Dynamic Risk Stratification for Predicting Treatment Response in Differentiated Thyroid Cancer.
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ABSTRACT:
SUBMITTER: Giannoula E
PROVIDER: S-EPMC7565378 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Dynamic Risk Stratification for Predicting Treatment Response in Differentiated Thyroid Cancer.
Giannoula Evanthia E Melidis Christos C Papadopoulos Nikitas N Bamidis Panagiotis P Raftopoulos Vasilios V Iakovou Ioannis I
Journal of clinical medicine 20200821 9
Prognosis in Differentiated Thyroid Cancer (DTC) patients is excellent, but a significant degree of overtreatment still exists because of the inability to accurately identify small patient cohorts who experience a more aggressive form of the disease, often associated with certain poor prognostic factors. Identifying these cohorts at an early stage would allow patients at high risk to receive more aggressive treatment while avoiding unnecessary and invasive treatments in those at low risk. Most r ...[more]
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Project description:The concept of response to therapy in differentiated thyroid cancer (DTC) was introduced as a dynamic risk stratification used to assess the status of the disease at the time of the evaluation during the follow-up and the risk of recurrence in the future. Our aim in this study was to evaluate the natural course over time of different response to therapy statuses.MethodsWe studied 501 nonselected DTC patients (102 males and 399 females) with a median age of 37 years (interquartile range [IQR] 29-48). All patients underwent near-total or total thyroidectomy followed by I-131 ablation (initial management).ResultsOf the 501 patients, 387 patients (77.2%) did not have any additional therapuetic interventions after the initial management. In this group, the response to therapy status at the time of the first evaluation after I-131 (median 17 months, IQR 14-22) was an excellent response in 258 (66.7%), an indeterminate response in 101 (26.1%), biochemically incomplete in 17 (4.4%), and structurally incomplete in 11 patients (2.8%). The status changed spontaneously without any intervention in many of them. At the last follow-up visit (median duration 101 months, IQR 71-126), 357 patients (92.2%) achieved an excellent response, 4 (1%) an indeterminate response, 8 (2.1%) a biochemically incomplete status, 16 (4.1%) a structurally incomplete status, and 2 (0.5%) died secondary to DTC with a structurally incomplete status. The response to therapy in the other 114 patients who underwent additional interventions changed from before intervention to the last evaluation as follows: excellent response, 0 to 60 patients (52.6%), indeterminate response, 20 (17.5%) to 1 patient (0.9%), biochemically incomplete 25 (21.9%) to 10 patients (9%), and structurally incomplete 69 (60.5%) to 43 patients (37.7%). Overall, at the last evaluation, 417 (83.2%) were in an excellent response, 5 (1%) in an indeterminate response, 18 (3.6%) in a biochemically incomplete status, 50 (10.2%) in a structurally incomplete status, and 11 (2.2%) died secondary to DTC with a structurally incomplete status.ConclusionsThe response to therapy at the initial evaluation is predictive of the long-term outcome. Most patients with the indeterminate response and some in the biochemically incomplete statuses spontaneously regress to an excellent status. Mortality and progression of DTC occur mostly in the structurally incomplete status.
| S-EPMC8216009 | biostudies-literature
Project description:ContextAlthough 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.ObjectiveThis study aimed to validate the response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI.Design and settingThis was a retrospective study, which took place at a referral center.PatientsA 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 measureMain outcome measured was recurrent/persistent structural evidence of disease (SED) during a median followup period of 100.5 months (24-510).ResultsRecurrent/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.ConclusionsOur 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.
| S-EPMC6287503 | biostudies-literature
Project description:There has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course.This retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system.The PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases).The DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification.
