Structural Incomplete Response Research Articles

Shifting paradigms in the management of pediatric differentiated thyroid cancer from static to dynamic risk stratification: a step forward toward precision medicine.

This study aimed to assess the usefulness of a risk-adopted management system known as dynamic risk stratification (DRS) in comparison with the American (ATA) and European Thyroid Associations' (ETA) risk classifications in the management of pediatric patients with differentiated thyroid cancer (DTC). The current study included 50 pediatric patients with DTC who were treated with total or near total thyroidectomy and radioiodine ablation whose risk assessment was initially defined according to the ATA and ETA guidelines. During the two years after initial treatment, patients were reclassified according to their DRS. The study showed that the ability of the DRS system to predict the final outcome was superior to that of the ATA and ETA guidelines. The observed variance in predicting final outcome was 2.3 % for ETA, 14.8 % for ATA, and 83.4 % for DRS. In intermediate/high-risk patients, according to the ATA/ETA guidelines, an excellent response to initial therapy resulted in a noteworthy reduction (about 40 %) for detection of structural disease at the time of final follow-up. The risk of structural disease at the time of final follow-up was significantly higher in the structural incomplete response group (HR = 23.34, P = 0.00) and biochemical incomplete response group (HR = 13.83, P = 0.03) than in the excellent response group. The data documented the significance of re-stratifying pediatric patients with DTC on the basis of the findings obtained at the time of or after their initial therapy (total thyroidectomy and radioiodine ablation), predominantly in the intermediate/high-risk patients. In addition, DRS helped to better modulate the later follow-up, excluding a large number of intermediate/high risk patients from needless intensive workups, allowing personalization of follow-up management.

SAT-451 Acromegaly and Thyroid Cancer

Introduction Acromegaly is associated with higher morbidity and mortality due to malignant neoplasms. However, data on the incidence and evolution of thyroid cancer in acromegaly is controversial. Objectives: To describe the clinical and biochemical characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC). Identify any predicting factor for DTC evolution. Analyze risk of recurrence (RR), initial response to treatment and response at the end of follow-up (RFU), comparing the outcomes with non-acromegalic patients with DTC. Patients and methodsRetrospective, multicenter study of 16 acromegalic patients with DTC. Acromegaly control or remission was defined with an IGF-1 ≤1 ULN with or without medical treatment (MT) respectively. AJCC Staging System 8th Edition was used for TNM staging, and the initial RR, initial response and RFU were defined according to ATA Guidelines 2015. As a control group, 56 patients with DTC without acromegaly were selected. Statistical analyses were done using SPSS Statistics 2.0. Results Median age of patients at the diagnosis of acromegaly was 44 years (range 12-69). Delay in diagnosis of acromegaly was a median of 2.5 years (range 0.5-10). Basal mean IGF-1 level was 3.2 ± 1.2 xULN. Surgery was performed in 85.7%. Post surgically, the best mean IGF-1 was 1.24 ± 0.34 xULN. Control with MT was achieved in 80%, with a median time to control since diagnosis of 21 months (6-132). Mean age at CDT diagnosis was 46.5 years (18-69). No patient had personal history of cervical irradiation. Most patients (86.7%) had normal thyroid function tests At the moment of diagnosis of DTC 62.5% of the patients had active acromegaly, IGF-1 of 2.5 ± 1.4 xULN. Median time from CDT diagnosis to acromegaly control was 1 year (0.5-7). Mean DTC tumor diameter of the bigger lesion was 13.7 ± 7.4 mm, being multifocal in 40% of the cases. All were papillary carcinoma, one case an aggressive variety. In 6/15 lymph node dissection was done, 50% with metastasis. One patient had distant metastasis. Radioiodine ablation was given to 87.5%, mean dose 115 ± 64.5 mCi. Twelve of the patients were stage I, 3 stage II and 1 IVb. Initial RR was low in 14/16, intermediate in 1 and high in 1 patient. RFU was: 13/15 with no evidence of disease, 1 patient with biochemical incomplete response and 1 with structural incomplete response, on average at 47.7 ± 33.3 months of FU. No statistically significant correlations were found between characteristics of the acromegalics and DTC outcomes. When comparing response on FU between acromegalics and controls no statistically significant differences were found. Conclusions The acromegalics with DTC had a low initial RR, that could be related to an early diagnosis of DTC (anticipated bias). We did not find any predisposing factor for unfavorable evolution. When comparing with the control group, we can conclude that DTC in acromegaly does not have a worse evolution.

