1. CONCLUSION: Subjective worsening of xerostomia, xerophthalmia, nasal symptoms, and changes in the nasal mucosa in group 1 was observed.

Cytotoxic and genotoxic effects of 131 I and 60 Co in follicular thyroid cancer cell (WRO) with and without recombinant human thyroid-stimulating hormone treatment.

Normally, differentiated thyroid cancer (DTC) tends to be biologically indolent, highly curable and has an excellent prognosis. However, the treatment may fail when the cancer has lost radioiodine avidity. The present study was carried out in order to evaluate the cytotoxic and genotoxic effects of 131 I and 60 Co and radioiodine uptake in WRO cells, derived from DTC, harboring the BRAFV600E mutation. WRO cells showed a relatively slow cell cycle of 96.3 h with an unstable karyotype containing various double minutes. The genotoxicity assay (micronucleus test) showed a relative high radioresistance to 131 I (0.07-3.70 MBq/mL), independent of treatment with recombinant human thyroid-stimulating hormone (rhTSH). For the cytotoxicity assay, WRO cells were also relatively resistant to 60 Co (range: 0.2-8.3 Gy), but with a gradual decrease of viability as a function of time for higher doses (20 and 40 Gy, starting from the fifth to sixth day). For internal irradiation with 131 I, WRO cells showed a decline in viability at radioactive concentration higher than 1.85 MBq/mL; this was even more effective at 3.70 MBq/mL, but only when preceded by rhTSH, in coincidence with the highest level of 131 I uptake. These data show promising results, since the loss of the ability of thyroid cells to concentrate radioiodine is considered to be one of the main factors responsible for the failure of 131 I therapy in patients with DTC. The use of tumor-derived cell lines as a model for in vivo tumor requires, however, further investigations and deep evaluation of the corresponding in vivo effects. Environ. Mol. Mutagen. 58:451-461, 2017. © 2017 Wiley Periodicals, Inc.

Estimation of Second Primary Cancer Risk After Treatment with Radioactive Iodine for Differentiated Thyroid Carcinoma.

BACKGROUND: An increase in the incidence of second primary cancers is the late effect of greatest concern that could occur in differentiated thyroid carcinoma (DTC) patients treated with radioactive iodine (RAI). The decision to treat a patient with RAI should therefore incorporate a careful risk-benefit analysis. The objective of this work was to adapt the risk-estimation models developed by the Biological Effects of Ionizing Radiation Committee to local epidemiological characteristics in order to assess the carcinogenesis risk from radiation in a population of Brazilian DTC patients treated with RAI. Absorbed radiation doses in critical organs were also estimated to determine whether they exceeded the thresholds for deterministic effects. METHODS: A total of 416 DTC patients treated with RAI were retrospectively studied. Four organs were selected for absorbed dose estimation and subsequent calculation of carcinogenic risk: the kidney, stomach, salivary glands, and bone marrow. Absorbed doses were calculated by dose factors (absorbed dose per unit activity administered) previously established and based on standard human models. The lifetime attributable risk (LAR) of incidence of cancer as a function of age, sex, and organ-specific dose was estimated, relating it to the activity of RAI administered in the initial treatment. RESULTS: The salivary glands received the greatest absorbed doses of radiation, followed by the stomach, kidney, and bone marrow. None of these, however, surpassed the threshold for deterministic effects for a single administration of RAI. Younger patients received the same level of absorbed dose in the critical organs as older patients did. The lifetime attributable risk for stomach cancer incidence was by far the highest, followed in descending order by salivary-gland cancer, leukemia, and kidney cancer. CONCLUSION: RAI in a single administration is safe in terms of deterministic effects because even high-administered activities do not result in absorbed doses that exceed the thresholds for significant tissue reactions. The Biological Effects of Ionizing Radiation Committee mathematical models are a practical method of quantifying the risks of a second primary cancer, demonstrating a marked decrease in risk for younger patients with the administration of lower RAI activities and suggesting that only the smallest activities necessary to promote an effective ablation should be administered in low-risk DTC patients.

Thyroglobulin levels before radioactive iodine therapy and dynamic risk stratification after 1 year in patients with differentiated thyroid cancer.

