ΔTg Assesses Radioiodine Treatment Response and Predicts Prognosis in Pediatric Differentiated Thyroid Cancer

ΔTg Assesses Radioiodine Treatment Response and Predicts Prognosis in Pediatric Differentiated Thyroid Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article ΔTg Assesses Radioiodine Treatment Response and Predicts Prognosis in Pediatric Differentiated Thyroid Cancer Shuo Huang, Shaoyan Wang, Zhiyi Ye, Weiwei Cheng, Chao Li, Shuqi Wu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7567986/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Dec, 2025 Read the published version in Endocrine → Version 1 posted 10 You are reading this latest preprint version Abstract Purpose: This study aims to define the relationship between the thyroglobulin change rate (ΔTg) after radioactive iodine (RAI) therapy and treatment response, determine its optimal threshold, and validate its prognostic value in pediatric patients with differentiated thyroid cancer (DTC). Methods: This retrospective study analyzed 123 RAI courses in 57 pediatric DTC patients with postoperative persistent disease. Treatment response was assessed at 6 months. Optimal ΔTg thresholds were determined using ROC analysis with bootstrap validation. Prognostic value for no evidence of disease (NED) and progression-free survival (PFS) was evaluated. Results: ΔTg significantly differed among response categories ( p <0.001): Complete Response (CR): 84.5%, Partial Response (PR): 53.8%, Stable Disease (SD): 4.9%, Progressive Disease (PD): -69.0%. ROC analysis defined optimal ΔTg thresholds: ΔTg ≥32% for Objective Response (OR=CR+PR; AUC=0.96, p <0.001), ΔTg ≤-14% for PD (AUC=0.93, p <0.001); patients with -14%<ΔTg<32% were classified as SD. Longitudinally, initial ΔTg ≥32% (n=29) vs. ΔTg ≤-14% (n=17) showed superior PFS (133.5 vs. 13.9 months, p 0.05). The intermediate group (-14%<ΔTg0.05), while PFS (126.4 months) resembled ΔTg ≥32% ( p >0.05). Multivariable analysis confirmed ΔTg ≤-14% predicted an 11.7-fold higher progression hazard (HR=11.70, 95%CI:3.27-41.89; p <0.001). Conclusions: This study establishes validated ΔTg thresholds for response assessment in pediatric DTC (OR: ≥32%; PD: ≤-14%; SD: -14%<ΔTg<32%). Initial ΔTg is a powerful independent prognostic factor. These evidence-based thresholds provide actionable guidance for personalized pediatric DTC management. Differentiated thyroid cancer Pediatric thyroid carcinoma Thyroglobulin Radioiodine therapy Tg change rate Figures Figure 1 Figure 2 1. Introduction Differentiated thyroid carcinoma (DTC) is the most common malignant tumor of the endocrine system in pediatric patients [ 1 ]. Over the past three decades, the global incidence of pediatric DTC has shown a continuous upward trend [ 2 ]. Compared to adult patients, pediatric DTC exhibit distinct clinical characteristics: they often present with more aggressive features at initial diagnosis, including significantly higher rates of extrathyroidal extension, lymph node metastasis, and pulmonary metastasis. However, this group enjoys a superior long-term prognosis, with a 30-year cause-specific mortality (CSM) rate of only 1.1% [ 3 – 5 ]. Thyroglobulin (Tg) serves as a critical biomarker for monitoring treatment response and disease status in DTC [ 6 ]. The 2015 American Thyroid Association (ATA) guidelines recommend serial serum Tg measurements at 3–6 month intervals following radioactive iodine (RAI) therapy to evaluate treatment efficacy [ 7 ]. In pediatric patients with radioiodine-avid lesions, confirmation of prior RAI effectiveness is essential for determining subsequent treatment strategies [ 7 ]. Although declining post-therapeutic Tg levels typically correlate with biochemical remission, whereas rising levels indicate progression, the clinical significance of quantitative Tg change rate (ΔTg) —particularly its validated threshold— remains undefined in pediatric DTC populations. This ambiguity poses challenges for clinical decision-making [ 8 – 10 ]. Existing studies propose categorical criteria where ΔTg reductions ≥ 25% suggest partial response (PR), fluctuations within ± 25% indicate stable disease (SD), and increases > 25% denote progressive disease (PD) [ 11 – 13 ]. However, these thresholds are empirically derived and lack robust validation in pediatric cohorts. Consequently, establishing evidence-based correlations between ΔTg dynamics and treatment outcomes is imperative for optimizing pediatric DTC management. Based on a retrospective cohort over a 13-year period from a single center, this study establishes the correlation between ΔTg and treatment response, providing evidence-based guidance for precision RAI therapy in pediatric patients. 2. Materials and methods 2.1 Study subjects This single-center retrospective cohort study was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-D-2023-178). Written informed consent was obtained from all patients' legal guardians. The study, conducted in accordance with the Declaration of Helsinki (2013 revision), included 57 pediatric DTC patients who underwent a total of 123 courses of RAI therapy in the Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between January 2011 and November 2023. All patients underwent total thyroidectomy, with or without central neck dissection and/or lateral neck dissection. Prior to RAI therapy, a protocol-driven thyroid hormone withdrawal regimen was strictly implemented: levothyroxine was discontinued for ≥ 3 weeks, and serum thyroid-stimulating hormone (TSH) levels on the treatment day ≥ 30 mU/L. Radioiodine doses were calculated based on the actual body weight of pediatric patients, with proportional adjustments relative to the recommended adult dose for a 70 kg body weight. 2.2 Inclusion criteria Patients met all the following criteria:(1) Age at first RAI therapy ≤ 18 years; (2) Postoperative evidence of persistent structural disease (metastasis or residual tumor), confirmed by either whole-body scan (WBS) or histopathology; (3) No prior history of neck radiotherapy or anticancer therapy; (4) Negative TgAb status; (5) Complete imaging data and Tg records available for the treatment cycle. 2.3 Tg testing This study analyzed stimulated Tg (sTg) to eliminate interference from levothyroxine (LT4) suppression therapy. Valid sTg measurements required LT4 withdrawal for ≥ 3 weeks with concurrent TSH > 30 mU/L. The ΔTg = [(6-month post-therapy sTg - pre-therapy sTg) / pre-therapy sTg] × 100% (negative ΔTg indicates sTg increase). From 2010–2021, Tg was quantified using an immunometric assay with functional sensitivity of ≤ 0.1 ng/mL. Since 2021, a high-sensitivity electrochemiluminescence immunoassay has been employed, with limit of detection (LoD) ≤ 0.040 ng/mL. Due to assay sensitivity improvements during the decade-long study (from ≤ 0.1 ng/mL to ≤ 0.040 ng/mL), we used a short 6-month ΔTg interval to minimize variability. This approach ensured that pre- and post-therapy sTg for each patient were likely measured on comparable platforms. Within this brief period, it is highly probable that both pre-therapy and 6-month post-therapy sTg measurements for a given patient utilized comparable assay platforms and methodologies, thereby minimizing potential variability attributable to technical shifts. Serum TgAb levels were quantified using standardized chemiluminescent immunoassays. Specimens were classified as TgAb-negative when measured values fell below the manufacturer's reference threshold, whereas values exceeding this threshold were deemed TgAb-positive, strictly per kit specifications. 2.4 Therapeutic Response Assessment Each treatment course served as an independent observation unit for evaluation, with the patient's status immediately prior to the commencement of that given course defined as its baseline. Early treatment response at 6 months post-RAI therapy was assessed using a combination of structural imaging (ultrasonography, CT, MRI/PET-CT if indicated) and WBS according to the following modified criteria, primarily referenced to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 but adapted for pediatric DTC characteristics: Complete Response (CR):(1) Disappearance of all target lesions confirmed on both structural imaging and WBS; (2) For lymph nodes: short-axis diameter ≤ 5 mm on structural imaging AND disappearance of iodine uptake on WBS. PR:(1) Significant reduction in the number of lesions (with some disappearing); (2) ≥ 30% decrease in the sum of the long-axis diameters of target lesions or in short-axis diameter of target lymph nodes on structural imaging, OR (3) Reduction in lesions/lymph nodes not meeting the above criteria, but with markedly decreased iodine uptake on WBS. Objective response (OR) was defined as CR + PR. PD: (1) New lesion(s) with confirmed iodine uptake on WBS or histopathology; OR (2) ≥ 20% increase in the sum of the long-axis diameters of target lesions or in the short-axis diameter of target lymph nodes on structural imaging; OR (3) New findings highly suspicious for malignancy, without confirmation by either WBS or pathology, prompted independent re-evaluation by two experienced readers. PD was confirmed only when both readers independently identified the new lesions as metastatic lesions based on imaging evidence. SD: (1) Failure to fulfill criteria for CR, PR, or PD; OR (2) Discordant responses between lesion sites. Indeterminate Response: New suspicious structural lesions failed PD adjudication consensus. 2.5 Follow-up and Outcome Assessment Final Outcome Assessment: Disease status at the last follow-up was determined based on comprehensive review of all available clinical, serological, and imaging data [ 14 ]: No Evidence of Disease (NED): No structural evidence on imaging (US, CT, DxWBS, MRI/PET-CT if indicated) AND fulfilling either: (1) Serum Tg < 1 ng/mL under TSH suppression with negative TgAb, or (2) sTg 30 mU/L, and confirmed successful ablation) with negative TgAb. Non-NED: Patients not meeting the NED criteria at the last follow-up. Given the excellent overall prognosis and exceedingly low mortality in this pediatric cohort [ 3 – 5 ], we additionally evaluated progression-free survival (PFS) as a longitudinal outcome measure. PFS was defined as the interval from the first RAI therapy to documented disease progression or last follow-up. 2.6 Statistical Methods Data analysis was performed using SPSS 26.0 and R 4.4.3 software. The normality of continuous variables was assessed by the Kolmogorov-Smirnov test. Non-normally distributed data were analyzed after natural logarithmic transformation. Categorical variables are presented as frequency (percentage), and non-normally distributed continuous variables as median (range/interquartile range, IQR). For intergroup comparisons of categorical variables, Fisher's exact test was employed when expected cell frequencies were < 5, with post-hoc pairwise comparisons adjusted by Bonferroni correction (significance threshold α = 0.0167). Continuous variables were compared using the Kruskal-Wallis nonparametric test, with post-hoc multiple comparisons adjusted by the Bonferroni correction. The cutoff value of ΔTg for treatment response was evaluated via receiver operating characteristic (ROC) curve analysis, with the optimal cutoff determined by maximizing the Youden index. To assess the stability and optimism-corrected performance of the ROC-derived AUC values, bootstrap internal validation was performed with 1000 resampling iterations. The 95% confidence intervals for the AUCs were derived using the bias-corrected and accelerated (BCa) bootstrap method. PFS was calculated via the Kaplan-Meier method. Intergroup survival differences were assessed using the log-rank test. Cox proportional hazards regression was performed to identify independent prognostic factors for PFS time. All statistical analyses were two-sided, and p < 0.05 was considered statistically significant, except for post-hoc comparisons where the adjusted threshold was applied. 