In properly selected patients with differentiated thyroid cancer, antithyroglobulin antibodies decline after thyroidectomy and their sole presence should not be an indication for radioiodine ablation.

Our objective was to evaluate the trend of antithyroglobulin antibodies (TgAb) during follow-up of patients with differentiated thyroid cancer (DTC) treated without RAI, as well as their role in the risk of recurrence. This was a prospective, descriptive study. A total of 152 consecutive patients with DTC treated in a single institution undergoing total thyroidectomy without RAI and followed for a median of 2.3 years (0.5-10.3) were divided in two groups: TgAb(-) (n = 111) and TgAb(+) (n = 41). Patients were classified according to AJCC 7th and 8th editions, as well as to their risk of recurrence and response to treatment categories. Both groups, TgAb(-) and TgAb(+), were similar regarding patient and tumor characteristics. At the end of follow-up, 90 (59.2%), 57 (37.5%), 3 (2%) and 2 (1.3%) patients achieved excellent, indeterminate, biochemically incomplete and structurally incomplete response, respectively. The risk of structural recurrence was similar in both groups (TgAb[-] 0.9% vs. TgAb[+] 2.4%, p = 0.46). In the TgAb(+) group, TgAb became negative in 10 (24.4%), decreased ≥ 50% without negativization in 25 (60.9%), decreased < 50% in 4 (9.8%) and remained stable or increased in 2 (4.9%) cases. The only incomplete structural response had increasing TgAb during follow-up. In properly selected patients with DTC, TgAb concentration immediately after total thyroidectomy should not mandate RAI ablation, and their trend during follow-up may impact the risk of recurrence.

New molecular biomarkers in differentiated thyroid carcinoma: Impact of miR-146, miR-221 and miR-222 levels in the evolution of the disease.

MircroRNAs (miR) are small, noncoding RNA molecules of 18-25 nucleotides. Their dysregulation has been widely studied in many human tumours including differentiated thyroid cancer (DTC). miRs more frequently associated with these kinds of tumours are miR-146, miR-221 and miR-222. Our objective was to assess the relationship among circulating miR levels and the evolution and outcomes of disease. We analysed a sample of 60 patients with DTC assigning them to one of three groups according to the dynamic scale of risk (excellent response, incomplete biochemical response and incomplete structural response). At study inclusion, we determined thyroid-stimulating hormone, thyroxine, thyroglobulin, antithyroglobulin antibodies and plasma levels of miR-146, miR-221 and miR-222. Male sex and advanced age at diagnosis were associated with the worst disease progression. miR-222 was twofold to threefold higher in tall cell papillary carcinomas (P=0.038). miR-146 (P=0.016) and miR-221 (P=0.050) had a positive correlation with thyroglobulin at the time of sampling. In regression analysis, miR-146 (P=0.006), miR-221 (P=0.004) and miR-222 (P=0.007) predicted more than 70% of the variation in thyroglobulin levels at the time of sampling. Elevated miR-222 and miR-146 levels are associated with poorer outcomes of the disease and may have a prognostic value in the management and follow-up of DTC.

Should familial disease be considered as a negative prognostic factor in micropapillary thyroid carcinoma?

