Proportion Of Explained Variation Research Articles

Rethinking the prognosis model of differentiated thyroid carcinoma.

The prediction efficiency of long-term cancer-specific survival (CSS) in guiding the treatment of differentiated thyroid carcinoma (DTC) patients is still unsatisfactory. We need to refine the system so that it more accurately correlates with survival. This is a retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database, and included patients who underwent surgical treatment and were diagnosed with DTC from 2004 to 2020. Patients were divided into a training cohort (2004-2015) and validation cohort (2016-2020). Decision tree methodology was used to build the model in the training cohort. The newly identified groups were verified in the validation cohort. DTC patient totals of 52,917 and 48,896 were included in the training and validation cohorts, respectively. Decision tree classification of DTC patients consisted of five categorical variables, which in order of importance were as follows: M categories, age, extrathyroidal extension, tumor size, and N categories. Then, we identified five TNM groups with similar within-group CSS. More patients were classified as stage I, and the number of stage IV patients decreased significantly. The new system had a higher proportion of variance explained (PVE) (5.04%) and lower Akaike information criterion (AIC) (18,331.906) than the 8th TNM staging system (a PVE of 4.11% and AIC of 18,692.282). In the validation cohort, the new system also showed better discrimination for survival. The new system for DTC appeared to be more accurate in distinguishing stages according to the risk of mortality and provided more accurate risk stratifications and potential treatment selections.

Predictors of recurrence after total thyroidectomy in 1,611 patients with papillary thyroid carcinoma: postoperative stimulated serum thyroglobulin and ATA initial and dynamic risk assessment.

Despite a favorable prognosis, some patients with papillary thyroid carcinoma (PTC) develop recurrence. The objective of this study was to examine the impact of the combination of initial American Thyroid Association (ATA) risk stratification with serum level of postoperative stimulated thyroglobulin (s-Tg) in predicting recurrence in patients with PTC and compare the results with an assessment of response to initial therapy (dynamic risk stratification). We retrospectively analyzed 1,611 patients who had undergone total thyroidectomy for PTC, followed in most cases (87.3%) by radioactive iodine (RAI) administration. Clinicopathological features and s-Tg levels obtained 3 months postoperatively were evaluated. The patients were stratified according to ATA risk categories. Nonstimulated thyroglobulin levels and imaging studies obtained during the first year of follow-up were used to restage the patients based on response to initial therapy. After a mean follow-up of 61.5 months (range 12-246 months), tumor recurrence was diagnosed in 99 (6.1%) patients. According to ATA risk, recurrence was identified in 2.3% of the low-risk, 9% of the intermediate-risk, and 25% of the high-risk patients (p < 0.001). Using a receiver operating characteristic curve approach, a postoperative s-Tg level of 10 ng/mL emerged as the ideal cutoff value, with positive and negative predictive values of 24% and 97.8%, respectively (p < 0.001). Patients with low to intermediate ATA risk with postoperative s-Tg levels < 10 ng/mL and excellent response to treatment had a very low recurrence rate (<0.8%). In contrast, higher recurrence rates were observed in intermediate-riskto high-risk patients with postoperative s-Tg > 10 ng/mL and indeterminate response (25%) and in those with incomplete response regardless of ATA category or postoperative s-Tg value (38.5-87.5%). Using proportion of variance explained (PVE), the predicted recurrence using the ATA initial risk assessment alone was 12.7% and increased to 29.9% when postoperative s-Tg was added to the logistic regression model and 49.1% with dynamic risk stratification. The combination of ATA staging system and postoperative s-Tg can better predict the risk of PTC recurrence. Initial risk estimates can be refined based ondynamic risk assessment following response to therapy, thus providing a useful guide for follow-up recommendations.