3. Research Results 3.1 Clinical Characteristics The study cohort comprised 57 pediatric DTC patients. Clinical characteristics are summarized in Table 1 . The median age at diagnosis was 10 years (range: 4–18 years), with a male-to-female ratio of 1.28:1. Primary tumors had a median diameter of 2.5 cm (range: 0.2–8.0 cm), and bilateral thyroid involvement was present in 66.7% (38/57) of patients. TNM staging revealed T3/T4 disease in 42.1% (24/57) of cases. Regional lymph node metastases (N1b) were identified in 96.5% (46/57) of patients, and distant metastases (M1) were found in 56.1% (32/57). Structural disease distribution analysis demonstrated: thyroid bed residual disease in 8.8% (5/57) of patients, metastatic lymph nodes in 89.5% (51/57), and pulmonary metastases in 56.1% (32/57). Critically, pulmonary metastases without concurrent cervical disease (lymph node or thyroid bed involvement) occurred in only 8.8% (5/57) of cases. Table 1 Clinical Characteristics of 57 Pediatric DTC with Postoperative Persistent Structural Disease Characteristics of all patients (n = 57) n (%)/median (range) Age at diagnosis (y) 10.0(4–18) Sex Male 32(56.1%) Female 25(43.9%) Primary tumor size (cm) 2.5(0.2-8) Bilaterality 38(66.7%) Pathological type PTC 55(96.5%) Classical PTC 50(87.7%) Follicular-variant PTC 3(5.3%) Diffuse sclerosing PTC 1(1.8%) Tall cell PTC 1(1.8%) FTC 2(3.5%) T stage* T1a 6(10.5%) T1b 11(19.3%) T2 16(28.1%) T3a 7(12.3%) T3b 6(10.5%) T4a 10(17.5%) T4b 1(1.8%) N stage* N0 2(3.5%) N1a 9(15.8%) N1b 46(80.7%) M stage* M0 25(43.9%) M1 32(56.1%) Distribution of Disease Components Lymph node metastasis 51(89.5%) Only lymph node metastasis 26(51.0%) With Other Metastatic Components 25(49.0%) Pulmonary metastasis 32(56.1%) Only pulmonary metastasis 6(18.8%) With Other Metastatic Components 26(81.3%) Thyroid bed residual disease 5(8.8%) Only thyroid bed residual disease 0 With Other Metastatic Components 5(100.0%) * American Joint Committee on Cancer (AJCC) 8th edition A total of 123 treatment courses were evaluated as independent observation units, with baseline status re-established prior to each course initiation (Table 2 ). Therapeutic response was assessed at 6 months after each RAI treatment using predefined criteria. OR (CR + PR) was achieved in 55 courses (44.7%). Among these, CR was observed in 11 courses (8.9%), characterized by the disappearance of all target lesions in 6 cases (54.5% of CRs) or Lymph node short-axis diameter ≤ 5 mm and disappearance of iodine uptake in 5 cases (45.5% of CRs). PR occurred in 44 courses (35.8%), comprising: lesion number reduction in 3 cases (6.8% of PRs), lesion/lymph node size reduction meeting criteria (≥ 30% decrease in long-axis/short-axis diameter) in 28 cases (63.6% of PRs), and lesion/lymph node reduction that does not reach the ≥ 30% threshold above but is accompanied by markedly decreased RAI uptake on WBS in 13 cases (29.5% of PRs). SD was documented in 46 courses (37.4%), while PD occurred in 22 courses (17.9%). PD was attributed to new lesions or lymph node (5 courses, 22.7% of PDs), significant growth of existing lesions or lymph nodes (11 courses, 50.0% of PDs), and new highly suspicious metastatic lesions confirmed by two experienced readers (6 courses, 27.3% of PDs). Table 2 Treatment Responses in 123 Therapeutic Courses of pediatric DTC Therapeutic Response Assessment(n = 123) n (%) Objective Response (OR):CR + PR 55 (44.7%) Complete Response (CR) 11 (8.9%) Target lesion disappearance 6 (54.5%) Lymph nodes ≤ 5 mm short-axis + disappearance of RAI uptake 5 (45.5%) Partial Response (PR) 44 (35.8%) lesion number reduction 3 (6.8%) ≥30% decrease in long-axis diameter of lesions or in lymph node short-axis diameter 28 (63.6%) Lesion/lymph node reduction that does not reach the ≥ 30% threshold above but is accompanied by markedly decreased RAI uptake on WBS 13 (29.5%) Progressive Disease (PD) 22 (17.9%) New lesions/lymph node 5 (22.7%) ≥20% increase in long-axis diameter of lesions or in lymph node short-axis diameter. 11 (50.0%) New highly suspicious metastatic lesions confirmed by 2 readers 6 (27.3%) Stable Disease (SD) : 46 (37.4%) Not meeting criteria for CR, PR, or PD 45(97.8%) Discordant responses between lesion sites 1(2.2%) Indeterminate Response 0 3.2 Analysis of the Association between ΔTg and Treatment Response Pediatric DTC is characterized by aggressive behavior, particularly in patients with pulmonary metastases or unresectable thyroid bed lesions, who commonly present with multi-site metastases before RAI therapy [ 15 ]. In this cohort, pulmonary metastases and thyroid bed disease predominantly coexisted with metastases at other sites, with rates of 81.3% and 100%, respectively. Given this pattern, isolated analysis of ΔTg for lymph node, pulmonary, or thyroid bed lesions may have limited clinical utility. Therefore, we analyzed lesions across all sites within each patient as an integrated entity to enhance clinical applicability. The Kruskal-Wallis test revealed highly statistically significant differences in ΔTg across treatment response groups (H = 94.056, p < 0.001) (Table 3 ). Patients with CR (n = 11) exhibited the most substantial Tg reduction (median ΔTg = 84.5% , IQR = 28% ), demonstrating significantly greater decline than those with PR (n = 44; median ΔTg = 53.8% , IQR = 42% ; p < 0.05). Whereas the SD group (n = 46) showed only marginal Tg decrease (median ΔTg = 4.9% , IQR = 22% ), the PD group (n = 22) displayed pronounced Tg elevation (median ΔTg= -69.0% , IQR = 91% ). Both SD and PD groups demonstrated statistically significant differences ( p < 0.001) compared to each of the other response groups in pairwise comparisons. These findings confirm that ΔTg serve as a valid biomarker for treatment efficacy assessment, with the magnitude of reduction positively correlating with therapeutic outcomes. Table 3 Distribution of Δ Tg Levels and Group Comparisons Across Treatment Response Categories Treatment Response Sample size Δ Tg Median (IQR) Kruskal-Wallis H Test Pairwise Comparisons (Bonferroni-Adjusted) CR 11 84.5% (28%) H = 94.056 p < 0.001 vs PR : p < 0.05 vs SD, PD : p < 0.001 PR 44 53.8% (42%) vs CR : p < 0.05 vs SD, PD : p < 0.001 SD 46 4.9% (22%) vs CR, PR, PD: all p < 0.001 PD 22 -69.0%(91%) vs CR, PR, PD: all p < 0.001 Note: A negative ΔTg value indicates an increase in sTg levels. 3.3 Optimal ΔTg cut-off values for predicting treatment response To establish optimal ΔTg cut-off values for predicting treatment response, we conducted ROC analysis (Fig. 1 ). For distinguishing OR from non-OR (including SD and PD), the AUC reached 0.96 (95% CI: 0.93–0.99; p < 0.001). The Youden index-derived optimal cut-off was ΔTg = 31.7%, yielding 92.7% sensitivity and 92.6% specificity. When discriminating non-PD (including CR, PR and SD) from PD, the AUC was 0.93 (95% CI: 0.85–1.000; p < 0.001) with an optimal cut-off of ΔTg=-13.9%, achieving 97.0% sensitivity and 91.3% specificity. The robustness of these AUC estimates was further confirmed through internal validation using bootstrap resampling with 1000 iterations. The bootstrap-corrected performance remained strong, with a mean AUC of 0.96 (95% bootstrap CI: 0.92–0.99) for OR prediction and 0.93 (95% bootstrap CI: 0.75–0.99) for non-PD prediction. The narrow width of these confidence intervals indicates high precision and reliability of the model estimates. Given the high diagnostic performance and the close proximity of theoretical cut-offs to clinically practical integer values, we propose the following criteria for 6-month post-treatment evaluation: OR defined as ΔTg ≥ 32%, PD indicated by ΔTg≤-14%, and SD classified as -14%<ΔTg < 32%. 3.4 Predictive Value of Initial ΔTg for NED and PFS Following RAI Therapy Based on the established ΔTg stratification criteria, this study evaluated the predictive value of the initial ΔTg (measured at 6 months after the first RAI therapy) for NED status at final follow-up (mean 61.8 ± 37.4 months) (Table 4 ). Among 57 patients, 22 (38.6%) achieved NED. A statistically significant difference in NED rates was observed across the cohorts ( p < 0.05), with the ΔTg ≥ 32% group (n = 29) demonstrating the highest rate (55.2%, 16/29) compared to the − 14%<ΔTg < 32% group (18.2%, 2/11) and the ΔTg≤-14% group (23.5%, 4/17). However, pairwise comparisons revealed no significant differences between individual groups: Group 1 vs. Group 2 ( p = 0.073), Group 1 vs. Group 3 ( p = 0.064), and Group 2 vs. Group 3 ( p = 1.000). Notably, one patient in the ΔTg≤-14% group died from respiratory failure secondary to tracheal compression at 4 months after RAI therapy and was included in the non-NED cases. Table 4 Association Between Initial Post-Treatment ΔTg Stratification and NED Status at Final Follow-up ΔTg at 6 months after the first RAI therapy(n = 57) NED Non-NED P- Value ΔTg ≥ 32% (n = 29) 16(55.2%) 13(44.8%) p ≤ 0.05 -14%<ΔTg <32% (n = 11) 2(18.2%) 9(81.8%) ΔTg ≤-14% (n = 17) 4(23.5%) 13(76.5%) Note: All p -values were calculated using two-sided Fisher's exact tests, due to the presence of cells with expected counts < 5. Furthermore, in the cohort of 57 patients, initial ΔTg stratification demonstrated high discriminative power in PFS (Fig. 2 ). Patients with initial ΔTg ≥ 32% showed mean PFS of 133.5 ± 7.9 months (95% CI: 118.1–149.0), comparable to the − 14%<ΔTg 0.05). In contrast, the ΔTg ≤ − 14% group had significantly reduced mean PFS of 13.9 ± 5.1 months (95% CI: 3.9–23.9; p < 0.001 vs. both groups). Integrating NED status and long-term PFS outcomes, these results demonstrate that patients with initial ΔTg ≥ 32% derived unequivocal clinical benefit from RAI therapy, while those with initial ΔTg ≤-14% showed no significant benefit. Patients in the intermediate range (-14%<initial ΔTg < 32%) achieved long-term PFS comparable to the high-response group, despite significantly reduced NED attainment. This discordance indicates uncertain therapeutic value of RAI in this subgroup, warranting further investigation to determine whether RAI provides meaningful clinical advantage for these patients. 3.5 Independent Prognostic Factors for Progression-Free Survival Multivariable Cox regression identified ΔTg as the dominant prognostic factor (Table 5 ). Patients with ΔTg≤-14% had an 11.5-fold higher progression risk than those with ΔTg>-14% (HR = 11.70, 95% CI: 3.27–41.89; p < 0.001). When analyzed as a continuous variable, each 1% increase in ΔTg was independently associated with a 41% reduction in progression risk (HR = 0.59, 95% CI: 0.35–0.99; p < 0.05). Tumor stage and size showed no significant association. The model explained 62.3% of PFS variability (Nagelkerke R²=0.623) with excellent fit (χ²=47.15, df = 4, p -14%) 11.70 (3.27–41.89) p < 0.001 Initial ΔTg (continuous) 0.59 (0.35–0.99) p 0.05 Tumor size (≥ 3cm vs. 0.05 4. Discussion Serum Tg is a crucial biomarker in pediatric DTC, as its dynamic trend reflects the response to treatment and disease status. However, there is currently a lack of standardized criteria for evaluating Tg changes following RAI therapy in this population. By analyzing 123 courses of RAI therapy administered to 57 pediatric DTC patients with persistent structural disease, this study established quantitative assessment thresholds based on ΔTg: OR was defined as ΔTg ≥ 32%; PD was defined as ΔTg≤-14%, SD was defined as -14%<ΔTg < 32%. Importantly, this study revealed significant associations between the ΔTg thresholds and treatment response, NED and PFS, providing critical evidence for optimizing precision treatment pathways in pediatric DTC. Among 181 patients aged ≤ 18 years with DTC treated with RAI at our center since 2011, this study enrolled 57 (31.5%) who had postoperative evidence of persistent structural disease (metastasis or residual tumor) and were Tgab-negative. The median age at diagnosis in this cohort was 10 years (range: 4–18 years), higher than the median age (16 years) reported in Bal et al.'s cohort [ 16 ]. The male-to-female ratio (1.28:1) indicated male predominance, differing from most previous reports [ 17 ]. Papillary Thyroid Carcinoma (PTC) constituted the predominant histology (96.5%, 55/57), with classical PTC accounting for 87.7% (50/57), follicular-variant PTC for 5.3% (3/57), diffuse sclerosing and tall cell PTC each for 1.8% (1/57 each). Follicular Thyroid Carcinoma (FTC) constituted 3.5% (2/57) of cases. This distribution aligns with studies focusing on pulmonary metastases in DTC (> 96% PTC) [ 11 ]. Conducting decade-long Tg-related research requires addressing the challenge of differing sTg assay methods [ 18 – 19 ]. To minimize errors arising from variations in sTg sensitivity over time, we calculate short-interval ΔTg. Within this brief period, the pre-therapy and 6-month sTg measurements for each patient were highly likely performed using the same assay platform and methodology. All sTg measurements included concurrent TgAb testing. Recognizing TgAb positivity may cause sTg underestimation [ 20 ], our primary analyses focused on TgAb-negative patients to ensure ΔTg reliability. While perfect longitudinal assay consistency was unattainable in our retrospective study, our core strategy provided a practical approach [ 20 ]. Utilizing a short interval ΔTg and excluding the impact of TgAb positivity maximized the validity and clinical relevance of sTg response kinetics within historical data constraints. To investigate Tg distribution across different treatment responses, this study established criteria based on structural and functional imaging changes to assess RAI efficacy against metastatic lesions, with primary reference to RECIST 1.1. Given the limitations of RECIST 1.1 in pediatric DTC, where iodine-avid lymph nodes can be present even with short-axis diameters < 1 cm, the CR criterion for lymph nodes was modified to short-axis diameter < 5 mm and disappearance of iodine uptake. Cases exhibiting only diffuse pulmonary iodine uptake without distinct structural lesions were excluded, as the absence of discrete measurable lesions precluded independent imaging-based response assessment. Within this framework, new lesions considered highly suspicious for malignancy, but without RAI uptake or pathological confirmation, required independent review by two readers. Six treatments were classified as PD using this standard. All six cases showed new non-RAI-avid pulmonary nodules appearing after initial therapy in patients with existing bilateral lung metastases; both readers independently confirmed these as metastases based on their imaging characteristics and comparison with prior imaging studies. Previous studies have reported the overall therapeutic efficacy in pediatric DTC patients after completion of all RAI treatment courses [ 11 ], while our