OBJECTIVES: We sought to assess the relationship between stimulated thyroglobulin (sTg) before radioactive iodine therapy (RIT), and the dynamic risk stratification 1 year after treatment, and to establish the utility of the sTg as a predictor of response to therapy in these patients. A retrospective chart review of patients with differentiated thyroid cancer (DTC) who underwent RIT after surgery and were followed for at least 1 year, was carried out. SUBJECTS AND METHODS: Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The sTg values before RIT were compared among the groups. ROC curve analysis was performed. RESULTS: Fifty-six patients were enrolled (mean age 44.7 ± 14.4 years, 80.7% had papillary carcinoma). Patients with excellent response had sTg = 2.1 ± 3.3 ng/mL, those with indeterminate response had sTg = 8.2 ± 9.2 ng/mL and those with incomplete response had sTg = 22.4 ± 28.3 ng/mL before RIT (p = 0.01). There was a difference in sTg between excellent and incomplete response groups (p = 0.009) while no difference was found between indeterminate and either excellent or incomplete groups. The ROC curve showed an area under the curve of 0.779 assuming a sTg value of 3.75 ng/mL. CONCLUSION: Our study results suggest that the higher the sTg before RIT, the greater the likelihood of an incomplete response to initial treatment. A sTg cut-off of 3.75 ng/mL was found to be a good predictor of response to initial treatment in patients with DTC.

Lacrimal System Obstruction After Radioiodine Therapy in Differentiated Thyroid Carcinomas: A Prospective Comparative Study.

BACKGROUND: Radioiodine therapy (RIT) is an established treatment for differentiated thyroid carcinomas, and is widely used throughout the world, given the increasing incidence of this malignancy. Although serious adverse effects are infrequent, complications such as dry mouth, sialadenitis, and dysphagia have been described. The involvement of the eyes and accessory visual structures is not commonly discussed, despite dry eye, keratoconjunctivitis, and lacrimal system obstruction (LSO) being reported, especially after high cumulative doses of radiopharmaceuticals. The incidence of LSO is not well established. OBJECTIVES: The aim of this study was to determine the frequency of LSO in patients undergoing RIT at 2, 4, 6, and 12 months after treatment. METHODS: Patients with differentiated thyroid carcinoma undergoing (group 1) and not undergoing (group 2) RIT were evaluated in the preoperative and postoperative periods and 2, 4, 6, and 12 months post surgery or post RIT. Patients underwent tear film evaluation and lacrimal system probing and irrigation. RESULTS: Group 1 (n = 44; 88 eyes) contained three patients (four eyes) with LSO, corresponding to an incidence of 4.55% (four events in 88 eyes) or 6.8% (three cases in 44 patients). Group 2 (n = 43; 86 eyes) did not present any cases of LSO. CONCLUSIONS: In this study, an active prospective investigation allowed LSO detection during the first six months after RIT. This finding demonstrates the importance of making this association clear to patients and health professionals, with a view to early diagnosis, appropriate treatment, and preventing LSO-related complications.

Is thyroid stunning clinically relevant? A retrospective analysis of 208 patients.

OBJECTIVE: Current guidelines have advised against the performance of (131)I-iodide diagnostic whole body scintigraphy (dxWBS) to minimize the occurrence of stunning, and to guarantee the efficiency of radioiodine therapy (RIT). The aim of the study was to evaluate the impact of stunning on the efficacy of RIT and disease outcome. SUBJECTS AND METHODS: This retrospective analysis included 208 patients with differentiated thyroid cancer managed according to a same protocol and followed up for 12-159 months (mean 30 ± 69 months). Patients received RIT in doses ranging from 3,700 to 11,100 MBq (100 mCi to 300 mCi). Post-RIT-whole body scintigraphy images were performed 10 days after RIT in all patients. In addition, images were also performed 24-48 hours after therapy in 22 patients. Outcome was classified as no evidence of disease (NED), stable disease (SD) and progressive disease (PD). RESULTS: Thyroid stunning occurred in 40 patients (19.2%), including 26 patients with NED and 14 patients with SD. A multivariate analysis showed no association between disease outcome and the occurrence of stunning (p = 0.3476). CONCLUSION: The efficacy of RIT and disease outcome do not seem to be related to thyroid stunning.