An increased aggressiveness of familial papillary thyroid carcinoma (FPTC) compared with sporadic form has been reported. On the contrary, the biological behavior of familial microPTC (FmPTC) is still debated. To assess if familial diseases should be considered as a negative prognostic factor in mPTC, the clinical presentation and outcome of FmPTC and sporadic mPTC (SmPTC) were compared. We retrospectively analyzed 291 mPTC (SmPTC n = 248, FmPTC n = 43) patients followed for a median follow-up of 8.3years. FmPTC was defined as the presence of PTC in two or more first-degree relatives, after excluding hereditary syndromes associated with PTC. FmPTC patients had more frequently bilateral tumor (32.6% versus 16.5%, p = 0.01) and lymph node metastases at diagnosis (30.2% versus 14.9%, p = 0.02). At the first follow-up, FmPTC patients had a higher rate of structural disease and a lower rate of remission compared to SmPTC (p = 0.01). Also in a multivariate model, using a "CHAID tree-building algorithm", familial disease correlated with a worse clinical presentation and outcome of mPTC patients. Familial disease was associated with a higher rate of intermediate risk patients in non incidental mPTC and with a higher rate of structural incomplete response in mPTC without lymph node metastases (p = 0.01). Like in macroPTC, the familial form of the diseases has been shown to be a negative prognostic factor also in mPTC, therefore, it should be highly regarded in the management of mPTC patients.

Radioguided occult lesion localization in patients with recurrent thyroid cancer.

Well planned re-surgery is critical for recurrent/persistent thyroid cancer (TC). We aimed to investigate the clinical outcome of radioguided-occult lesion localization (ROLL) guided surgery in patients with recurrent/persistent TC. This study includes 29 patients [F/M: 22/7, median age 43 ± 12years (18-58)] with a diagnosis of TC (22 papillary, 2 follicular and 5 medullary). Before surgery, all patients underwent ultrasonography (USG) guided mapping and intra-lesional radioactivity injection. Surgery was performed based on the excision of radioactivity injected lesions by a gamma probe and non-injected tumor foci via USG-neck map. Researchers determined surgical success by post-operative tumor markers and neck-USG. Among 29 patients, 60 metastatic lesions were identified by USG [median size 10 ± 6.3mm (range 5-30)]. Neck-USG performed after surgery provided no evidence of disease (NED) in %97 (28/29) of TC patients. In the follow-up, stimulated thyroglobulin (Tg) levels were less than 1ng/ml in 79%(19/24) of DTC patients and suppressed Tg < 0.2ng/ml was noted in 92% (22/24).In patients with DTC with an incomplete structural response, we dramatically changed the American Thyroid Association (ATA) response category and achieved an excellent response in 92% (22/24) of patients. Among patients with MTC, 5/5 patients had normal USG and calcitonin levels were reduced by 60-80% in 4/5 and > 80% in1/5 patients. In this study we have shown that, ROLL-guided surgery yielded NED rate of %97 (28/29) and increased excellent response rates according to ATA guidelines. Further studies with larger patient groups and longer follow-up should be performed to confirm the efficacy of this surgery.

The importance in diagnosing patients with conflicting observational data for post surgery radioiodinated ablation of thyroid remnants.

