Persistent Disease is 3.5-Fold More Common Than Recurrent Disease After Initial Therapy for Differentiated Thyroid Cancer

Introduction. Differentiated thyroid cancer (DTC) has an overall excellent prognosis. Patients who develop recurrent disease have a more unfavorable disease course than those with no recurrence. Higher recurrence rates are seen with incomplete surgical resection and gross positive margins. It is unclear whether microscopic positive margin affects disease recurrence rates as much as grossly positive margin. Aim of the Study. To assess whether microscopic positive margin is an independent predictor of disease recurrence in patients with overall low-risk DTC. Patients and Methods. We conducted a retrospective single-center institutional review of 1,583 consecutive patients’ charts from 1995–2013 using the Canadian Thyroid Cancer Consortium Registry. We included adult patients with nonmetastasizing T1 and T2 DTC with a minimum of three years follow-up. Univariate and multivariate analyses were used to study factors that may influence the risk of persistent/recurrent disease. Strict definitions of persistent versus recurrent disease were applied. Results. 963 patients (152 men and 811 women) were included in the study with a mean age of 46 years. Microscopic positive margins were present in 12% of the specimens and were associated with an increased rate of persistent disease (8% versus 2% in the controls) but not with an increased risk of recurrent disease (1% in both groups). T2 tumors had a significantly higher incidence of positive margins than T1 tumors (48% versus 36%) and significantly higher nodal staging. Conclusions. Microscopic positive margin in the histopathology report in patients with low-risk DTC was associated with a higher rate of persistent disease but did not increase the risk of disease recurrence. A close follow-up of biomarkers and occult residual cancerous lesions is needed, especially in the first year. Further studies are needed to determine whether additional therapeutic measures to prevent recurrence are indicated in T1 and T2 DTC with positive microscopic surgical margins.

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ISTHMUS TOPOGRAPHY IS A RISK FACTOR FOR PERSISTENT DISEASE IN PATIENTS WITH DIFFERENTIATED THYROID CANCER

Acta Endocrinologica ◽

10.1530/eje-21-0328 ◽

2021 ◽

Author(s):

Alfredo Campennì ◽

Rosaria Maddalena Ruggeri ◽

Massimiliano Siracusa ◽

Giulia Giacoppo ◽

Flavia La Torre ◽

...

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Disease Free Survival ◽

Initial Therapy ◽

Response To Therapy ◽

Rank Test ◽

Additional Risk Factor ◽

Persistent Disease ◽

Incomplete Response

Aim: The risk of differentiated thyroid cancer (DTC) recurrence is widely evaluated according to the 2015 ATA Risk Stratification System. Topography of malignant nodules has been previously reported as an additional risk factor but is not included in the ATA system. Thus, our study aimed to evaluate the relationship between DTC topography and response to initial therapy. Patients and Methods: We enrolled 401 low- to intermediate-risk patients with DTC who had undergone thyroidectomy and radioiodine therapy. DTC topography was recorded and compared with the response to therapy as assessed 12 months after end of therapy. Results: Overall, 366/401 (91.3%) patients had an excellent response to initial therapy while 22/401 (5.5%) and 13/401 (3.2%) had incomplete biochemical or structural response, respectively. Incomplete response occurred in 10/36 (27.8%), 5/125 (4.0%), and 4/111 (3.6%) patients whose unifocal malignant nodules were located in the isthmus, right lobe, or left lobe. Incomplete response was also observed in 4/54 (7.4%) and 12/75 (16%) patients carrying multifocal cancers in one or both lobes, respectively. Patients with isthmic cancer more frequently demonstrated incomplete response compared with those who had cancer in other locations (p=0.00). No significant relationship was found with age, gender, maximum size of malignant nodule, Hashimoto’s thyroiditis, vascular invasion, and extrathyroidal extension (p=0.78, p=0.77, p=0.52, p=0.19, p=0.73, and p=0.26, respectively). The risk of incomplete response was about 65% higher in patients with isthmic lesions compared with other patients (odds ratio=6.725). A log-rank test demonstrated that disease-free survival (DFS) of patients with isthmic lesions was significantly shorter than that of other patients (p=0.02). Conclusion: Our data show that isthmus topography of malignant thyroid nodules is a risk factor for having both persistent disease 12 months after primary treatment and reduced DFS.