Abstract 6262: Optimal cut-off age for AJCC staging system in Middle Eastern patients with differentiated thyroid cancer

Abstract Background: Differentiated Thyroid Cancer (DTC) has an indolent nature and generally has favorable prognosis. AJCC TNM classification is the most adopted system to evaluate the biological behavior of DTC. Age cut-off of 55 years has been included in the eighth edition of TNM staging system since it led to better prediction of disease specific survival (DSS) of patients with DTC. However, optimal age cut-off in DTC patients from Middle Eastern ethnicity has not been fully explored. We evaluated the optimal age cut-off for the TNM staging system to predict DSS in Middle Eastern patients with DTC. Methods: We retrospectively analyzed a large cohort of 1721 adult DTC patients who underwent surgery between 1990 to 2018. The optimal age cut-off value was determined using several age cut-offs (between 20 and 85 years) to assess DSS. Harrel’s C-Index, Akaike information criterion (AIC) and Bayesian Information Criterion (BIC) were used to assess the statistical model performance of the TNM staging system (eighth edition), with different age cut-offs for prediction of DSS. The proportion of variation explained (PVE) was also calculated to compare predictability of DSS in patients with DTC. Results: The median age of patients at diagnosis was 39.9 years (IQR 31.0 - 51.7 years) and 75.5% (1299/1721) were female. Median follow up was 9.3 years and 10 years DSS was 97.1%. For DTC overall, an age cut-off of 50 years had the best statistical model performance. On receiver operating characteristic curve analysis, the optimal age cut-off for prediction of DSS was 50.5 years (area under the curve = 0.872, p &amp;lt; 0.0001). Conclusion: In this large cohort of Middle Eastern DTC patients, an age cut-off of 50 years was more appropriate for TNM staging to achieve better predictability for DSS. Therefore, implementation of different age cut-off for DTC in Middle Eastern patients could improve the predictive value for TNM staging system, and allow for better therapeutic and surveillance approach for these patients. Citation Format: Sandeep K. Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Saeeda O. Ahmed, Nabil Siraj, Zeeshan Qadri, Saud Azam, Khawla S. Al-Kuraya. Optimal cut-off age for AJCC staging system in Middle Eastern patients with differentiated thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6262.

Morphometric Analysis of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma Using Digital Pathology.

Digital pathology uses digitized images for cancer research. We aimed to assess morphometric parameters using digital pathology for predicting recurrence in patients with papillary thyroid carcinoma (PTC) and lateral cervical lymph node (LN) metastasis. We analyzed 316 PTC patients and assessed the longest diameter and largest area of metastatic focus in LNs using a whole slide imaging scanner. In digital pathology assessment, the longest diameters and largest areas of metastatic foci in LNs were positively correlated with traditional optically measured diameters (R = 0.928 and R2 = 0.727, p < 0.001 and p < 0.001, respectively). The optimal cutoff diameter was 8.0mm in both traditional microscopic (p = 0.009) and digital pathology (p = 0.016) evaluations, with significant differences in progression-free survival (PFS) observed at this cutoff (p = 0.006 and p = 0.002, respectively). The predictive area's cutoff was 35.6 mm2 (p = 0.005), which significantly affected PFS (p = 0.015). Using an 8.0-mm cutoff in traditional microscopic evaluation and a 35.6-mm2 cutoff in digital pathology showed comparable predictive results using the proportion of variation explained (PVE) methods (2.6% vs. 2.4%). Excluding cases with predominant cystic changes in LNs, the largest metastatic areas by digital pathology had the highest PVE at 3.9%. Furthermore, high volume of LN metastasis (p = 0.001), extranodal extension (p = 0.047), and high ratio of metastatic LNs (p = 0.006) were associated with poor prognosis. Both traditional microscopic and digital pathology evaluations effectively measured the longest diameter of metastatic foci in LNs. Moreover, digital pathology offers limited advantages in predicting PFS of patients with lateral cervical LN metastasis of PTC, especially those without predominant cystic changes in LNs.

Newly proposed survival staging system for poorly differentiated thyroid cancer: a SEER-based study.

Despite the recent release of the 8th edition TNM staging system, the risk stratification for poorly differentiated thyroid cancer (PDTC) remains controversial. Retrospective study. SEER database and the First Hospital of China Medical University (FHCMU) database. Between 2004 and 2015, 1201 PDTC patients from the SEER database were enrolled to propose a new staging system. 38 PDTC patients were included from the FHCMU. A retrospective analysis of 1201 PDTC cases was performed, and a new staging classification was developed as follows: stage I: age < 55 and T1/any N/M0 (n = 127, 10.57%); stage II: age < 55 and T2-4/any N/M0 or age ≥ 55 and T1-2/any N/M0 (n = 523, 43.55%); stage III: age < 55 and any T/N0/M1 or age ≥ 55 and any T3/any N/M0 (n = 239, 19.90%); stage IV: age < 55 and any T/N1/M1 or age ≥ 55 and T4/any N/M0, and T/any N/M1 (n = 312, 25.98%). The 10-year disease-specific survival rates of patients in the new stages I, II, III, and IV were 97.9%, 77.9%, 35.3%, and 12.1%, respectively. The proportion of variation explained (PVE) for disease-specific survival of the proposed system was higher than that of the 8th AJCC TNM staging (30.61% vs. 27.15%). The accuracy of the staging system was verified in 38 PDTC patients from the FHCMU. The proposed staging system provided a more accurate risk stratification for PDTC patients. The new staging model may facilitate the design of personalized treatment strategies for PDTC patients.

