Daniel Alves Bulzico

Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy

To validate the American Thyroid Association (ATA) initial risk of recurrence scheme and the Memorial Sloan Kettering Cancer Center (MSKCC) response to therapy re‐stratification approach in a large cohort of patients with differentiated thyroid cancer (DTC) treated outside of the United States.

Dynamic Risk Stratification in Patients with Differentiated Thyroid Cancer Treated Without Radioactive Iodine

CONTEXT Although response to therapy assessment is a validated tool for dynamic risk stratification in patients with differentiated thyroid cancer (DTC) treated with total thyroidectomy (TT) and radioactive iodine therapy (RAI), it has not been well studied in patients treated with lobectomy or TT without RAI. Because these responses to therapy definitions are heavily dependent on serum thyroglobulin (Tg) levels, modifications of the original definitions were needed to appropriately classify patients treated without RAI. OBJECTIVE This study aimed to validate the response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI. DESIGN AND SETTING This was a retrospective study, which took place at a referral center. PATIENTS A total of 507 adults with DTC were treated with lobectomy (n = 187) or TT (n = 320) without RAI. They had a median age of 43.7 y, 88% were female, 85.4% had low risk, and 14.6% intermediate risk. MAIN OUTCOME MEASURE Main outcome measured was recurrent/persistent structural evidence of disease (SED) during a median followup period of 100.5 months (24-510). RESULTS Recurrent/persistent SED was observed in 0% of the patients with excellent response to therapy (nonstimulated Tg for TT < 0.2 ng/mL and for lobectomy < 30 ng/mL, undetectable Tg antibodies [TgAb] and negative imaging; n = 326); 1.3% with indeterminate response (nonstimulated Tg for TT 0.2-5 ng/mL, stable or declining TgAb and/or nonspecific imaging findings; n = 2/152); 31.6% of the patients with biochemical incomplete response (nonstimulated Tg for TT > 5 ng/mL and for lobectomy > 30 ng/mL and/or increasing Tg with similar TSH levels and/or increasing TgAb and negative imaging; n = 6/19) and all (100%) patients with structural incomplete response (n = 10/10) (P < .0001). Initial American Thyroid Association risk estimates were significantly modified based on response to therapy assessment. CONCLUSIONS Our data validate the newly proposed response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI as an effective tool to modify initial risk estimates of recurrent/persistent SED and better tailor followup and future therapeutic approaches. This study provides further evidence to support a selective use of RAI in DTC.

Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

BACKGROUND Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS Patients ages ranged from 4 to 20 years (median 14). The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up). Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014). The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

Thyroid Lobectomy Is Associated with Excellent Clinical Outcomes in Properly Selected Differentiated Thyroid Cancer Patients with Primary Tumors Greater Than 1 cm

Background and Objective. An individualized risk-based approach to the treatment of thyroid cancer is being extensively discussed in the recent literature. However, controversies about the ideal surgical approach remain an important issue with regard to the impact on prognosis and follow-up strategies. This study was designed to describe clinical outcomes in a cohort of low and intermediate risk thyroid cancer patients treated with thyroid lobectomy. Methods. Retrospective review of 70 patients who underwent lobectomy. Results. After a median follow-up of 11 years, 5 patients (5/70, 7.1%) recurred and 5 had a completion for benign lesions, while 60 patients (86%) continued to be observed without evidence for disease recurrence. Suspicious ultrasound findings were significantly more common in patients that had structural disease recurrence (100% versus 4.3%, P < 0.001). Furthermore, a rising suppressed Tg value over time was also associated with structural disease recurrence (80% versus 21.5%, P = 0.01). After additional therapy, 99% of the patients had no evidence of disease. Conclusions. Properly selected thyroid cancer patients can be treated with lobectomy with excellent clinical outcomes.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review

Spindle epithelial tumor with thymus-like element (SETTLE) is a rare malignant neoplasm of the thyroid, occurring predominantly in children, adolescents, and young adults. SETTLE usually presents itself as a thyroid mass, without metastases at diagnosis. It is believed to derive from branchial pouch or thymic remnant tissue showing primitive thymic differentiation. This article reports the clinical, cytological, histological and immunohistochemical features of a SETTLE in a 3-year-old girl. Microscopic exam revealed a nodular, highly cellular neoplasm displayed in the classic biphasic pattern, with mixture of prominent spindle cell component and a minor glandular component lined by mucinous or respiratory-type epithelium. The immunohistochemical study showed strong and diffuse positivity for pan-CK, vimentin and smooth muscle actin. The present case is the first SETTLE case reported in Brazil. To date, the patient described remains without evidence of recurrence or metastasis 5 years after surgery.

Recurrence and mortality prognostic factors in childhood adrenocortical tumors: Analysis from the Brazilian National Institute of Cancer experience

ABSTRACT Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.