There is a special group of patients, according to 2015 American Thyroid Association guidelines. This group is defined as "the patients with conflicting observational data for post-surgery radioiodine ablation (COD for PSRIA)". For this special group of patients RIA is applied after a thorough reassessment of histopathological, clinical and biochemical features, including thyroglobulin (Tg). However, there is no consensus on what is the suitable cut-off value for the radioiodine ablation (RIA) decision or for therapy prediction. Moreover, is also unclear which Tg parameters should be used for these purposes. If we can determine useful and practical cut-off values for excellent response (ER) and non-structural incomplete response (non-SIR) response categories, this will facilitate our therapy response prediction before RIA and may allow us to categorize the group of "COD for PSRIA" based on a higher risk of recurrence/relapse or disease specific mortality rates according to serum thyroglobulin (Tg). This categorization may also enable us to plan the follow-up frequency of patients more scientifically. Consequently, it may provide the more efficient use of medical facility and healthcare system resources. Two hundred forty-nine patients (out of 577 examined) with "COD for PSRIA" were included in this study. Firstly, patients with indeterminate, biochemical incomplete and structural incomplete responses were considered as the non-ER group and compared to the ER group. Secondly, patients with excellent, indeterminate, and biochemically incomplete responses were considered as the non-SIR group and compared to the SIR group. The data were evaluated by MedCalc Statistical Software version 18.9. The cut-off value for ER patients was calculated as ≤6.57ng/mL. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 67.9%, 75.4%, 55.6% and 83.8%, respectively. The cut-off value for non-SIR patients was calculated as ≤12.7ng/mL. Sensitivity, specificity, PPV and NPV were 78.5%, 91.7%, 35.5% and 98.6%, respectively. If a patient has ≤6.57ng/mL pre-ablative Tg, follow-up intervals of patients with "COD for PSRIA" may be extended due to lower recurrence/relapse rates. However, if a patient has >12.7ng/mL pre-ablative Tg, these patients should be followed-up more frequently in order to determine SIR earlier. This approach may enable more efficient use of medical facility and healthcare system resources and a more scientific planning of their follow-up treatment. This approach seems to have the potential to contribute significantly to cost-effectiveness.

Long-Term Efficacy of Lymph Node Reoperation for Persistent Papillary Thyroid Cancer: 13-Year Follow-Up.

Current recommendations for persistent or recurrent locoregional papillary thyroid cancer (PTC) include consideration of surgical resection versus active surveillance. The purpose of this study is to determine long-term outcomes after surgical resection of recurrent or persistent metastatic PTC in cervical lymph nodes after failure of initial surgery and radioactive iodine therapy using newer validated clinical outcomes measures. Outcomes of 70 patients who underwent cervical lymphadenectomy (n = 110) from 1999 to 2013 for recurrent or persistent locoregional PTC metastases were reviewed. Measures included biochemical remission (BCR) based on Tg levels, American Thyroid Association classifications for response to treatment [biochemical incomplete response (BIR), structural incomplete response (SIR), indeterminate response (IR), and excellent response (ER)], need for reoperation, surgical complications, disease progression, and death. The median follow-up was 13.1years, with only two additional reoperations since 2010, one of which had no metastasis on pathology with the other developing anaplastic thyroid cancer in background PTC. ER was achieved in 31 (44%) patients, all of whom remained in ER at time of last follow-up (median 14.1years). There were no structural recurrences in patients with persistent BIR or IR after reoperation. Patients with SIR had stable disease, except for one who died due to anaplastic thyroid cancer. Patients who achieved ER after reoperation had no need for further treatment. Patients with persistent detectable Tg levels after reoperation rarely developed structural recurrence. ATA outcomes can be safely used to guide treatment decisions over a decade after reoperation for PTC.

Differentiated Thyroid Cancer Outcomes After Surgery and Activity-Adjusted 131I Theragnostics.

The aim of this study was to determine clinical outcomes in patients with differentiated thyroid cancer after surgery and activity-adjusted I therapy informed by diagnostic I scans with SPECT/CT (Dx scan). Single-institution retrospective cohort study analysis of clinical outcomes after 1 to 5 years (mean, 39.6 ± 23.4 months) of follow-up in 350 patients with differentiated thyroid cancer associated with histopathologic risk factors, nodal metastases, and/or distant metastases. Postoperatively, all patients underwent Dx scans for completion of staging and risk stratification, and I therapy was based on integration of information from histopathology, stimulated thyroglobulin and scintigraphy. Twenty-three patients (6.6%) underwent reoperative neck dissection for removal of unsuspected residual nodal metastases identified on Dx scans. Clinical outcomes were as follows: 84.3% complete response, 1.4% biochemical incomplete response, 2.3% indeterminate response, and 12% structural incomplete response. Of the entire cohort, only 8 patients (2.3%) had persistent iodine-avid metastatic disease, which required repeated I therapy. Of 31 patients with iodine-avid distant metastases identified on Dx scans, 13 patients (42%) achieved complete response with a single I treatment. Detection of regional and distant metastases on postoperative Dx scans permits adjustment of prescribed I activity for targeted treatment, as compared with fixed-activity ablation. This approach resulted in complete response after a single I treatment in 88% patients with histopathologic risk factors and regional metastases and 42% patients with distant metastases. Most patients with structural incomplete response (81%) had elevated thyroglobulin levels with negative follow-up I scans and positive PET/CT and/or CT scans consistent with altered tumor biology (non-iodine-avid disease).