Abstract 9843: Dynamic Importance of Genomic and Nongenomic Risk Factors for Coronary Artery Disease Over the Life Course

Introduction: Current cardiovascular risk models are limited by fixed window estimates of risk rather than lifetime trajectories. We create a novel framework to understand the time-varying profiles of genomic and non-genomic risk factors over the life span. Methods: We examine 325,948 individuals from the UK Biobank (UKB) (57% female, enrollment age 40-70 years, mean follow-up 11.9 years) with baseline clinical risk factors, composite Pooled Cohort Equations (PCE), and coronary artery disease (CAD) polygenic risk score (PRS). We compare Cox hazard ratios (HR) and the proportion of variation explained (PVE) at each age of enrollment. We extend analyses to a younger cohort of 3,821 individuals from the Framingham Health Study (FHS) Offspring Cohort, (51% female, enrollment ages 18-57, mean follow-up 35.1 years). Results: Results: HR and PVE of CAD PRS are greater early in life with HR 2.47, [95% CI 2.45-2.50] at age 40 to HR 1.67 [1.64,1.70] at age 70 in UKB; PVE of 7.8% to 2.3% in UKB. Parallel results were observed in FHS (Fig 1A-C) earlier in the life span. While the variation in lifetime risk increases with time, the HR for single risk factors estimated at each age are dynamic. The PCE, via inclusion of age, absorb much of this variation. Reclassification of intermediate 10-year PCE risk (7.5-19.9%) using PRS is most informative in younger individuals. In the UKB, the top-quintile of PRS, when compared to PCE alone, accurately predicts more individuals under age 55 (1108 versus 844) who ultimately develop CAD, but loses superiority over age 55 (Fig. 1D). Conclusions: Depending on when the question is asked, the HR of CAD of both genomic and non-genomic risk factors changes dramatically, with PRS demonstrating superiority early on. Our novel framework incorporates time-varying effects in portraying risk trajectory rather than fixed-window estimates. We show that polygenic scores also predict lifetime risk of disease early on rather than predicting only early-onset disease.

Genetic prediction of myopia in different ethnic ancestries

Purpose. Myopia has been shown to have a complex mode of inheritance, being influenced by both genetic and environ- mental factors. Here, an introduction into myopia genetics is given, with the shortcomings of current genetic prediction for myopia discussed, including the proportionally limited research on genetic prediction in people of non-European ancestry. A previously developed genetic risk score derived from European participants was evaluated in participants of non-European ancestry. Methods. Participants from UK Biobank who self-reported their ethnicity as “Asian”, “Chinese”, or “Black” and who had refractive error and genetic data available were included in the analysis. Ancestral homogeneity was confirmed using principal component analysis, resulting in samples of 3500 Asian, 444 Chinese, and 3132 Black participants. A published refractive error GWAS meta-analysis of 711,984 participants of European ancestry was used to create a weighted genetic risk score model which was then applied to participants from each ethnic group. Accuracy of genetic prediction of refractive error was estimated as the proportion of variance explained (PVE). Receiver operating characteristic (ROC) curves were developed to estimate myopia prediction performance at three thresholds: any myopia (equal to or more than 0.75D), moderate myopia (between −3.00D and −4.99D) and high myopia (equal to or more than −5.00D). Odds ratios for myo- pia were calculated for the participants in the top 10th or 5th percentile of genetic risk score distribution, comparing them to the remainder of the population. Results. The PVE value for refractive error was 6.4 %, 6.2 %, and 1.5 % for those with Asian, Chinese and Black ethnicity, respectively (compared to 11.2 % in Europeans). Odds ra- tios for any myopia and moderate myopia development for those within the top 10th and 5th percentile of genetic risk were significant in all ethnic groups (P &lt; 0.05). However, the genetic risk score was not able to reliably identify those at risk of high myopia, other than for participants of Chinese ethnicity (P &lt; 0.05). Conclusion. Prediction of refractive error in Asian, Chinese and Black participants was ~ 57 %, 55 % and 13 % as accurate in comparison to prediction in European participants. Further research in diverse ethnic populations is needed to improve prediction accuracy. Keywords Myopia, Genetic Prediction, Refractive Error, Polygenic Risk Score

