Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system.
Tuttle R Michael,Tala Hernan,Shah Jatin,Leboeuf Rebecca,Ghossein Ronald,Gonen Mithat,Brokhin Matvey,Omry Gal,Fagin James A,Shaha Ashok
Thyroid : official journal of the American Thyroid Association
BACKGROUND:A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. METHODS:This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. RESULTS:Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediate-risk, and 68% of the high-risk patients (p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. CONCLUSIONS:Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.
10.1089/thy.2010.0178
Disease Progression in Papillary Thyroid Cancer with Biochemical Incomplete Response to Initial Therapy.
Zern Nicole K,Clifton-Bligh Roderick,Gill Anthony J,Aniss Ahmad,Sidhu Stan,Delbridge Leigh,Learoyd Diana,Robinson Bruce,Sywak Mark
Annals of surgical oncology
BACKGROUND:Dynamic risk stratification is utilized in the follow-up of patients with papillary thyroid carcinoma (PTC). Analysis of outcomes after biochemical incomplete response (BIR) to initial therapy will allow better individualization of care. METHODS:A total of 494 patients with PTC were followed prospectively. Immunohistochemistry (IHC) for BRAF mutation was completed on all surgical specimens. After exclusion of patients with inadequate data, 353 patients were stratified into four categories of response to initial therapy: excellent, biochemical incomplete, structural incomplete, or indeterminate. Patients with BIR, defined as elevated stimulated thyroglobulin >2 µg/L with negative imaging, were analysed for progression of disease. The primary outcome measure was development of structural recurrence. RESULTS:Forty-nine of 353 (13.9%) patients had BIR. BRAF mutation was present in 32 of 49 (65.3%) with BIR. Progression to structural recurrence occurred in 8 of 49 (16.3%) with BIR, all of whom were positive for the BRAF mutation (p = 0.02). Nine patients (18%) with BIR remitted during follow-up to no evidence of disease (6 had additional RAI therapy). After mean follow-up of 35 months, 12 patients with BIR (24%) remained biochemically abnormal with no structural evidence of disease. CONCLUSIONS:Patients with BIR following initial treatment for PTC have generally favorable outcomes. Positive IHC for BRAF identifies patients at risk of structural disease recurrence.
10.1245/s10434-017-5911-6
Differentiated Thyroid Cancer with Biochemical Incomplete Response: Clinico-Pathological Characteristics and Long Term Disease Outcomes.
Steinschneider Miriam,Pitaro Jacob,Koren Shlomit,Mizrakli Yuval,Benbassat Carlos,Muallem Kalmovich Limor
Cancers
Although most patients with differentiated thyroid cancer (DTC) and biochemical incomplete response (BIR) follow a good clinical outcome, progression to structural disease may occur in 8-17% of patients. We aimed to identify factors that could predict the long-term outcomes of BIR patients. To this end, we conducted a retrospective review study of 1049 charts from our Differential Thyroid Cancer registry of patients who were initially treated with total thyroidectomy between 1962 and 2019. BIR was defined as suppressed thyroglobulin (Tg) > 1 ng/mL, stimulated Tg > 10 ng/mL or rising anti-Tg antibodies, who did not have structural evidence of disease, and who were assessed 12-24 months after initial treatment. We found 83 patients (7.9%) matching the definition of BIR. During a mean follow-up of 12 ± 6.6 years, 49 (59%) patients remained in a state of BIR or reverted to no evidence of disease, while 34 (41%) progressed to structural disease. At the last follow-up, three cases (3.6%) were recorded as disease-related death. The American Thyroid Association (ATA) Initial Risk Stratification system and/or AJCC/TNM (8th ed.) staging system at diagnosis predicted the shift from BIR to structural disease, irrespective of their postoperative Tg levels. We conclude that albeit 41% of BIR patients may shift to structural disease, and most have a rather indolent disease. Specific new individual data enable the Response to Therapy reclassification to become a dynamic system to allow for the better management of BIR patients in the long term.
10.3390/cancers13215422
Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy.
Vaisman Fernanda,Momesso Denise,Bulzico Daniel A,Pessoa Cencita H C N,Dias Fernando,Corbo Rossana,Vaisman Mário,Tuttle R Michael
Clinical endocrinology
OBJECTIVE: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. DESIGN:Retrospective chart review. PATIENTS:Five hundred and six patients with DTC followed for a median of 10 years after total thyroidectomy and RAI remnant ablation at a major cancer centre in Brazil. MEASUREMENTS:Final clinical outcomes were assessed based on American Joint Cancer Committee (AJCC)/Union Internationale Contre le Cancer (UICC) staging, ATA risk stratification and response to therapy assessment (excellent, acceptable, biochemical incomplete and structural incomplete). RESULTS:The AJCC/UICC staging system did not adequately stratify patients with regard to the risk of recurrence/persistent disease. However, the ATA system demonstrated a 13% risk of recurrent/persistent disease in low-risk patients, 36% in intermediate risk patients, and 68% in high-risk patients. Furthermore, an excellent response to therapy decreased the risk of recurrent/persistent disease to 1·4%. At the time of final follow-up, 34% of the biochemical incomplete response patients had been re-classified as having no evidence of disease (NED) without having received any additional therapy beyond continue levothyroxine suppression. Conversely, even after additional therapies, only 9% of the patients with an incomplete structural response were eventually re-classified as NED. CONCLUSIONS:These data validate the ATA risk classification as an excellent initial predictor of recurrent/persistent disease and confirm the clinical utility of the MSKCC dynamic risk assessment system in a cohort of patients evaluated and treated outside the United States.
10.1111/j.1365-2265.2012.04342.x
Nomogram for the Prediction of Biochemical Incomplete Response in Papillary Thyroid Cancer Patients.
Cancer management and research
PURPOSE:To develop a nomogram for predicting biochemical incomplete response (BIR) in the dynamic risk stratification (DRS) of papillary thyroid carcinoma (PTC) patients without structural recurrence, and to investigate its validity. PATIENTS AND METHODS:Overall, 1705 (1005 and 700 in the training and validation cohorts, respectively) PTC patients treated with total thyroidectomy without structural recurrence were included. multivariate logistic regression analyses were performed to determine the significant predictors of BIR in the training cohort. A nomogram was subsequently constructed for BIR risk prediction. Assessments for the predictive accuracy, discrimination, and calibration of the nomogram were performed. Subsequently, internal and external validations were conducted. RESULTS:In the multivariate analysis, age, sex, lymph node metastasis site, extrathyroidal extension, and lymphovascular invasion showed significant predictive value; using these predictive factors and tumor size, a nomogram for BIR risk prediction was constructed. In the training cohort, the nomogram showed good predictive performance and discrimination in the receiver operating characteristic (ROC) curve analysis, with an area under the curve (AUC) of 0.765. In internal validation, the bootstrap-corrected AUC was 0.76. The calibration plot showed good agreement between the predicted and actual observation. The Hosmer-Lemeshow (HL) test did not suggest a lack of fit (p=0.1613). In the external validation, the AUC was 0.828 in the ROC curve analysis; the calibration plot showed good quality, and the HL test did not suggest a lack of fit (p=0.2161). CONCLUSION:The constructed nomogram may effectively predict the risk of BIR in DRS in PTC patients without structural recurrence. LEVEL OF EVIDENCE:Level 4.
10.2147/CMAR.S320993