Is thyroid stunning clinically relevant? A retrospective analysis of 208 patients / O atordoamento da tireoide é clinicamente relevante? Análise retrospectiva de 208 pacientes

Objective : Current guidelines have advised against the performance of 131I-iodide diagnostic whole body scintigraphy (dxWBS) to minimize the occurrence of stunning, and to guarantee the efficiency of radioiodine therapy (RIT). The aim of the study was to evaluate the impact of stunning on the efficacy of RIT and disease outcome.Subjects and methods : This retrospective analysis included 208 patients with differentiated thyroid cancer managed according to a same protocol and followed up for 12-159 months (mean 30 ± 69 months). Patients received RIT in doses ranging from 3,700 to 11,100 MBq (100 mCi to 300 mCi). Post-RIT-whole body scintigraphy images were performed 10 days after RIT in all patients. In addition, images were also performed 24-48 hours after therapy in 22 patients. Outcome was classified as no evidence of disease (NED), stable disease (SD) and progressive disease (PD).Results : Thyroid stunning occurred in 40 patients (19.2%), including 26 patients with NED and 14 patients with SD. A multivariate analysis showed no association between disease outcome and the occurrence of stunning (p = 0.3476).Conclusion : The efficacy of RIT and disease outcome do not seem to be related to thyroid stunning. Arq Bras Endocrinol Metab. 2014;58(3):292-300.

Objetivo : As diretrizes atuais alertam contra a execução da cintigrafia de corpo inteiro com iodo-131 (dxWBS) para minimizar a ocorrência de atordoamento e garantir a eficiência do tratamento com radioiodo (RIT). O objetivo deste estudo foi avaliar o impacto do atordoamento sobre a eficácia do RIT e desfechos da doença.Sujeitos e métodos : Esta análise retrospectiva incluiu 208 pacientes com câncer diferenciado de tireoide submetidos ao mesmo protocolo e acompanhados por 12-159 semanas (média de 30 ± 69 meses). Os pacientes receberam RIT com doses variando de 3.700 a 11.100 MBq (100 mCi a 300 mCi). As imagens da cintigrafia após a RIT foram feitas 10 dias depois da RIT em todos os pacientes. Além disso, as imagens foram também obtidas após 24-48h em 22 pacientes. O desfecho foi classificado como nenhuma evidência de doença (NED), doença estável (SD) e doença progressiva (PD).Resultados : O atordoamento da tireoide ocorreu em 40 pacientes (19,2%), incluindo 26 pacientes com NED e 14 pacientes com SD. A análise multivariada não mostrou associação entre o desfecho da doença e a ocorrência de atordoamento (p = 0,3476).Conclusão : A eficácia da RIT e o desfecho da doença não parecem estar relacionados com o atordoamento da tireoide. Arq Bras Endocrinol Metab. 2014;58(3):292-300.

Differentiated thyroid carcinoma: presentation and follow-up in children and adolescents.

UNLABELLED: To review our Pediatric Endocrinology Division's experience with differentiated thyroid carcinoma (DTC) we analyzed retrospectively the records of patients with DTC that had been seen between June 1988 and June 2008. RESULTS: Forty-five patients (median age 13.7 years, 36 female) were diagnosed (papillary: 40, follicular: 5) with DTC presenting as a solitary nodule (n: 25), thyroid nodule with cervical adenopathy (n: 9) and multinodular goiter (n: 11). All underwent total thyroidectomy with resection of suspicious cervical lymph nodes (CLN). DTC was multicentric in 59% and revealed extrathyroidal extension in 44%. Initially, 44% had CLN metastases and 24% distant metastases. All patients underwent thyroid remnant ablation with 131I and suppressive treatment. Median follow-up was 5.1 years with a disease-free survival rate at 5 years of follow-up of 75%. Eleven percent presented recurrences. CONCLUSION: Pediatric DTC has an aggressive behavior at presentation. Higher preoperative TSH levels were significantly associated with a more advanced disease at diagnosis. CLT was present concomitantly in a quarter of the patients and further studies are needed to establish differences in these patients' outcome. Diagnostic approach, total thyroidectomy, 131I treatment and thyrotropin suppression allowed a good progression-free survival rate.

