Guidelines from the Brazilian society of surgical oncology regarding indications and technical aspects of neck dissection in papillary, follicular, and medullary thyroid cancers.

Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians' Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results and conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II-V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; "berry node picking" is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

Guidelines from the Brazilian society of surgical oncology regarding indications and technical aspects of neck dissection in papillary, follicular, and medullary thyroid cancers

ABSTRACT Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians' Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results/conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II-V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; "berry node picking" is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

The Impact of Zoledronic Acid and Radioactive Iodine Therapy on Morbi-Mortality of Patients with Bone Metastases of Thyroid Cancer Derived from Follicular Cells.

OBJECTIVE: Bone metastases bring greater morbi-mortality to patients with differentiated thyroid carcinoma (DTC). Treatment was limited to radioactive iodine (RAI) and local approaches. Currently, bisphosphonates are included in the therapeutic arsenal. The aim of this study is to evaluate the impact of bone metastases and their treatment with zoledronic acid (ZA) and RAI therapy. METHODS: We retrospectively review 50 DTC patients with structurally evident bone metastases followed in a tertiary cancer center from 1994 to 2018. Clinical-pathologic characteristics, skeletal related events (SRE), and therapeutic approaches were recorded. RESULTS: Among the 50 patients analyzed, 22 underwent ZA adjuvant therapy and 28 did not. Mortality rate was 44%. Those patients presented SREs more frequently (90.9 vs. 67.9% the survival group, p = 0.05) and also had a greater number of bone lesions (40.9 vs. 10.7% had more than 6 metastatic sites, p = 0.03). The same group of patients was analyzed before and after therapy with ZA and the incidence of SRE decreased from 1.81 (0-8) before therapy to 0.29 (0-7) after therapy (p = 0.006). Comparing similar groups of 22 patients treated with ZA with 28 patients not treated, there was a trend of better overall survival (OS) in the group that received this drug (147 vs. 119 months, p = 0.06) and significantly improvement when bone metastases were RAI avid 155 (125-185) versus 120 (85-157) months, p < 0.01. Conclusion : ZA can successfully diminish the chance of having new SRE and possibly affect OS in DTC patients with bone metastases. The positive impact of RAI adjuvant treatment on OS is directly associated with RAI uptake.

Impact of an inpatient multidisciplinary glucose control management program.

OBJECTIVE: Glycemic control has been increasingly recognized as a critical element in inpatient care, but optimal management of blood glucose in the hospital setting remains challenging. The aims of this study were to describe and evaluate the impact of the implementation of an inpatient multidisciplinary glucose control management program on glucose control in hospitalized patients. MATERIALS AND METHODS: Retrospective analysis of medical records and glucose monitoring data obtained by point- of-care testing (POCT) in hospitalized patients before (May 2014) and after (June 2015 and May 2017) the implementation of the program. RESULTS: We analyzed 6888, 7290, and 7669 POCTs from 389, 545, and 475 patients in May 2014, June 2015, and May 2017, respectively. Hyperglycemia (≥ 180 mg/ dL) occurred in 23.5%, 19.6%, and 19.3% POCTs in May 2014, June 2015, and May/2017, respectively (p < 0.001), while severe hyperglycemia (≥ 300 mg/dL) was observed in 2.5%, 2.2%, and 1.8% of them, respectively (p = 0.003). Hyperglycemia (≥ 180 mg/dL) reduced significantly from May 2014 to June 2015 (16.3%, p < 0.001) and from May 2014 to May 2017 (178%, p < 0.001). No significant changes occurred in hypoglycemic parameters. CONCLUSIONS: The implementation of an inpatient multidisciplinary glucose control management program led to significant reductions in hyperglycemic events. The key elements for this achievement were the development of institutional inpatient glycemic control protocols, establishment of a multidisciplinary team, and continuing educational programs for hospital personnel. Altogether, these actions resulted in improvements in care processes, patient safety, and clinical outcomes of hospitalized patients.

Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy.