Development of quantitative structure-retention relationship models to improve the identification of leachables in food packaging using non-targeted analysis

Quantitative structure-retention relationship (QSRR) models can be used to predict the chromatographic retention time of chemicals and facilitate the identification of unknown compounds, notably with non-targeted analysis. In this study, QSRR models were developed from the data obtained for 178 pure chemical standards and four types of analytical columns (C18, phenylhexyl, pentafluorophenyl, cyano) in liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). First, different data partitioning ratios and feature selection methods [random forest (RF) and support vector machine (SVM)] were tested to build models to predict chromatographic retention times based on 2D molecular descriptors. The internal and external performances of the non-linear (RF) and corresponding linear predictive models were systematically compared, and RF models resulted in better predictive capacities [p < 0.05, with an average PVE (proportion of variance explained) value of 0.89 ± 0.02] than linear models (0.79 ± 0.03). For each column, the resulting model was applied to identify leachables from actual plastic packaging samples. An in-depth investigation of the top 20 most intense molecular features revealed that all false-positives could be identified as outliers in the QSRR models (outside of the 95% prediction bands). Furthermore, analyzing a sample on multiple chromatographic columns and applying the associated QSRR models increased the capacity to filter false positives. Such an approach will contribute to a more effective identification of unknown or unexpected leachables in plastics (e.g. non-intended added substances), therefore refining our understanding of the chemical risks associated with food contact materials.

Comparison of the prognostic value of AJCC cancer staging system 7th and 8th editions for differentiated thyroid cancer

BackgroundIn the last American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) 8th edition (TNM8), several changes were introduced to this risk stratification system to improve the prognosis of differentiated thyroid cancer (DTC).AimTo validate the impact of TNM8 vs. TNM 7th edition (TNM7) in DTC in terms of predictive value in two hospitals from Buenos Aires, Argentina.MethodsRetrospective study of DTC patients from two institutions. Reclassification from TNM7 to TNM8, disease-specific survival (DSS), and final clinical outcomes at the end of follow-up (recurrent/persistent structural disease) (median 5 years) were analyzed. The proportion of variation explained (PVE) was used to compare the predictive capability of DSS of both classification systems.ResultsReclassification of 245 patients, aged (mean ± SD) 55 ± 15.36 years, 91% women, to TNM8 from TNM7 showed: 82% vs 57% stage I (SI), 10% vs 8.5% SII, 5% vs 22% SIII, 3% vs 12% SIV (p < 0.01). Forty percent of the population was downstaged with TNM8. Ten-year DSS rates for SI, SII, SIII and SIV in TNM7 were 100, 100, 100 and 74%, respectively and in TNM8: 97.6, 100, 100 and 37.5%, respectively. Out of 4 disease-specific deaths in SIV TNM7, one was subclassified to SI TNM8, corresponding to a 53-year-old patient with structural persistence. PVE for TNM8 (29%) was more than twice that of TNM7 (13%).ConclusionIn this Argentinian DTC patients sample, it was confirmed that the new TNM8 classification is more accurate in predicting survival attributable to cancer than its previous version.

Serum parameters as prognostic biomarkers in a real world cancer patient population treated with anti PD-1/PD-L1 therapy

