Dynamic risk allows us to adequately select patients with differentiated thyroid cancer who do not require radioiodine treatment

ABSTRACT Objective: The treatment of patients with differentiated thyroid cancer (DTC) was modified in the last decade towards a more individualized approach according to the risk of recurrence (RR). We compared the outcomes of patients with low and intermediate RR (LRR and IRR) who received or did not receive radioiodine remnant ablation (RRA) after assessing the dynamic risk. Materials and methods: We included 307 DTC patients with LRR and IRR submitted to total thyroidectomy. All patients were reclassified according to the dynamic risk stratification (low or high). Patients with high dynamic risk received RRA (141 patients). Results: LRR patients who received RRA presented a frequency of structural incomplete response (SIR) of 5% at the end of the follow-up, compared to 2% in those who did not receive it (p=0.353). IRR patients treated with RRA had a frequency of SIR of 22%, compared to 5% in patients without RRA (p=0.008). Conclusions: This study demonstrates the usefulness of dynamic risk assessment to decide RRA in a cohort with a long-term follow-up. The lower prevalence of SIR at the end of the follow-up in patients who did not receive RRA highlights the adequate selection of those who would not benefit from RRA, even with an intermediate risk of recurrence.

Riesgo dinámico en cáncer diferenciado de tiroides: comparación entre pacientes ablacionados con aquellos no ablacionados de bajo riesgo y riesgo intermedio de recurrencia

RESUMEN El enfoque actual de los pacientes con carcinoma diferenciado de tiroides (CDT) es individualizado de acuerdo al riesgo de recurrencia (RR) de la enfermedad. La clasificación estática del RR inicial podría mejorarse al aplicar el denominado riesgo dinámico, que resulta de adicionar al RR, los hallazgos que surgen durante el seguimiento. Los objetivos de este trabajo fueron comparar pacientes ablacionados de bajo RR y riesgo intermedio estático que recibieron ablación inmediatamente luego de la cirugía vs. los no ablacionados de bajo riesgo dinámico. Secundariamente, comparar la población de pacientes ablacionados de bajo riesgo estático vs. los no ablacionados de bajo riesgo dinámico. Se incluyeron 412 pacientes, 309 ablacionados (Grupo 1: G1), y 103 no ablacionados (Grupo 2: G2). El G1 también incluyó a 29 pacientes que fueron ablacionados al observar el riesgo dinámico (Tg bajo terapia hormonal > 5 ng/ml). La frecuencia de respuesta estructural incompleta (REI) al inicio y al final del seguimiento fue mayor en el grupo de pacientes ablacionados de bajo RR y riesgo intermedio estático comparados con los no ablacionados de bajo riesgo dinámico (11,3% vs 0,9%: p=<0,001). La frecuencia de respuesta excelente al final del seguimiento fue mayor en los no ablacionados de bajo riesgo dinámico vs. ablacionados de bajo RR y riesgo intermedio estático (72,8% vs 62,1%: p=0,058). En conclusión, los pacientes ablacionados de bajo RR y riesgo intermedio presentaron una mayor frecuencia de REI que los no ablacionados adecuadamente seleccionados, al tener en cuenta el RR inicial. En cambio, al comparar pacientes ablacionados de bajo RR estático vs. no ablacionados de bajo riesgo dinámico, la REI fue similar. Estos resultados avalan la conducta de no ablacionar a aquellos pacientes de riesgo intermedio de recurrencia que presentan en el seguimiento un bajo riesgo dinámico.