BACKGROUND: To study pancreatic fat deposition and beta-cell function in familial partial lipodystrophy (FPLD) patients. METHODS: In a cross-sectional study, eleven patients with FPLD, and eight healthy volunteers were matched for age and body mass index and studied at a referral center. Body composition was assessed using dual-energy X-ray absorptiometry and the Dixon method of magnetic resonance imaging was used to quantify pancreatic and liver fat. Fasting plasma glucose, insulin, leptin, lipids and homeostasis model assessment of insulin resistance values were measured, and an oral glucose tolerance test was performed. The insulinogenic index, Matsuda insulin sensitivity index and beta-cell disposition index were calculated. RESULTS: The FPLD group presented a higher waist-to-hip ratio and fat mass ratio and lower total, truncal and lower-limb fat masses. Pancreatic and liver fat contents (log transformed) were significantly higher in the FPLD group (5.26 ± 1.5 vs. 4.08 ± 0.64, p = 0.034 and 0.77 ± 0.50 vs. 0.41 ± 0.18, p = 0.056, respectively). Pancreatic fat was inversely related to the DI (r = - 0.53, p = 0.027) and HDL-cholesterol (r = - 0.63, p = 0.003) and directly related to WHR (r = 0.60; p = 0.009), HbA1c (r = 0.58; p = 0.01) and serum triglyceride (r = 0.48, p = 0.034). Higher triglyceride and lower HDL-cholesterol levels were observed in the FPLD group. CONCLUSIONS: This study demonstrated for the first time that pancreatic fat deposition is increased in FPLD. Moreover, an inverse relationship was demonstrated between pancreatic fat and beta-cell function. The findings of this study may be consistent with the expandability hypothesis and the twin cycle hypothesis.

Impact of an inpatient multidisciplinary glucose control management program

ABSTRACT Objective: Glycemic control has been increasingly recognized as a critical element in inpatient care, but optimal management of blood glucose in the hospital setting remains challenging. The aims of this study were to describe and evaluate the impact of the implementation of an inpatient multidisciplinary glucose control management program on glucose control in hospitalized patients. Materials and methods: Retrospective analysis of medical records and glucose monitoring data obtained by point- of-care testing (POCT) in hospitalized patients before (May 2014) and after (June 2015 and May 2017) the implementation of the program. Results: We analyzed 6888, 7290, and 7669 POCTs from 389, 545, and 475 patients in May 2014, June 2015, and May 2017, respectively. Hyperglycemia (≥ 180 mg/ dL) occurred in 23.5%, 19.6%, and 19.3% POCTs in May 2014, June 2015, and May/2017, respectively (p < 0.001), while severe hyperglycemia (≥ 300 mg/dL) was observed in 2.5%, 2.2%, and 1.8% of them, respectively (p = 0.003). Hyperglycemia (≥ 180 mg/dL) reduced significantly from May 2014 to June 2015 (16.3%, p < 0.001) and from May 2014 to May 2017 (178%, p < 0.001). No significant changes occurred in hypoglycemic parameters. Conclusions: The implementation of an inpatient multidisciplinary glucose control management program led to significant reductions in hyperglycemic events. The key elements for this achievement were the development of institutional inpatient glycemic control protocols, establishment of a multidisciplinary team, and continuing educational programs for hospital personnel. Altogether, these actions resulted in improvements in care processes, patient safety, and clinical outcomes of hospitalized patients.

TERTp mutation is associated with a shorter progression free survival in patients with aggressive histology subtypes of follicular-cell derived thyroid carcinoma.

PURPOSE: Evaluate the impact of TERTp mutation on the outcomes after initial treatment of 45 patients with thyroid carcinomas derived from follicular cells (TCDFC) with aggressive histology, in which the role of this mutation is not yet well defined. METHODS: Analysis of the presence of TERTp (-124C > T and -146C > T), BRAF (V600E), and NRAS (Q 61R) mutations by Sanger sequencing and analysis of their correlation with the patient's outcomes. RESULTS: Forty-five patients with aggressive histopathologic variants were included in the study. Of these, 68.9% had aggressive variants of papillary thyroid cancer (PTC), 22.2% had poorly differentiated thyroid carcinoma (PDTC)/insular carcinoma, and 8.9% had invasive follicular thyroid cancer (FTC) with Hurthle cell features (Hurthle cell carcinoma). Lymph node metastases were present in 46.7% and distant metastases in 54.6%. The response to the initial therapy was excellent in 45.5% and structurally incomplete in 50%. During the follow-up period (median of 56 months; 5-360 months), 47.7% presented with disease progression and 17.8% experienced disease-related death. In 53.3% of the cases at least one molecular alteration (TERTp in 33.4%, BRAF in 24.5%, RAS in 8.9%) was detected. In the multivariate analysis, TERTp mutation was the factor associated with the highest risk (6 times) of having structural disease after initial therapy (p = 0.01), followed by vascular invasion (p = 0.02), gross extrathyroidal extension (ETE) (p = 0.02) and distant metastasis (p = 0.04). Regarding mutational status, only TERTp mutation was associated with disease progression, and diminished disease progression-free survival (PFS). The presence of distant metastasis, vascular invasion and gross ETE were significantly associated with the risk of disease progression. CONCLUSIONS: TERTp mutation appears be an indicator of both persistence and progression of structural disease after initial therapy in aggressive variants of TCDFC, and associates with a shorter progression free survival regardless of the therapy employed.