Background Immune checkpoint inhibitors (ICI) are regarded as a standard of care in multiple malignancies. We hypothesized that serum parameters are of prognostic value in ICI treated patients suffering from solid tumours. Methods Data from 114 patients treated with ICIs for solid malignancies from 2015 to 2019 at the Medical University of Vienna were collected retrospectively. Data included baseline characteristics, cancer type, serum parameters such as lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (Alb) and lymphocyte counts as well as overall survival (OS) and progression free survival. Additionally, the Gustave Roussy Immune Score (GRIm score) and the Glasgow prognostic score (GPS) were calculated. Cox regression models including time-dependent effects and strata for tumour type were used. Prognostic factors were pre-selected using a relaxed LASSO approach. Results The majority of patients were male (64.9%). The most common cancer types were non-small cell lung cancer (30.7%) and renal cell carcinoma (21.9%). Increased LDH and CRP were associated with poor 6-month OS (Hazard ratios (HR)=1.16 and 1.06 per 20% LDH/CRP increase; 95% CI 1.07–1.26 and 95% CI 1.03–1.09, respectively; p < .001). Both GRIm Score and GPS had a significant influence on OS (GRIm: HR = 2.84, 95% CI 1.72–4.69; p < .001 for high vs. low; GPS HR 3.57, 95% CI 1.76–7.25; p < .001 for poor vs. good). The proportion of explained variation (PEV) of our full multivariable model was significantly higher compared to the GRIm and GPS (PEV = 29.5% vs. 14.8% and 14.65%). When grouped into quartiles according to the individual 8-weeks change, both increased LDH and CRP correlated with poor OS (LDH (p=.001) and CRP (p < .001)). Conclusion The results of this analysis suggest that serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type. Key messages In this retrospective analysis, 114 patients with solid tumours were included. The results of this analysis point out that pre-treatment LDH, CRP and albumin levels are strongly prognostic for a poor 6-month OS. In addition to that, a high GRIm-score and poor GPS were associated with a worse OS (GRIm: HR = 2.84, 95% CI 1.72–4.69; p < .001 for high vs. low; GPS HR = 3.57, 95% CI 1.76–7.25; p < .001 for poor vs. good). Pre-treatment serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type.

Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations

Follicular thyroid carcinoma (FTC) has different clinicopathological characteristics than papillary thyroid carcinoma. However, there are no independent systems to predict cancer-specific survival (CSS) in FTC. Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. Thus, it could be a potential prognostic marker. The aim of this study was to refine the CSS risk prediction using TERT promoter mutations in combination with the fourth edition of World Health Organization (WHO 2017) morphological classification. We investigated 77 FTC patients between August 1995 and November 2020. Cox regression was used to calculate hazard ratios to derive alternative groups. Disease-free survival (DFS) and CSS predictability were compared using Proportion of variation explained (PVE) and C-index. CSS was significantly different in encapsulated angioinvasive (EA)-FTC patients stratified by TERT promoter mutations [wild-type (WT-TERT) vs. mutant (M-TERT); P < 0.001] but not in minimally invasive (MI)-FTC and widely invasive (WI)-FTC patients (P = 0.691 and 0.176, respectively). We defined alternative groups as follows: Group 1 (MI-FTC with WT-TERT and M-TERT; EA-FTC with WT-TERT), Group 2 (WI-FTC with WT-TERT), and Group 3 (EA-FTC with M-TERT; WI-FTC with M-TERT). Both PVE (22.44 vs. 9.63, respectively) and C-index (0.831 vs. 0.731, respectively) for CSS were higher in the alternative groups than in the WHO 2017 groups. Likewise, both PVE (27.1 vs. 14.9, respectively) and C-index (0.846 vs. 0.794, respectively) for DFS were also higher in the alternative groups than in the WHO 2017 groups. Alternative group harmonizing of the WHO 2017 classification and TERT promoter mutations is effective in predicting CSS in FTC patients, thereby improving DFS predictability.

Microscopic Extrathyroidal Extension Results in Increased Rate of Tumor Recurrence and Is an Independent Predictor of Patient's Outcome in Middle Eastern Papillary Thyroid Carcinoma.