Value of the Postablative Thyroglobulin Measurements for Assessment of Disease-Free Status in Patients with Differentiated Thyroid Cancer.

Aim:The aim of the study is to evaluate the value of thyroid-stimulating hormone (TSH)-stimulated thyroglobulin (sTg) measurements by the end of the 1st-year postablation in differentiated thyroid cancer (DTC) patients with biochemical non complete response (indeterminate and incomplete response).Patients and Methods:One hundred patients with DTC underwent near-total thyroidectomy and radioactive remnant ablation by iodine-131 (I131) with regular follow-up every 6 months during the first 2 years and at 6–12-month intervals thereafter by I131 whole-body scan (WBS), neck ultrasound, and sTg measurement in the hypothyroid state (TSH >30 mU/L). Patients were divided according to the imaging findings and sTg level into three groups: excellent response (ER) – no evidence of disease by imaging and sTg <1 ng/mL, indeterminate or acceptable response (AR) – nonspecific findings on imaging studies and sTg < 10 ng/mL, and incomplete response (IR) – patients with incomplete structural and/or incomplete biochemical response (sTg > 10 ng/mL).Results:The follow-up at 6-month postablation showed ER in 3 (3%) patients, AR in 29 (29%) patients, and IR in 68 (68%) patients. The second follow-up at 9–12-month postablation showed dramatic biochemical response with ER, indeterminate, and IR in 50 (50%), 34 (34%), and 16 (16%) patients, respectively, and 14 (14%) patient had structural recurrence. This change is highly statistically significant (P = 0.00). In the last follow-up (ranges from 3 to 10 years), 53 (55.8%) patients achieved ER, 42 (44.2%) AR and no patient with non complete response. The change in patients with IR between the second and the last follow-up is also statistically significant (P = 0.001).Conclusion:sTg measurement by the end of the 1st year is more reliable in the follow-up of patients with DTC and biochemical non complete response and considered significant predictor of disease-free status. Patients with biochemical IR still have the chance to achieve ER or AR by the passage of time without additional therapies.

Structural model updating using sensitivity of wavelet transform coefficients of incomplete structural response

In this paper, a structural model updating technique is presented based on the wavelet analysis of the structural responses. The sensitivity of the wavelet coefficients of the dynamic response with respect to the structural parameters is evaluated using the incomplete measured responses. To achieve an accurate sensitivity equation, measured data are incorporated in mathematical formulation. The least-square algorithm with the appropriate weighting algorithm is used for solving the over-determined system of equations. The proposed method is applied numerically to the simulated data of a 2D truss model and a 3D frame model. The results show the great promise of the wavelet transform via the proposed sensitivity-based approach for structural model updating and damage detection.

Dynamic Risk Stratification in the Follow-Up of Children and Adolescents with Differentiated Thyroid Cancer.

