Impact of historic histopathologic sample review on the risk of recurrence in patients with differentiated thyroid cancer.

OBJECTIVE: To compare the historic risk of recurrence (RR) and response to therapy to risk stratification estimated with historical pathology reports (HPRs) and contemporary re-review of the pathological slides in patients with differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: Out of 210 DTC patients with low and intermediate RR who underwent total thyroidectomy and remnant ablation in our hospital, 63 available historic pathologic samples (HPS) were reviewed. The RR and the response to therapy were evaluated considering historical histological features (histological type, tumor size, capsular invasion, number of lymph node metastases) and then, reassessed after observing additional histological features (vascular invasion, extrathyroidal extension, size of lymph node metastases, presence of extranodal extension, and/or status of the resection margins). RESULTS: A change in the RR category was observed in 16 of 63 cases (25.4%). Out of 46 patients initially classified as low RR, 2 patients were reclassified as intermediate RR, 4 as high RR, and 1 as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Out of 17 patients initially classified as intermediate RR, 3 were reassigned to the low RR group, 5 as high RR, and 1 as NIFTP. The percentages of structural incomplete response at final follow-up changed from 2.2 to 0% (p = 1) in patients with low RR and from 6.3 to 20% (p = 0.53) in patients with intermediate RR. CONCLUSION: A detailed report of specific features in the HPR of patients with DTC might give a more accurate RR classification and a better estimation of the response to treatment.

Impact of historic histopathologic sample review on the risk of recurrence in patients with differentiated thyroid cancer

ABSTRACT Objective To compare the historic risk of recurrence (RR) and response to therapy to risk stratification estimated with historical pathology reports (HPRs) and contemporary re-review of the pathological slides in patients with differentiated thyroid cancer (DTC). Subjects and methods Out of 210 DTC patients with low and intermediate RR who underwent total thyroidectomy and remnant ablation in our hospital, 63 available historic pathologic samples (HPS) were reviewed. The RR and the response to therapy were evaluated considering historical histological features (histological type, tumor size, capsular invasion, number of lymph node metastases) and then, reassessed after observing additional histological features (vascular invasion, extrathyroidal extension, size of lymph node metastases, presence of extranodal extension, and/or status of the resection margins). Results A change in the RR category was observed in 16 of 63 cases (25.4%). Out of 46 patients initially classified as low RR, 2 patients were reclassified as intermediate RR, 4 as high RR, and 1 as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Out of 17 patients initially classified as intermediate RR, 3 were reassigned to the low RR group, 5 as high RR, and 1 as NIFTP. The percentages of structural incomplete response at final follow-up changed from 2.2 to 0% (p = 1) in patients with low RR and from 6.3 to 20% (p = 0.53) in patients with intermediate RR. Conclusion A detailed report of specific features in the HPR of patients with DTC might give a more accurate RR classification and a better estimation of the response to treatment.

Prevalencia de enfermedades tiroideas en una población del área metropolitana de Buenos Aires / Prevalence of thyroid diseases in a population of the metropolitan area of Buenos Aires

La prevalencia de alteraciones morfológicas palpables tiroideas no supera el 8% en la población adulta. En el Hospital de Clínicas de la Universidad de Buenos Aires se llevó a cabo un programa gratuito para la detección de enfermedades tiroideas, convocándose a sujetos que desconocieran antecedentes tiroideos. Nuestro objetivo fue establecer la frecuencia de patología morfológica palpable tiroidea, en una población seleccionada de pacientes, y comparar dichos resultados con los hallazgos de un programa de detección similar, realizado en el año 2001¹. Adicionalmente, evaluar la prevalencia de alteraciones funcionales y de autoinmunidad tiroidea. Los individuos que concurrieron se dividieron en 3 grupos: Grupo 1 (n = 186) pacientes con antecedentes personales de enfermedad tiroidea conocida (excluidos del análisis); Grupo 2 (n = 184) sujetos con antecedentes familiares, otras enfermedades autoinmunes, o sintomatología que pudiera atribuirse a alteración de la función tiroidea (grupo inducido), y Grupo 3 (n = 288) sujetos que consultaron por mera curiosidad (grupo random). La función y autoinmunidad tiroidea se evaluó en 144 participantes del Grupo 3, citados al azar. En el grupo random, la prevalencia de alteraciones morfológicas tiroideas, detectadas por palpación, fue del 11,09%. Al comparar estos resultados con los obtenidos 12 años atrás en un estudio similar, realizado en nuestro hospital, no se encontraron diferencias estadísticamente significativas (8,7 vs. 11,09%; p = 0,25). En cuanto a la función tiroidea, se halló hipotiroidismo subclínico en el 6,25%, hipertiroidismo subclínico en el 0,7% y autoinmunidad en el 11% de los sujetos evaluados. En conclusión, la prevalencia de alteraciones palpables de la glándula tiroides no cambió en laúltima década. Esta investigación realizada en una población correctamente seleccionada constituye una herramienta útil para referencias futuras como población control en Argentina.