BackgroundPapillary Thyroid Cancer (PTC) is the most common endocrine malignancy, with recurrence rate as high as 30%. A great deal of controversy surrounds the significance of microscopic extrathyroidal extension (m-ETE) as a prognostic factor. The most recent edition (8th) of American Joint Committee on Cancer (AJCC) staging system has removed m-ETE from the definition of pT3, which suggests that m-ETE may lack prognostic impact in PTC patients. Moreover, data about m-ETE prevalence and clinical impact on Middle Eastern PTC remains unknown. We therefore investigate the prevalence of m-ETE and its clinico-pathological correlation and prognostic impact in Middle Eastern PTC. We also compared the AJCC 7th and 8th staging systems and their prognostic performance.MethodsPTCs from 1430 consecutive adult (> 18 years) patients from single tertiary care hospital were included in this study. A retrospective analysis of PTC patients’ survival and recurrence were compared between AJCC 8th and AJCC 7th staging systems using Proportion of Variation Explained (PVE) and Harrell’s C-index.ResultsMedian follow up of the study cohort was 9.3 years. 31.2% (446/1430) of patients had m-ETE. In the overall cohort, m-ETE was associated with multiple adverse features such as older age (p < 0.0001), male sex (p = 0.0245), tall cell variant (p < 0.0001), bilateral tumors (p < 0.0001), multifocality (p < 0.0001), lymphovascular invasion (p < 0.0001), lymph node metastasis (p < 0.0001), distant metastasis (p = 0.0166), tumor recurrence (p < 0.0001), radioactive iodine refractoriness (p < 0.0001), BRAF mutation (p < 0.0001) and reduced recurrence-free survival (RFS; HR = 1.75; 95% CI = 1.30 – 2.35; p < 0.0001) irrespective of tumor size. Of the 611 patients with T3 disease based on AJCC 7th edition, 359 (58.8%) were down-staged in AJCC 8th edition classification. Overall, the prognostic performance of AJCC 8th edition was inferior to AJCC 7th on the basis of lower PVE (3.04% vs. 3.73%) and lower C-index (0.40 vs. 0.48).ConclusionsIn Middle Eastern PTC, m-ETE is significantly associated with compromised survival and acts as an independent predictor of RFS. Given these findings, m-ETE should be included in the thyroid cancer treatment guidelines.

Improving the prediction of persistent and recurrent differentiated thyroid cancer using the American Thyroid Association 2015 risk stratification system.

The 2015 American Thyroid Association risk stratification system (ATA RSS) is used in patients with differentiated thyroid carcinoma (DTC) to assess their risk of persistent/recurrent disease. Our aims were to validate the 2015 ATA RSS in a registry of DTC patients and to examine whether the addition of factors not included in it, such as pre-radioactive iodine therapy stimulated thyroglobulin (pre-RAI sTg), gender, and age could increase its predictive ability. We studied 403 patients with DTC, treated at a tertiary center from 1990 to 2018 and subjected to total thyroidectomy. All patients had received RAI therapy, except those with low-risk papillary microcarcinoma. Of our patients, 81.9% were women and 91.1% had papillary thyroid carcinoma. After a median follow-up of 5.0years, 53 cases of persistent and 21 cases of recurrent disease were recorded. The proportion of variance explained (PVE) regarding the outcome (presence or absence of recurrent/persistent disease) using the 2015 ATA RSS alone was 18.3% (persistence) and 16.9% (recurrence), increasing to 74.4% and 52.0%, respectively, when pre-RAI sTg was added to the logistic regression model. Gender and age were not associated with the disease outcome. In ROC analysis, pre-RAI sTg had a high predictive value for persistent (AUC 0.983, 95% CI 0.962-1.000) and recurrent disease (AUC 0.856, 95% CI 0.715-0.997). The optimal cut-offs and sensitivity, specificity, and positive and negative predictive value for pre-RAI sTg were the following: for persistence 12.75ng/ml, 100%, 90.5%, 64%, and 100%, and for recurrence 8.05ng/ml, 77.8%, 85.5%, 36.8%, and 97%. The 2015 ATA RSS displayed moderate performance in predicting recurrent/persistent disease in patients with DTC, which improved with the inclusion of pre-RAI sTg values; pre-RAI sTg was an independent predictor of the disease outcome, with high negative prognostic value.

Comparison of the abilities of staging and risk stratification systems to predict the long-term structural recurrence in patients with differentiated thyroid carcinoma after total thyroidectomy and radioactive iodine remnant ablation.

In patients with differentiated thyroid carcinoma (DTC), various staging and risk stratification systems have been applied to estimate long-term recurrence, which is a major issue during the postoperative follow-up period. However, the efficacy of these systems remains unclear in this context. The present historical cohort study included 510 patients with DTC who underwent a total thyroidectomy followed by radioactive iodine (RAI) remnant ablation. Enrolled patients were categorized according to the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) Tumor Node Metastasis (TNM) staging system, the 2015 American Thyroid Association (ATA) initial risk stratification system, and the dynamic risk stratification (DRS) system. The ability of each system to predict long-term structural recurrence was compared using proportion of variance explained (PVE) by logistic regression models. The median follow-up period was 108 months. Structural recurrence occurred in 7.6% of the patients (n=39/510). Disease-free survival (DFS) curves of the patients within each category in the TNM staging system, the ATA initial risk stratification system, and the DRS system were significantly different (P<0.001). The PVE of the DRS system (20.7%) was higher than those of the TNM staging system and the ATA initial risk estimates. The DRS system may effectively predict long-term structural recurrence and guide long-term management and follow-up strategies in patients with DTC undergoing total thyroidectomy and RAI remnant ablation.