study quantified early overall response per RAI course (n = 123 courses): CR 8.9% (11/123), PR 35.8% (44/123), SD 37.4% (46/123), and PD 17.9% (22/123). Focusing specifically on pulmonary metastases (n = 87 courses), we observed: CR 4.6% (4/87), PR 32.2% (28/87), SD 43.7% (38/87), and PD 19.5% (17/87). Notably, these early single-course response rates in pulmonary metastases showed CR and PD rates comparable to final outcomes reported in similar cohorts (CR 7.9%, PD 13.2%), despite differences in assessment timing [ 11 ]. The higher SD rate (43.7% vs 14.5%) suggests many lesions require multiple treatments to achieve measurable regression, however, the associated risk from increased cumulative radiation exposure requires careful consideration and warrants further investigation. Given the potential need for multiple RAI courses and the associated cumulative risks, identifying reliable predictors early in the treatment course becomes crucial to optimize therapeutic strategies and minimize unnecessary exposure. In this context, we evaluated the predictive value of the early ΔTg following the first RAI therapy for long-term disease status. Our findings suggest that the initial ΔTg level post-RAI therapy holds potential as a predictor for long-term NED status, evidenced by a statistically significant association overall ( p < 0.05). However, the lack of significant pairwise differences between the ΔTg response groups, despite clear numerical trends favoring the highest response group (55.2% NED vs. 18.2% and 23.5% in the other groups), is likely explained by limited statistical power. This limitation stems primarily from the relatively small sample size, especially within the intermediate response cohort (n = 11). Due to the presence of persistent, measurable structural disease at baseline in our cohort and the minimal number of death events (only 1 death, rendering overall survival [OS] analysis uninformative), we selected PFS as the key clinical outcome measure. A central finding was the comparable long-term PFS between patients achieving ΔTg ≥ 32% and those in the intermediate response group, despite the latter group demonstrating a significantly lower rate of achieving NED (18.2% vs. 55.2%). This dissociation suggests that RAI's therapeutic value may be uncertain for patients with intermediate ΔTg, though further validation is needed to establish causality. Two non-exclusive mechanisms could explain this discordance: 1) Patients with intermediate ΔTg responses may harbor indolent disease inherently unlikely to progress, regardless of RAI therapy, or 2) RAI therapy itself actively prevented progression in these patients, even though it failed to induce a significant Tg decline. As our study design cannot differentiate between these mechanisms, subsequent prospective studies, ideally multi-center trials with larger cohorts, are essential. These should specifically investigate whether RAI therapy provides a meaningful clinical advantage for this intermediate subgroup, potentially including strategies like randomized RAI withdrawal. This study has several limitations. First, as a single-center retrospective investigation, the cohort size remains relatively small (n = 57), which precluded separate analysis of lymph node metastasis and pulmonary metastasis subgroups despite their significant differences in both biological behavior and prognosis. Second, the median follow-up duration of 61.8 months is still insufficient for robust assessment of long-term outcomes. Third, while internal validation using bootstrap resampling was performed, external validation in an independent cohort was not feasible due to the single-center nature of this study, potentially limiting the generalizability of the proposed ΔTg thresholds. Fourth, standardization of Tg measurement protocols is critical for ensuring result comparability, highlighting an area requiring future harmonization efforts. Future research should focus on: (1) validating the established ΔTg thresholds in larger cohorts with dedicated subgroup analyses for lymph node metastasis and pulmonary metastasis subgroups; (2) characterizing the natural history and long-term trajectories of SD patients; and (3) conducting large-scale multicenter studies to enhance statistical power and generalizability. Declarations Conflict of interest statement: All authors declare no competing financial or non-financial interests. Funding Information: This research was partially supported by the National Natural Science Foundation of China (NSFC, Grant #82001856) . Author Contribution Shuo Huang and Hongliang Fu conceived and designed the study. Shuo Huang developed software, performed formal analysis, conducted investigation, and written the initial draft. Medical imaging interpretation was performed by Zhiyi Ye and Chao Li. All authors contributed to methodology design, critically revised the manuscript for intellectual content, and approved the final version. Shaoyan Wang managed project administration. Hongliang Fu and Sheng liang provided supervision throughout the research. Acknowledgement We thank the Institution and, in particular, the patients and their families for enabling and supporting scientific advancement. Data Availability Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request. References Qian ZJ, Jin MC, Meister KD, et al. Pediatric thyroid cancer incidence and mortality trends in the United States, 1973-2013. JAMA Otolaryngol Head Neck Surg. 2019;145(7):617-623. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33. Hay ID, Johnson TR, Kaggal S, et al. Papillary thyroid carcinoma (PTC) in children and adults: comparison of initial presentation and long-term postoperative outcome in 4432 patients consecutively treated at the Mayo Clinic during eight decades (1936-2015). World J Surg. 2018;42(2):329-342. Hay ID, Gonzalez-Losada T, Reinalda MS, et al. Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008. World J Surg. 2010;34:1192-1202. Nies M, Vassilopoulou-Sellin R, Bassett RL, et al. Distant metastases from childhood differentiated thyroid carcinoma: clinical course and mutational landscape. J Clin Endocrinol Metab. 2021;106(4):e1683-e1697. Evans C, Tennant S & Perros P. Thyroglobulin in differentiated thyroid cancer. Clin Chim Acta. 2015;444:310-317. Francis GL, Waguespack SG, Bauer AJ, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid. 2015;25(7):716-759. Zampella E, Piscopo L, Manganelli M, et al. Prognostic value of 12-month response to therapy in pediatric patients with differentiated thyroid cancer. Endocrine. 2023;80(3):612-618. Chen W, Luo YK, Zhang Y & Tang J. Ultrasound-guided implantation of radioactive 125I seed in radioiodine refractory differentiated thyroid carcinoma. BMC Cancer. 2021;21(1):834. He Y, Pan MZ, Huang JM, et al. Iodine-131: an effective method for treating lymph node metastases of differentiated thyroid cancer. Med Sci Monit. 2016;22:4924-4928. Zhang XY, Song HJ, Qiu ZL, et al. Pulmonary metastases in children and adolescents with papillary thyroid cancer in China: prognostic factors and outcomes from treatment with 131I. Endocrine. 2018;62(1):149-158. Song HJ, Qiu ZL, Shen CT & Luo QY. Pulmonary metastases in differentiated thyroid cancer: efficacy of radioiodine therapy and prognostic factors. Eur J Endocrinol. 2015;173(3):399-408. Qiu ZL, Song HJ, Xu YH & Luo QY. Efficacy and survival analysis of 131I therapy for bone metastases from differentiated thyroid cancer. J Clin Endocrinol Metab. 2011;96(10):3078-3086. Luster M, Clarke SE, Dietlein M, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008;35(10):1941-1959. Kim SY, Yun HJ, Chang H, et al. Aggressiveness of Differentiated Thyroid Carcinoma in Pediatric Patients Younger Than 16 years: A Propensity Score-Matched Analysis. Front Oncol. 2022;12:872130. Bal CS, Garg A, Chopra S, et al. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases. J Pediatr Endocrinol Metab. 2015;28(7-8):745-751. Rivkees SA, Mazzaferri EL, Verburg FA, et al. The treatment of differentiated thyroid cancer in children: emphasis on surgical approach and radioactive iodine therapy. Endocr Rev. 2011;32(6):798-826. Alves-Junior PAG, Barreto MCA, Andrade FA, et al. Stimulated thyroglobulin and diagnostic 131-iodine whole-body scan as a predictor of distant metastasis and association with response to treatment in pediatric thyroid cancer patients. Endocrine. 2024;84(3):1081-1087. Cistaro A, Quartuccio N, Garganese MC, et al. Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study. Eur J Nucl Med Mol Imaging. 2022;49(4):1374-1385. Giovanella L, D'Aurizio F, Algeciras-Schimnich A, et al. Thyroglobulin and thyroglobulin antibody: an updated clinical and laboratory expert consensus. Eur J Endocrinol. 2023;189(2):R11-R27. Tables Table 1. Clinical Characteristics of 57 Pediatric DTC with Postoperative Persistent Structural Disease Characteristics of all patients (n = 57) n (%)/median (range) Age at diagnosis (y) 10.0(4-18) Sex Male 32(56.1%) Female 25(43.9%) Primary tumor size (cm) 2.5(0.2-8) Bilaterality 38(66.7%) Pathological type PTC 55(96.5%) Classical PTC 50(87.7%) Follicular-variant PTC 3(5.3%) Diffuse sclerosing PTC 1(1.8%) Tall cell PTC 1(1.8%) FTC 2(3.5%) T stage* T1a 6(10.5%) T1b 11(19.3%) T2 16(28.1%) T3a 7(12.3%) T3b 6(10.5%) T4a 10(17.5%) T4b 1(1.8%) N stage* N0 2(3.5%) N1a 9(15.8%) N1b 46(80.7%) M stage* M0 25(43.9%) M1 32(56.1%) Distribution of Disease Components Lymph node metastasis 51(89.5%) Only lymph node metastasis 26(51.0%) With Other Metastatic Components 25(49.0%) Pulmonary metastasis 32(56.1%) Only pulmonary metastasis 6(18.8%) With Other Metastatic Components 26(81.3%) Thyroid bed residual disease 5(8.8%) Only thyroid bed residual disease 0 With Other Metastatic Components 5(100.0%) * American Joint Committee on Cancer (AJCC) 8th edition Table 2. Treatment Responses in 123 Therapeutic Courses of pediatric DTC Therapeutic Response Assessment （ n=123 ） n (%) Objective Response (OR) :CR+PR 55 (44.7%) Complete Response (CR) 11 (8.9%) Target lesion disappearance 6 (54.5%) Lymph nodes ≤5 mm short-axis + disappearance of RAI uptake 5 (45.5%) Partial Response (PR) 44 (35.8%) lesion number reduction 3 (6.8%) ≥30% decrease in long-axis diameter of lesions or in lymph node short-axis diameter 28 (63.6%) Lesion/lymph node reduction that does not reach the ≥30% threshold above but is accompanied by markedly decreased RAI uptake on WBS 13 (29.5%) Progressive Disease (PD) 22 (17.9%) New lesions/lymph node 5 (22.7%) ≥20% increase in long-axis diameter of lesions or in lymph node short-axis diameter. 11 (50.0%) New highly suspicious metastatic lesions confirmed by 2 readers 6 (27.3%) Stable Disease (SD) : 46 (37.4%) Not meeting criteria for CR, PR, or PD 45(97.8%) Discordant responses between lesion sites 1(2.2%) Indeterminate Response 0 Table 3. Distribution of ΔTg Levels and Group Comparisons Across Treatment Response Categories Treatment Response Sample size Δ Tg Median (IQR) Kruskal-Wallis H Test Pairwise Comparisons (Bonferroni-Adjusted) CR 11 84.5% (28%) H =94.056 p <0.001 vs PR: p <0.05 vs SD, PD: p <0.001 PR 44 53.8% (42%) vs CR: p <0.05 vs SD, PD: p <0.001 SD 46 4.9% (22%) vs CR, PR, PD: all p <0.001 PD 22 -69.0 %(91%) vs CR, PR, PD: all p <0.001 Note：A negative ΔTg value indicates an increase in sTg levels. Table 4. Association Between Initial Post-Treatment ΔTg Stratification and NED Status at Final Follow-up ΔTg at 6 months after the first RAI therapy （ n=57 ） NED Non-NED P- V alue ΔTg≥32% (n=29) 16(55.2%) 13(44.8%) p < 0.05 -14%＜ΔTg＜32% (n=11) 2(18.2%) 9(81.8%) ΔTg≤-14% (n=17) 4(23.5%) 13(76.5%) Note：All p -values were calculated using two-sided Fisher's exact tests, due to the presence of cells with expected counts -14%) 11.70 (3.27-41.89) p <0.001 Initial ΔTg (continuous) 0.59 (0.35-0.99) p 0.05 Tumor size (≥3cm vs. 0.05 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Dec, 2025 Read the published version in Endocrine → Version 1 posted Editorial decision: Revision requested 03 Nov, 2025 Reviews received at journal 03 Nov, 2025 Reviewers agreed at journal 25 Oct, 2025 Reviews received at journal 22 Oct, 2025 Reviewers agreed at journal 03 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviewers invited by journal 01 Oct, 2025 Editor assigned by journal 10 Sep, 2025 Submission checks completed at journal 10 Sep, 2025 First submitted to journal 08 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7567986","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":524398066,"identity":"49e20fc6-49e6-4fc5-9063-b1791a0248ad","order_by":0,"name":"Shuo Huang","email":"","orcid":"","institution":"XinHua Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shuo","middleName":"","lastName":"Huang","suffix":""},{"id":524398067,"identity":"7ad0667f-f440-444b-8667-06cc1538a164","order_by":1,"name":"Shaoyan Wang","email":"","orcid":"","institution":"XinHua 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08:53:30","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101358,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7567986/v1/96643a5a8d1b9a07b7e99917.html"},{"id":93568896,"identity":"e0b06a20-2f60-4aea-ae0c-263e02c1eda9","added_by":"auto","created_at":"2025-10-15 08:53:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":4105275,"visible":true,"origin":"","legend":"\u003cp\u003eROC Curves of ΔTg for Predicting Therapeutic Response. a)ROC analysis of ΔTg in distinguishing OR from non-OR. The model achieved an AUC of 0.96 (95% CI: 0.93-0.99, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), with an optimal cutoff at ΔTg ≥ 32% (sensitivity: 92.7%, specificity: 92.6%). b) ROC analysis of ΔTg for predicting non-PD from PD. The AUC remained comparably high at 0.93 (95% CI: 0.84–1.00, \u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001), with the optimal threshold at ΔTg ≤ -14% (sensitivity: 97.0%, specificity: 91.3%).