ABSTRACT The current approach of patients with differentiated thyroid carcinoma (DTC) is individualized according to the risk of recurrence (RR) of the disease. The static classification of the initial RR could be improved by applying the dynamic risk of recurrence to decide remnant ablation. The dynamic risk definition arise from the findings obtained during the initial follow-up. The aim of this manuscript is to compare the response to treatment in patients with low and intermediate static RR in whom the decision for radioiodine remnant ablation (RRA) was performed immediately after surgery with those non-ablated patients with low dynamic RR. Secondary, to compare the responses to treatment in ablated patients with low static RR compared with those non-ablated low dynamic RR. We included 412 patients, they were divided in two groups Group 1 (G1): n=309 ablated patients and Group 2 (G2): n=103 non-ablated patients. G1 also included 29 patients who received remnant ablation considering the dynamic risk (Tg levels > 5 ng/ml). The initial structural incomplete response (SIR) was greater in G1 compared with G2 (11.3% vs 0.9%: p = <0.001). The frequency of an excellent response at the end of follow-up was similar in G2 compared with low initial RR of G1 (72.8% vs. 62.1%: p = 0.058). In conclusion, low and intermediate static RR ablated patients had a higher frequency of SIR compared with non-ablated patients in the dynamic risk assessment. In contrast, the frequency of SIR was similar when ablated patients of low static RR were compared with those non-ablated patients of low dynamic risk. These results show how the dynamic RR helps to move those intermediate RR patients on the low RR decreasing the need for RRA.

Comparación de la respuesta inicial luego de la ablación con 30 mCi de 131I versus no ablación en pacientes con cáncer diferenciado de tiroides de bajo riesgo de recurrencia. Estudio prospectivo multicéntrico / Comparison of initial response to treatment after remnant ablation (RA) with 30 mCi of 131 I versus no RA in patients with differentiated thyroid cancer with low risk of recurrence. Multicentric prospective study

RESUMEN Material y métodos Estudio prospectivo multicéntrico. Se incluyeron 174 pacientes con CDT tratados consecutivamente desde junio 2014 hasta mayo 2015. Se los dividió en 2 grupos (ablacionados y no ablacionados) con 87 pacientes incluidos en cada uno. La respuesta inicial al tratamiento se determinó con la medición de tiroglobulina, anticuerpos anti-tiroglobulina y ecografía de cuello. Resultados Se compararon las características basales de ambos grupos y no se evidenciaron diferencias estadísticamente significativas: sexo femenino 84% y 88% (p = 0,5); edad promedio de 46,8 y 47,5 años (p = 0,7); carcinoma papilar variedad clásico 68% y 75,9% (p = 0,15), respectivamente. El resto de las características basales como tamaño tumoral, bilateralidad, multifocalidad, tiroiditis de Hashimoto y estadio tumoral tampoco mostraron diferencias significativas. La evaluación de la respuesta inicial al tratamiento se realizó en 64 pacientes del grupo ablacionado y en 76 del grupo no ablacionado. Se observó una respuesta excelente en 81% de pacientes ablacionados vs. 87% del grupo no ablacionado, con una frecuencia de respuesta estructural incompleta de 1,6% y 1,4%, respectivamente, (p = 0,9). Un 17% de los ablacionados y 12% de los no ablacionados presentaron una respuesta indeterminada. Conclusión: Los pacientes de bajo riesgo, ablacionados o no, presentan similares frecuencias de respuesta inicial excelente y estructural incompleta. El seguimiento a largo plazo podrá definir si estas respuestas iniciales se mantienen en el tiempo, lo que permitirá reducir la indicación de ablación con radioyodo en este grupo de pacientes con CDT.

ABSTRACT Patients and methods We included 174 patients; 87 patients in each group (ablated and nonablated). Assessment of the initial response to treatment was performed by measurement of thyroglobulin and anti-thyroglobulin antibodies and by neck ultrasonography. Results Baseline characteristics of both groups were compared, and no statistically significant differences were found: female sex 84% and 88,5%, respectively, (p = 0.5); mean age of 46.8 and 47.5 years, respectively (p = 0.7); papillary carcinoma classic variant 68% and 75.9%, respectively (p = 0.15). The remaining of the baseline characteristics such as tumor size, presence of bilaterality, multifocality, Hashimoto's thyroiditis and tumor stage were not statistically significant, either. The evaluation of the response to treatment was finally performed in 64 patients from the ablated group and in 76 from the non-ablated group. An excellent response to treatment was observed in 81% of ablated patients vs. 87% of the non-ablated group, with a frequency of structural incomplete response of 1.6% and 1.4%, respectively (p = 0.9). On the other hand, 17% and 12% of patients in each group had an indeterminate response. Conclusion Low-risk ablated and non-ablated patients have a similar frequency of excellent initial and structural incomplete response to treatment. Long-term follow-up is needed to establish whether these initial responses are maintained over time, and thus further refine the indications of RA in this group of patients with DTC.

Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq

BACKGROUND: After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of 131I on whole body scans (WBSs), called a ‘star artifact.’ We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis. METHODS: Total 636 patients who received 131I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS. RESULTS: In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts. CONCLUSION: Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Riesgo dinámico en pacientes con cáncer diferenciado de tiroides no ablacionados / Dynamic risk assessment in patients with differentiated thyroid cancer without remnant ablation

En la actualidad, el enfoque terapéutico y el seguimiento de los pacientes con carcinoma diferenciado de tiroides (CDT) es individualizado de acuerdo con el riesgo de recurrencia de la enfermedad, con una menor tendencia a ablacionar a pacientes de bajo riesgo de recurrencia. Por otro lado, la evaluación de las respuestas al tratamiento se validó en pacientes tratados con tiroidectomía total (TT) y ablación con radioyodo (RAI), pero son escasos los estudios en pacientes no ablacionados. Los objetivos de este estudio fueron describir las características de una población de pacientes con CDT no ablacionados y validar las respuestas al tratamiento durante el seguimiento. Se incluyó a 88 pacientes con un seguimiento mínimo de 12 meses. El 87,6% eran mujeres y la edad promedio en el momento del diagnóstico fue de 47,5 años. Basados en el Consenso Intersocietario Argentino, el 97,7% de la cohorte fue clasificada como de bajo riesgo y el 2,3% como de riesgo intermedio de recurrencia. Los pacientes presentaron una respuesta inicial excelente en el 73% de los casos, con un estado sin evidencia de enfermedad al final del seguimiento en el 85,5%. Una minoría de los pacientes (1%) presentó una respuesta inicial estructural incompleta, la cual fue similar al final del seguimiento (1%). Por otro lado, el 26% de los pacientes presentó una respuesta inicial indeterminada, aunque solo el 13,5% permaneció con esta respuesta al final del seguimiento. Nuestros datos validan las respuestas al tratamiento en pacientes con CDT que recibieron TT no ablacionados como una herramienta efectiva para la estratificación del riesgo dinámico. Los pacientes apropiadamente seleccionados tratados sin RAI tienen un excelente pronóstico, con una baja frecuencia de respuesta estructural incompleta en el seguimiento, inclusive menor que la de los pacientes de bajo riesgo ablacionados.

The therapeutic approach and the follow-up of patients with differentiated thyroid cancer (DTC) is currently individualised according to the risk of recurrence, with a lower tendency to perform remnant ablation (RA) in patients with low risk of recurrence. While response to therapy assessment has been validated for DTC patients treated by total thyroidectomy (TT) and RA, it has not been widely confirmed in patients treated with TT without RA. The aims of this study were to describe the characteristics of the population of patients treated with TT without RA, and to validate the response to therapy. The study included 88 patients followed-up for at least 12 months after surgery. In the entire cohort, 87.9% were female and the mean age was 47.5 years old. Based on the Argentine Intersociety Consensus, 97.7% and 2.3% were classified as low risk and intermediate risk of recurrence, respectively. Patients had an initial excellent response to treatment in 73% of cases, with a disease-free status at the end of follow-up of 85.5%. A minority of patients (1%) presented with an initial structural incomplete response, which was similar at the end of follow-up (1%). On the other hand, 26% of the patients had an initial indeterminate response, although only 13.5% remained with this response at the end of follow-up. These results validate the responses to treatment in DTC patients treated with TT without RA as an effective tool for the dynamic risk stratification. Patients appropriately selected who did not receive RA have an excellent outcome, with a low frequency of structural incomplete response, even lower than that observed in low risk ablated patients.