The prevalence of palpable thyroid morphological abnormalities does not exceed 8% in the adult population. A free program was conducted in the Hospital de Clínicas (University of Buenos Aires) for the detection of thyroid diseases, inviting subjects who were unaware of a history of these diseases. The aim was to establish the frequency of goitre in the selected population, as well as to evaluate the prevalence of functional disorders and thyroid autoimmunity, and to compare these results with the findings of a similar study performed in 2001¹. The subjects were divided into three groups: Group 1 (n = 186) patients with a history of previously known thyroid disorders (excluded subjects); Group 2 (n = 184) subjects with a family history of thyroid disease, other autoimmune diseases, or symptoms that could be attributed to changes in thyroid function (Induced Group), and Group 3 (n = 288) subjects who participated in this program due to mere curiosity (Random Group). Autoimmunity and thyroid function was assessed in 144 randomly selected participants in Group 3. In Group 3, the prevalence of morphological alterations of the thyroid gland was 11.09%. Comparing these results with those obtained 12 years ago in a similar study performed in our hospital, no statistically significant differences were found when the prevalence of morphological thyroid alterations were compared (8.7% vs 11.09%, p=.25). As for thyroid function, subclinical hypothyroidism was found in 6.25%, subclinical hyperthyroidism in 0.7%, and autoimmunity in 11% of subjects evaluated. It was concluded that the prevalence of palpable thyroid abnormalities had not change in the last decade. This study, made in a correctly selected population, is a useful tool for future reference as a control population in Argentina.

Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer.

Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.

Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer

Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.

Implementing the Modified 2009 American Thyroid Association Risk Stratification System in Thyroid Cancer Patients with Low and Intermediate Risk of Recurrence.

OBJECTIVE: The primary purpose of this study was to validate the proposed modified 2009 American Thyroid Association Risk Stratification System (M-2009-RSS) in patients with thyroid cancer and to compare the findings with those of the 2009 ATA Risk of Recurrence (2009 ATA-RR) and the Ongoing Risk of recurrence system. The secondary purpose was to assess which risk stratification system had the best predictive value to foresee the probability of structural incomplete response or the no evidence of disease (NED) status at the end of follow-up. SUBJECTS AND METHODS: This retrospective review included 149 patients with differentiated thyroid cancer who had low and intermediate 2009 ATA-RR and were treated at a single experienced center and followed-up for a median of 6 years (range 3-12 years). Each patient was risk stratified using both the 2009 ATA-RR and the M-2009-RSS. The primary endpoints were 1) the best response to initial therapy defined as either excellent response, biochemical or structural incomplete response, or indeterminate response; 2) clinical status at final follow-up defined as either NED, biochemical incomplete response, structural incomplete response, indeterminate response, or recurrence (biochemical or structural disease identified after a period of NED), and 3) ongoing RR defined as low or high risk according several outcomes after initial treatment. RESULTS: Mean age of included patients was 45.3±13 years. Both the ATA 2009-RR and the M-2009-RSS provided clinically meaningful graded estimates with regard to the status of NED at the end of follow-up in low-risk patients (84% for 2009 ATA-RR and 74% for M-2009-RSS) or the likelihood of having persistent structural disease (0% for 2009 ATA RR and 3.6% for the M-2009-RSS). When patients were classified as low risk, the positive predictive value (PPV) and negative predictive value (NPV) to predict structural disease was 0% and 88.7% for the 2009 ATA-RR, 3.6% and 86.5% for the M-2009-RSS, and 1.6% and 68.2% for the ongoing RR (p=0.022 and 0.055 of chi-square test for PPV and NPV, respectively). CONCLUSIONS: Despite expanding the definition of low risk to include small-volume lymph node metastases, minor extrathyroidal extension, and minimally invasive follicular thyroid cancer, the M-2009-RSS predicts clinical outcomes (structural incomplete response and NED at the end of follow-up) that are very similar to the previously validated 2009 ATA RR classification system.

Insulin resistance is another factor that increases the risk of recurrence in patients with thyroid cancer.

The objective of this study was to evaluate the initial response to treatment and the long-term outcome of patients with papillary thyroid cancer (PTC), according to the modified 2014 risk of recurrence classification of the American Thyroid Association and the presence or absence of insulin resistance (IR). We retrospectively reviewed our database of 636 records and selected 171 patients in whom we had previously validated the ATA risk of recurrence (RR) classification. From these patients, 38 non-diabetic subjects were included for analysis according to the following criteria: age older than 18 years, classic papillary thyroid carcinoma, stable body mass index 5 years previous to PTC diagnosis and during the entire time of follow-up, low and intermediate RR, follow-up after initial treatment at least for 3 years, and absence of any drug treatment for the metabolic syndrome. The IR was evaluated through the homeostasis model assessment (HOMA) index. When equal or higher than 2.5, patients were considered as harboring IR. The initial response to treatment was classified as remission or persistent disease (biochemical and/or structural). The clinical status at final follow-up was defined as no evidence of disease, biochemical persistent disease, structural persistent disease, or recurrence (biochemical or structural disease identified after a period of no evidence of disease). RR was as follows: low: n=15, intermediate: n=23. The median follow-up of this patient cohort was 5.5 years (range 3-22 years). We found no statistically significant differences when the response to initial treatment was considered in low-risk patients with or without IR. However, remission was more frequently found in those patients without IR when the intermediate RR was considered (36 vs. 11%, p=0.01). When considering the status at final follow-up, we found more frequency of structural persistent disease in both, low and intermediate RR patients with IR (10 vs. 0%, p=0.02 and 45 vs.7%, p=0.01, respectively). In this series of patients with PTC, the state of IR was associated with increased frequency of structural persistent disease at final follow-up. The IR could have a deleterious effect on the outcome of patients with PTC.