Metastatic Medullary Thyroid Cancers: Challenges in Diagnosis with Nuclear Medicine Techniques and the Role of Radionuclide Therapy

Medullary thyroid cancer is a rare tumor driven from neuroendocrine cells. In the last decade there has been important discoveries regarding its genetics and relationship between genotype and phenotype on familial cases. However remains unknown the best approach for patient with maintained high levels of tumor markers such as calcitonin. Most available imaging techniques are able to accurately find metastatic lesions only in advanced disease. Traditionaly, nuclear medicine images are able to find metastatic suspicious lesions before they reach the size to be considered suspicious in conventional studies such as computed tomography scans or magnetic resonance imaging. However in patients with medullary thyroid cancer the ideal radiopharmaceutical for this purpose is yet to be found. Based on the biology of the tumor, some radiopharmaceuticals have been studied for diagnosis and also for therapy in those patients. The aim of this review is to describe the radiopharmaceuticals used for diagnosis and treatment until today and the role of each of them in medical care. In conclusion, the medullary thyroid cancer is a rare tumor and the review shows that despite all studies there is still no consensus on the importance of nuclear medicine in the diagnosis and treatment of these patients. Further studies are still needed.

Cavernous angioma mimicking a differentiated thyroid carcinoma brain metastasis.

A 30-year-old man diagnosed with follicular thyroid carcinoma treated previously with total thyroidectomy was referred to radioiodine treatment. Post-therapy scan performed 10 days after a 150 mCi 131NaI revealed radioiodine uptake in left temporal region. To elucidate the abnormal head uptake, Tc-99m MDP bone scan and head magnetic resonance image was performed. No anomalous uptake was observed in the bone scan. Head magnetic resonance image found a well-circumscribed lesion in temporal was compatible with a vascular malformation. Angioresonance confirmed the diagnosis of cavernous angioma, a benign vascular tumor.

Somatostatin receptor subtype 1 might be a predictor of better response to therapy in medullary thyroid carcinoma

PurposeMedullary thyroid carcinoma (MTC) is a malignant neoplasm of parafollicular cells. Because it is a neuroendocrine tumor, it has known somatostatin receptors (SSTRs). The actual frequencies of the SSTR subtypes and their potential influences (by binding with endogenous somatostatin) on MTC cell proliferation have not been fully elucidated to date. The present study evaluated the occurrence of SSTR subtypes 1, 2, 3 and 5 as well as the possible role that each subtype plays in the clinical evolution of patients with MTC.MethodsThis retrospective, longitudinal study analyzed thyroid surgical material from 42 patients with MTC. Immunohistochemical staining was performed with monoclonal antibodies against subtypes 1, 2, 3 and 5 of SSTR. The histological material was classified as negative, focal positive or diffuse positive, in relation to each of the SSTR subtypes. The initial response to treatment, clinical course and patient mortality rate were assessed and related to the presence of SSTR subtypes.ResultsThe most prevalent SSTR subtype was SSTR 3, which was found in 81% of the patients, when considering any pattern of positivity. However, subtype 2 had the lowest number of positive patients, with 28.6% demonstrating any positive pattern. Subtypes 1 and 5 had an intermediate prevalence of positivity, with subtype 1 present in 45.2% of the patients and subtype 5 positive in 54.8% of the patients, when considering any pattern of positivity. The presence of STR 1, in the form of diffuse positivity, independently predicted a better response to the initial therapy, with a hazard ratio (HR) of 4.80 (p = 0.03).ConclusionThis is the first study to show the correlation of the presence of SSTR1, detected by monoclonal immunohistochemical techniques, and better response to initial treatment and possibly better long-term clinical response in patients with MTC. In addition, these patients had low positivity rates for SSTR2, which might explain the low sensitivity of diagnostic and limited therapeutic response to octrotide based radioisotopes.

Recurrence and mortality in adulthood adrenocortical tumors: analysis from the Brazilian National Institute of Cancer experience.

Introduction: While adrenocortical adenomas (ACA) are usually of indolent course, carcinomas (ACC) are very aggressive, extremely rare and harbor a poor prognosis. This study aimed to describe the experience of a highcomplexity cancer center in the management of adrenocortical tumors (ACT) and additionally to identify clinical and pathology prognostic factors of recurrence and death in this population. Methods: Clinical, pathology, demographic, staging, and therapy data from patients with adulthood ACT treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed in this retrospective study. Univariate and bivariate analysis were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Results: Twenty-six patients with adrenocortical carcinoma (ACC) and 22 with adrenocortical adenoma (ACA) were included. The median tumor size was 14 cm and 3.1 cm respectively. Complete resection was achieved in only 13 patients (50%) with ACC. Mitotane was the most common adjuvant/palliative therapy (n=15). Recurrence occurred in six ACC patients, after a median time of 1.7 year. Thirteen (54%) patients with ACC died from the disease. Advanced stage (p<0.001), metastatic disease (p=0.004), incomplete tumor resection (p=0.04), and capsular invasion (p=0.04) were all associated with increased death risk. Conclusion: Complete tumor resection remains the only potential curable strategy for ACC patients. Therefore, prompt diagnosis of malignant adrenocortical tumors is essential.