Late side effects of radioactive iodine on salivary gland function in patients with thyroid cancer.

BACKGROUND: The purpose of this study was to assess the late side effects of radioiodine therapy (RIT) on salivary gland function. One hundred eighty two patients were evaluated. METHODS: Assessment of salivary gland function was performed with salivary gland scintigraphy (SGS), sialometry, and subjective open questions to determine common side effects of RIT on salivary gland function. RESULTS: RIT had a strong association with decreased elimination counts by SGS. Patient age was the only variable associated with sialometry; age and the use of xerostomic drugs were strongly associated with decreased mean values of salivary flow. Dysphagia was strongly associated with RIT. Using multiple logistic regression analysis, age was determined to be an important factor associated with salivary gland dysfunction, and RIT was associated with impairment of saliva excretion. CONCLUSION: These results show that patients subjected to RIT have more difficulty in draining saliva, mainly from the parotid glands, which is associated with clinical dysphagia in this subset of patients.

Blood thyroglobulin and TSH receptor mRNA detection by RT-PCR in the follow-up of differentiated thyroid cancer patients.

OBJECTIVE: During the last years several groups have used the technique of RT-PCR for the detection of circulating thyroid cells, through the amplification of thyroglobulin (Tg) and TSH receptor(TSH-R) mRNA; however the published results are controversial. In this study we investigated the utility for the detection of Tg and TSH-R mRNA by RT-PCR in patients with differentiated thyroid cancer (DTC) during treatment with levothyroxine. SUBJECTS AND METHODS: We investigated the expression of Tg and TSH-R mRNA by single and nested RT-PCR in the blood of 3 groups of subjects: (A) 34 patients with DTC and no evidence of disease, (B) 8 patients with DTC and evidence of local or distant metastasis and (C) 13 normal subjects. Expression levels of Tg mRNA were also analysed by comparative semi-quantitative RT-PCR. RESULTS: Tg and TSH-R mRNA signals were detected in all subjects (patients with DTC with and without evidence of disease and in normal subjects) by single or nested RT-PCR. By semi-quantitative RT-PCR and densitometric analysis of PCR products, mean levels of circulating Tg mRNA of the 3 groups were: Group A 0.182+/-0.107, Group B 0.329+/-0.298 and Group C 0.305+/-0.217. CONCLUSIONS: Single or nested RT-PCR for Tg and TSH-R mRNA is not a suitable tool in the follow-up of patients with DTC. Lower levels of Tg mRNA in patients with DTC without evidence of disease, although not significant, may indicate that small numbers of thyroid cells may be normally present in the circulation or may represent an ectopic transcription of messengers from blood cells.

Long-term survival rates in young patients with thyroid carcinoma.

BACKGROUND: Thyroid carcinoma in patients younger than 18 years is rare. It is associated with a greater risk of metastases. However, the prognosis for these patients is better when compared with that of adults. OBJECTIVE: To present the experience of a single institution in the treatment of patients with thyroid carcinoma during childhood and adolescence. PATIENTS AND METHODS: Thirty-eight patients, ranging in age from 4 to 18 years, were diagnosed as having thyroid carcinoma. Pathologic types of carcinoma included 29 papillary, 4 follicular, 1 Hürthle cell, and 4 medullary cases. RESULTS: Hypocalcemia was the main complication, being transitory in 9 patients (24%) and permanent in 6 patients (16%). Vocal cord palsy occurred in 2 patients (5%). Two patients (5%) had a surgical site infection. After a mean follow-up of 9.5 years (range, 1-40 years), 28 patients (74%) were alive and had no evidence of disease, 3 (8%) were alive and had recurrent disease, 4 (11%) died (2 of the disease and 2 of non-cancer-related causes), and 3 (8%) were lost to follow-up. The survival rates at 10 years for the patients with papillary, follicular, and medullary carcinoma were 93%, 100%, and 50%, respectively. CONCLUSIONS: Thyroid carcinoma in patients younger than 18 years has a good prognosis even in the presence of neck or distant metastasis. Total thyroidectomy, associated with adjuvant radioactive iodine therapy and thyroidal suppression or not, is effective in patients with a well-differentiated thyroid carcinoma.