\u003c/p\u003e","description":"","filename":"Figure1.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7567986/v1/774994aa6e5eaf75c882abd9.jpg"},{"id":93568833,"identity":"b77ce236-1d40-422a-bb48-c8a6657f2a63","added_by":"auto","created_at":"2025-10-15 08:53:33","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":6595146,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves for PFS stratified by initial ΔTg（n=57）: Patients with initial ΔTg ≥32% had the most favorable outcomes (n=29, mean PFS=133.5±7.9 months, 95% CI: 118.1-149.0). The initial −14%\u0026lt;ΔTg\u0026lt;32% group showed comparable PFS (n=11, mean PFS=126.4±11.9 months, 95% CI: 103.0-149.8). In contrast, initial ΔTg ≤−14% was associated with significantly reduced PFS (n=17, mean=13.9 months; 95% CI: 3.9–23.9). Overall cohort mean PFS was 93.1 months (95% CI: 75.5–110.6).\u003c/p\u003e","description":"","filename":"Figure2.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7567986/v1/526fc3730da65127be83dcb7.jpg"},{"id":99545371,"identity":"1c2aa28c-c99a-468d-8640-eeb9500a9632","added_by":"auto","created_at":"2026-01-05 16:06:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":12180143,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7567986/v1/f4f6b0b7-98c6-44f5-ae28-fff826f8e975.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"ΔTg Assesses Radioiodine Treatment Response and Predicts Prognosis in Pediatric Differentiated Thyroid Cancer","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eDifferentiated thyroid carcinoma (DTC) is the most common malignant tumor of the endocrine system in pediatric patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Over the past three decades, the global incidence of pediatric DTC has shown a continuous upward trend [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Compared to adult patients, pediatric DTC exhibit distinct clinical characteristics: they often present with more aggressive features at initial diagnosis, including significantly higher rates of extrathyroidal extension, lymph node metastasis, and pulmonary metastasis. However, this group enjoys a superior long-term prognosis, with a 30-year cause-specific mortality (CSM) rate of only 1.1% [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThyroglobulin (Tg) serves as a critical biomarker for monitoring treatment response and disease status in DTC [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The 2015 American Thyroid Association (ATA) guidelines recommend serial serum Tg measurements at 3\u0026ndash;6 month intervals following radioactive iodine (RAI) therapy to evaluate treatment efficacy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In pediatric patients with radioiodine-avid lesions, confirmation of prior RAI effectiveness is essential for determining subsequent treatment strategies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Although declining post-therapeutic Tg levels typically correlate with biochemical remission, whereas rising levels indicate progression, the clinical significance of quantitative Tg change rate (ΔTg) \u0026mdash;particularly its validated threshold\u0026mdash; remains undefined in pediatric DTC populations. This ambiguity poses challenges for clinical decision-making [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Existing studies propose categorical criteria where ΔTg reductions\u0026thinsp;\u0026ge;\u0026thinsp;25% suggest partial response (PR), fluctuations within \u0026plusmn;\u0026thinsp;25% indicate stable disease (SD), and increases\u0026thinsp;\u0026gt;\u0026thinsp;25% denote progressive disease (PD) [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, these thresholds are empirically derived and lack robust validation in pediatric cohorts. Consequently, establishing evidence-based correlations between ΔTg dynamics and treatment outcomes is imperative for optimizing pediatric DTC management.\u003c/p\u003e\u003cp\u003eBased on a retrospective cohort over a 13-year period from a single center, this study establishes the correlation between ΔTg and treatment response, providing evidence-based guidance for precision RAI therapy in pediatric patients.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Study subjects\u003c/h2\u003e\u003cp\u003e This single-center retrospective cohort study was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-D-2023-178). Written informed consent was obtained from all patients' legal guardians. The study, conducted in accordance with the Declaration of Helsinki (2013 revision), included 57 pediatric DTC patients who underwent a total of 123 courses of RAI therapy in the Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between January 2011 and November 2023. All patients underwent total thyroidectomy, with or without central neck dissection and/or lateral neck dissection. Prior to RAI therapy, a protocol-driven thyroid hormone withdrawal regimen was strictly implemented: levothyroxine was discontinued for \u0026ge;\u0026thinsp;3 weeks, and serum thyroid-stimulating hormone (TSH) levels on the treatment day\u0026thinsp;\u0026ge;\u0026thinsp;30 mU/L. Radioiodine doses were calculated based on the actual body weight of pediatric patients, with proportional adjustments relative to the recommended adult dose for a 70 kg body weight.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Inclusion criteria\u003c/h2\u003e\u003cp\u003ePatients met all the following criteria:(1) Age at first RAI therapy\u0026thinsp;\u0026le;\u0026thinsp;18 years; (2) Postoperative evidence of persistent structural disease (metastasis or residual tumor), confirmed by either whole-body scan (WBS) or histopathology; (3) No prior history of neck radiotherapy or anticancer therapy; (4) Negative TgAb status; (5) Complete imaging data and Tg records available for the treatment cycle.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Tg testing\u003c/h2\u003e\u003cp\u003eThis study analyzed stimulated Tg (sTg) to eliminate interference from levothyroxine (LT4) suppression therapy. Valid sTg measurements required LT4 withdrawal for \u0026ge;\u0026thinsp;3 weeks with concurrent TSH\u0026thinsp;\u0026gt;\u0026thinsp;30 mU/L. The ΔTg = [(6-month post-therapy sTg - pre-therapy sTg) / pre-therapy sTg] \u0026times; 100% (negative ΔTg indicates sTg increase). From 2010\u0026ndash;2021, Tg was quantified using an immunometric assay with functional sensitivity of \u0026le;\u0026thinsp;0.1 ng/mL. Since 2021, a high-sensitivity electrochemiluminescence immunoassay has been employed, with limit of detection (LoD)\u0026thinsp;\u0026le;\u0026thinsp;0.040 ng/mL. Due to assay sensitivity improvements during the decade-long study (from \u0026le;\u0026thinsp;0.1 ng/mL to \u0026le;\u0026thinsp;0.040 ng/mL), we used a short 6-month ΔTg interval to minimize variability. This approach ensured that pre- and post-therapy sTg for each patient were likely measured on comparable platforms. Within this brief period, it is highly probable that both pre-therapy and 6-month post-therapy sTg measurements for a given patient utilized comparable assay platforms and methodologies, thereby minimizing potential variability attributable to technical shifts. Serum TgAb levels were quantified using standardized chemiluminescent immunoassays. Specimens were classified as TgAb-negative when measured values fell below the manufacturer's reference threshold, whereas values exceeding this threshold were deemed TgAb-positive, strictly per kit specifications.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Therapeutic Response Assessment\u003c/h2\u003e\u003cp\u003eEach treatment course served as an independent observation unit for evaluation, with the patient's status immediately prior to the commencement of that given course defined as its baseline. Early treatment response at 6 months post-RAI therapy was assessed using a combination of structural imaging (ultrasonography, CT, MRI/PET-CT if indicated) and WBS according to the following modified criteria, primarily referenced to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 but adapted for pediatric DTC characteristics:\u003c/p\u003e\u003cp\u003eComplete Response (CR):(1) Disappearance of all target lesions confirmed on both structural imaging and WBS; (2) For lymph nodes: short-axis diameter\u0026thinsp;\u0026le;\u0026thinsp;5 mm on structural imaging AND disappearance of iodine uptake on WBS.\u003c/p\u003e\u003cp\u003ePR:(1) Significant reduction in the number of lesions (with some disappearing); (2)\u0026thinsp;\u0026ge;\u0026thinsp;30% decrease in the sum of the long-axis diameters of target lesions or in short-axis diameter of target lymph nodes on structural imaging, OR (3) Reduction in lesions/lymph nodes not meeting the above criteria, but with markedly decreased iodine uptake on WBS.\u003c/p\u003e\u003cp\u003eObjective response (OR) was defined as CR\u0026thinsp;+\u0026thinsp;PR.\u003c/p\u003e\u003cp\u003ePD: (1) New lesion(s) with confirmed iodine uptake on WBS or histopathology; OR (2)\u0026thinsp;\u0026ge;\u0026thinsp;20% increase in the sum of the long-axis diameters of target lesions or in the short-axis diameter of target lymph nodes on structural imaging; OR (3) New findings highly suspicious for malignancy, without confirmation by either WBS or pathology, prompted independent re-evaluation by two experienced readers. PD was confirmed only when both readers independently identified the new lesions as metastatic lesions based on imaging evidence.\u003c/p\u003e\u003cp\u003eSD: (1) Failure to fulfill criteria for CR, PR, or PD; OR (2) Discordant responses between lesion sites.\u003c/p\u003e\u003cp\u003eIndeterminate Response: New suspicious structural lesions failed PD adjudication consensus.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Follow-up and Outcome Assessment\u003c/h2\u003e\u003cp\u003eFinal Outcome Assessment: Disease status at the last follow-up was determined based on comprehensive review of all available clinical, serological, and imaging data [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]: No Evidence of Disease (NED): No structural evidence on imaging (US, CT, DxWBS, MRI/PET-CT if indicated) AND fulfilling either: (1) Serum Tg\u0026thinsp;\u0026lt;\u0026thinsp;1 ng/mL under TSH suppression with negative TgAb, or (2) sTg\u0026thinsp;\u0026lt;\u0026thinsp;2 ng/mL (measured after \u0026ge;\u0026thinsp;3 weeks LT4 withdrawal, TSH\u0026thinsp;\u0026gt;\u0026thinsp;30 mU/L, and confirmed successful ablation) with negative TgAb. Non-NED: Patients not meeting the NED criteria at the last follow-up.\u003c/p\u003e\u003cp\u003eGiven the excellent overall prognosis and exceedingly low mortality in this pediatric cohort [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], we additionally evaluated progression-free survival (PFS) as a longitudinal outcome measure. PFS was defined as the interval from the first RAI therapy to documented disease progression or last follow-up.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6 Statistical Methods\u003c/h2\u003e\u003cp\u003eData analysis was performed using SPSS 26.0 and R 4.4.3 software. The normality of continuous variables was assessed by the Kolmogorov-Smirnov test. Non-normally distributed data were analyzed after natural logarithmic transformation. Categorical variables are presented as frequency (percentage), and non-normally distributed continuous variables as median (range/interquartile range, IQR). For intergroup comparisons of categorical variables, Fisher's exact test was employed when expected cell frequencies were \u0026lt;\u0026thinsp;5, with post-hoc pairwise comparisons adjusted by Bonferroni correction (significance threshold α\u0026thinsp;=\u0026thinsp;0.0167). Continuous variables were compared using the Kruskal-Wallis nonparametric test, with post-hoc multiple comparisons adjusted by the Bonferroni correction. The cutoff value of ΔTg for treatment response was evaluated via receiver operating characteristic (ROC) curve analysis, with the optimal cutoff determined by maximizing the Youden index. To assess the stability and optimism-corrected performance of the ROC-derived AUC values, bootstrap internal validation was performed with 1000 resampling iterations. The 95% confidence intervals for the AUCs were derived using the bias-corrected and accelerated (BCa) bootstrap method. PFS was calculated via the Kaplan-Meier method. Intergroup survival differences were assessed using the log-rank test. Cox proportional hazards regression was performed to identify independent prognostic factors for PFS time. All statistical analyses were two-sided, and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant, except for post-hoc comparisons where the adjusted threshold was applied.