Risk stratification for persistent disease is an important step in pediatric differentiated thyroid cancer (DTC) management. The dynamic risk stratification (DRS) is a well validated system for adults, but not yet for children and adolescents. This study evaluated the DRS as well as other prognostic factors in pediatric DTC. Patients aged ≤18 years from four DTC tertiary teaching hospitals in Southern Brazil were included. Clinical characteristics were systematically retrieved, and all patients were classified according to the risk-stratification system of the 2015 American Thyroid Association pediatric DTC guidelines (ATA risk) and according to DRS (excellent, indeterminate, biochemical, or structural incomplete responses). Disease status was evaluated after initial therapy and at last follow-up visit. Sixty-six patients aged 14.5 ± 3.0 years were studied of whom 54 (81.8%) were girls and 62 (93.9%) had papillary thyroid carcinomas. Tumor size was 2.3 cm (P25-75 1.6-3.5); 41 (63.1%) had cervical and 18 (27.7%) distant metastasis at diagnosis. All patients underwent total thyroidectomy, and 63 (95.5%) received radioiodine. Patients were classified according to DRS after initial therapy (n = 63) as follows: 21 (33%) excellent, 13 (21%) indeterminate, 6 (9%) biochemical, and 23 (37%) structural incomplete responses. Notably, after six years (P25-75 2.7-10.0), most patients remained in the same category. Interestingly, the cutoff analysis of stimulated postoperative thyroglobulin (sPOTg) through receiver operating characteristic curve showed that the value of 37.8 ng/mL showed 81% sensitivity and 100% specificity to predict an excellent response. Prognostic factors associated with persistent disease in the univariate analysis were TNM, ATA risk, DRS, and sPOTg. DRS after initial therapy and sPOTg are strong predictors of disease outcome and might be helpful for defining follow-up strategies in pediatric DTC.

Low-Dose Radioiodine Ablation in Patients with Low-Risk Differentiated Thyroid Cancer

Aim: Based on the response criteria of the 2015 American Thyroid Associations guidelines, our objectives were to ­determine the response rate when using a low dose of ­131-I GBq in patients with low-risk differentiated thyroid cancer (LRDTC) and the influence of clinical and analytical variables on the prediction of complete response. Methods: We performed a multicentre and longitudinal study, including patients who were operated for LRDTC and who underwent radioiodine remnant ablation with a low-dose of 131-I. All patients were assessed at 6–12 months, and their status was classified as complete (excellent response) or incomplete response (structural incomplete, biochemical incomplete or indeterminate response). Various factors including age, gender, histology, tumour focality and size, stage, time from surgery to treatment, type of thyroid-stimulating hormone (TSH) stimulation, preablation serum thyroglobulin (pTg), antiTg antibodies (pAntiTgAb) and TSH (pTSH) levels were also analysed in order to predict the complete response rate. Results: Of 108 patients, 79.6% achieved complete response and the remaining showed incomplete response (2.9, 5.5 and 12% due to biochemical incomplete, structural incomplete and indeterminate response respectively). Six patients received a new dose of 131-I. Tumour size and pAntiTgAb were the only factors related to therapeutic response (p = 0.03 and p < 0.01, respectively). However, pAntiTgAb was the only independent factor related to complete ­response. Patients with complete response showed lower pTg than those with incomplete response (5.1 ± 12.9 vs. 11.2 ± 25 ng/mL) although without statistical significance (p = 0.14). There was no significant difference in the response rate depending on the thyrotropin stimulation methods. Conclusions: A low dose of 131-I was sufficient for reaching a complete response at 6–12 months of follow-up in the majority of patients with LRDTC. Tumour size and pAntiTgAb variables were related to therapeutic response.

Do aggressive variants of papillary thyroid carcinoma have worse clinical outcome than classic papillary thyroid carcinoma?

Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes. Retrospective cohort study. This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV) and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis and extrathyroidal extension. The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR = 2.16, 95% CI: 1.12-4.16, P = 0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n = 121) and matched cPTC. However, CCV group (n = 18) had significantly poorer DFS than matched cPTC group (HR = 12.19, 95% CI: 2.11-70.33, P = 0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (P = 0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR = 4.28; 95% CI: 1.66-11.00, P = 0.001). When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome, whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.