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Prognosis of Thyroid Cancer Related to Pregnancy: A Systematic Review

Journal of Thyroid Research ◽

10.4061/2011/691719 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 17

Author(s):

Gustavo Vasconcelos Alves ◽

Ana Paula Santin ◽

Tania Weber Furlanetto

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Primary Outcome ◽

Recurrent Disease ◽

Persistent Disease ◽

Common Cancer ◽

Cancer In Pregnancy ◽

Recent Retrospective Study

Differentiated thyroid cancer (DTC) is the second most common cancer in pregnancy. Its management is a challenge for both doctors and patients, and the best timing for surgery is unclear. A systematic review evaluating the prognosis of DTC in pregnant patients was conducted. After reviewing 401 unique citations and 54 full texts, 4 studies that compared the prognosis of patients with DTC related to pregnancy (DTC diagnosed during pregnancy or within 12 months after childbirth) or not were included. In two studies the primary outcome was overall survival, in one study the primary outcomes were recurrent disease and death related to thyroid cancer, and in one study the primary outcome was recurrent or persistent disease. In the first two studies, there was no difference in overall survival in patients with pregnancy-related DTC, when compared with matched controls; in one study, there was no difference in death caused by DTC nor recurrence in DTC related to pregnancy. Nevertheless, in a recent retrospective study, a higher rate of recurrent or persistent DTC was observed in patients with DTC related to pregnancy. There are not many studies on which to base treatment decisions in pregnant patients with DTC.

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Time to Separate Persistent From Recurrent Differentiated Thyroid Cancer: Different Conditions With Different Outcomes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01383 ◽

2018 ◽

Vol 104 (2) ◽

pp. 258-265 ◽

Cited By ~ 19

Author(s):

Giulia Sapuppo ◽

Martina Tavarelli ◽

Antonino Belfiore ◽

Riccardo Vigneri ◽

Gabriella Pellegriti

Keyword(s):

Thyroid Cancer ◽

Initial Treatment ◽

Differentiated Thyroid Cancer ◽

Recurrent Disease ◽

Treatment Strategies ◽

Distant Metastases ◽

Persistent Disease ◽

Tertiary Referral Center ◽

N Status

Abstract Context Differentiated thyroid cancer (DTC) has an excellent prognosis, but up to 20% of patients with DTC have disease events after initial treatment, indistinctly defined as persistent/recurrent disease. Objective To evaluate the prevalence and outcome of “recurrent” disease (relapse after being 12 months disease-free) compared with “persistent” disease (present ab initio since diagnosis). Design Retrospective analysis of persistent/recurrent disease in patients with DTC (1990 to 2016) with 6.5 years of mean follow-up. Setting Tertiary referral center for thyroid cancer. Patients In total, 4292 patients all underwent surgery ± 131I treatment of DTC. Main Outcome Measures DTC cure of disease persistence or recurrence. Results A total of 639 of 4292 (14.9%) patients had disease events after initial treatment, most (498/639, 78%) with persistent disease and 141 (22%) with recurrent disease. Relative to patients with recurrent disease, patients with persistent disease were significantly older (mean age 46.9 vs 45.7 years) and with a lower female to male ratio (1.9/1 vs 4.8/1). Moreover, in this group, structured disease was more frequent (65.7% vs 41.1%), and more important, distant metastases were significantly more frequent (38.4% vs 17.0%). At multivariate analysis, male sex (OR = 1.7), age (OR = 1.02), follicular histotype (OR = 1.5), T status (T3; OR = 3), and N status (N1b; OR = 7.7) were independently associated with persistent disease. Only the N status was associated with recurrent disease (N1b; OR = 2.5). Conclusions In patients with DTC not cured after initial treatment, persistent disease is more common and has a worse outcome than recurrent disease. Postoperative status evaluated during first-year follow-up may have important clinical implications for planning tailored treatment strategies and long-term follow-up procedures.

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Performance of the American Thyroid Association Risk Classification in a Single Center Cohort of Pediatric Patients with Differentiated Thyroid Cancer: A Retrospective Study

Journal of Thyroid Research ◽

10.1155/2019/5390316 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Raad Alwithenani ◽

Sarah DeBrabandere ◽

Irina Rachinsky ◽

S. Danielle MacNeil ◽

Mahmoud Badreddine ◽

...