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Research Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Clinical Characteristics\u003c/h2\u003e\u003cp\u003eThe study cohort comprised 57 pediatric DTC patients. Clinical characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age at diagnosis was 10 years (range: 4\u0026ndash;18 years), with a male-to-female ratio of 1.28:1. Primary tumors had a median diameter of 2.5 cm (range: 0.2\u0026ndash;8.0 cm), and bilateral thyroid involvement was present in 66.7% (38/57) of patients. TNM staging revealed T3/T4 disease in 42.1% (24/57) of cases. Regional lymph node metastases (N1b) were identified in 96.5% (46/57) of patients, and distant metastases (M1) were found in 56.1% (32/57). Structural disease distribution analysis demonstrated: thyroid bed residual disease in 8.8% (5/57) of patients, metastatic lymph nodes in 89.5% (51/57), and pulmonary metastases in 56.1% (32/57). Critically, pulmonary metastases without concurrent cervical disease (lymph node or thyroid bed involvement) occurred in only 8.8% (5/57) of cases.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical Characteristics of 57 Pediatric DTC with Postoperative Persistent Structural Disease\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics of all patients (n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en (%)/median (range)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge at diagnosis (y)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.0(4\u0026ndash;18)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32(56.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25(43.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrimary tumor size (cm)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.5(0.2-8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBilaterality\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38(66.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePathological type\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePTC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55(96.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClassical PTC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50(87.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFollicular-variant PTC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(5.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiffuse sclerosing PTC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(1.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTall cell PTC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(1.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFTC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(3.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eT stage*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(10.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT1b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(19.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16(28.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT3a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(12.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT3b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(10.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT4a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10(17.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT4b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(1.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eN stage*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(3.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN1a\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(15.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN1b\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46(80.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eM stage*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eM0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25(43.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eM1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32(56.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDistribution of Disease Components\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymph node metastasis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51(89.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnly lymph node metastasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26(51.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWith Other Metastatic Components\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25(49.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePulmonary metastasis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32(56.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnly pulmonary metastasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWith Other Metastatic Components\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26(81.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eThyroid bed residual disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(8.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnly thyroid bed residual disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWith Other Metastatic Components\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(100.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cb\u003e*\u003c/b\u003eAmerican Joint Committee on Cancer (AJCC) 8th edition\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA total of 123 treatment courses were evaluated as independent observation units, with baseline status re-established prior to each course initiation (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Therapeutic response was assessed at 6 months after each RAI treatment using predefined criteria. OR (CR\u0026thinsp;+\u0026thinsp;PR) was achieved in 55 courses (44.7%). Among these, CR was observed in 11 courses (8.9%), characterized by the disappearance of all target lesions in 6 cases (54.5% of CRs) or Lymph node short-axis diameter\u0026thinsp;\u0026le;\u0026thinsp;5 mm and disappearance of iodine uptake in 5 cases (45.5% of CRs). PR occurred in 44 courses (35.8%), comprising: lesion number reduction in 3 cases (6.8% of PRs), lesion/lymph node size reduction meeting criteria (\u0026ge;\u0026thinsp;30% decrease in long-axis/short-axis diameter) in 28 cases (63.6% of PRs), and lesion/lymph node reduction that does not reach the \u0026ge;\u0026thinsp;30% threshold above but is accompanied by markedly decreased RAI uptake on WBS in 13 cases (29.5% of PRs). SD was documented in 46 courses (37.4%), while PD occurred in 22 courses (17.9%). PD was attributed to new lesions or lymph node (5 courses, 22.7% of PDs), significant growth of existing lesions or lymph nodes (11 courses, 50.0% of PDs), and new highly suspicious metastatic lesions confirmed by two experienced readers (6 courses, 27.3% of PDs).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTreatment Responses in 123 Therapeutic Courses of pediatric DTC\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTherapeutic Response Assessment(n\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eObjective Response (OR):CR\u0026thinsp;+\u0026thinsp;PR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (44.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComplete Response (CR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (8.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTarget lesion disappearance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (54.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymph nodes\u0026thinsp;\u0026le;\u0026thinsp;5 mm short-axis\u0026thinsp;+\u0026thinsp;disappearance of RAI uptake\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (45.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePartial Response (PR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44 (35.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003elesion number reduction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (6.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;30% decrease in long-axis diameter of lesions or in lymph node short-axis diameter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (63.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLesion/lymph node reduction that does not reach the \u0026ge;\u0026thinsp;30% threshold above but is accompanied by markedly decreased RAI uptake on WBS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (29.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProgressive Disease (PD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (17.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNew lesions/lymph node\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (22.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;20% increase in long-axis diameter of lesions or in lymph node\u003c/p\u003e \u003cp\u003eshort-axis diameter.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNew highly suspicious metastatic lesions confirmed by 2 readers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (27.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStable Disease (SD)\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (37.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNot meeting criteria for CR, PR, or PD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45(97.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiscordant responses between lesion sites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(2.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIndeterminate Response\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Analysis of the Association between ΔTg and Treatment Response\u003c/h2\u003e\u003cp\u003ePediatric DTC is characterized by aggressive behavior, particularly in patients with pulmonary metastases or unresectable thyroid bed lesions, who commonly present with multi-site metastases before RAI therapy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In this cohort, pulmonary metastases and thyroid bed disease predominantly coexisted with metastases at other sites, with rates of 81.3% and 100%, respectively. Given this pattern, isolated analysis of ΔTg for lymph node, pulmonary, or thyroid bed lesions may have limited clinical utility. Therefore, we analyzed lesions across all sites within each patient as an integrated entity to enhance clinical applicability.\u003c/p\u003e\u003cp\u003eThe Kruskal-Wallis test revealed highly statistically significant differences in ΔTg across treatment response groups (H\u0026thinsp;=\u0026thinsp;94.056, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Patients with CR (n\u0026thinsp;=\u0026thinsp;11) exhibited the most substantial Tg reduction (median ΔTg\u0026thinsp;=\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e84.5%\u003c/span\u003e, IQR\u0026thinsp;=\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e28%\u003c/span\u003e), demonstrating significantly greater decline than those with PR (n\u0026thinsp;=\u0026thinsp;44; median ΔTg\u0026thinsp;=\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e53.8%\u003c/span\u003e, IQR\u0026thinsp;=\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e42%\u003c/span\u003e; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Whereas the SD group (n\u0026thinsp;=\u0026thinsp;46) showed only marginal Tg decrease (median ΔTg\u0026thinsp;=\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e4.9%\u003c/span\u003e, IQR\u0026thinsp;=\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e22%\u003c/span\u003e), the PD group (n\u0026thinsp;=\u0026thinsp;22) displayed pronounced Tg elevation (median ΔTg=\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e-69.0%\u003c/span\u003e, IQR\u0026thinsp;=\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e91%\u003c/span\u003e). Both SD and PD groups demonstrated statistically significant differences (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to each of the other response groups in pairwise comparisons. These findings confirm that ΔTg serve as a valid biomarker for treatment efficacy assessment, with the magnitude of reduction positively correlating with therapeutic outcomes.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eDistribution of\u003c/span\u003e Δ\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eTg Levels and Group Comparisons Across Treatment Response Categories\u003c/span\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eTreatment Response\u003c/span\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eSample size\u003c/span\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eΔ\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eTg\u003c/span\u003e\u003c/p\u003e \u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eMedian (IQR)\u003c/span\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eKruskal-Wallis H Test\u003c/span\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePairwise Comparisons (Bonferroni-Adjusted)\u003c/span\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eCR\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e11\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e84.5% (28%)\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003eH\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e=\u0026thinsp;94.056\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003evs PR\u003c/span\u003e: \u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.05\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003evs SD, PD\u003c/span\u003e: \u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePR\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e44\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e53.8% (42%)\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003evs CR\u003c/span\u003e: \u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.05\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003evs SD, PD\u003c/span\u003e: \u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eSD\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e46\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e4.9% (22%)\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003evs CR, PR, PD: all\u003c/span\u003e \u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePD\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e22\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e-69.0%(91%)\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003evs CR, PR, PD: all\u003c/span\u003e \u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: A negative ΔTg value indicates an increase in sTg levels.