Optimal Timing of Initiating Dynamic Risk Stratification During the Early Postoperative Period in Patients with Differentiated Thyroid Carcinoma After Thyroidectomy and Radioactive Iodine Remnant Ablation.

This study investigated the optimal timing to initiate assessment of the response to initial therapy during the early postoperative period in patients with differentiated thyroid carcinoma (DTC) using dynamic risk stratification (DRS). This historical cohort study included 510 patients with DTC who underwent a total thyroidectomy followed by radioactive iodine (RAI) remnant ablation. DRS for these patients was categorized into subgroups according to the time into the follow-up period at which the response to initial therapy was assessed. The ability of each DRS subgroup to predict the long-term structural recurrence of cancer was compared using the proportion of variance explained (PVE) from logistic regression models. The median follow-up period was 108 months. Structural recurrence occurred in 7.6% of patients (n=39/510). The PVE for long-term structural recurrence was higher among DRS subgroups (28.8-34.19%) compared with the American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis staging system (both the 7th and 8th editions; 4.01% and 6.13%, respectively) and the American Thyroid Association initial risk estimate (4.59%). Among the DRS subgroups, DRS assessed between 2 and 3years after the initial surgery was associated with the highest PVE (34.19%). The first assessment of DRS optimally predicts long-term structural recurrence in patients with DTC who underwent a total thyroidectomy and subsequent RAI remnant ablation at that 2- to 3-year postoperative period.

Clinical Implication of World Health Organization Classification in Patients with Follicular Thyroid Carcinoma in South Korea: A Multicenter Cohort Study.

BackgroundThe study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC).MethodsThis multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS).ResultsIn total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS.ConclusionWHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

Clinical Value of Lymph Node Ratio Integration with the 8th Edition of the UICC TNM Classification and 2015 ATA Risk Stratification Systems for Recurrence Prediction in Papillary Thyroid Cancer

Recently, the 2015 American Thyroid Association (ATA) risk stratification and the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system were released. This study was conducted to assess the clinical value of the lymph node ratio (LNR) as a predictor of recurrence when integrated with these newly released stratification systems, and to compare the predictive accuracy of the modified systems with that of the newly released systems. The optimal LNR threshold value for predicting papillary thyroid cancer (PTC) recurrence was 0.17857 using the Contal and O’Quigley method. The 8th edition of the AJCC/UICC TNM staging system with the LNR and the 2015 ATA risk stratification system with the LNR were significant predictors of recurrence. Furthermore, calculation of the proportion of variance explained (PVE), the Akaike information criterion (AIC), Harrell’s c index, and the incremental area under the curve (iAUC) revealed that the 8th edition of the TNM staging system with the LNR, and the 2015 ATA risk stratification system with the LNR, showed the best predictive performance. Integration of the LNR with the TNM staging and the ATA risk stratification systems should improve prediction of recurrence in patients with PTC.

Eighth edition of tumor-node-metastasis staging system improve survival predictability for papillary, but not follicular thyroid carcinoma: A multicenter cohort study

ObjectivesThis study aimed to evaluate the proposed changes in the eighth edition of the tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in terms of pathologic subtypes, using a large multicenter thyroid cancer cohort. Materials and methodsWe retrospectively reviewed 7717 patients with papillary (PTC) and 273 with follicular thyroid carcinoma (FTC) who underwent thyroid surgery between 1996 and 2005. We assessed the proportion of variation explained (PVE) to compare the predictive accuracy of disease-specific survival (DSS). ResultsDuring a median 11.3 years of follow-up, 169 (2%) disease-specific deaths were recorded. In patients with PTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 99.6%, 95.7%, 81.5%, and 54.8%, respectively; the corresponding rates in TNM-7 were 99.6%, 98.4%, 98.4%, and 90.1%, respectively. In patients with FTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 97.2%, 69.8%, 50.0%, and 45.5%, respectively; the corresponding rates in TNM-7 were 98.3%, 90.0%, 92.3%, and 42.1%, respectively. Comparing TNM-7 and TNM-8, the PVE values increased from 3.4% to 4.7% in the PTC group, whereas they decreased from 17.5% to 14.5% in the FTC group. ConclusionOur study suggests that the changes in TNM-8 have improved the clinical usefulness of the TNM staging system in terms of predicting DSS in patients with PTC but not FTC. Further studies to establish a more predictable TNM staging system that focuses on patients with FTC are necessary.