The impact of lymph node metastatic rate on clinical outcome following131I therapy in patients with papillary thyroid carcinoma / 中国癌症杂志

Background and purpose:This study aimed to investigate the relationship between lymph node metastatic rate (LR) and response to radioiodine therapy in patients with papillary thyroid carcinoma (PTC).Methods:A total number of 143 PTC patients after radioiodine therapy were included and classified into 4 groups [Ⅰ(0%-10%),Ⅱ(>10%-25%),Ⅲ(>25%-50%),Ⅳ(>50%)] according to the lymph node metastatic rate, and the responses to initial radioiodine therapy after a median follow-up period of 20.7 months were evaluated. They were classiifed into 4 groups [excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and struc-tural incomplete response (SIR)] according to the guideline proposed by 2015 American Thyroid Association. One-Way analysis of variance,χ2 test and Kruskal-Wallis test were used to evaluate the differences in basic clinicopathological features and clinical responses among the 4 groups. The ROC curve was analyzed to evaluate the clinical value of lymph node metastatic rate for predicting ER and optimal cut-off point.Results:There were no signiifcant differences in gender and T-stage among 4 groups (P>0.05). However,Ⅰ group was signiifcantly older than the other 3 groups (P=0.001). With the increase of lymph node metastatic rate, the number of ER cases decreased, while cases of BIR and SIR generally increased. Compared with the other 3 groups, less cases of ER (27.8%), while more BIR (27.8%) or SIR (11.1%) were observed in groupⅣ (H=18.816,P=0.000). Cut-off value of lymph node involved rate was 52.27%, with a better speciifcity of predicting ER. Area under the ROC curve was 0.668.Conclusion:The higher lymph node metastatic rate in patients with PTC, the worse clinical outcome it could be. A cut-off value of lymph node metastatic rate 52.27% is a speciifc independent predictor for the clinical outcome in PTC patients treated with radioiodine therapy.

Changes in Quality of Life and Related Factors in Thyroid Cancer Patients with Radioactive Iodine Remnant Ablation

PURPOSE: To investigate changes in Quality of life (QOL) and related factors in patients with thyroid cancer undergoing Radioactive Iodine remnant ablation (RAI). METHODS: Data were collected longitudinally 3 times for 6 months (2 weeks post-surgery, post RAI, 3 months post RAI) in a hospital located in Seoul. Questionnaires were used to measure levels of physical symptoms, anxiety, depression, and QOL. Ninety-eight patients with thyroid cancer who had RAI were included in the analysis. Data were analyzed using SPSS (18.0). RESULTS: Findings for the three data collection times respectfully were: mean scores for physical symptoms, 0.53, 1.21 and 0.62, patients with depression, 47%, 36.7% and 37.7%, patients with anxiety, 18.4%, 19.4% and 20.4%, mean scores for QOL, 7.06, 7.01 and 7.28. QOL score was highest 3 months post RAI (p=.031). In the stepwise multiple regression analysis, depression and fatigue were predicting factors for low QOL at all data collection times. Dysponia was a predicting factor for low QOL post RAI and 3 months post RAI. CONCLUSION: To increase QOL, it is necessary to provide information in advance regarding physical & psychological symptoms and to develop nursing intervention programs to decrease depression and fatigue.

Value of the Serum Thyroglobulin Level Alteration at the First High Dose Radioiodine Treatment in Patients with Differentiated Thyroid Carcinoma / 핵의학분자영상

PURPOSE: The purpose of this study was to evaluate if short-term serum thyroglobulin (Tg) elevation after radioiodine administration can predict successful radioiodine remnant ablation (RRA) and whether comparable RRA effectiveness is exhibited between a group administered with recombinant human thyrotropin (rhTSH) and a group experiencing thyroid hormone withdrawal (THW), in preparation for RRA. MATERIALS AND METHODS: A retrospective chart review was performed on 39 patients in the rhTSH group and 46 patients in the THW group. They were treated for differentiated thyroid carcinoma by total or near total thyroidectomy, and referred for RRA between 2003 and 2006 (the rhTSH group) and between January and June of 2006 (the THW group). They were assessed for serum Tg levels just before I-131 administration (TgD0), reassessed 9 days later (TgD9), and again 6-12 months later. RESULTS: RRA was successful in 64 (37 from the THW group and 27 from the rhTSH group) of the total 85 patients. The success rates of RRA had no statistically significant differences between the two groups. In both groups, TgD9/TgD0 values were significantly higher in the RRA success group (the rhTSH group; P=0.03, the THW group; P=0.04). By combining cutoff values of TgD0 and TgD9/TgD0, the successful RRA value was determined to be 96.7% (29/30) with TgD04.37 in both groups (the rhTSH group; 100% (16/16), the THW group; 92.9% (13/14)). Using logistic multivariate analysis, only TgD0 was independently associated with successful RRA. CONCLUSION: We may predict successful ablation by evaluating short-term serum Tg elevation after I-131 administration for RRA, in both rhTSH and THW patients.