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy.

OBJECTIVE: To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). SUBJECTS AND METHODS: A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. RESULTS: From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). CONCLUSIONS: Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy

ABSTRACT Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Metastatic lymph node characteristics as predictors of recurrence/persistence in the neck and distant metastases in differentiated thyroid cancer

ABSTRACT Objective: The aim of this study was to evaluate the association between this characteristic and outcomes in patients with lymph node metastasis in a Brazilian cohort. Subjects and methods: This study examined a retrospective cohort of adult patients diagnosed with differentiated thyroid cancer and lymph node metastases from 1998 to 2015 in two referral centers. Number, location, size and extranodal extension (ENE) of metastatic lymph nodes were assessed and correlated with response to initial therapy. Results: A greater number of metastatic nodes, larger size, presence of lateral neck disease and ENE were all associated with a lower probability of achieving an excellent response to initial therapy (p ≤ 0.05 for all these parameters). Local recurrent disease had a significant association with lymph node number (6 in the recurrence/persistence group versus 4 in the non-recurrent group; p = 0.02) and ENE (19.2 versus 75%, p = 0.03). Lateral neck disease was the only characteristic associated with distant metastasis and was present in 52.1% of the group without metastasis and 70.4% of the group with metastasis (p = 0.001). Conclusion: The lymph node characteristics were associated with response to initial therapy and neck recurrence/persistence, confirming the importance of the analysis of these factors in risk stratification in a Brazilian population and its possible use to tailor initial staging and long term follow-up.

Predictors of subclinical atherosclerosis evaluated by carotid intima-media thickness in asymptomatic young women with type 1 diabetes mellitus

ABSTRACT Objective This study aimed to evaluate the occurrence and clinical predictors of subclinical atherosclerosis in asymptomatic, young adult women with type 1 DM. Subjects and methods The study included 45 women with type 1 diabetes mellitus (DM) (aged 36 ± 9 years) who underwent carotid Doppler ultrasound evaluation to determine the carotid artery intima-media thickness (CIMT) and to assess the occurrence of carotid artery plaques. Insulin sensitivity was assessed by estimated glucose disposal rate (eGDR), and metabolic syndrome (MS) was defined by the World Health Organization criteria. Results The cohort had a mean age of 36 ± 9 years, diabetes duration of 18.1 ± 9.5 years, and body mass index (BMI) of 24.6 ± 2.4 kg/m2. MS was present in 44.4% of the participants. The CIMT was 0.25 ± 0.28 mm, and the prevalence of carotid artery plaques was 13%. CIMT correlated positively with hypertension (p = 0.04) and waist-to-hip ratio (r = 0.37, p = 0.012). The presence of carotid artery plaques correlated positively with age (p = 0.018) and hypertension (p = 0.017). eGDR correlated negatively with CIMT (r = -0.39, p = 0.009) and carotid plaques (p = 0.04). Albuminuria showed a correlation trend with CIMT (p = 0.06). Patients with carotid artery plaques were older, had a higher prevalence of hypertension, and lower eGDR. No correlation was found between CIMT and carotid plaques with diabetes duration, MS, BMI, cholesterol profile, glycated hemoglobin, high-sensitivity C-reactive protein, or fibrinogen. Conclusion Insulin resistance, central obesity, hypertension, and older age were predictors of subclinical atherosclerosis in asymptomatic, young adult women with type 1 DM.

Predictors of subclinical atherosclerosis evaluated by carotid intima-media thickness in asymptomatic young women with type 1 diabetes mellitus.