Recovery rate in differentiated thyroid cancer. Experiences of one of the Hungarian clinical centers

The worldwide incidence of differentiated thyroid cancer (DTC) has markedly increased during the last few decades. According to the international guidelines, principles of DTC management are in transformation. The aim of our work was to evaluate patients' current likelihood of recovery. Data of 380 patients treated between 1/Jan/2005 and 1/May/2016 at the PTE KK Ist Department of Internal Medicine were retrospectively analyzed. Female/male ratio was 306/74. Median age at diagnosis was 46 years (13-86 years), while median follow-up time was 55 months (0-144 months). Response to therapy was evaluable in 337 patients. Statistical analysis was done using SPSS (version 22.0). Based on the prevalence of papillary (PTC) and follicular (FTC) carcinomas (79/21%), moderate iodine deficiency has to be considered in this region. PTC patients were significantly younger and were diagnosed in earlier tumor stage. The ratio of lymph node and distant metastases was 35%/4% in PTC and 15%/14% in FTC. Radioiodine treatment was performed in a total of 542 times. 264 patients with PTC were followed up. 59% of patients were tumor-free, in 20% uncertain response, in 7% incomplete biochemical response, in 14% incomplete structural response were diagnosed and 6 patients died. Patients with FTC (n = 73) were tumor-free in 59%, uncertain response was found in 10%, incomplete structural response was diagnosed in 31%, while 10% of the patients died. In summary, although DTC has a favorable prognosis, in 31% of FTC patients and in 14% of PTC patients, tumor-free status was not achieved. During the median 55-month follow-up period, the disease-specific mortality was 10% in FTC and 2% in PTC. Orv Hetil. 2018; 159(22): 878-887.

Dynamic risk stratification system in post-lobectomy low-risk and intermediate-risk papillary thyroid carcinoma patients.

The dynamic risk stratification (DRS) and its current definition of each response-to-therapy category in post-lobectomy papillary thyroid carcinoma (PTC) patients have not been well studied. This study aimed to validate the DRS system and to investigate useful thyroglobulin (Tg) or anti-Tg antibody (Ab)-related parameters in defining each response-to-therapy category. Retrospective observational study. This historical cohort study included 619 patients with PTC treated by thyroid lobectomy. All enrolled participants were stratified according to the American Thyroid Association (ATA) initial risk stratification system and DRS system, respectively. The association between these stratifications and structural recurrence was evaluated. The median follow-up period was 103months. Structural recurrence occurred in 1.6% of the patients with excellent response, 3.8% of those with indeterminate response, 2.9% of those with biochemical incomplete response, and all patients with structural incomplete response. Five (1.5%) of the low-risk patients and 14 (5.0%) of the intermediate-risk patients had structural recurrence. The disease-free survival curves showed significant differences according to the DRS (P<.001) and ATA initial risk stratification (P=.012), respectively. The proportion of variance explained the DRS system and ATA risk stratification system for structural recurrence was 32.4% and 29.4%, respectively. A thyroid-stimulating hormone (TSH) level >2.75μU/mL at 1year after the initial operation (P<.001) was the only valuable risk factor for structural recurrence identified in this study. The long-term postoperative management of PTC patients treated with thyroid lobectomy could be guided based on the DRS.

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

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). 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). 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. 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.

Successful Treatment of Differentiated Thyroid Carcinoma with Transaxillary Robotic Surgery and Radioiodine: The First European Experience