Analysis of Urine Iodine Excretion Decrease by Two-Week Stringent Low Iodine Diet for Remnant Thyroid Ablation with Radioactive Iodine in Korean Patients with Thyroid Cancer; Prospective Study / 핵의학분자영상

A low iodine diet (LID) is the recommended preparation for radioactive iodine treatment. However, the recommended duration and stringency of LID are different among each recommendation. More stringent LID is expected in Korea because Korea is a iodine-rich region. We investigated the decrement of urine iodine excretion by two-week stringent LID for remnant thyroid ablation with radioactive iodine in Korean patients with thyroid cancer, prospectively. MATERIAL AND METHOD: From November 2006, patients who referred to our hospital for remnant ablation after total thyroidectomy were included in this study. To decrease total body iodine, our protocol included three strategies. First, we checked medication which could inhibit the radioactive iodine uptake. Second, the date of I-131 treatment was scheduled at least 3 months later if contrast agent had been used. The last strategy was two-week stringent LID education by specialized nutritionist. Before and after two-week stringent LID, 24hr-urine iodine was analyzed respectively. 24hr-urine creatinine was also analyzed for determining more valid 24hr urine sampling subgroup. RESULTS: Total 51 patients were finally enrolled. Average of 24hr-urine iodine excretion was significantly lowered (787+/-2242 -> 85+/-85 microgram/d, p=0.03) after LID and 74.4% of patients reached below the recommended urine iodine excretion level ( 99+/-116 microgram/d, p=0.05) and 78.6% of patients met the criteria. CONCLUSION: Most patients could reach below the recommended urine iodine level after two-week stringent LID. Therefore, in our opinion, at least two-week stringent LID should be recommended in Korea.

Comparison of Urine Iodine/Creatinine ratio between Patients following Stringent and Less Stringent Low Iodine Diet for Radioiodine Remnant Ablation of Thyroid Cancer / 핵의학분자영상

A low iodine diet (LID) for 1~2 weeks is recommended for patients who undergoing radioiodine remnant ablation. However, the LID educations for patients are different among centers because there is no concrete recommendation for protocol of LID. In this investigation, we compared two representative types of LID protocols performed in several centers in Korea using urine iodine to creatinine ratio (urine I/Cr). METHODS: From 2006, April to June, patients referred to our center for radioiodine remnant ablation of thyroid cancer from several local hospitals which had different LID protocols were included. We divided into two groups, stringent LID for 1week and less stringent LID for 2 weeks, then measured their urine I/Cr ratio with spot urine when patients were admitted to the hospital. RESULTS: Total 27 patients were included in this investigation (M:F=1:26; 13 in one-week stringent LID; 14 in two-week less stringent LID). Average of urine I/Cr ratio was 127.87+/-78.52 microgram/g in stringent LID for 1 week, and 289.75+/-188.24 microgram/g in less stringent LID for 2 weeks. It was significantly lower in stringent LID for 1 week group (p=0.008). The number of patients whose urine I/Cr ratios were below 100 microgram/g was 6 of 13 in stringent LID for 1 week group, and 3 of 14 in less stringent LID for 2 weeks group. CONCLUSION: Stringent LID for 1 week resulted in better urinary I/Cr ratio in our investigation compared with the other protocol. However it still resulted in plenty of inadequate range of I/Cr ratio, so more stringent protocol such as stringent LID for 2 weeks is expected more desirable.