| S-EPMC4831829 | biostudies-other
Project description:IntroductionDifferentiated thyroid cancer (DTC) is the most common of endocrine cancers. Many studies have focused on recurrence-free survival of DTC patients, however, few studies have addressed overall survival rates. Given its very good prognosis, estimating overall or long-term survival in patients with DTC seems rational. So far, neither the impact of pre- and post-ablation thyroglobulin, nor that of initial American Thyroid Association (ATA) risk stratification on long-term disease-specific survival, have been sufficiently studied.ObjectiveThe aim of this study was to determine the factors that influence long-term disease-specific survival and thyroglobulin levels in patients with DTC who have been previously treated with thyroidectomy and radioactive iodine (RAI) remnant ablation.Patients and methodsThis observational retrospective study included 1093 patients who were treated for DTC between 1995 and 2010 and are still monitored in our tertiary center. Only patients who needed RAI ablation after thyroidectomy were included in this study. Patients who were treated with RAI following rhTSH stimulation, patients who presented positive anti-thyroglobulin antibodies, and patients who had micro-cancers were excluded. Pre-ablation stimulated thyroglobulin (Pre-ablation sTg) was measured after thyroid hormone withdrawal (THW), just before RAI.ResultsAccording to ATA standards, 29 patients (2.7%) were classified as high-risk patients. Initial ATA high-recurrence risk rating (HR 21.9; 95% CI: 8.5-56.3), age>55 years (HR 23.8; 95%-CI: 7.5-75.3) and pre-ablation sTg?30 ?g/l (HR 8.4; 95% CI: 4.6-15.3) significantly impacted ten-year survival. Moreover, age over 45 years, ATA moderate-risk and follicular DTC were also significant. Ten-year survival was lower in ATA high-risk patients (51% vs 95% and 93% for the low and intermediate risk; p<10-7), patients older than 55 years (82% vs 98%; p<10-7), and in patients with pre-ablation sTg?30 (78% vs 95%; p<10-7). Three rates of long-term survival were distinguished: excellent (survival rate of 99% in patients<55 years with pre-ablation sTg <30?g/l) representing 59% of the cohort, moderate (survival rate of 94.5% in patients <55 years with pre-ablation sTg ?30?g/l or ?55 years with pre-ablation sTg <30 ?g/l) representing 38% of the cohort, and low (survival rate of 49% in patients ?55 years with pre-ablation sTg ?30?g/l) representing 3% of the cohort.ConclusionInitial ATA high-risk classification, age over 55 years old and pre-ablation sTg ?30 ?g/l are the main negative factors that influence the ten-year survival in DTC. We suggest three categories of overall survival rates. Patients older than 55 years with pre-ablation sTg ?30 ?g/l have the worst survival rate.
| S-EPMC6699685 | biostudies-literature
Project description:Derived from follicular epithelial cells, differentiated thyroid cancer (DTC) accounts for the majority of thyroid malignancies. The threefold increase in DTC incidence over the last three decades has been largely attributed to advancements in detection of papillary thyroid microcarcinomas. Efforts to address the issue of overtreatment have notably included the reclassification of encapsulated follicular variant papillary thyroid cancers (EFVPTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). In the last 5 years, the overall management approach for this relatively indolent cancer has become less aggressive. Although surgery and radioiodine ablation remain the mainstay of DTC therapy, the role of active surveillance is being explored. Furthermore, the most recent American Thyroid Association (ATA) guidelines offer flexibility between lobectomy and total thyroidectomy for thyroid nodules between 1 cm and 4 cm in the absence of extrathyroidal extension or nodal disease. As our understanding of the natural history and molecular underpinnings of DTC evolves, so might our approach to managing low-risk patients, obviating the need for invasive intervention. Simultaneously, advances in interventional and systemic therapies have greatly expanded treatment options for high-risk surgical candidates and patients with widespread disease, and continue to be areas of active investigation. Continued research efforts are essential to improve our ability to offer effective individualized therapy to patients at all disease stages and to reduce the incidence of recurrent and progressive disease.