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Optimal ΔTg cut-off values for predicting treatment response\u003c/h2\u003e\u003cp\u003eTo establish optimal ΔTg cut-off values for predicting treatment response, we conducted ROC analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). For distinguishing OR from non-OR (including SD and PD), the AUC reached 0.96 (95% CI: 0.93\u0026ndash;0.99; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The Youden index-derived optimal cut-off was ΔTg\u0026thinsp;=\u0026thinsp;31.7%, yielding 92.7% sensitivity and 92.6% specificity. When discriminating non-PD (including CR, PR and SD) from PD, the AUC was 0.93 (95% CI: 0.85\u0026ndash;1.000; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) with an optimal cut-off of ΔTg=-13.9%, achieving 97.0% sensitivity and 91.3% specificity. The robustness of these AUC estimates was further confirmed through internal validation using bootstrap resampling with 1000 iterations. The bootstrap-corrected performance remained strong, with a mean AUC of 0.96 (95% bootstrap CI: 0.92\u0026ndash;0.99) for OR prediction and 0.93 (95% bootstrap CI: 0.75\u0026ndash;0.99) for non-PD prediction. The narrow width of these confidence intervals indicates high precision and reliability of the model estimates.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eGiven the high diagnostic performance and the close proximity of theoretical cut-offs to clinically practical integer values, we propose the following criteria for 6-month post-treatment evaluation: OR defined as ΔTg\u0026thinsp;\u0026ge;\u0026thinsp;32%, PD indicated by ΔTg\u0026le;-14%, and SD classified as -14%\u0026lt;ΔTg\u0026thinsp;\u0026lt;\u0026thinsp;32%.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Predictive Value of Initial ΔTg for NED and PFS Following RAI Therapy\u003c/h2\u003e\u003cp\u003eBased on the established ΔTg stratification criteria, this study evaluated the predictive value of the initial ΔTg (measured at 6 months after the first RAI therapy) for NED status at final follow-up (mean 61.8\u0026thinsp;\u0026plusmn;\u0026thinsp;37.4 months) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Among 57 patients, 22 (38.6%) achieved NED. A statistically significant difference in NED rates was observed across the cohorts (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with the ΔTg\u0026thinsp;\u0026ge;\u0026thinsp;32% group (n\u0026thinsp;=\u0026thinsp;29) demonstrating the highest rate (55.2%, 16/29) compared to the \u0026minus;\u0026thinsp;14%\u0026lt;ΔTg\u0026thinsp;\u0026lt;\u0026thinsp;32% group (18.2%, 2/11) and the ΔTg\u0026le;-14% group (23.5%, 4/17). However, pairwise comparisons revealed no significant differences between individual groups: Group 1 vs. Group 2 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.073), Group 1 vs. Group 3 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.064), and Group 2 vs. Group 3 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000). Notably, one patient in the ΔTg\u0026le;-14% group died from respiratory failure secondary to tracheal compression at 4 months after RAI therapy and was included in the non-NED cases.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociation Between Initial Post-Treatment ΔTg Stratification and NED Status at Final Follow-up\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔTg at 6 months after the first RAI therapy(n\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNED\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-NED\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003eP-\u003c/em\u003eValue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔTg\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026ge;\u0026thinsp;32% (n\u0026thinsp;=\u0026thinsp;29)\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16(55.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13(44.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e-14%\u0026lt;ΔTg\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026lt;32% (n\u0026thinsp;=\u0026thinsp;11)\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2(18.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e9(81.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔTg\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e\u0026le;-14% (n\u0026thinsp;=\u0026thinsp;17)\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4(23.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13(76.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: All \u003cem\u003ep\u003c/em\u003e-values were calculated using two-sided Fisher's exact tests, due to the presence of cells with expected counts\u0026thinsp;\u0026lt;\u0026thinsp;5.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFurthermore, in the cohort of 57 patients, initial ΔTg stratification demonstrated high discriminative power in PFS (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Patients with initial ΔTg\u0026thinsp;\u0026ge;\u0026thinsp;32% showed mean PFS of 133.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9 months (95% CI: 118.1\u0026ndash;149.0), comparable to the \u0026minus;\u0026thinsp;14%\u0026lt;ΔTg\u0026thinsp;\u0026lt;\u0026thinsp;32% group's 126.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9 months (95% CI: 103.0-149.8; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In contrast, the ΔTg\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;14% group had significantly reduced mean PFS of 13.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1 months (95% CI: 3.9\u0026ndash;23.9; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 vs. both groups). Integrating NED status and long-term PFS outcomes, these results demonstrate that patients with initial ΔTg\u0026thinsp;\u0026ge;\u0026thinsp;32% derived unequivocal clinical benefit from RAI therapy, while those with initial ΔTg \u0026le;-14% showed no significant benefit. Patients in the intermediate range (-14%\u0026lt;initial ΔTg\u0026thinsp;\u0026lt;\u0026thinsp;32%) achieved long-term PFS comparable to the high-response group, despite significantly reduced NED attainment. This discordance indicates uncertain therapeutic value of RAI in this subgroup, warranting further investigation to determine whether RAI provides meaningful clinical advantage for these patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.5 Independent Prognostic Factors for Progression-Free Survival\u003c/h2\u003e\u003cp\u003eMultivariable Cox regression identified ΔTg as the dominant prognostic factor (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Patients with ΔTg\u0026le;-14% had an 11.5-fold higher progression risk than those with ΔTg\u0026gt;-14% (HR\u0026thinsp;=\u0026thinsp;11.70, 95% CI: 3.27\u0026ndash;41.89; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). When analyzed as a continuous variable, each 1% increase in ΔTg was independently associated with a 41% reduction in progression risk (HR\u0026thinsp;=\u0026thinsp;0.59, 95% CI: 0.35\u0026ndash;0.99; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Tumor stage and size showed no significant association. The model explained 62.3% of PFS variability (Nagelkerke R\u0026sup2;=0.623) with excellent fit (χ\u0026sup2;=47.15, df\u0026thinsp;=\u0026thinsp;4, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariable Cox Regression Analysis for Progression-Free Survival\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP-\u003c/em\u003eValue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial ΔTg \u0026le;-14% (vs. \u0026gt;-14%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11.70 (3.27\u0026ndash;41.89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial ΔTg (continuous)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.59 (0.35\u0026ndash;0.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage II (vs. Stage I)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.59 (0.21\u0026ndash;1.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor size (\u0026ge;\u0026thinsp;3cm vs. \u0026lt;3cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.56 (0.21\u0026ndash;1.52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eSerum Tg is a crucial biomarker in pediatric DTC, as its dynamic trend reflects the response to treatment and disease status. However, there is currently a lack of standardized criteria for evaluating Tg changes following RAI therapy in this population. By analyzing 123 courses of RAI therapy administered to 57 pediatric DTC patients with persistent structural disease, this study established quantitative assessment thresholds based on ΔTg: OR was defined as ΔTg\u0026thinsp;\u0026ge;\u0026thinsp;32%; PD was defined as ΔTg\u0026le;-14%, SD was defined as -14%\u0026lt;ΔTg\u0026thinsp;\u0026lt;\u0026thinsp;32%. Importantly, this study revealed significant associations between the ΔTg thresholds and treatment response, NED and PFS, providing critical evidence for optimizing precision treatment pathways in pediatric DTC.\u003c/p\u003e\u003cp\u003eAmong 181 patients aged\u0026thinsp;\u0026le;\u0026thinsp;18 years with DTC treated with RAI at our center since 2011, this study enrolled 57 (31.5%) who had postoperative evidence of persistent structural disease (metastasis or residual tumor) and were Tgab-negative. The median age at diagnosis in this cohort was 10 years (range: 4\u0026ndash;18 years), higher than the median age (16 years) reported in Bal et al.'s cohort [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The male-to-female ratio (1.28:1) indicated male predominance, differing from most previous reports [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Papillary Thyroid Carcinoma (PTC) constituted the predominant histology (96.5%, 55/57), with classical PTC accounting for 87.7% (50/57), follicular-variant PTC for 5.3% (3/57), diffuse sclerosing and tall cell PTC each for 1.8% (1/57 each). Follicular Thyroid Carcinoma (FTC) constituted 3.5% (2/57) of cases. This distribution aligns with studies focusing on pulmonary metastases in DTC (\u0026gt;\u0026thinsp;96% PTC) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eConducting decade-long Tg-related research requires addressing the challenge of differing sTg assay methods [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. To minimize errors arising from variations in sTg sensitivity over time, we calculate short-interval ΔTg. Within this brief period, the pre-therapy and 6-month sTg measurements for each patient were highly likely performed using the same assay platform and methodology. All sTg measurements included concurrent TgAb testing. Recognizing TgAb positivity may cause sTg underestimation [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], our primary analyses focused on TgAb-negative patients to ensure ΔTg reliability. While perfect longitudinal assay consistency was unattainable in our retrospective study, our core strategy provided a practical approach [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Utilizing a short interval ΔTg and excluding the impact of TgAb positivity maximized the validity and clinical relevance of sTg response kinetics within historical data constraints.\u003c/p\u003e\u003cp\u003eTo investigate Tg distribution across different treatment responses, this study established criteria based on structural and functional imaging changes to assess RAI efficacy against metastatic lesions, with primary reference to RECIST 1.1. Given the limitations of RECIST 1.1 in pediatric DTC, where iodine-avid lymph nodes can be present even with short-axis diameters\u0026thinsp;\u0026lt;\u0026thinsp;1 cm, the CR criterion for lymph nodes was modified to short-axis diameter\u0026thinsp;\u0026lt;\u0026thinsp;5 mm and disappearance of iodine uptake. Cases exhibiting only diffuse pulmonary iodine uptake without distinct structural lesions were excluded, as the absence of discrete measurable lesions precluded independent imaging-based response assessment. Within this framework, new lesions considered highly suspicious for malignancy, but without RAI uptake or pathological confirmation, required independent review by two readers. Six treatments were classified as PD using this standard. All six cases showed new non-RAI-avid pulmonary nodules appearing after initial therapy in patients with existing bilateral lung metastases; both readers independently confirmed these as metastases based on their imaging characteristics and comparison with prior imaging studies.