Keyword(s):

Risk Factors ◽

Thyroid Cancer ◽

High Risk ◽

Initial Treatment ◽

Differentiated Thyroid Cancer ◽

Recurrent Disease ◽

Risk Classification ◽

American Thyroid Association ◽

Persistent Disease

Introduction. Differentiated thyroid cancer (DTC) is the most common endocrine malignancy in children. Retrospective studies show conflicting results regarding predictors of persistent and recurrent disease after initial therapy. In 2015, the American Thyroid Association (ATA) proposed a clinical classification system to identify pediatric thyroid cancer patients at risk for persistent/recurrent disease. Material and Methods. We retrospectively included all patients in our registry diagnosed with papillary DTC at ≤ 18 years of age. We analyzed the prognostic performance of the ATA classification and other risk factors for predicting response to initial treatment and final outcome in pediatric DTC. Results. We included 41 patients, 34 females and 7 males, diagnosed with papillary DTC at a mean (SD) age of 16.2 (1.8) years. Based on the ATA pediatric risk classification, patients were categorized as low (61%), intermediate (10%), or high risk (29%). The median follow-up period was 7.3 (1-41) years. After initial treatment, disease free status was achieved in 92%, 50%, and 42% of the low, intermediate, and high risk groups, respectively (P <0.01). At the last visit, persistent disease was present in 12%, 25%, and 33% (P=0.27). Assessing other risk factors, only the presence of distant metastases at diagnosis resulted in increased presence of persistent disease at last follow-up (P=0.03). Conclusion. This study supports the clinical relevance of the ATA risk classification for predicting the response to initial treatment. There was no clear prediction of long-term outcome, but this may be due to limited power caused by the small number of patients.

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Post-surgical thyroid ablation with low or high radioiodine activities results in similar outcomes in intermediate risk differentiated thyroid cancer patients

Acta Endocrinologica ◽

10.1530/eje-12-0954 ◽

2013 ◽

Vol 169 (1) ◽

pp. 23-29 ◽

Cited By ~ 56

Author(s):

Maria Grazia Castagna ◽

Gabriele Cevenini ◽

Alexandra Theodoropoulou ◽

Fabio Maino ◽

Silvia Memmo ◽

...

Keyword(s):

Thyroid Cancer ◽

Cancer Patients ◽

Differentiated Thyroid Cancer ◽

Radioactive Iodine ◽

Recurrent Disease ◽

Intermediate Risk ◽

Persistent Disease ◽

Thyroid Ablation ◽

The Impact

BackgroundIn differentiated thyroid cancer (DTC) patients at intermediate risk of recurrences, no evidences are provided regarding the optimal radioactive iodine (RAI) activity to be administered for post-surgical thyroid ablation.MethodsThis study aimed to evaluate the impact of RAI activities on the outcome of 225 DTC patients classified as intermediate risk, treated with low (1110–1850 MBq) or high RAI activities (≥3700 MBq).ResultsSix to 18 months after ablation, remission was observed in 60.0% of patients treated with low and in 60.0% of those treated with high RAI activities, biochemical disease was found in 18.8% of patients treated with low and in 14.3% of patients treated with high RAI activities, metastatic disease was found in 21.2% of patients treated with low and in 25.7% of patients treated with high RAI activities (P=0.56). At the last follow-up (low activities, median 4.2 years; high activities, median 6.9 years), remission was observed in 76.5% of patients treated with low and in 72.1% of patients treated with high RAI activities, persistent disease was observed in 18.8% of patients treated with low and in 23.5% of patients treated with high RAI activities, recurrent disease was 2.4% in patients treated with low and 2.1% in patients treated with high RAI activities, deaths occurred in 2.4% of patients treated with low and in 2.1% of patients treated with high RAI activities (P=0.87).ConclusionOur study provides the first evidence that in DTC patients at intermediate risk, high RAI activities at ablation have no major advantage over low activities.

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BRAF V600E Status and Stimulated Thyroglobulin at Ablation Time Increase Prognostic Value of American Thyroid Association Classification Systems for Persistent Disease in Differentiated Thyroid Carcinoma

International Journal of Endocrinology ◽

10.1155/2019/3081497 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Andrea Repaci ◽

Valentina Vicennati ◽

Alexandro Paccapelo ◽

Ottavio Cavicchi ◽

Nicola Salituro ◽

...

Keyword(s):