| S-EPMC7975487 | biostudies-literature
Project description:BackgroundThe diagnosis of radioiodine refractory differentiated thyroid cancer (RAIR-DTC) is primarily based on clinical evolution and iodine uptake over the lesions, which is still time-consuming, thus urging a predictive model for timely RAIR-DTC informing. The aim of this study was to develop a nomogram model for RAIR prediction among DTC patients with distant metastases (DM).MethodsData were extracted from the treatment and follow-up databases of Peking Union Medical College Hospital between 2010 and 2021. A total of 124 patients were included and divided into RAIR (n=71) and non-RAIR (n=53) according to 2015 ATA guidelines. All patients underwent total thyroidectomy followed by at least two courses of RAI treatment. Serological markers and various clinical, pathological, genetic status, and imaging factors were integrated into this study. The pre-treatment stimulated Tg and pre- and post-treatment suppressed Tg at the first and second course RAI treatment were defined as s-Tg1, s-Tg2, sup-Tg1, and sup-Tg2, respectively. Δs-Tg denoted s-Tg1/s-Tg2, and Δs-TSH denoted s-TSH1/s-TSH2. Multivariate logistic regression and correlation analysis were utilized to determine the independent predictors of RAIR. The performance of the nomogram was assessed by internal validation and receiver operating characteristic (ROC) curve, and benefit in clinical decision-making was assessed using decision curve.ResultsIn univariate logistic regression, nine possible risk factors were related to RAIR. Correlation analysis showed four of the above factors associated with RAIR. Through multivariate logistic regression, Δs-Tg/Δs-TSH<1.50 and age upon diagnosis were obtained to develop a convenient nomogram model for predicting RAIR. The model was internally validated and had good predictive efficacy with an AUC of 0.830, specificity of 0.830, and sensitivity of 0.755. The decision curve also showed that if the model is used for clinical decision-making when the probability threshold is between 0.23 and 0.97, the net benefit of patients is markedly higher than that of the TreatAll and TreatNone control groups.By using 1.50 as a cut-off ofΔs-Tg/Δs-TSH, differing biochemical progression among the generally so-called RAIR can be further stratified as meaningfully rapidly or slowly progressive patients (P=0.012).ConclusionsA convenient user-friendly nomogram model was developed with good predictive efficacy for RAIR. The progression of RAIR can be further stratified as rapidly or slowly progressive by using 1.50 as a cut-off value of Δs-Tg/Δs-TSH.
| S-EPMC9950494 | biostudies-literature
Project description:Patient's age at the time of diagnosis is an important prognostic factor for differentiated thyroid cancer (DTC) as reflected in various staging and risk stratification systems. However, discrepancies exist among the different staging systems on an optimal cut-off age for predicting the clinical outcome of patients with DTC. To determine the age at diagnosis most predictive of clinical outcomes of DTC, a population-based cohort study was performed composed of 35,323 patients with DTC between 1988 and 2010 using the Surveillance, Epidemiology, and End Results (SEER) database. The Youden index J was used to determine the most predictive age-at-diagnosis for thyroid-cancer-specific death. The multivariate Cox proportional hazards model was used to determine the hazard ratios (HRs) for each age group. With a median follow-up of 5.4 years (range, 0-22.9 years), DTC-associated mortality was 1.5% (n = 533) and the rate of death from overall cause was 7.0% (n = 2482). The optimal cutoff age at diagnosis for thyroid-cancer-specific death was 57. Multivariate analysis found that the age-at-diagnosis is the most prognostic factor for thyroid-cancer-specific death (HR 10.02, 95% CI 8.18-12.28). Age at diagnosis is the most important prognostic factor for DTC patients. Based on our analysis, age at diagnosis of 57 might be the optimal predictor of thyroid-cancer-specific death. This finding might be used as consideration in revision of the risk stratification system for treatment of DTC patients.
| S-EPMC4477980 | biostudies-literature
Project description:Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided.