Survival in Differentiated Thyroid Cancer: Comparing the AJCC Cancer Staging Seventh and Eighth Editions.

The American Joint Committee on Cancer Cancer Staging System for differentiated thyroid cancer has been recently revised. The purpose of this study was to compare survival prognostication between the seventh and eighth editions. We retrospectively reviewed 2579 differentiated thyroid cancer patients who underwent surgery at MD Anderson Cancer Center between 2000 and 2015. Disease-specific survival (DSS) and overall survival were estimated using the Kaplan-Meier method and compared using log rank test. The effect of potential predictor was estimated using Cox proportional hazards model. Power of survival prediction was estimated using Harrell's C concordance index (C-index), and predictive capacities for DSS were estimated using proportion of variance explained (PVE). Revision of tumor-node-metastasis (TNM) categories, age cutoff, and stage reassignment in the 8th edition caused reclassification of overall stage compared with the seventh edition. The proportion of patients in stage I and II increased from 62% to 83% and 5% to 12%, respectively, while the proportion of patients in stage III and IV decreased from 20% to 2% and 14% to 3%, respectively. Ten-year DSS for stages I-IV based on the seventh edition were 100%, 97.5%, 98.3%, and 82.6%, respectively, while 10-year DSS for the corresponding stage in the eighth edition were 99.8%, 88.3%, 72.4%, and 71.9%, respectively. In multivariate analysis for both seventh edition (C-index 0.94, PVE 4.6%) and eighth edition (C-index 0.94, PVE 4.8%), the factors predictive of worse outcome for DSS were older age, advanced tumor size category, and distant metastasis while cervical lymph node metastases did not predict worse survival. For the eighth edition, patients <55 years of age with stage II disease had significantly worse DSS (p < 0.001) than patients ≥55 years with stage II disease but appeared to be similar to patients ≥55 years with stage III (p = 0.742) and IV disease (p = 0.566). Patients ≥55 years old with T3a and T3b disease had 10-year DSS of 67% and 92%, respectively (p = 0.390). The AJCC eighth edition is similar to the seventh edition in disease-specific survival prediction. Potential modifications that may improve disease-specific survival prediction in future renditions include reconsideration of T3b tumor category and upstaging classification of patients <55 years of age with distant metastases.

Clinical Validation of the Prognostic Stage Groups of the Eighth-Edition TNM Staging for Medullary Thyroid Carcinoma.

Despite advances in thyroid cancer staging systems, considerable controversy about the current staging system for medullary thyroid carcinoma (MTC) continues. We aimed to evaluate the prognostic performance of the current eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control TNM staging system (TNM-8) and the alternative proposed prognostic stage groups based on recursive partitioning analysis (TNM-RPA). We retrospectively analyzed 182 patients with MTC treated at a single tertiary Korean hospital between 1995 and 2015. Survival analysis was conducted according to TNM-8 and TNM-RPA. The area under the receiver-operating characteristic curve (AUC), the proportion of variation explained (PVE), and the Harrell concordance index (C-index) were used to evaluate predictive performance. Under TNM-8, only two (1.1%) patients were downstaged compared with the seventh edition of the AJCC TNM staging system (TNM-7). The AUC at 10 years, PVE, and C-index were 0.679, 8.7%, and 0.744 for TNM-7 and 0.681, 8.9%, and 0.747 for TNM-8, respectively. Under TNM-RPA, 104 (57.14%) patients were downstaged compared with TNM-8. TNM-RPA had better prognostic performance with respect to cancer-specific survival (AUC at 10 years, 0.750; PVE, 20.9%; C-index, 0.881). The predictive performance of the revised TNM-8 in patients with MTC has not changed despite its modification from TNM-7. The proposed changes in TNM-RPA were statistically valid and may present a more reproducible system that better estimates cancer-specific survival of individual patients.