Biochemical persistence in thyroid cancer: is there anything to worry about?

To evaluate the outcome of differentiated thyroid cancer (DTC) patients with biochemical persistence of disease (BP) after initial treatment (total thyroidectomy with or without lymph node dissection (LND) and thyroid remnant ablation). BP was defined as suppressed thyroglobulin (Tg) levels <1 ng/ml and rhTSH-stimulated thyroglobulin (St-Tg) >1ng/ml, with no evidence of structural disease. Structural persistence/recurrence (SPR): clinically identifiable disease. We reviewed 278 records of DTC patients. Tg-Ab positive patients (n = 73) were excluded and 32 were included in the analysis (median age 45 years, range 18-77 years); risk of recurrence ATA was: low in 38 %, Intermediate in 47 %, and high in 15 % of patients. All subjects had Tg levels <1 ng/ml under thyroid hormone therapy. Patients were divided into three groups: Group 1: St-Tg 1-2 ng/ml, n = 6; Group 2: St-Tg 2-10 ng/ml, n = 17; Group 3: St-Tg > 10 ng/ml, n = 9. In 5/32 (16 %) patients, SPR was observed after a median follow-up of 6 years (range 2-23 years). In Group 1: all patients were considered with no evidence of disease after a median follow-up of 2 years (range 1-2.5 years). In Group 2: 13/17 (76.5 %) patients continued with only a BP after a median follow-up of 4 years (range 2-10 years) and 4/17 (23.5 %) patients with intermediate risk of recurrence had a structural persistence (lymph nodes metastasis) diagnosed between 1 and 3.5 years after initial assessment. Following LND, all of them remained with BP after a median of 2 years (range 1.5-5 years). In Group 3: 8/9 (89 %) patients had BP after a median follow-up of 7 years (range 2-23 years) and 1/9 (11 %) had a SPR diagnosed 28 months after initial assessment, LND was indicated but he continued with BP, 5 years after the second surgery. Most patients with DTC and BP present an indolent course of the disease. In these patients the diagnosis of the structural recurrence did not change the outcome because all of them continued with BP.

Outcomes of patients with differentiated thyroid cancer risk-stratified according to the American thyroid association and Latin American thyroid society risk of recurrence classification systems.

OBJECTIVES: The aims of this study were to validate the proposed Latin American Thyroid Society (LATS) risk of recurrence stratification system and to compare the findings with those of the American Thyroid Association (ATA) risk of recurrence stratification system. SUBJECTS AND METHODS: This study is a retrospective review of papillary thyroid cancer patients treated with total thyroidectomy and radioactive iodine at a single experienced thyroid cancer center and followed according to the LATS management guidelines. Each patient was risk-stratified using both the LATS and ATA staging systems. The primary endpoints were (i) the best response to initial therapy defined as either remission (stimulated thyroglobulin [Tg] <1 ng/mL, negative ultrasonography) or persistent disease (biochemical and/or structural), and (ii) clinical status at final follow-up defined as no evidence of disease (suppressed Tg <1 ng/mL, negative ultrasonography), biochemical persistent disease (suppressed Tg >1 ng/mL in the absence of structural disease), structural persistent disease (locoregional or distant metastases), or recurrence (biochemical or structural disease identified after a period of no evidence of disease). RESULTS: One hundred seventy-one papillary thyroid cancer patients were included (mean age 45 ± 16 years, followed for a median of 4 years after initial treatment). Both the ATA and LATS risk stratification systems provided clinically meaningful graded estimates with regard to (i) the likelihood of achieving remission in response to initial therapy, (ii) the likelihood of having persistent structural disease in response to initial therapy and at final follow-up, (iii) the likely locations of the persistent structural disease (locoregional vs. distant metastases), (iv) the likelihood of recurrence, and (v) the likelihood of being no evidence of disease at final follow-up. The likelihood of having persistent biochemical evidence of disease was not significantly different across the staging categories. CONCLUSIONS: Both the ATA and LATS risk of recurrence systems effectively risk-stratify patients with regard to multiple important clinical outcomes. When used in conjunction with a staging system that predicts disease-specific mortality, either of these systems can be used to guide risk-adapted individualized initial management recommendations.