| S-EPMC4206652 | biostudies-literature
Project description:BackgroundWe identified differentiated thyroid cancer (DTC) survivors from SEER registries and performed Poisson regression to calculate the relative risks (RRs) of subsequent malignancies (SMs) by different sites associated with radioactive iodine (RAI) treatment, and the attributable risk proportion of RAI for developing different SMs.ResultsWe identified 4628 of 104,026 DTC patients developing a SM after two years of their DTC diagnosis, with a medium follow-up time of 113 months. The adjusted RRs of developing SM associated with RAI varied from 0.98 (0.58-1.65) for neurologic SMs to 1.37 (1.13-1.66) for hematologic SMs. The RRs of developing all cancer combined SMs generally increased with age at DTC diagnosis and decreased with the latency time. We estimated that the attributable risk proportion of RAI treatment is only 0.9% for all cancer combined SMs and 20% for hematologic SMs, which is the highest among all SMs. The tumor features and mortalities in patients treated with and without RAI are generally comparable.ConclusionWith the large population based analyses, we concluded that a low percentage of DTC survivors would develop SMs during their follow-up. Although the adjusted RR of SMs development increased slightly in patients receiving RAI, the attributable risk proportion associated with RAI was low, suggesting the absolute number of SMs induced by RAI in DTC survivors would be low. The attributable risk proportion of RAI treatment is the highest in hematological SMs, but when in consideration of its low incidence among all DTC survivors, the absolute number of hematological SMs was low.
| S-EPMC8117631 | biostudies-literature
Project description:BackgroundPrecise risk stratification-based treatment of solitary intrathyroidal papillary thyroid cancer (SI-PTC) that is larger than 1.0 cm and 4.0 cm or less is undefined.MethodsA genetic-clinical risk study was performed on BRAF V600E in 955 patients (768 women and 187 men) with SI-PTC, with median age of 46 years and median clinical follow-up time of 64 months at 11 medical centers in six countries. The chi-square test or, for analyses with small numbers, Fisher's exact test was performed to compare recurrence rates. Recurrence-free probability was estimated by Kaplan-Meier (KM) analysis, and the independent effect of BRAF mutation on the recurrence was analyzed by Cox regression and Cox proportional hazard analyses. All statistical tests were two-sided.ResultsRecurrence of SI-PTC larger than 1.0 cm and 4.0 cm or less was 9.5% (21/221) vs 3.4% (11/319) in BRAF mutation vs wild-type BRAF patients, with a hazard ratio (HR) of 3.03 (95% confidence interval [CI] = 1.46 to 6.30) and a patient age- and sex-adjusted hazard ratio of 3.10 (95% CI = 1.49 to 6.45, P = .002). Recurrence rates of SI-PTC larger than 2.0 cm and 4.0 cm or less were 16.5% (13/79) vs 3.6% (5/139) in mutation vs wild-type patients (HR = 5.44, 95% CI = 1.93 to 15.34; and adjusted HR = 5.58, 95% CI = 1.96 to 15.85, P = .001). Recurrence rates of SI-PTC larger than 3.0 cm and 4 cm or less were 30.0% (6/20) vs 1.9% (1/54) in mutation vs wild-type patients (HR = 18.40, 95% CI = 2.21 to 152.98; and adjusted HR = 14.73, 95% CI = 1.74 to 124.80, P = .01). Recurrences of mutation-positive SI-PTC were comparable with those of counterpart invasive solitary PTC, around 20% to 30%, in tumors larger than 2.0 cm to 3.0 cm. BRAF mutation was associated with a statistically significant decrease in recurrence-free patient survival on KM analysis, particularly in SI-PTC larger than 2.0 cm and 4.0 cm or less. Similar results were obtained in conventional SI-PTC. The negative predictive values of BRAF mutation for recurrence were 97.8% (95% CI = 96.3% to 98.8%) for general SI-PTC and 98.2% (95% CI = 96.3% to 99.3%) for conventional SI-PTC.ConclusionsBRAF V600E identifies a subgroup of SI-PTC larger than 1.0 cm and 4.0 cm or less, particularly tumors larger than 2.0 cm and 4.0 cm or less, that has high risk for recurrence comparable with that of invasive solitary PTC, making more aggressive treatment reasonable.
| S-EPMC6658860 | biostudies-literature