\u003c/p\u003e\u003cp\u003ePrevious studies have reported the overall therapeutic efficacy in pediatric DTC patients after completion of all RAI treatment courses [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], while our study quantified early overall response per RAI course (n\u0026thinsp;=\u0026thinsp;123 courses): CR 8.9% (11/123), PR 35.8% (44/123), SD 37.4% (46/123), and PD 17.9% (22/123). Focusing specifically on pulmonary metastases (n\u0026thinsp;=\u0026thinsp;87 courses), we observed: CR 4.6% (4/87), PR 32.2% (28/87), SD 43.7% (38/87), and PD 19.5% (17/87). Notably, these early single-course response rates in pulmonary metastases showed CR and PD rates comparable to final outcomes reported in similar cohorts (CR 7.9%, PD 13.2%), despite differences in assessment timing [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The higher SD rate (43.7% vs 14.5%) suggests many lesions require multiple treatments to achieve measurable regression, however, the associated risk from increased cumulative radiation exposure requires careful consideration and warrants further investigation.\u003c/p\u003e\u003cp\u003eGiven the potential need for multiple RAI courses and the associated cumulative risks, identifying reliable predictors early in the treatment course becomes crucial to optimize therapeutic strategies and minimize unnecessary exposure. In this context, we evaluated the predictive value of the early ΔTg following the first RAI therapy for long-term disease status. Our findings suggest that the initial ΔTg level post-RAI therapy holds potential as a predictor for long-term NED status, evidenced by a statistically significant association overall (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, the lack of significant pairwise differences between the ΔTg response groups, despite clear numerical trends favoring the highest response group (55.2% NED vs. 18.2% and 23.5% in the other groups), is likely explained by limited statistical power. This limitation stems primarily from the relatively small sample size, especially within the intermediate response cohort (n\u0026thinsp;=\u0026thinsp;11).\u003c/p\u003e\u003cp\u003eDue to the presence of persistent, measurable structural disease at baseline in our cohort and the minimal number of death events (only 1 death, rendering overall survival [OS] analysis uninformative), we selected PFS as the key clinical outcome measure. A central finding was the comparable long-term PFS between patients achieving ΔTg\u0026thinsp;\u0026ge;\u0026thinsp;32% and those in the intermediate response group, despite the latter group demonstrating a significantly lower rate of achieving NED (18.2% vs. 55.2%). This dissociation suggests that RAI's therapeutic value may be uncertain for patients with intermediate ΔTg, though further validation is needed to establish causality. Two non-exclusive mechanisms could explain this discordance: 1) Patients with intermediate ΔTg responses may harbor indolent disease inherently unlikely to progress, regardless of RAI therapy, or 2) RAI therapy itself actively prevented progression in these patients, even though it failed to induce a significant Tg decline. As our study design cannot differentiate between these mechanisms, subsequent prospective studies, ideally multi-center trials with larger cohorts, are essential. These should specifically investigate whether RAI therapy provides a meaningful clinical advantage for this intermediate subgroup, potentially including strategies like randomized RAI withdrawal.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, as a single-center retrospective investigation, the cohort size remains relatively small (n\u0026thinsp;=\u0026thinsp;57), which precluded separate analysis of lymph node metastasis and pulmonary metastasis subgroups despite their significant differences in both biological behavior and prognosis. Second, the median follow-up duration of 61.8 months is still insufficient for robust assessment of long-term outcomes. Third, while internal validation using bootstrap resampling was performed, external validation in an independent cohort was not feasible due to the single-center nature of this study, potentially limiting the generalizability of the proposed ΔTg thresholds. Fourth, standardization of Tg measurement protocols is critical for ensuring result comparability, highlighting an area requiring future harmonization efforts. Future research should focus on: (1) validating the established ΔTg thresholds in larger cohorts with dedicated subgroup analyses for lymph node metastasis and pulmonary metastasis subgroups; (2) characterizing the natural history and long-term trajectories of SD patients; and (3) conducting large-scale multicenter studies to enhance statistical power and generalizability.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of interest statement:\u003c/h2\u003e\u003cp\u003eAll authors declare no competing financial or non-financial interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding Information:\u003c/h2\u003e\u003cp\u003eThis research was partially supported by the National Natural Science Foundation of China (NSFC, Grant #82001856) .\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eShuo Huang and Hongliang Fu conceived and designed the study. Shuo Huang developed software, performed formal analysis, conducted investigation, and written the initial draft. Medical imaging interpretation was performed by Zhiyi Ye and Chao Li. All authors contributed to methodology design, critically revised the manuscript for intellectual content, and approved the final version. Shaoyan Wang managed project administration. Hongliang Fu and Sheng liang provided supervision throughout the research.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank the Institution and, in particular, the patients and their families for enabling and supporting scientific advancement.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eSome or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eQian ZJ, Jin MC, Meister KD, et al. Pediatric thyroid cancer incidence and mortality trends in the United States, 1973-2013. JAMA Otolaryngol Head Neck Surg. 2019;145(7):617-623.\u003c/li\u003e\n\u003cli\u003eSiegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.\u003c/li\u003e\n\u003cli\u003eHay ID, Johnson TR, Kaggal S, et al. Papillary thyroid carcinoma (PTC) in children and adults: comparison of initial presentation and long-term postoperative outcome in 4432 patients consecutively treated at the Mayo Clinic during eight decades (1936-2015). World J Surg. 2018;42(2):329-342.\u003c/li\u003e\n\u003cli\u003eHay ID, Gonzalez-Losada T, Reinalda MS, et al. Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008. World J Surg. 2010;34:1192-1202.\u003c/li\u003e\n\u003cli\u003eNies M, Vassilopoulou-Sellin R, Bassett RL, et al. Distant metastases from childhood differentiated thyroid carcinoma: clinical course and mutational landscape. J Clin Endocrinol Metab. 2021;106(4):e1683-e1697.\u003c/li\u003e\n\u003cli\u003eEvans C, Tennant S \u0026amp; Perros P. Thyroglobulin in differentiated thyroid cancer. Clin Chim Acta. 2015;444:310-317.\u003c/li\u003e\n\u003cli\u003eFrancis GL, Waguespack SG, Bauer AJ, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid. 2015;25(7):716-759.\u003c/li\u003e\n\u003cli\u003eZampella E, Piscopo L, Manganelli M, et al. Prognostic value of 12-month response to therapy in pediatric patients with differentiated thyroid cancer. Endocrine. 2023;80(3):612-618.\u003c/li\u003e\n\u003cli\u003eChen W, Luo YK, Zhang Y \u0026amp; Tang J. Ultrasound-guided implantation of radioactive 125I seed in radioiodine refractory differentiated thyroid carcinoma. BMC Cancer. 2021;21(1):834.\u003c/li\u003e\n\u003cli\u003eHe Y, Pan MZ, Huang JM, et al. Iodine-131: an effective method for treating lymph node metastases of differentiated thyroid cancer. Med Sci Monit. 2016;22:4924-4928.\u003c/li\u003e\n\u003cli\u003eZhang XY, Song HJ, Qiu ZL, et al. Pulmonary metastases in children and adolescents with papillary thyroid cancer in China: prognostic factors and outcomes from treatment with 131I. Endocrine. 2018;62(1):149-158.\u003c/li\u003e\n\u003cli\u003eSong HJ, Qiu ZL, Shen CT \u0026amp; Luo QY. Pulmonary metastases in differentiated thyroid cancer: efficacy of radioiodine therapy and prognostic factors. Eur J Endocrinol. 2015;173(3):399-408.\u003c/li\u003e\n\u003cli\u003eQiu ZL, Song HJ, Xu YH \u0026amp; Luo QY. Efficacy and survival analysis of 131I therapy for bone metastases from differentiated thyroid cancer. J Clin Endocrinol Metab. 2011;96(10):3078-3086.\u003c/li\u003e\n\u003cli\u003eLuster M, Clarke SE, Dietlein M, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008;35(10):1941-1959.\u003c/li\u003e\n\u003cli\u003eKim SY, Yun HJ, Chang H, et al. Aggressiveness of Differentiated Thyroid Carcinoma in Pediatric Patients Younger Than 16 years: A Propensity Score-Matched Analysis. Front Oncol. 2022;12:872130.\u003c/li\u003e\n\u003cli\u003eBal CS, Garg A, Chopra S, et al. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases. J Pediatr Endocrinol Metab. 2015;28(7-8):745-751.\u003c/li\u003e\n\u003cli\u003eRivkees SA, Mazzaferri EL, Verburg FA, et al. The treatment of differentiated thyroid cancer in children: emphasis on surgical approach and radioactive iodine therapy. Endocr Rev. 2011;32(6):798-826.\u003c/li\u003e\n\u003cli\u003eAlves-Junior PAG, Barreto MCA, Andrade FA, et al. Stimulated thyroglobulin and diagnostic 131-iodine whole-body scan as a predictor of distant metastasis and association with response to treatment in pediatric thyroid cancer patients. Endocrine. 2024;84(3):1081-1087.\u003c/li\u003e\n\u003cli\u003eCistaro A, Quartuccio N, Garganese MC, et al. Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study. Eur J Nucl Med Mol Imaging. 2022;49(4):1374-1385.\u003c/li\u003e\n\u003cli\u003eGiovanella L, D\u0026apos;Aurizio F, Algeciras-Schimnich A, et al. Thyroglobulin and thyroglobulin antibody: an updated clinical and laboratory expert consensus. Eur J Endocrinol. 2023;189(2):R11-R27.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Clinical Characteristics of 57 Pediatric DTC with Postoperative Persistent Structural Disease\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics of all patients (n = 57) \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003en (%)/median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis (y)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e10.0(4-18)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; Male\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e32(56.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; Female\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e25(43.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor size (cm)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e2.5(0.2-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBilaterality\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e38(66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathological type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e55(96.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003eClassical PTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e50(87.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003eFollicular-variant PTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; 3(5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003eDiffuse sclerosing PTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; 1(1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003eTall cell PTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; 1(1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFTC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; 2(3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT stage*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; T1a\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e6(10.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; T1b\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e11(19.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; T2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e16(28.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; T3a\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e7(12.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; T3b\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e6(10.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; T4a\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e10(17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; T4b\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e1(1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN stage*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; N0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e2(3.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; N1a\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e9(15.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; N1b\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e46(80.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM stage*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e25(43.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; M1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e32(56.