Objectives: Transaxillary robotic thyroidectomy surgery (TARS) has been reported to be a safe approach in patients with differentiated thyroid carcinoma, and oncological responses are promising. Study Design: This study aimed to evaluate the oncological outcomes of TARS followed by radioiodine (RAI) therapy in patients with differentiated thyroid carcinoma. Between 2011 and 2016, patients treated for differentiated thyroid carcinoma by TARS in a single institution, followed by RAI, were retrospectively included. The oncological response was performed according to the 2015 American Thyroid Association (ATA) guidelines 6–12 months later and at the last available visit. Results: A total of 42 patients (30 females) were included, with a median tumor size of 20 mm (12 cases of N1a and 5 cases of N1b on initial pathology report). According to ATA classification of recurrence risk after surgery, 17 and 25 patients were classified as low and intermediate risk, respectively. After RAI, all patients had a normal posttherapeutic whole body scan (except 1 patient, who had pathological lymph node uptake), but no unusual uptake was seen. At the 6- to 12-month evaluation (n = 37), 24 patients had excellent response, 8 had indeterminate response, and 5 had incomplete response (2 biological and 3 structural); no distant metastasis was found. At the last evaluation (median follow-up 15.9 months), 35 patients had no evidence of disease and 1 patient had a structural incomplete response. In total, a second open surgery was necessary for 3 patients to treat persistent lymph nodes (all intermediate risk). Conclusion: In this study, TARS followed by RAI therapy seems to be curative, even for patients with lymph node metastases, after good preoperative staging. More studies are required to confirm the findings.

Delayed initial radioiodine therapy related to incomplete response in low- to intermediate-risk differentiated thyroid cancer.

Whether the initiating time of radioiodine (RAI) therapy will affect the clinical outcome in differentiated thyroid cancer (DTC) remains controversial. The objective of this study was to evaluate the impact of RAI therapy initiating time on response to initial therapy in low- to intermediate-risk DTC. A total of 235 consecutive patients with low- to intermediate-risk DTC were retrospectively reviewed. According to the time interval between thyroidectomy and RAI therapy, patients were divided into Group 1 (interval<3months, n=187) and Group 2 (interval≥3months, n=48). Response to RAI therapy was evaluated as excellent, indeterminate, biochemical incomplete or structural incomplete response (ER, IDR, BIR or SIR) with a median follow-up of 780days. The univariate and multivariate analyses were further conducted to identify factors associated with incomplete response (IR, including BIR and SIR). Response to initial therapy was significantly different between 2 groups (P<.05), after excluding the impact of other risk factors (age, gender, histological type, status of T and N, RAI dose, thyrotropin, stimulated thyroglobulin and follow-up time). A significantly higher IR rate (18.8% vs 4.3%, P=.001) and a lower ER proportion (62.5% vs 78.1%, P=.027) were observed in Group 2. By univariate analysis, both T status and N status, stimulated thyroglobulin and time interval were significant risk factors for IR (P<.05). Multivariate analysis demonstrated that the time interval was an independent risk factor for IR (P=.008). Delayed initial RAI therapy (≥3months after thyroidectomy) related to incomplete response in low- to intermediate-risk DTC.

An Increased Neutrophil-to-Lymphocyte Ratio Predicts Incomplete Response to Therapy in Differentiated Thyroid Cancer

Background: Previously we have shown that an elevated baseline neutrophil-to-lymphocyte ratio (NLR) was associated with a high risk of recurrence in patients with differentiated thyroid cancer. The clinical significance of the longitudinal changes in NLR following treatment remained unestablished.Methods: Adults patients with differentiated thyroid cancer were included in the study if the follow-up NLR data at 6 to 18 months after initial treatment were available. The response to treatment was categorized as excellent, indeterminate, biochemical incomplete, and structural incomplete as per guidelines of the American Thyroid Association.Results: Among 151 patients with thyroid cancer, a significant decrease in NLR following treatment was observed in those with stage I disease, those with low risk of recurrence, and those with an excellent response to therapy. Patients with a structural incomplete response had a significant increase in NLR at follow-up (p = 0.012). On multivariate analysis, incomplete response to therapy was associated with male sex (odds ratio [OR] = 3.35), tumor size (OR = 1.63), lymph node metastasis (OR = 4.80), distant metastasis (OR = 12.95), and increased NLR (OR = 13.68).Conclusions: An increase in systemic inflammation following treatment as measured by NLR is independently associated with an incomplete response to therapy in differentiated thyroid cancer.