Thyroid Cancer ◽

Risk Stratification ◽

Prognostic Value ◽

Differentiated Thyroid Cancer ◽

Risk Classification ◽

Classification Systems ◽

Braf V600e ◽

American Thyroid Association ◽

Persistent Disease ◽

Ablation Time

Background. Stimulated thyroglobulin levels measured at the time of remnant ablation (A-hTg) and BRAFV600E mutation had shown prognostic value in predicting persistent disease in differentiated thyroid cancer (DTC). The aim of this study was to evaluate the prognostic role of A-hTg combined with the BRAFV600E status in association with the revised American Thyroid Association (ATA) risk stratification. Material and Methods. 620 patients treated for a DTC were included in this study with a median follow-up duration of 6.1 years. All patients underwent total thyroidectomy followed by radioiodine ablation. Patients with positive anti-thyroglobulin antibodies were excluded. The predictive value of A-hTg was calculated by receiver operating characteristic curve (ROC curve) analysis. The Cox proportional hazard regression model, including the BRAF status, A-hTg, and ATA classification system, was assessed to evaluate the existing persistent disease risk. Results. Taken together, the BRAF status and A-hTg levels improve the ATA risk classification in all categories. In particular, in the low-risk ATA classification, only the combination of BRAFV600E+A-hTg>8.9ng/ml was associated with persistent disease (P=0.001, HR 60.2, CI 95% 5.28-687). In the intermediate-risk ATA classification, BRAFWT+A-hTg>8.9ng/ml was associated with persistent disease (P=0.029, HR 2.71, CI 95% 1.106-6.670) and BRAFV600E+A-hTg>8.9ng/ml was also associated with persistent disease (P<0.001, HR 5.001, CI 95% 2.318-10.790). In the high-risk ATA classification, both BRAFV600E+A-hTg<8.9ng/ml and BRAFV600E+A-hTg>8.9 ng/ml were associated with persistent disease (P=0.042, HR 5.963, CI 95% 1.069-33.255 and P=0.002, HR 11.564, CI 95% 2.543-52.576, respectively). Conclusions. The BRAF status and stimulated thyroglobulin levels at ablation time improve the ATA risk stratification of differentiated thyroid cancer; therefore, even A-hTg could be included in risk classification factors.

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Value of Diagnostic Radioiodine Whole-body Scanning after Initial Therapy in Patients with Differentiated Thyroid Cancer at Intermediate and High Risk for Recurrence

Thyroid ◽

10.1089/thy.2012-0026 ◽

2012 ◽

pp. 120724120054001

Author(s):

Pedro Weslley Rosario ◽

Mariana de Souza Furtado ◽

Augusto Flavio Campos Mineiro Filho ◽

Rafaela Xavier Lacerda ◽

Maria Regina Calsolari

Keyword(s):

Thyroid Cancer ◽

High Risk ◽

Differentiated Thyroid Cancer ◽

Initial Therapy ◽

Whole Body ◽

Body Scanning

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Prevalence of iodine- and thyroglobulin negative findings in differentiated thyroid cancer

Nuklearmedizin ◽

10.1055/s-0038-1623879 ◽

2001 ◽

Vol 40 (05) ◽

pp. 143-147 ◽

Cited By ~ 5

Author(s):

S. Klutmann ◽

L. Jenicke ◽

M. Geiss-Tönshoff ◽

J. Mester ◽

M. Clausen ◽

...

Keyword(s):

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Progressive Disease ◽

Recurrent Disease ◽

University Hospital ◽

Follicular Thyroid Cancer ◽

Negative Findings ◽

Additional Imaging ◽

Iodine Scan

Summary Aim: The prevalence of iodine- and thyroglobulin-nega-tive findings was evaluated in all patients with differentiated thyroid cancer (DTC) treated from 1961 until 1998 at the Department of Nuclear Medicine, University Hospital Hamburg-Eppendorf. Methods: A total of 490 patients with papillary thyroid cancer (PCA) and 242 patients with follicular thyroid cancer (FCA) were analyzed retrospectively. Patients were divided into four groups: 1: no recurrence, 2: recurrent disease, 3: primary metas-tatic/progressive disease and 4: inconclusive follow-up. Results of iodine scan, serum-TG, and additional imaging modalities as well as histology were compared in all patients. Results: 21/490 (4,3%) of patients with PCA and 16/242 (6,6%) with FCA suffered from recurrent disease. 62/490 (12,7%) of patients with PCA and 59/242 (24,4%) with FCA had primary metastatic/progressive disease. 12/21 patients with PCA and 12/16 with FCA showing up with recurrent disease had a negative iodinescan. 11/21 of patients with PCA and 4/16 with FCA and tumor recurrence had negative serum-TG levels. 14/62 patients with PCA and 14/59 with FCA presenting with primary metastatic/ progressive disease had negative iodinescan. 14/62 patients with PCA and 6/59 with FCA had negative serum-TG. Conclusion: The prevalence of iodine-negative recurrent"/metastatic disease is in accordance to the literature, whereas the prevalence of TG-negative recurrent/metastatic was noted higher than reported previously. Thus, the commonly used follow-up scheme of DTC is confirmed. However, iodine scan should be regularly performed in patients with high risk of recurrence.

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