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDistribution of Disease Components\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymph node metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e51(89.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003eOnly lymph node metastasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;26(51.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; With Other Metastatic Components\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;25(49.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary metastasis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e32(56.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003eOnly pulmonary metastasis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; 6(18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; With Other Metastatic Components\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;26(81.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eThyroid bed residual disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e5(8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003eOnly thyroid bed residual disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64.3116%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; With Other Metastatic Components\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 35.6884%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 5(100.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003eAmerican Joint Committee on Cancer (AJCC) 8th edition\u003c/p\u003e\n\u003cp\u003eTable 2. Treatment Responses in 123 Therapeutic Courses of pediatric DTC\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTherapeutic Response Assessment\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=123\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eObjective Response (OR)\u003c/strong\u003e\u003cstrong\u003e:CR+PR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e55 (44.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u003cstrong\u003eComplete Response (CR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e11 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Target lesion disappearance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;6 (54.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Lymph nodes \u0026le;5 mm short-axis +\u0026nbsp;disappearance of RAI uptake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;5 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u003cstrong\u003ePartial Response (PR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e44 (35.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;lesion number reduction\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;3 (6.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026ge;30% decrease in long-axis diameter of lesions or in lymph node short-axis diameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;28 (63.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;Lesion/lymph node reduction that does not reach the \u0026ge;30% threshold above but is accompanied by markedly decreased RAI uptake on WBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;13 (29.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProgressive Disease (PD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e22 (17.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; New lesions/lymph node\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026ge;20% increase in long-axis diameter of lesions or in lymph node\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eshort-axis diameter.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;11 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003eNew highly suspicious metastatic lesions confirmed by 2 readers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStable Disease (SD)\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e46 (37.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003eNot meeting criteria for CR, PR, or PD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;45(97.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003eDiscordant responses between lesion sites\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1(2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 73.7374%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndeterminate Response\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26.2626%;\"\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3. \u0026nbsp;Distribution of \u0026Delta;Tg Levels and Group Comparisons Across Treatment Response Categories\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment Response\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSample size\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026Delta;\u003cstrong\u003eTg\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eKruskal-Wallis H Test\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePairwise Comparisons (Bonferroni-Adjusted)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e84.5% (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e\u003cem\u003eH\u003c/em\u003e =94.056\u003c/p\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e \u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003evs PR: \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u0026nbsp;\u003c/p\u003e\n \u003cp\u003evs SD, PD: \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e53.8% (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003evs CR: \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05 \u0026nbsp;\u003c/p\u003e\n \u003cp\u003evs SD, PD: \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.9% (22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003evs CR, PR, PD: all \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-69.0 %(91%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003evs CR, PR, PD: all \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote：A negative \u0026Delta;Tg value indicates an increase in sTg levels.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAssociation Between Initial Post-Treatment \u0026Delta;Tg Stratification and NED Status at Final Follow-up\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026Delta;Tg at 6 months after the first RAI therapy\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=57\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNED\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-NED\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eV\u003c/strong\u003e\u003cstrong\u003ealue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026Delta;Tg\u0026ge;32% (n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e16(55.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e13(44.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e-14%＜\u0026Delta;Tg＜32% (n=11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e2(18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e9(81.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026Delta;Tg\u0026le;-14% (n=17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e4(23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e13(76.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote：All \u003cem\u003ep\u003c/em\u003e-values were calculated using two-sided Fisher\u0026apos;s exact tests, due to the presence of cells with expected counts \u0026lt;5.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 5 Multivariable Cox Regression Analysis for Progression-Free Survival\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eV\u003c/strong\u003e\u003cstrong\u003eariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003eV\u003c/strong\u003e\u003cstrong\u003ealue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eInitial \u0026Delta;Tg \u0026le;-14% (vs. \u0026gt;-14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e11.70 (3.27-41.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eInitial \u0026Delta;Tg (continuous)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e0.59 (0.35-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eStage II (vs. Stage I)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e0.59 (0.21-1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eTumor size (\u0026ge;3cm vs. \u0026lt;3cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e0.56 (0.21-1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"endocrine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"endo","sideBox":"Learn more about [Endocrine](https://www.springer.com/journal/12020)","snPcode":"12020","submissionUrl":"https://submission.nature.com/new-submission/12020/3","title":"Endocrine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Differentiated thyroid cancer, Pediatric thyroid carcinoma, Thyroglobulin, Radioiodine therapy, Tg change rate","lastPublishedDoi":"10.21203/rs.3.rs-7567986/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7567986/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eThis study aims to define the relationship between the thyroglobulin change rate (ΔTg) after radioactive iodine (RAI) therapy and treatment response, determine its optimal threshold, and validate its prognostic value in pediatric patients with differentiated thyroid cancer (DTC).\u003cbr\u003e\n \u003cstrong\u003eMethods:\u003c/strong\u003e This retrospective study analyzed 123 RAI courses in 57 pediatric DTC patients with postoperative persistent disease. Treatment response was assessed at 6 months. Optimal ΔTg thresholds were determined using ROC analysis with bootstrap validation. Prognostic value for no evidence of disease (NED) and progression-free survival (PFS) was evaluated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eΔTg significantly differed among response categories (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001): Complete Response (CR): 84.5%, Partial Response (PR): 53.8%, Stable Disease (SD): 4.9%, Progressive Disease (PD): -69.0%. ROC analysis defined optimal ΔTg thresholds: ΔTg ≥32% for Objective Response (OR=CR+PR; AUC=0.96, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), ΔTg ≤-14% for PD (AUC=0.93, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001); patients with -14%\u0026lt;ΔTg\u0026lt;32% were classified as SD. Longitudinally, initial ΔTg ≥32% (n=29) vs. ΔTg ≤-14% (n=17) showed superior PFS (133.5 vs. 13.9 months, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) and higher NED rates (55.2% vs. 23.5%, \u003cem\u003ep\u003c/em\u003e\u0026gt;0.05). The intermediate group (-14%\u0026lt;ΔTg\u0026lt;32%, n=11) exhibited outcome dissociation: NED rate (18.2%) aligned with ΔTg ≤-14% (\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05), while PFS (126.4 months) resembled ΔTg ≥32% (\u003cem\u003ep\u003c/em\u003e\u0026gt;0.05). Multivariable analysis confirmed ΔTg ≤-14% predicted an 11.7-fold higher progression hazard (HR=11.70, 95%CI:3.27-41.89; \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eThis study establishes validated ΔTg thresholds for response assessment in pediatric DTC (OR: ≥32%; PD: ≤-14%; SD: -14%\u0026lt;ΔTg\u0026lt;32%). Initial ΔTg is a powerful independent prognostic factor. These evidence-based thresholds provide actionable guidance for personalized pediatric DTC management.\u003c/p\u003e","manuscriptTitle":"ΔTg Assesses Radioiodine Treatment Response and Predicts Prognosis in Pediatric Differentiated Thyroid Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-15 08:53:15","doi":"10.21203/rs.3.rs-7567986/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-03T22:49:21+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-03T12:50:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"179945285646466318587143715353068597172","date":"2025-10-25T09:39:46+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-22T21:21:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"14172324711938932493255486890613076960","date":"2025-10-03T17:25:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"260212061370131420939215379642854809390","date":"2025-10-01T17:41:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-01T15:37:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-10T04:20:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-10T04:20:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Endocrine","date":"2025-09-09T00:25:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"endocrine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"endo","sideBox":"Learn more about [Endocrine](https://www.springer.com/journal/12020)","snPcode":"12020","submissionUrl":"https://submission.nature.com/new-submission/12020/3","title":"Endocrine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ca3badf6-8b0d-4915-9b80-405e4e964e0b","owner":[],"postedDate":"October 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-05T16:01:58+00:00","versionOfRecord":{"articleIdentity":"rs-7567986","link":"https://doi.org/10.1007/s12020-025-04484-5","journal":{"identity":"endocrine","isVorOnly":false,"title":"Endocrine"},"publishedOn":"2025-12-29 15:58:24","publishedOnDateReadable":"December 29th, 2025"},"versionCreatedAt":"2025-10-15 08:53:15","video":"","vorDoi":"10.1007/s12020-025-04484-5","vorDoiUrl":"https://doi.org/10.1007/s12020-025-04484-5","workflowStages":[]},"version":"v1","identity":"rs-7567986","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7567986","identity":"rs-7567986","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}