Denise Momesso

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.

Update on differentiated thyroid cancer staging.

In this review, we demonstrate how initial estimates of the risk of disease-specific mortality and recurrent/persistent disease should be used to guide initial treatment recommendations and early management decisions and to set appropriate patient expectations with regard to likely outcomes after initial therapy of thyroid cancer. The use of ongoing risk stratification to modify these initial risk estimates is also discussed. Novel response to therapy definitions are proposed that can be used for ongoing risk stratification in thyroid cancer patients treated with lobectomy or total thyroidectomy without radioactive iodine remnant ablation.

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.

Survival from Differentiated Thyroid Cancer: What Has Age Got to Do with It?

BACKGROUND In most staging systems, 45 years of age is used to differentiate low risk thyroid cancer from high risk thyroid cancer. However, recent studies have questioned both the precise 45 year age point and the concept of using a binary cut off as accurate predictors of disease specific mortality. METHODS A cohort of 3664 thyroid cancer patients that received surgery and adjuvant treatment at Memorial Sloan Kettering Cancer Center (MSKCC) from the years 1985 to 2010 were analyzed to determine the significance of age at diagnosis as a categorical variable at a variety of age cutoffs (5 year intervals between 30 and 70 years of age). The unadjusted and adjusted hazard ratio for the association between disease-specific survival and age was determined using a Cox proportional hazards model adjusted for other predictive variables sex, histology, and pathological T, N, and M status. Furthermore, predictive nomograms of disease-specific mortality were created and validated on an external dataset of 4551 patients to evaluate the impact of age at diagnosis as both a categorical and continuous variable. RESULTS In the MSKCC cohort, with a median follow-up time of 54 months (range 1-332), there were 59 deaths from thyroid cancer with a 10 year disease-specific survival of 96%. Adjusted hazard ratios for all age cutoffs from age 30 to age 70 years were significant. There was no specific cutoff age which risk stratifies patients with differentiated thyroid cancer (DTC). Categorizing age into five strata (<40, 40-49, 50-59, 60-69 and >70 years) showed a 37-fold increase in hazard ratio from age <40 years to age >70 years. A predictive nomogram using age as a continuous variable with other predictive variables had a high concordance index of 96%. Validation on the external cohort had a concordance index of 73%. CONCLUSIONS Mortality from DTC increases progressively with advancing age. There is no specific cutoff age which risk stratifies patients with DTC. A predictive nomogram using age as a continuous variable may be a more appropriate tool for stratifying patients with DTC and for predicting outcome.

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.

Small differentiated thyroid cancer: time to reconsider clinical management and treatment.

The incidence of differentiated thyroid cancer (DTC) is increasing worldwide, especially among small (≤2 cm) tumors. Overall, small DTC have an excellent prognosis and low mortality rate. Still, a proportion of these patients will experience recurrent/persistent disease. Careful risk stratification makes it possible to individualize treatment, avoiding unnecessary procedures and guarantees a good long-term prognosis with low recurrence risk. Recent studies evaluated the impact of the extent of surgery and radioiodine therapy, providing new evidence regarding treatment approach. Therefore, is time to reconsider clinical management and treatment of small DTC. Based on current data, in patients with small tumors and no additional risk factors, a conservative surgical approach without radioiodine therapy might be appropriated. More extensive surgery and radioiodine therapy could be proposed for small tumors exhibiting more aggressive features, such as lymph node metastasis, multifocality, vascular involvement, extra-thyroidal invasion or unfavorable molecular biology.

Long-term follow-up of patients with differentiated thyroid cancer who had negative 131I whole-body scan at first evaluation after treatment.

Purpose of the ReportThe evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglobulin (Tg) measurement and 131I whole-body scan (WBS). The first follow-up (6–12 months after initial treatment) shows the response to therapy, a prognostic factor.The aims of the study were to describe the clinical outcome during a long-term follow-up of patients with negative 131I WBS in the first evaluation, and to assess clinical and histological characteristics related to the outcome in this patient population. Patients and MethodsThis retrospective study reviewed data from 209 patients followed at 2 Brazilian hospitals. A minimum of 10 years of follow-up was required. ResultsDuring mean follow-up of 13.7 ± 4.2 years, 20% of patients developed recurrence. At the end of follow-up, 21% of patients had persistent disease. The clinical and histological characteristics related to adverse outcomes (recurrence or persistent disease) were lymph node metastases at diagnosis, high risk according to American Thyroid Association (ATA) classification, and incomplete response to treatment. Stimulated Tg levels (under thyroid hormone withdrawal) and basal Tg levels (with thyroid hormone) greater than 10 ng/mL at first evaluation were associated with an adverse outcome. ConclusionNegative WBS at first evaluation should not be used as an isolated prognostic factor. This must be considered together with histopathological (ATA classification, lymph node metastases) and clinical/laboratory characteristics (stimulated and basal Tg; response to therapy).

On the crucial ventilatory setting adjustment from two- to one-lung ventilation

Lung mechanics, histology, oxygenation and type-III procollagen (PCIII) mRNA were studied aiming to evaluate the need to readjust ventilatory pattern when going from two- to one-lung ventilation (OLV). Wistar rats were assigned to three groups: the left lung was not ventilated while the right lung received: (1) tidal volume (V(T))=5 ml/kg and positive end-expiratory pressure (PEEP)=2 cm H(2)O (V5P2), (2) V(T)=10 ml/kg and PEEP=2 cm H(2)O (V10P2), and (3) V(T)=5 ml/kg and PEEP=5 cm H(2)O (V5P5). At 1-h ventilation, V5P2 showed hypoxemia, alveolar collapse and impaired lung function. Higher PEEP minimized these changes and prevented hypoxemia. Although high V(T) prevented hypoxemia and maintained a higher specific compliance than V5P2, a morphologically inhomogeneous parenchyma and higher PCIII expression resulted. In conclusion, the association of low V(T) and an adequate PEEP level could be useful to maintain arterial oxygenation without inducing a possible inflammatory/remodeling response.

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.