OBJECTIVE: This study aimed to evaluate the occurrence and clinical predictors of subclinical atherosclerosis in asymptomatic, young adult women with type 1 DM. SUBJECTS AND METHODS: The study included 45 women with type 1 diabetes mellitus (DM) (aged 36 ± 9 years) who underwent carotid Doppler ultrasound evaluation to determine the carotid artery intima-media thickness (CIMT) and to assess the occurrence of carotid artery plaques. Insulin sensitivity was assessed by estimated glucose disposal rate (eGDR), and metabolic syndrome (MS) was defined by the World Health Organization criteria. RESULTS: The cohort had a mean age of 36 ± 9 years, diabetes duration of 18.1 ± 9.5 years, and body mass index (BMI) of 24.6 ± 2.4 kg/m2. MS was present in 44.4% of the participants. The CIMT was 0.25 ± 0.28 mm, and the prevalence of carotid artery plaques was 13%. CIMT correlated positively with hypertension (p = 0.04) and waist-to-hip ratio (r = 0.37, p = 0.012). The presence of carotid artery plaques correlated positively with age (p = 0.018) and hypertension (p = 0.017). eGDR correlated negatively with CIMT (r = -0.39, p = 0.009) and carotid plaques (p = 0.04). Albuminuria showed a correlation trend with CIMT (p = 0.06). Patients with carotid artery plaques were older, had a higher prevalence of hypertension, and lower eGDR. No correlation was found between CIMT and carotid plaques with diabetes duration, MS, BMI, cholesterol profile, glycated hemoglobin, high-sensitivity C-reactive protein, or fibrinogen. CONCLUSION: Insulin resistance, central obesity, hypertension, and older age were predictors of subclinical atherosclerosis in asymptomatic, young adult women with type 1 DM.

Health-related quality of life and utility values associated to hypoglycemia in patients with type 1 diabetes mellitus treated in the Brazilian Public Health System: a multicenter study.

BACKGROUND: Hypoglycemia is a critical and limiting factor of a good metabolic control and can adversely affect the quality of life of diabetic patients. The aim of the study was to evaluate the health-related quality of life and calculate utilities values associated with hypoglycemia in patients with type 1 diabetes mellitus (T1DM). METHODS: A multicenter, cross-sectional and observational study with T1DM patients from reference centers of the Brazilian public health system was conducted in three cities. Demographic and clinical data were collected, besides details on the frequency and severity of hypoglycemia. Health-related quality of life was assessed using EQ-5D instrument and utility values generated. RESULTS: 221 patients (107 women, 114 men), aged 29.8 ± 11.6 and disease duration of 14.2 ± 9.1 years were included. Most patients (n = 214, 96.8%) reported at least one symptomatic hypoglycemia in the last three months, 68% (n = 150) reported nocturnal episodes and 34.8% (n = 77) reported severe episodes. High frequency (daily or weekly) was observed in 38.6 and 26% of those reporting nocturnal or severe hypoglycemia, respectively. The median visual analog scale was 70 [60-85] for all patients, with differences between those with and without severe hypoglycemia (70 [60-80] vs 80 [61-90]; p = 0.006) and those with high and low frequency (62.5 [50-72.25] vs 70 [60-80]; p = 0.007). The median utility values was 0.801 [0.756-1.000] for all patients, with difference between those with high and low frequency of severe episodes (0.737 [0.628-1.000] vs 0.801 [0.756-1.000]; p = 0.02). CONCLUSIONS: This study shows the high frequency of hypoglycemia in a sample of T1DM patients treated in three reference centers of the Brazilian public health system and the impact of severe episodes on health-related quality of life. Utility values were generated and can be used in economic analysis for treatments that could decrease hypoglycemia and consequently improve quality of life.

Metastatic lymph node characteristics as predictors of recurrence/persistence in the neck and distant metastases in differentiated thyroid cancer.

OBJECTIVE: The aim of this study was to evaluate the association between this characteristic and outcomes in patients with lymph node metastasis in a Brazilian cohort. SUBJECTS AND METHODS: This study examined a retrospective cohort of adult patients diagnosed with differentiated thyroid cancer and lymph node metastases from 1998 to 2015 in two referral centers. Number, location, size and extranodal extension (ENE) of metastatic lymph nodes were assessed and correlated with response to initial therapy. RESULTS: A greater number of metastatic nodes, larger size, presence of lateral neck disease and ENE were all associated with a lower probability of achieving an excellent response to initial therapy (p ≤ 0.05 for all these parameters). Local recurrent disease had a significant association with lymph node number (6 in the recurrence/persistence group versus 4 in the non-recurrent group; p = 0.02) and ENE (19.2 versus 75%, p = 0.03). Lateral neck disease was the only characteristic associated with distant metastasis and was present in 52.1% of the group without metastasis and 70.4% of the group with metastasis (p = 0.001). CONCLUSION: The lymph node characteristics were associated with response to initial therapy and neck recurrence/persistence, confirming the importance of the analysis of these factors in risk stratification in a Brazilian population and its possible use to tailor initial staging and long term follow-up.

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.

An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer.

BACKGROUND: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. METHODS: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. RESULTS: Using age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. CONCLUSIONS: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.

Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer?

Objective Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors.