Which factors affect treatment success/prognosis in thyroid cancers with pulmonary metastases and what is/how should be the effective cumulative cure/dose as a current approach; A retrospective study

Which factors affect treatment success/prognosis in thyroid cancers with pulmonary metastases and what is/how should be the effective cumulative cure/dose as a current approach; A retrospective study | 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 Which factors affect treatment success/prognosis in thyroid cancers with pulmonary metastases and what is/how should be the effective cumulative cure/dose as a current approach; A retrospective study Fatih Tamer, Mertcan Güven, Aylin Oral, Bülent Yazici, Ayşegül Akgün This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5841558/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 May, 2025 Read the published version in Annals of Nuclear Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Objective Our primary objective in this study was to analyse clinical-prognostic factors, to evaluate their effects on response to RAIT and survival in pulmonary metastatic differantiated thyroid cancer. Another aim was to evaluate the treatment cycles/doses to achive effective treatment at the end of the follow-up. Methods 68 patients with pulmonary metastatic differentiated thyroid cancer who met all inclusion criteria were included. Clinical-pathological features and imaging findings of patients were collected and analysed retrospectively. Results Advanced age (p 0.037, OR 1.045), > 2 cm primary tumor (p: 0.009, OR 8), macronodular pulmonary metastases (p: 0.024, OR 3.7) and non-RAI-avidity (p: 0.045, OR 4.5) were independent factors associated with non-response to RAIT. When cumulative RAIT responses in the first 3 cycles were compared, no significant change was observed until the 3rd cycle (up to a cumulative dose of 21.27 GBq). That is, excluding patients who achieved excellent response in ≤ 2 cycles, it would be appropriate to administer at least 3 cycles (21.27 GBq) to achieve indeterminate resonse, which constitutes another pillar of the good prognostic group. Conclusion Collectively, it would be appropriate to consider that response and survival to RAIT decreases in advanced age and in the presence of macronodular pulmonary metastases. In addition to this, it was concluded that at least 3 cycles of RAIT (21.27 GBq) may be appropriate in the determination of treatment-resistant cases, in other words, in the determination of cases in which biochemical-structural incomplete response can be obtained during follow-up. Differantiated thyroid cancer Pulmonary metastases Radioactive iodine treatment Cumulative dose Figures Figure 1 Figure 2 Introduction Thyroid cancer (TC) is the most common group of endocrine tumors and the majority of them is differentiated thyroid cancers (DTC, around 90% of TC) consisting of papillary (PTC, 85%) and follicular (FTC, 10–15%) subtypes [ 1 , 2 ]. Its incidence increases worldwide, mainly due to developments in diagnostic methods/screening programs [ 3 – 4 ]. Although DTC is not a uniform group due to different clinical features in its subgroups, it generally has an excellent prognosis and good treatment response (10-year survival up to 90–95%) [ 2 ]. Distant metastasis (DM) is not rare and lung is the most common distant metastatic organ, followed by bones, brain and kidney [ 5 ]. DM is the leading cause of cancer-specific mortality, although DTC is associated with a favourable prognosis [ 5 , 6 ]. The main treatment scheme for DTC to minimize the recurrence is total or near-total thyroidectomy followed by thyrotropin (TSH) suppression and, if necessary, RAIT according to risk classification [ 3 ]. Long-term follow-up is carried out after the initial treatment, with serum thyroglobulin (Tg), thyroglobulin antibody (TgAb) and ultrasonography of the neck (US) being the most important factors. In the presence of unresectable local disease or DM, RAI therapy (RAIT) is the main treatment modality that can be applied in different and repeated doses [ 3 , 4 , 7 ]. However, resistance to RAIT is the most important problem in this regard, and its presence decreases survival [ 7 ]. In addition to RAIT, surgical excision, external beam radiotherapy, radiofrequency ablation, cryoablation, tyrosine kinase inhibitors are other local/systemic therapies that can be applied and have been reported to be effective in improving survival [ 3 , 8 ]. Pulmonary metastases (PM) can be classified into sub-categories with different disease courses and prognosis based on clinical, scintigraphy and radiological findings. Miliary metastases are characterized by the presence of multiple micronodules and diffuse involvement of lung, which are often diagnosed by PT-WBS. Another pattern is macronodular metastasis and characterized by > 1 cm lung nodule(s) showing focal uptake on PT-WBS. Apart from these, there are also non-RAI-avid metastases characterized by non-avid nodule(s) where the pulmonary lesions do not show 131 Iodine ( 131 I) uptake on PT-WBS. Pulmonary metastatic-DTC (PM-DTC) does not usually cause clinical signs. However, symptoms such as pain, hemoptysis, dyspnea can be observed especially in the presence of advanced disease. Considering the positive effect of early detection of DM on prognosis, early diagnosis of patients who do not produce symptoms, who are M0, who have small tumors limited to a single metastatic focus and who are in the excellent response (ER, recurrence rates 1–4) group with relatively low recurrence rates is very important [ 3 ]. Although there is no clear consensus on the frequency, doses and intervals of RAIT in patients with RAI-avid PM-DTC, treatment is repeated at intervals ranging from 6 to 12 months as treatment efficacy is demonstrated [ 3 , 4 ]. Various factors such as dose-limiting side effects, disease-related parameters and response to treatments are influential in determining the cumulative dose to be administered, which is a kind of personalized treatment approach [ 9 ]. To prevent possible side effects, methods such as low effective dose application and longer intervals between treatments are applied considering the risk of recurrence/progression [ 3 ]. Several factors, including age at diagnosis, tumour histology, size, extrapulmonary metastases, macronodular pulmonary metastases, elevated thyroglobulin levels, RAI avidity, and time of diagnosis of pulmonary metastases, have been described as effective in determining treatment efficacy/prognosis in PM-DTC [ 10 – 14 ]. Our primary objective in this study was to analyse clinical-prognostic factors, to evaluate their effects on response to RAIT and survival in pulmonary metastatic differantiated thyroid cancer. Another aim was to evaluate the treatment cycles/doses to achive good prognosis at the end of the follow-up. Materials and Methods 1. Patient group In this study, 68 patients who met all inclusion criteria among 108 DTC patients who underwent total/near-total thyroidectomy ± central/lateral lymph node dissection, underwent RAIT, had PM at diagnosis/follow-up, and were followed up according to the relevant guidelines in our unit between 2000 and 2021 were evaluated. Demographic characteristics (age at diagnosis, age at diagnosis of PM, age at initial RAIT, gender), disease-related clinical/pathological features (pathological subtype, size of primary tumor and pulmonary metastases, multicentricity, extrathyroidal extension, soft tissue invasion, regional LN involvement, presence of extrapulmonary DM), serum markers used in follow-up (serum TSH, Tg and TgAb levels after TSH stimulation at the time of RAIT or at the time of diagnostic WBS), imaging findings (CT, 18 FDG PET/CT), treatment features (preparation for treatment, number of doses administered, cumulative dose), parameters related to treatment response/prognosis (treatment response status, date of last follow-up and disease status at the end of follow-up) were obtained and analysed retrospectively. The study was approved by the Ege University Ethics Committee, number 21-8T/68. 1.1. Inclusion – exclusion criteria Inclusion criteria: i) Adult patients who underwent total/near-total thyroidectomy ± central/lateral lymph node dissection with a diagnosis of DTC followed by RAIT and who had PM at the time of diagnosis/during follow-up; ii) cases in which at least 2 doses of RAIT were administered during follow-up and the response to these treatments was evaluated. Exclusion criteria: i) TC other than DTC (medullary, anaplastic); ii) Patients with secondary malignancy or comorbid disease with a significant effect on prognosis; iii) Patients with a follow-up period of less than 12 months; iv) Those who are missing data to be used in the evaluation of the objectives of the study. 1.2. Diagnosis and classification of pulmonary metastases PMs were diagnosed by scintigraphy and/or radiological imaging (CT, PT-WBS, 18 FDG-PET/CT) performed for risk assessment/staging/restaging, either at the time of diagnosis or during follow-up, for reasons such as explaining elevated serum Tg-TgAb. In our group, most of whom were not pathologically confirmed, data confirmed by comparative evaluation with at least two of the biochemical, scintigraphy and radiological methods were included in the study to identify and exclude pulmonary pathologies unrelated to the disease (non-specific pulmonary nodules, infection, bronchiectasis, atelectasis, primary lung malignancy). PMs were divided into two groups in two different categories according to PT-WBS. Based on the 131 I uptake of the lung lesions; i) RAI-avid (cases with focal and/or miliary 131 I accumulation above background activity); ii) non-RAI-avid. According to the 131 I uptake pattern; i) Miliary metastasis, a pattern of diffuse I-131 uptake in both lungs (regardless of whether it is detected by radiological examinations); ii) Focal metastasis, a pattern of at least one focal 131 I uptake in the lung. Furthermore, PMs were morphologically divided into two groups as micronodular and macronodular, those <1 cm (including cases with miliary pattern but negative radiological imaging) and those ≥1 cm. 1.3. Criteria related to treatment response and disease state Biochemical, scintigraphy and radiological findings were noted during follow-up and treatment success was evaluated at least 3 months after each treatment cycle. The measurement of serum Tg and TgAb has changed over the years (radioimmunoassay and chemiluminescence) and the lower limit of sensitivity for serum Tg has evolved over the years from 1 ng/mL to 0.1 ng/mL. Therefore, to ensure uniformity in patients and also as recommended by current guidelines, the cut-off value determined in the suppressed Tg level was set as 1 ng/mL. RAI teatment response was determined according to the following criteria for macronodular/focal (i+ii), micronodular/miliary (i±ii) and non-RAI-avid (i+ii) groups (Table 1). Based on biochemical, scintigraphy and/or structural response criteria, response to treatment was determined as complete regression (CR) and partial regression (PR). At the end of follow-up, patients were categorised according to the 2015 ATA guideline for biochemical, scintigraphy and radiological response into the following categories (Table 2). Effective treatment group (in other words, the good prognostic group) was defined as excellent response (ER) and indeterminate response (IR). As can be seen, different definitions are observed in the literature in determining the response to RAIT (complete response and partial response), the effective treatment group at the end of follow-up (excellent response and indeterminate response) and the decision to continue RAIT (patients who are observed to benefit/stable from RAIT and whose disease status is biochemical-structural incomplete response). Therefore, the evaluation of prognostic data related to remission was based on the effective number of cycles/cumulative dose instead of time-related parameters (disease-free survival, progression-free survival). In addition, in patients with RAI-avid metastases who received at least 3 cycles of RAIT, differences in treatment response between cycles were compared and the number of cycles/cumulative dose associated with effective treatment (ER-IR) was defined. 2. Patient preparation After the diagnosis and surgery, thyroid scintigraphy ( 99m Tc pertechnetate), neck US and serumTg/TgAb levels were performed for risk stratification before RAI teraphy. Additional scintigraphy/radiological imaging (bone scintigraphy, CT, 18 FDG PET/CT) was performed in the presence of findings suspicious for local/systemic spread. After risk stratification, hypothyroidy was induced (4-week L-T4 withdrawal) or thyrotropin alpha injection was performed to fulfil the TSH ≥ 30 mIU/L criterion in preparation for RAIT. In addition, a two-week low iodine diet was administered to the patients before treatment. 3. Disease management Patients received variable doses of RAIT within a mean of 4-6 weeks following the diagnosis of DTC in the light of current guidelines and information at the time of administration. An initial RAI dose of 1.85-8.51 GBq was given for residual ablation or treatment of metastatic disease. Levothyroxine (LT4) was started 48-72 hours after RAI in the patient group classified as high recurrence risk, with the aim of achieving TSH values below 0.1 mU/L. PT-WBS was performed on post-treatment days 7-11 and evaluated in stages by two different nuclear medicine specialists (interpreted by observer 1, crosschecked by observer 1 and 2). Despite changes observed in the literature over time due to the large follow-up and there is no consensus on the treatment cycle/cumulative dose has been reached even today, repeated treatments were performed in cases fulfilling the following criteria, provided that the interval between the two cycles was at least 6 months; i) Patients with RAI-avid PM detected on PT-WBS after the last treatment; ii) Patients with an non-suppressed Tg level> 10 ng/dL and/or continued positive TgAb. RAIT was ceased in cases with the following; i) Those with biochemical, scintigraphy or morphological progression suggestive of non-response to RAIT in repeated treatments (>1 cycle); ii) Patients with PM that lose RAI avidity during follow-up; iii) Patients with ER; iv) The presence of serious adverse effects (restrictive lung disease) or cases reaching a cumulative dose that may lead to an increased risk of major adverse effects. Patients in remission with ER/IR were followed up routinely at 6-12 months intervals. Recurrence was defined in the presence of findings outside the remission criteria during the follow-up (>10 ng/mL serum Tg level, TgAb positivity on the current examination and/or newly developed metastatic lesion on PT-WBS). In the SIR/BIR group, repeated high doses were administered and were evaluated for additional treatment modalities in the presence of treatment discontinuation criteria. 4. Statistical analysis The data were analysed with SPSS version 25 (SPSS Inc. Chicago, IL). Normality was analysed by Shapiro-Wilk tests in the whole group and subcategories. Numerical data are expressed as mean±standard deviation and median with interquartile range [IQR], categorical data as number and percentage (depending on whether it has a normal or skewed distribution). χ2 and Fisher exact (categories with expected values <5) probability tests were used to analyse categorical variables. The independent two-sample t test and Mann-Whitney U test were used to analyse the relationship between the categorical and numerical data. All factors that statistically defined the efficacy of RAIT and disease status at the end of follow-up in univariate analysis (p<0.05) were evaluated by binary logistic regression in multivariate analysis. Survival was calculated from diagnosis to the date of last follow-up or date of death. Cumulative survival plots were evaluated by Kaplan-Meier method and Log-rank tests were applied to compare differences between groups. The Cox proportional hazard model was used to determine the prognostic factors associated with overall survival (OS). Cochran's Q test was used to evaluate the difference between categorical variables in repeated measures. The confidence interval for the tests was 95% and the statistical significance level (p) was accepted as 0.05, and the p value, odds ratio (OR) and ratio (HR) were reported. Results 1. Clinical, pathological and imaging characteristics 68 patients with DTC who fulfilled all inclusion criteria and had PM were evaluated. The patients ranged in age from 19 to 78 years. The mean age was 50.2 ± 14.1 years. Females and males comprised 70.6% and 29.4%, respectively. Older age, absence of regional LN involvement (p:0 < 0.001), diagnosis of PM during follow-up (p:0.048) and absence of response to treatment (p:0.008) were more common. 82.4% of the cases were PTC, 7.4% were FTC and 10.3% were hurtle cell carcinoma. The most common subtype was the classical variant. Regional LN involvement was higher in patients with PTC (p:<0.001) and soft tissue invasion (p:0.006). PMs were RAI-avid in 52 cases (76,5%) and non-RAI-avid in 16 cases (26,5%). In the RAI-avid group, 131 I uptake was focal in 61.5% and miliary in 38.5%. Descriptive and classifying data were presented in Tables 3 – 4 . Comparing RAI-avid and non-RAI-avid cases, there was a significant association between the non-RAI-avid group and age (p:0.011), PM diagnosis (p:0.003), treatment response (p:0.034) and treatment efficiency (p:0.009). In this group, PMs diagnosed during follow-up, non-response to RAIT and poor prognosis (SIR-BIR) were more frequent. Furthermore, there was a significant relation between focal 131 I uptake and tumor diameter (p:0.021) and > 4 cm primary tumor was more common in this group (Table 5 ). Table 1: RAI treatment response in terms of biochemical-scintigraphy and structural findings Biochemical and scintigraphy (i) Structural (ii) Complete Regression Stimulated Tg<1 ng/dL, negligible TgAb and no abnormal uptake on PT-WBS Complete regression of metastatic lesions Partial Regression ≥25% decrease in serum Tg value ± no increase in TgAb titres and/or decrease in disease spread/volume on PT-WBS ≥30% reduction in the diameter of the PMs Stable Disease Change in serum Tg, TgAb levels between the values defining regression/progression and/or no significant change observed on PT-WBS No morphological change Progressive Disease ≥25% increase in serum Tg value ± development of TgAb positivity/TgAb titres increase and/or increase in disease spread/volume on PT-WBS An increase of ≥20% and/or ≥5mm in the diameter of the pulmonary lesion(s) PM: Pulmonary metastases, PT-WBS: Post-treatment whole-body scan Table 2 : Disease status at the end of follow-up (ATA) Excellent response Negative imaging and either suppressed Tg<0.2 ng/mL or stimulated Tg<1 ng/mL Biochemical incomplete response Negative imaging and stimulated Tg ≥ 10 ng/mL or suppressed Tg ≥ 1 ng/mL or rising TgAb levels Structural incomplete response Structural or functional evidence of disease with any Tg level ± TgAb positivity Indeterminate response Stimulated Tg< 10 ng/mL or stable/declining TgAb levels in the presence of nonspecific imaging findings in the absence of structural or functional disease Table 3 Descriptive features – 1 Subcategory n % Gender Female 48 70,6% Male 20 29,4% Type of Surgery BTT 40 58,8% BTT + LND 28 41,20% Pathology Papillary 56 82,4% Follicular 5 7,4% Hurtle 7 10,3% Tumor location Unifocal 40 58,8% Multifocal 28 41,2% Tumor diameter 4 cm 26 38,2% STI Yes 32 47,1% No 36 52,9% LVI Yes 35 51,5% No 33 48,5% Regional LN involvement Yes 34 50% No 34 50% Pulmonary nodul size 6 month 18 26,5% RAI avidity Yes 52 76,5% No 16 23,5% 131 I uptake pattern Diffuse 20 38,5% Focal 32 61,5% Extrapulmonary metastases Yes 16 23,5% No 52 76,5% RAIT response during follow up Yes 35 51,5% No 33 48,5% Statue at last follow up ER-IR 17 25% ER 6 8,9% IR 11 16,2% SIR-BIR 51 75% PM: Pulmonary metastasis, STI: Soft tissue invasion, LVI: Lymphovascular invasion, LN: Lymph node, BTT: Bilateral total thyroidectomy, LND: Lymph node dissection, ER: Excellent response, IR: Indetermined response, SIR: Structural incomplete response, BIR: Biochemical incomple trespponse Table 4 Descriptive features − 2 Characteristic Range Median ± IQR Treatment cycles 2–7 Cumulative dose 275–1600 800 [438,75] ER 100–400 300 [225] IR 250–975 500 [425] SIR-BIR 275–1600 700 [550] 1st cycle dose 50–230 175 [50] 2st cycle dose 150–200 200 3rd cycle dose 150–225 200 First cycle with response ER 1 IR ≤ 2 SIR-BIR 1–4 Follow up (month) 12–204 72 [72] IQR: Interquartile range, ER: Excellent response, IR: Indetermined response, SIR: Structural incomplete response, BIR: Biochemical incomplete response Table 5 Factors associated with RAI avidity and 131-I uptake pattern Characteristic RAI avidity 131 I uptake pattern Age of diagnosis 0.011 0.13 Gender 0.33 0.74 Pathology 0.85 0.85 Tumor location Tumor diameter 0.20 0.42 0.25 0.021 STI 0.92 0.09 LVI 0.73 0.83 Regional LN involvement 0.82 0.25 Extrapulmonary metastasis Diagnosis of PM 0.63 0.003 0.33 0.79 Treatment response 0.034 0.29 Statue at last follow up 0.009 0.18 PM: Pulmonary metastasis, STI: Soft tissue invasion, LVI: Lymphovascular invasion, LN: Lymph node, those found to be statistically significant are given in bold. 2.Treatment response and survival When patients were categorised according to the defined response criteria at each treatment cycle and at the end of the follow-up, 35 patients (51.5%) responded to at least one treatment cycle and 17 patients (25%) were in the effective treatment group (ER-IR) at the end of the follow-up. Treatment response was lower in macronodular PM (p: 0.022) and at advanced age (0.008). In poor prognostic (SIR-BIR) group, non-RAI avidity (p: 0.009), PMs diagnosed during follow-up (p: 0.003) and > 2 cm primary tumors were more frequent (p: 0.029). Parameters found to be significant in the univariate analysis were evaluated in the multivariate analysis in terms of treatment response and treatment efficacy (Table 6 ). The independent factors for treatment response were advanced age (p 0.037, OR 1.045 [1.01–1.09], macronodular metastases (p: 0.024, OR 3.7 [1.19–11.6]) and non-RAI avidity (p: 0.045, OR 4.5 [1.03–19.92]). Among the factors evaluated in the multivariate analysis for treatment efficacy, the only independent factor was primary tumor diameter > 2 cm (p: 0.009, OR 8 [1.69–37.67]) (Table 6 ). In univariate and multivariate analyses, there were differences in OS, pulmonary nodule diameter, presence of extrapulmonary metastasis, and age at diagnosis (Fig. 1 – 2 ). Overall survival was lower in the presence of macronodular metastasis (p:<0.001, HR 3.46 [1.13–10.6]) and extrapulmonary metastasis (p:0.038, HR 1.06 [1.01–1.12]) as well as at older age (p:0.003, HR 1.36 [1.54–8.55]) (Table 7 ). Table 6 Factors associated with treatment response and treatment efficiency Treatment response Statue at last follow up Univariate Multivariate Univariate Multivariate Age of diagnosis 0.008 0.023 0.18 Gender 0.22 0.07 Pathology 0.52 0.12 Tumor location 0.65 0.14 Tumor diameter 0.45 0.029 0.009 STI 0.21 0.88 LVI 0.40 0.42 Regional LN involvement 0.47 0.78 RAI avidity 0.034 0.045 0.009 > 0.05 I-131 uptake pattern 0.29 0.18 Pulmonary nodule size 0.022 0.024 0.74 Extrapulmonary metastasis 0.06 0.19 Diagnosis of PM 0.07 0.003 > 0.05 Those found to be statistically significant are given in bold. Table 7 Factors associated with OS Characteristic Univariate analysis Multivariate analysis Age of diagnosis 0.010 0.038 Gender 0.11 Patology 0.10 Tumour location Tumour diameter 0.95 0.38 STI 0.75 LVI 0.33 RAI avidity 0.19 131 I uptake pattern Pulmonary nodule size 0.93 0.011 0.030 Extrapulmonary metastasis < 0.001 0.003 Diagnosis of PM 0.55 Those found to be statistically significant are given in bold. 3. Effective treatment cycle and cumulative dose At the end of the follow-up, all 6 patients with excellent response were included in this category in the first two cycles of treatment and more than two cycles of treatment were not required. Accordingly, we investigated the effective number of cycles/cumulative dose in achieving indeterminate, which constitutes another pillar of the effective treatment group (ER + IR), in patients who received at least 3 cycles of treatment, excluding patients with excellent response in the first 2 cycles. When the cumulative treatment responses of the patients in the 1st, 2nd, and 3rd treatment cycles were compared, no significant change was observed in the 1st and 2nd treatment cycles, i.e. 6.47 GBq and 13.87 GBq cumulative doses, whereas after the 3rd cycle (21.27 GBq cumulative dose), the number of patients in the active treatment group was significantly higher than in the 1st cycle (p:0.016). Only 1 patient responded after ≥ 4 cycles and this patient was in the poor prognosis group (SIR-BIR) at endpoint. In other words, there was no patient who responded with 4 or more cycles and was in the effective treatment group (ER-IR). Discussion Lung, which is the first organ reached by the lymphatic system, is the most common extralymphatic metastatic organ in DTC patients, as in many other cancer groups [ 15 ]. Although DTC is recognised with a good prognosis, the presence of DM is the main cause of cancer-specific mortality [ 5 – 6 ]. In consideration of these findings, it is important to identify the presence of DM in patients with DTC, especially in the lung, and to determine the factors that are effective in treatment response and prognosis. Accordingly, in our study, we aimed to identify the clinical/prognostic factors associated with treatment response/survival in the whole patient group and also in subgroups (RAI avid or non-RAI-avid, miliary or focal) and to determine the effective treatment cycle/cumulative dose in patients with PM-DTC. Consistent with the literature, the RAI-avid pulmonary group (76.5%) was more predominant [ 16 – 18 ]. In non-RAI-avid group, PM diagnosed during follow-up, non-response to RAIT and poor prognosis (SIR-BIR) were more frequent. Wu et al. reported that non-RAI-avidity was higher in advanced age, like our findings [ 16 ]. The diagnosis of PM was made during the follow-up period (> 6 months) in 26.5% of the patients. Those were in the older age and non-RAI-avid, similar to previous data [ 14 – 19 ]. At the end of follow-up, effective treatment (ER + IR) was achieved in ¼ of the cases. In the literature, the findings regarding remission/good treatment response were reported on a wide scale (5.7–95.2%) due to differences in treatment efficacy (CR + PR, CR + PR + SD, being alive) and factors such as dose/cycle applied in treatment [ 10 , 11 , 16 , 20 ]. In this study, cases with PTC accounted for 82.4% of the group. Regional LN involvement was observed more frequently in patients with PTC than in those with FTC, in agreement with the literature [ 10 ]. Also, the most common extrapulmonary focus was bone [ 11 , 21 ]. Pulmonary nodule size, age and RAI avidity were the most frequently identified independent risk factors for treatment response [ 9 , 14 , 16 , 19 , 21 – 23 ]. As for 131 I uptake pattern, there were publications stating that miliary/diffuse or focal/multifocal involvement were effective factors in response to treatment as well as publications reporting the opposite [ 13 , 16 , 20 ]. With our criteria, we evaluated the response to RAIT after the treatment cycles and also at the end of the follow-up. Since there are different approaches and criteria in the literature on this subject and also a strong correlation was observed between both parameters in our study, we thought that it would be more accurate to interpret these findings, which we evaluated separately, together. In our study, advanced age, presence of > 2 cm primary tumor, macronodular metastases and non-RAI-avidity were the independent factors found to have a negative effect on response to RAIT and these findings were largely consistent with the literature data. In the literature, advanced age and the presence of extrapulmonary metastases were the most reported factors in OS and CSS [ 11 – 13 , 24 ]. Contrasting results have also been reported for the effect of RAI avidity and 131 I uptake pattern on survival [ 10 , 13 , 14 , 24 ]. In our study, advanced age, presence of extrapulmonary metastases and macronodular PMs were found to be effective independent prognostic factors in OS, but 131 I uptake pattern was not one of them. In addition, RAI avidity, which was found to be one of the effective parameters in treatment response, was not found to be one of the effective independent factors in OS. In line with Zhao et al., regional LN involvement did not have any negative effect on OS in our patient group [ 25 ]. In fact, there was a negative correlation between LN involvement and the presence of extrapulmonary metastasis in our patient group. This finding may be secondary to PM/DM masking the effect of regional LN involvement on survival, or to the high frequency of LN involvement in our group of patients with predominantly PTC, which is not associated with a poor prognosis. In sum, the presence of macronodular metastases was an effective independent factor for both response and OS, consistent with the literature, and 131 I uptake pattern, which has been reported with conflicting results in the literature, was an effective independent factor for response only. As it is known, RAI accumulation and response of macronodular metastases to this treatment are observed to be lower than miliary metastases, considering the distance travelled by β-radiation in the tissue [ 22 ]. Again, in relation to this finding, there are also publications reporting low response rates (although contradictory findings have been described) to RAIT in pulmonary lesions defined as focal on PT-WBS [ 21 ]. Overall, the 131 I uptake pattern and the pulmonary nodule size parameters can be considered as two important parameters that have an impact on disease progression. However, it should be remembered that both parameters come from an intersection set, considering the significant relationship we observed between them (p:0.004), and also that the 131 I uptake model should be considered with some limitations. At this point, we would like to highlight some important points that may be related to misinterpretation of the 131 I uptake pattern on PT-WBS; i) PMs below scintigraphy resolution, although identified by serum Tg and/or imaging modalities, may be classified as non-RAI-avid; ii) misinterpretation of treatment response/survival is possible in cases with a mixed pattern. It is thought that the miliary pattern and macronodular metastasis in some cases in our group may be explained by these conditions. Although we defined the presence of at least 1 focal uptake as a focal 131 I pattern to ensure uniformity in the evaluation of the 131 I uptake pattern, a change between miliary/focal subgroups was found in 14.7% of cases during follow-up, the significance of which has not been previously reported in the literature. It should be considered that these findings may cause differences in the results between previous studies and the current study in determining the 131 I uptake criterion (scintigraphy and radiological findings were defined as a single parameter in some studies) [ 10 , 22 , 26 ]. In this respect, we conclude that anatomical findings will be more significant than 131 I uptake pattern in evaluating the efficacy of PMs on treatment response/survival in adult patients (different from childhood where miliary pattern is frequently observed), contrary to the report of Cho et al [ 21 ]. Repeated RAIT in RAI-avid patients is highly effective in controlling DTC and is predictive of clinical outcome. However, there is no consensus on the number of treatment cycles and the cumulative dose to be administered. There were a few publications in the literature presenting data on cumulative dose in response to treatment [ 16 , 26 – 29 ]. In these studies, the evaluation was mainly based on descriptive data. In our study, in the effective treatment group (ER + IR), response rate was 94.1% (16 of 17 patients) in ≤ 3 treatment cycles and at a cumulative dose of ≤ 21.27 GBq. In this direction, the descriptive data we reported were largely consistent with the literature. Furthermore, when comparing the cumulative responses after each treatment in our cohort of patients who received at least 3 treatments, no significant change in treatment response was observed in the 1st and 2nd treatment cycles, i.e. 6.47 GBq and 13.87 GBq cumulative doses, whereas after the 3rd cycle (21.27 GBq), the number of patients in the effective treatment group was significantly higher than in the 1st (p:0.016). In this regard, when the patients who achieved ER in ≤ 2 cycles are excluded, we think that it would be appropriate to apply at least 3 treatment cycles – 21.27 GBq RAIT to achieve IR, which constitutes another pillar of the good prognostic group, and in cases where no treatment response is observed after the first 3 treatments, the decision of treatment non-response and discontinuation of it could be thougt in accordance with individualised management in the light of clinical/prognostic data. We would like to emphasise that our study has several limitations. Firstly, due to the retrospective nature of our study, it may be associated with possible bias in patient selection. Again, it is thought that a larger number of patients may be more meaningful in terms of making the evaluation stronger, especially in subcategories. Another limitation in the patient group, in which the follow-up period is relatively long, is that we could not report and interpret the difference, relationship and effect analyses between Tg values, which constitute an important pillar of disease follow-up, and other parameters, especially due to the changes observed in Tg measurement methods (upper limit, dilution, measurement method). Conclusion In conclusion, advanced age, presence of > 2 cm primary tumor, macronodular metastases and non-RAI avidity were found to be effective independent prognostic factors for treatment response in patients with PMs diagnosed with DTC. Also, advanced age, presence of extrapulmonary metastases and macronodular PMs were found to be effective in predicting OS. We thought that, when the patients who achieved ER in ≤ 2 cycles are excluded, it would be appropriate to apply at least 3 treatment cycles (21.27 GBq) RAIT to achieve IR, which constitutes another pillar of the good prognostic group. In this context, we concluded that even if RAI uptake is observed in pulmonary lesions, in cases where no response is observed after the first 3 treatments, it would be appropriate to reconsider discontinuation of RAIT due to treatment non-response. Declarations Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgement None. Author(s’) disclosure The authors declare that they have no conflict of interest. References Chen DW, Lang BHH, McLeod DSA, Newbold K, Haymart MR. Thyroid cancer. Lancet . 2023;401:1531-44. Boucai L, Zafereo M, Cabanillas ME. Thyroid Cancer: A Review. JAMA . 2024;331:425-35. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1-133. Fugazzola L, Elisei R, Fuhrer D, Jarzab B, Leboulleux S, Newbold K, et al. 2019 European Thyroid Association Guidelines for the Treatment and Follow-Up of Advanced Radioiodine-Refractory Thyroid Cancer. Eur Thyroid J. 2019;8:227-45. Li C, Wu Q, Sun S. Radioactive Iodine Therapy in Patients With Thyroid Carcinoma With Distant Metastases: A SEER-Based Study. Cancer Control. 2020;27. Nixon IJ, Whitcher MM, Palmer FL, Tuttle RM, Shaha AR, Shah JP, et al. The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland. Thyroid. 2012;22:884-9. Liu Y, Wang J, Hu X, Pan Z, Xu T, Xu J, et al. Radioiodine therapy in advanced differentiated thyroid cancer: Resistance and overcoming strategy. Drug Resist Updat. 2023;68:100939. Goodsell K, Ermer J, Amjad W, Swisher-McClure S, Wachtel H. External beam radiotherapy for thyroid cancer: Patients, complications, and survival. Am J Surg. 2023;225:994-9. Wang H, Shi L, Huang R, Liu B, Tian R. The association between the interval of radioiodine treatment and treatment response, and side effects in patients with lung metastases from differentiated thyroid cancer. Front Endocrinol (Lausanne). 2023;14:1117001. Maciel J, Cavaco D, Silvestre C, Simões Pereira J, Vilar H, Leite V. Clinical outcomes of a cohort of 271 patients with lung metastases from differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2022;97:814-21. Wang R, Zhang Y, Tan J, Zhang G, Zhang R, Zheng W, et al. Analysis of radioiodine therapy and prognostic factors of differentiated thyroid cancer patients with pulmonary metastasis: An 8-year retrospective study. Medicine. 2017;96. Zhang X, Liu DS, Luan ZS, Zhang F, Liu XH, Zhou W, et al. Efficacy of radioiodine therapy for treating 20 patients with pulmonary metastases from differentiated thyroid cancer and a meta-analysis of the current literature. Clin Transl Oncol. 2018;20:928-35. Qutbi M, Shafeie B, Amoui M, Tabeie F, Azizmohammadi Z, Mahmoud-Pashazadeh A, et al. Evaluation of Prognostic Factors Associated With Differentiated Thyroid Carcinoma With Pulmonary Metastasis. Clin Nucl Med. 2016;41:917-21. Sohn SY, Kim HI, Kim YN, Kim TH, Kim SW, Chung JH. Prognostic indicators of outcomes in patients with lung metastases from differentiated thyroid carcinoma during long-term follow-up. Clin Endocrinol (Oxf). 2018;88:318-26. Cucanic O, Farnsworth RH, Stacker SA. The cellular and molecular mediators of metastasis to the lung. Growth Factors. 2022;40:119-52. Wu XY, Li B, Zhang J, Duan LL, Hu BX, Gao YJ. Analysis of the clinical factors affecting excellent response of Iodine-131 treatment for pulmonary metastases from differentiated thyroid cancer. Heliyon. 2023;9:e20853. Akatani N, Wakabayashi H, Kayano D, Inaki A, Takata A, Hiromasa T, et al. Long-term outcomes and prognostic factors of patients with lung metastases from differentiated thyroid cancer after radioiodine therapy in Japan. Endocr J. 2023;70:315-22. Sabra MM, Ghossein R, Tuttle RM. Time Course and Predictors of Structural Disease Progression in Pulmonary Metastases Arising from Follicular Cell-Derived Thyroid Cancer. Thyroid. 2016;26:518-24. Chopra S, Garg A, Ballal S, Bal CS. Lung metastases from differentiated thyroid carcinoma: prognostic factors related to remission and disease-free survival. Clin Endocrinol (Oxf). 2015;82:445-52. Long B, Yang M, Yang Z, Yi H, Li L. Assessment of radioiodine therapy efficacy for treatment of differentiated thyroid cancer patients with pulmonary metastasis undetected by chest computed tomography. Oncol Lett. 2016;11:965-8. Cho SW, Choi HS, Yeom GJ, Lim JA, Moon JH, Park DJ, et al. Long-term prognosis of differentiated thyroid cancer with lung metastasis in Korea and its prognostic factors. Thyroid. 2014;24:277-86. Sunny SS, Hephzibah J, Shanthly N, Oommen R, Cherian AJ, Mathew D. Treatment Response following Radioactive Iodine Therapy in Miliary versus Macronodular Pulmonary Metastases in Papillary Thyroid Carcinoma. World J Nucl Med. 2022;21:52-8. Chen P, Feng HJ, Ouyang W, Wu JQ, Wang J, Sun YG, Xian JL, et al. RISK FACTORS FOR NONREMISSION AND PROGRESSION-FREE SURVIVAL AFTER I-131 THERAPY IN PATIENTS WITH LUNG METASTASIS FROM DIFFERENTIATED THYROID CANCER: A SINGLE-INSTITUTE, RETROSPECTIVE ANALYSIS IN SOUTHERN CHINA. Endocr Pract. 2016;22:1048-56. doi:10.4158/EP151139.OR Ronga G, Filesi M, Montesano T, Di Nicola AD, Pace C, Travascio L, et al. Lung metastases from differentiated thyroid carcinoma. A 40 years’experience. Q J Nucl Med Mol Imaging. 2024;48:12-9. Zhao H, Liu CH, Cao Y, Zhang LY, Zhao Y, Liu YW, et al. Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis. Front Oncol. 2022;12:990154. Pitoia F, Bueno F, Cross G. Long-term survival and low effective cumulative radioiodine doses to achieve remission in patients with 131Iodine-avid lung metastasis from differentiated thyroid cancer. Clin Nucl Med. 2014;39:784-90. Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91:2892-9. Huang IC, Chou FF, Liu RT, Tung SC, Chen JF, Kuo MC, et al. Long-term outcomes of distant metastasis from differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2012;76:439-47. Wang C, Zhang X, Li H, Li X, Lin Y. Quantitative thyroglobulin response to radioactive iodine treatment in predicting radioactive iodine-refractory thyroid cancer with pulmonary metastasis. PLoS One. 2017;12: e0179664. Cite Share Download PDF Status: Published Journal Publication published 19 May, 2025 Read the published version in Annals of Nuclear Medicine → Version 1 posted Reviewers agreed at journal 17 Apr, 2025 Reviewers invited by journal 14 Apr, 2025 Editor assigned by journal 08 Apr, 2025 First submitted to journal 08 Apr, 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. 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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-5841558","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442766347,"identity":"e2a30fc7-f63d-47ef-8ca9-24fcd76afc8f","order_by":0,"name":"Fatih Tamer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYDCCA4wPGBgMDkA4H4CYjZ2gFmYDhgMGByRAbMYZIC3MRGlhgGhh5gGTBHTw3T7M+PlDwZ06/mmHj322+bVNno+ZgfHDxxzcWiTPJTNLHDB4JiFxOy15dm7fbcM2ZgZmyZnbcGsxOMN/AKjlsATD7Rxj5tye24xALWzMvHi1MDP/AGmRv53/mdmy57Y9MVrYwLYY3M5hZmb4cTuRoBZJoBaLMwaHJTfeTjNm7G24ndzGzNiM1y98QIfdqPhzmF/udvJjhh9/btvOb28++OEjHi2ogLENTDYQqx4E/pCieBSMglEwCkYKAADOmFPgKYYBlQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-5656-9955","institution":"Nigde Omer Halisdemir University, Training and Research Hospital, Department of Nuclear Medicine","correspondingAuthor":true,"prefix":"","firstName":"Fatih","middleName":"","lastName":"Tamer","suffix":""},{"id":442766348,"identity":"a15d0f84-2ec6-4541-88d7-64570de446f4","order_by":1,"name":"Mertcan Güven","email":"","orcid":"","institution":"Bitlis State Hospital, Department of Nuclear Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mertcan","middleName":"","lastName":"Güven","suffix":""},{"id":442766349,"identity":"f8e2820e-8628-4009-86be-2ca3f9fbb7a5","order_by":2,"name":"Aylin Oral","email":"","orcid":"","institution":"Ege University Faculty of Medicine, Department of Nuclear Medicine","correspondingAuthor":false,"prefix":"","firstName":"Aylin","middleName":"","lastName":"Oral","suffix":""},{"id":442766350,"identity":"8fcf423b-3c8d-4a96-a7ed-ec2c514b2bc2","order_by":3,"name":"Bülent Yazici","email":"","orcid":"","institution":"Ege University Faculty of Medicine, Department of Nuclear Medicine","correspondingAuthor":false,"prefix":"","firstName":"Bülent","middleName":"","lastName":"Yazici","suffix":""},{"id":442766351,"identity":"a7ca4736-153f-46f9-be42-bcdc1011731b","order_by":4,"name":"Ayşegül Akgün","email":"","orcid":"","institution":"Ege University Faculty of Medicine, Department of Nuclear Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ayşegül","middleName":"","lastName":"Akgün","suffix":""}],"badges":[],"createdAt":"2025-01-16 11:52:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5841558/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5841558/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12149-025-02060-5","type":"published","date":"2025-05-19T15:56:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80791727,"identity":"5b146ae4-7bad-4acb-9278-3abe361f8f6e","added_by":"auto","created_at":"2025-04-17 06:52:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":144325,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival table delineated by pulmonary nodule size\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5841558/v1/9d37501329b9f029ef2a5491.png"},{"id":80789622,"identity":"60513947-1f92-4054-91b6-942813838bf8","added_by":"auto","created_at":"2025-04-17 06:36:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":145878,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival table delineated by extrapulmonary metastasis\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5841558/v1/3eb01abc3dbf69ccb003d559.png"},{"id":83459951,"identity":"897be8cb-fc16-4d99-bd1d-5e445d1527d3","added_by":"auto","created_at":"2025-05-26 16:05:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1131657,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5841558/v1/0e72ff1c-736c-45ea-b9d3-e7a20c685ef2.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eWhich factors affect treatment success/prognosis in thyroid cancers with pulmonary metastases and what is/how should be the effective cumulative cure/dose as a current approach; A retrospective study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThyroid cancer (TC) is the most common group of endocrine tumors and the majority of them is differentiated thyroid cancers (DTC, around 90% of TC) consisting of papillary (PTC, 85%) and follicular (FTC, 10\u0026ndash;15%) subtypes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Its incidence increases worldwide, mainly due to developments in diagnostic methods/screening programs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough DTC is not a uniform group due to different clinical features in its subgroups, it generally has an excellent prognosis and good treatment response (10-year survival up to 90\u0026ndash;95%) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Distant metastasis (DM) is not rare and lung is the most common distant metastatic organ, followed by bones, brain and kidney [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. DM is the leading cause of cancer-specific mortality, although DTC is associated with a favourable prognosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe main treatment scheme for DTC to minimize the recurrence is total or near-total thyroidectomy followed by thyrotropin (TSH) suppression and, if necessary, RAIT according to risk classification [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Long-term follow-up is carried out after the initial treatment, with serum thyroglobulin (Tg), thyroglobulin antibody (TgAb) and ultrasonography of the neck (US) being the most important factors. In the presence of unresectable local disease or DM, RAI therapy (RAIT) is the main treatment modality that can be applied in different and repeated doses [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, resistance to RAIT is the most important problem in this regard, and its presence decreases survival [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition to RAIT, surgical excision, external beam radiotherapy, radiofrequency ablation, cryoablation, tyrosine kinase inhibitors are other local/systemic therapies that can be applied and have been reported to be effective in improving survival [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePulmonary metastases (PM) can be classified into sub-categories with different disease courses and prognosis based on clinical, scintigraphy and radiological findings. Miliary metastases are characterized by the presence of multiple micronodules and diffuse involvement of lung, which are often diagnosed by PT-WBS. Another pattern is macronodular metastasis and characterized by \u0026gt;\u0026thinsp;1 cm lung nodule(s) showing focal uptake on PT-WBS. Apart from these, there are also non-RAI-avid metastases characterized by non-avid nodule(s) where the pulmonary lesions do not show \u003csup\u003e131\u003c/sup\u003eIodine (\u003csup\u003e131\u003c/sup\u003eI) uptake on PT-WBS.\u003c/p\u003e \u003cp\u003ePulmonary metastatic-DTC (PM-DTC) does not usually cause clinical signs. However, symptoms such as pain, hemoptysis, dyspnea can be observed especially in the presence of advanced disease. Considering the positive effect of early detection of DM on prognosis, early diagnosis of patients who do not produce symptoms, who are M0, who have small tumors limited to a single metastatic focus and who are in the excellent response (ER, recurrence rates 1\u0026ndash;4) group with relatively low recurrence rates is very important [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough there is no clear consensus on the frequency, doses and intervals of RAIT in patients with RAI-avid PM-DTC, treatment is repeated at intervals ranging from 6 to 12 months as treatment efficacy is demonstrated [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Various factors such as dose-limiting side effects, disease-related parameters and response to treatments are influential in determining the cumulative dose to be administered, which is a kind of personalized treatment approach [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. To prevent possible side effects, methods such as low effective dose application and longer intervals between treatments are applied considering the risk of recurrence/progression [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral factors, including age at diagnosis, tumour histology, size, extrapulmonary metastases, macronodular pulmonary metastases, elevated thyroglobulin levels, RAI avidity, and time of diagnosis of pulmonary metastases, have been described as effective in determining treatment efficacy/prognosis in PM-DTC [\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur primary objective in this study was to analyse clinical-prognostic factors, to evaluate their effects on response to RAIT and survival in pulmonary metastatic differantiated thyroid cancer. Another aim was to evaluate the treatment cycles/doses to achive good prognosis at the end of the follow-up.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e1. Patient group\u003c/p\u003e\n\u003cp\u003eIn this study, 68 patients who met all inclusion criteria among 108 DTC patients who underwent total/near-total thyroidectomy \u0026plusmn; central/lateral lymph node dissection, underwent RAIT, had PM at diagnosis/follow-up, and were followed up according to the relevant guidelines in our unit between 2000 and 2021 were evaluated. Demographic characteristics (age at diagnosis, age at diagnosis of PM, age at initial RAIT, gender), disease-related clinical/pathological features (pathological subtype, size of primary tumor and pulmonary metastases, multicentricity, extrathyroidal extension, soft tissue invasion, regional LN involvement, presence of extrapulmonary DM), serum markers used in follow-up (serum TSH, Tg and TgAb levels after TSH stimulation at the time of RAIT or at the time of diagnostic WBS), imaging findings (CT, \u003csup\u003e18\u003c/sup\u003eFDG PET/CT), treatment features (preparation for treatment, number of doses administered, cumulative dose), parameters related to treatment response/prognosis (treatment response status, date of last follow-up and disease status at the end of follow-up) were obtained and analysed retrospectively. The study was approved by the Ege University Ethics Committee, number 21-8T/68.\u003c/p\u003e\n\u003cp\u003e1.1. Inclusion \u0026ndash; exclusion criteria\u003c/p\u003e\n\u003cp\u003eInclusion criteria: i) Adult patients who underwent total/near-total thyroidectomy \u0026plusmn; central/lateral lymph node dissection with a diagnosis of DTC followed by RAIT and who had PM at the time of diagnosis/during follow-up; ii) cases in which at least 2 doses of RAIT were administered during follow-up and the response to these treatments was evaluated. Exclusion criteria: i) TC other than DTC (medullary, anaplastic); ii) Patients with secondary malignancy or comorbid disease with a significant effect on prognosis; iii) Patients with a follow-up period of less than 12 months; iv) Those who are missing data to be used in the evaluation of the objectives of the study.\u003c/p\u003e\n\u003cp\u003e1.2. Diagnosis and classification of pulmonary metastases\u003c/p\u003e\n\u003cp\u003ePMs were diagnosed by scintigraphy and/or radiological imaging (CT, PT-WBS, \u003csup\u003e18\u003c/sup\u003eFDG-PET/CT) performed for risk assessment/staging/restaging, either at the time of diagnosis or during follow-up, for reasons such as explaining elevated serum Tg-TgAb. In our group, most of whom were not pathologically confirmed, data confirmed by comparative evaluation with at least two of the biochemical, scintigraphy and radiological methods were included in the study to identify and exclude pulmonary pathologies unrelated to the disease (non-specific pulmonary nodules, infection, bronchiectasis, atelectasis, primary lung malignancy). PMs were divided into two groups in two different categories according to PT-WBS. \u003c/p\u003e\n\u003cp\u003eBased on the \u003csup\u003e131\u003c/sup\u003eI uptake of the lung lesions; i) RAI-avid (cases with focal and/or miliary\u003csup\u003e131\u003c/sup\u003eI accumulation above background activity); ii) non-RAI-avid. According to the \u003csup\u003e131\u003c/sup\u003eI uptake pattern; i) Miliary metastasis, a pattern of diffuse I-131 uptake in both lungs (regardless of whether it is detected by radiological examinations); ii) Focal metastasis, a pattern of at least one focal \u003csup\u003e131\u003c/sup\u003eI uptake in the lung. \u003c/p\u003e\n\u003cp\u003eFurthermore, PMs were morphologically divided into two groups as micronodular and macronodular, those \u0026lt;1 cm (including cases with miliary pattern but negative radiological imaging) and those \u0026ge;1 cm.\u003c/p\u003e\n\u003cp\u003e1.3. Criteria related to treatment response and disease state\u003c/p\u003e\n\u003cp\u003eBiochemical, scintigraphy and radiological findings were noted during follow-up and treatment success was evaluated at least 3 months after each treatment cycle. The measurement of serum Tg and TgAb has changed over the years (radioimmunoassay and chemiluminescence) and the lower limit of sensitivity for serum Tg has evolved over the years from 1 ng/mL to 0.1 ng/mL. Therefore, to ensure uniformity in patients and also as recommended by current guidelines, the cut-off value determined in the suppressed Tg level was set as 1 ng/mL.\u003c/p\u003e\n\u003cp\u003eRAI teatment response was determined according to the following criteria for macronodular/focal (i+ii), micronodular/miliary (i\u0026plusmn;ii) and non-RAI-avid (i+ii) groups (Table 1). Based on biochemical, scintigraphy and/or structural response criteria, response to treatment was determined as complete regression (CR) and partial regression (PR). \u003c/p\u003e\n\u003cp\u003eAt the end of follow-up, patients were categorised according to the 2015 ATA guideline for biochemical, scintigraphy and radiological response into the following categories (Table 2). Effective treatment group (in other words, the good prognostic group) was defined as excellent response (ER) and indeterminate response (IR). \u003c/p\u003e\n\u003cp\u003eAs can be seen, different definitions are observed in the literature in determining the response to RAIT (complete response and partial response), the effective treatment group at the end of follow-up (excellent response and indeterminate response) and the decision to continue RAIT (patients who are observed to benefit/stable from RAIT and whose disease status is biochemical-structural incomplete response). Therefore, the evaluation of prognostic data related to remission was based on the effective number of cycles/cumulative dose instead of time-related parameters (disease-free survival, progression-free survival).\u003c/p\u003e\n\u003cp\u003eIn addition, in patients with RAI-avid metastases who received at least 3 cycles of RAIT, differences in treatment response between cycles were compared and the number of cycles/cumulative dose associated with effective treatment (ER-IR) was defined.\u003c/p\u003e\n\u003cp\u003e2. Patient preparation\u003c/p\u003e\n\u003cp\u003eAfter the diagnosis and surgery, thyroid scintigraphy (\u003csup\u003e99m\u003c/sup\u003eTc pertechnetate), neck US and serumTg/TgAb levels were performed for risk stratification before RAI teraphy. Additional scintigraphy/radiological imaging (bone scintigraphy, CT, \u003csup\u003e18\u003c/sup\u003eFDG PET/CT) was performed in the presence of findings suspicious for local/systemic spread. After risk stratification, hypothyroidy was induced (4-week L-T4 withdrawal) or thyrotropin alpha injection was performed to fulfil the TSH \u0026ge; 30 mIU/L criterion in preparation for RAIT. In addition, a two-week low iodine diet was administered to the patients before treatment. \u003c/p\u003e\n\u003cp\u003e3. Disease management\u003c/p\u003e\n\u003cp\u003ePatients received variable doses of RAIT within a mean of 4-6 weeks following the diagnosis of DTC in the light of current guidelines and information at the time of administration. An initial RAI dose of 1.85-8.51 GBq was given for residual ablation or treatment of metastatic disease. Levothyroxine (LT4) was started 48-72 hours after RAI in the patient group classified as high recurrence risk, with the aim of achieving TSH values below 0.1 mU/L. PT-WBS was performed on post-treatment days 7-11 and evaluated in stages by two different nuclear medicine specialists (interpreted by observer 1, crosschecked by observer 1 and 2). \u003c/p\u003e\n\u003cp\u003eDespite changes observed in the literature over time due to the large follow-up and there is no consensus on the treatment cycle/cumulative dose has been reached even today, repeated treatments were performed in cases fulfilling the following criteria, provided that the interval between the two cycles was at least 6 months; i) Patients with RAI-avid PM detected on PT-WBS after the last treatment; ii) Patients with an non-suppressed Tg level\u0026gt; 10 ng/dL and/or continued positive TgAb. \u003c/p\u003e\n\u003cp\u003eRAIT was ceased in cases with the following; i) Those with biochemical, scintigraphy or morphological progression suggestive of non-response to RAIT in repeated treatments (\u0026gt;1 cycle); ii) Patients with PM that lose RAI avidity during follow-up; iii) Patients with ER; iv) The presence of serious adverse effects (restrictive lung disease) or cases reaching a cumulative dose that may lead to an increased risk of major adverse effects. Patients in remission with ER/IR were followed up routinely at 6-12 months intervals. \u003c/p\u003e\n\u003cp\u003eRecurrence was defined in the presence of findings outside the remission criteria during the follow-up (\u0026gt;10 ng/mL serum Tg level, TgAb positivity on the current examination and/or newly developed metastatic lesion on PT-WBS). In the SIR/BIR group, repeated high doses were administered and were evaluated for additional treatment modalities in the presence of treatment discontinuation criteria.\u003c/p\u003e\n\u003cp\u003e4. Statistical analysis\u003c/p\u003e\n\u003cp\u003eThe data were analysed with SPSS version 25 (SPSS Inc. Chicago, IL). Normality was analysed by Shapiro-Wilk tests in the whole group and subcategories. Numerical data are expressed as mean\u0026plusmn;standard deviation and median with interquartile range [IQR], categorical data as number and percentage (depending on whether it has a normal or skewed distribution). \u0026chi;2 and Fisher exact (categories with expected values \u0026lt;5) probability tests were used to analyse categorical variables. The independent two-sample t test and Mann-Whitney U test were used to analyse the relationship between the categorical and numerical data. All factors that statistically defined the efficacy of RAIT and disease status at the end of follow-up in univariate analysis (p\u0026lt;0.05) were evaluated by binary logistic regression in multivariate analysis. Survival was calculated from diagnosis to the date of last follow-up or date of death. Cumulative survival plots were evaluated by Kaplan-Meier method and Log-rank tests were applied to compare differences between groups. The Cox proportional hazard model was used to determine the prognostic factors associated with overall survival (OS). Cochran\u0026apos;s Q test was used to evaluate the difference between categorical variables in repeated measures. The confidence interval for the tests was 95% and the statistical significance level (p) was accepted as 0.05, and the p value, odds ratio (OR) and ratio (HR) were reported.\u003c/p\u003e\n"},{"header":"Results","content":"\u003cp\u003e1. Clinical, pathological and imaging characteristics\u003c/p\u003e \u003cp\u003e68 patients with DTC who fulfilled all inclusion criteria and had PM were evaluated. The patients ranged in age from 19 to 78 years. The mean age was 50.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1 years. Females and males comprised 70.6% and 29.4%, respectively. Older age, absence of regional LN involvement (p:0\u0026thinsp;\u0026lt;\u0026thinsp;0.001), diagnosis of PM during follow-up (p:0.048) and absence of response to treatment (p:0.008) were more common. 82.4% of the cases were PTC, 7.4% were FTC and 10.3% were hurtle cell carcinoma. The most common subtype was the classical variant. Regional LN involvement was higher in patients with PTC (p:\u0026lt;0.001) and soft tissue invasion (p:0.006). PMs were RAI-avid in 52 cases (76,5%) and non-RAI-avid in 16 cases (26,5%). In the RAI-avid group, \u003csup\u003e131\u003c/sup\u003eI uptake was focal in 61.5% and miliary in 38.5%. Descriptive and classifying data were presented in Tables \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Comparing RAI-avid and non-RAI-avid cases, there was a significant association between the non-RAI-avid group and age (p:0.011), PM diagnosis (p:0.003), treatment response (p:0.034) and treatment efficiency (p:0.009). In this group, PMs diagnosed during follow-up, non-response to RAIT and poor prognosis (SIR-BIR) were more frequent. Furthermore, there was a significant relation between focal \u003csup\u003e131\u003c/sup\u003eI uptake and tumor diameter (p:0.021) and \u0026gt;\u0026thinsp;4 cm primary tumor was more common in this group (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1:\u003c/strong\u003e RAI treatment response in terms of biochemical-scintigraphy and structural findings\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.957%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8657%;\"\u003e\n \u003cp\u003eBiochemical and scintigraphy (i)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.13081%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0465%;\"\u003e\n \u003cp\u003eStructural (ii)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.957%;\"\u003e\n \u003cp\u003eComplete Regression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.8657%;\"\u003e\n \u003cp\u003eStimulated Tg\u0026lt;1 ng/dL, negligible TgAb and no abnormal uptake on PT-WBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.13081%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0465%;\"\u003e\n \u003cp\u003eComplete regression of metastatic lesions\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.957%;\"\u003e\n \u003cp\u003ePartial Regression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.8657%;\"\u003e\n \u003cp\u003e\u0026ge;25% decrease in serum Tg value \u0026plusmn; no increase in TgAb titres and/or decrease in disease spread/volume on PT-WBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.13081%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0465%;\"\u003e\n \u003cp\u003e\u0026ge;30% reduction in the diameter of the PMs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.957%;\"\u003e\n \u003cp\u003eStable Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 37.8657%;\"\u003e\n \u003cp\u003eChange in serum Tg, TgAb levels between the values defining regression/progression and/or no significant change observed on PT-WBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.13081%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0465%;\"\u003e\n \u003cp\u003eNo morphological change\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.957%;\"\u003e\n \u003cp\u003eProgressive Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37.8657%;\"\u003e\n \u003cp\u003e\u0026ge;25% increase in serum Tg value \u0026plusmn; development of TgAb positivity/TgAb titres increase and/or increase in disease spread/volume on PT-WBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 4.13081%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 33.0465%;\"\u003e\n \u003cp\u003eAn increase of \u0026ge;20% and/or \u0026ge;5mm in the diameter of the pulmonary lesion(s)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cem\u003ePM: Pulmonary metastases, PT-WBS: Post-treatment whole-body scan\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e: Disease status at the end of follow-up (ATA)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4901%;\"\u003e\n \u003cp\u003eExcellent response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73.5099%;\"\u003e\n \u003cp\u003eNegative imaging and either suppressed Tg\u0026lt;0.2 ng/mL or stimulated Tg\u0026lt;1 ng/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4901%;\"\u003e\n \u003cp\u003eBiochemical incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73.5099%;\"\u003e\n \u003cp\u003eNegative imaging and stimulated Tg \u0026ge; 10 ng/mL or suppressed Tg \u0026ge; 1 ng/mL or rising TgAb levels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4901%;\"\u003e\n \u003cp\u003eStructural incomplete response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73.5099%;\"\u003e\n \u003cp\u003eStructural or functional evidence of disease with any Tg level \u0026plusmn; TgAb positivity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26.4901%;\"\u003e\n \u003cp\u003eIndeterminate response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 73.5099%;\"\u003e\n \u003cp\u003eStimulated Tg\u0026lt; 10 ng/mL or stable/declining TgAb levels in the presence of nonspecific imaging findings in the absence of structural or functional disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\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\u003eDescriptive features \u0026ndash; 1\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubcategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70,6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29,4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58,8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBTT\u0026thinsp;+\u0026thinsp;LND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41,20%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePapillary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82,4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFollicular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7,4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHurtle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10,3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnifocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58,8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultifocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41,2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;4 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35,3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38,2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47,1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52,9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional LN involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary nodul size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76,6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23,4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis of PM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;6 month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRAI avidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003csup\u003e131\u003c/sup\u003eI uptake pattern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiffuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtrapulmonary metastases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRAIT response during follow up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48,5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatue at last follow up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eER-IR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8,9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16,2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSIR-BIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePM: Pulmonary metastasis, STI: Soft tissue invasion, LVI: Lymphovascular invasion, LN: Lymph node, BTT: Bilateral total thyroidectomy, LND: Lymph node dissection, ER: Excellent response, IR: Indetermined response, SIR: Structural incomplete response, BIR: Biochemical incomple trespponse\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eDescriptive features \u0026minus;\u0026thinsp;2\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=\"left\" 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\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian\u0026thinsp;\u0026plusmn;\u0026thinsp;IQR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment cycles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCumulative dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e275\u0026ndash;1600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e800 [438,75]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100\u0026ndash;400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300 [225]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e250\u0026ndash;975\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e500 [425]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSIR-BIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e275\u0026ndash;1600\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e700 [550]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st cycle dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u0026ndash;230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e175 [50]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2st cycle dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150\u0026ndash;200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3rd cycle dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150\u0026ndash;225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst cycle with response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSIR-BIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow up (month)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u0026ndash;204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 [72]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIQR: Interquartile range, ER: Excellent response, IR: Indetermined response, SIR: Structural incomplete response, BIR: Biochemical incomplete response\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eFactors associated with RAI avidity and 131-I uptake pattern\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRAI avidity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003csup\u003e131\u003c/sup\u003eI uptake pattern\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003cp\u003eTumor diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional LN involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtrapulmonary metastasis\u003c/p\u003e \u003cp\u003eDiagnosis of PM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatue at last follow up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePM: Pulmonary metastasis, STI: Soft tissue invasion, LVI: Lymphovascular invasion, LN: Lymph node, those found to be statistically significant are given in bold.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e2.Treatment response and survival\u003c/p\u003e \u003cp\u003eWhen patients were categorised according to the defined response criteria at each treatment cycle and at the end of the follow-up, 35 patients (51.5%) responded to at least one treatment cycle and 17 patients (25%) were in the effective treatment group (ER-IR) at the end of the follow-up. Treatment response was lower in macronodular PM (p: 0.022) and at advanced age (0.008). In poor prognostic (SIR-BIR) group, non-RAI avidity (p: 0.009), PMs diagnosed during follow-up (p: 0.003) and \u0026gt;\u0026thinsp;2 cm primary tumors were more frequent (p: 0.029). Parameters found to be significant in the univariate analysis were evaluated in the multivariate analysis in terms of treatment response and treatment efficacy (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). The independent factors for treatment response were advanced age (p 0.037, OR 1.045 [1.01\u0026ndash;1.09], macronodular metastases (p: 0.024, OR 3.7 [1.19\u0026ndash;11.6]) and non-RAI avidity (p: 0.045, OR 4.5 [1.03\u0026ndash;19.92]). Among the factors evaluated in the multivariate analysis for treatment efficacy, the only independent factor was primary tumor diameter\u0026thinsp;\u0026gt;\u0026thinsp;2 cm (p: 0.009, OR 8 [1.69\u0026ndash;37.67]) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). In univariate and multivariate analyses, there were differences in OS, pulmonary nodule diameter, presence of extrapulmonary metastasis, and age at diagnosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Overall survival was lower in the presence of macronodular metastasis (p:\u0026lt;0.001, HR 3.46 [1.13\u0026ndash;10.6]) and extrapulmonary metastasis (p:0.038, HR 1.06 [1.01\u0026ndash;1.12]) as well as at older age (p:0.003, HR 1.36 [1.54\u0026ndash;8.55]) (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors associated with treatment response and treatment efficiency\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTreatment response\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eStatue at last follow up\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor location\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.029\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional LN involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRAI avidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.045\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-131 uptake pattern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary nodule size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtrapulmonary metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis of PM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eThose found to be statistically significant are given in bold.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors associated with OS\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" 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\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumour location\u003c/p\u003e \u003cp\u003eTumour diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSTI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRAI avidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003csup\u003e131\u003c/sup\u003eI uptake pattern\u003c/p\u003e \u003cp\u003ePulmonary nodule size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtrapulmonary metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis of PM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eThose found to be statistically significant are given in bold.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e3. Effective treatment cycle and cumulative dose\u003c/p\u003e \u003cp\u003eAt the end of the follow-up, all 6 patients with excellent response were included in this category in the first two cycles of treatment and more than two cycles of treatment were not required. Accordingly, we investigated the effective number of cycles/cumulative dose in achieving indeterminate, which constitutes another pillar of the effective treatment group (ER\u0026thinsp;+\u0026thinsp;IR), in patients who received at least 3 cycles of treatment, excluding patients with excellent response in the first 2 cycles. When the cumulative treatment responses of the patients in the 1st, 2nd, and 3rd treatment cycles were compared, no significant change was observed in the 1st and 2nd treatment cycles, i.e. 6.47 GBq and 13.87 GBq cumulative doses, whereas after the 3rd cycle (21.27 GBq cumulative dose), the number of patients in the active treatment group was significantly higher than in the 1st cycle (p:0.016). Only 1 patient responded after \u0026ge;\u0026thinsp;4 cycles and this patient was in the poor prognosis group (SIR-BIR) at endpoint. In other words, there was no patient who responded with 4 or more cycles and was in the effective treatment group (ER-IR).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLung, which is the first organ reached by the lymphatic system, is the most common extralymphatic metastatic organ in DTC patients, as in many other cancer groups [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although DTC is recognised with a good prognosis, the presence of DM is the main cause of cancer-specific mortality [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In consideration of these findings, it is important to identify the presence of DM in patients with DTC, especially in the lung, and to determine the factors that are effective in treatment response and prognosis.\u003c/p\u003e \u003cp\u003eAccordingly, in our study, we aimed to identify the clinical/prognostic factors associated with treatment response/survival in the whole patient group and also in subgroups (RAI avid or non-RAI-avid, miliary or focal) and to determine the effective treatment cycle/cumulative dose in patients with PM-DTC.\u003c/p\u003e \u003cp\u003eConsistent with the literature, the RAI-avid pulmonary group (76.5%) was more predominant [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In non-RAI-avid group, PM diagnosed during follow-up, non-response to RAIT and poor prognosis (SIR-BIR) were more frequent. Wu et al. reported that non-RAI-avidity was higher in advanced age, like our findings [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The diagnosis of PM was made during the follow-up period (\u0026gt;\u0026thinsp;6 months) in 26.5% of the patients. Those were in the older age and non-RAI-avid, similar to previous data [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. At the end of follow-up, effective treatment (ER\u0026thinsp;+\u0026thinsp;IR) was achieved in \u0026frac14; of the cases. In the literature, the findings regarding remission/good treatment response were reported on a wide scale (5.7\u0026ndash;95.2%) due to differences in treatment efficacy (CR\u0026thinsp;+\u0026thinsp;PR, CR\u0026thinsp;+\u0026thinsp;PR\u0026thinsp;+\u0026thinsp;SD, being alive) and factors such as dose/cycle applied in treatment [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, cases with PTC accounted for 82.4% of the group. Regional LN involvement was observed more frequently in patients with PTC than in those with FTC, in agreement with the literature [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Also, the most common extrapulmonary focus was bone [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePulmonary nodule size, age and RAI avidity were the most frequently identified independent risk factors for treatment response [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. As for \u003csup\u003e131\u003c/sup\u003eI uptake pattern, there were publications stating that miliary/diffuse or focal/multifocal involvement were effective factors in response to treatment as well as publications reporting the opposite [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. With our criteria, we evaluated the response to RAIT after the treatment cycles and also at the end of the follow-up. Since there are different approaches and criteria in the literature on this subject and also a strong correlation was observed between both parameters in our study, we thought that it would be more accurate to interpret these findings, which we evaluated separately, together. In our study, advanced age, presence of \u0026gt;\u0026thinsp;2 cm primary tumor, macronodular metastases and non-RAI-avidity were the independent factors found to have a negative effect on response to RAIT and these findings were largely consistent with the literature data.\u003c/p\u003e \u003cp\u003eIn the literature, advanced age and the presence of extrapulmonary metastases were the most reported factors in OS and CSS [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Contrasting results have also been reported for the effect of RAI avidity and \u003csup\u003e131\u003c/sup\u003eI uptake pattern on survival [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In our study, advanced age, presence of extrapulmonary metastases and macronodular PMs were found to be effective independent prognostic factors in OS, but \u003csup\u003e131\u003c/sup\u003eI uptake pattern was not one of them. In addition, RAI avidity, which was found to be one of the effective parameters in treatment response, was not found to be one of the effective independent factors in OS. In line with Zhao et al., regional LN involvement did not have any negative effect on OS in our patient group [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In fact, there was a negative correlation between LN involvement and the presence of extrapulmonary metastasis in our patient group. This finding may be secondary to PM/DM masking the effect of regional LN involvement on survival, or to the high frequency of LN involvement in our group of patients with predominantly PTC, which is not associated with a poor prognosis.\u003c/p\u003e \u003cp\u003eIn sum, the presence of macronodular metastases was an effective independent factor for both response and OS, consistent with the literature, and \u003csup\u003e131\u003c/sup\u003eI uptake pattern, which has been reported with conflicting results in the literature, was an effective independent factor for response only. As it is known, RAI accumulation and response of macronodular metastases to this treatment are observed to be lower than miliary metastases, considering the distance travelled by \u003cem\u003eβ-radiation\u003c/em\u003e in the tissue [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Again, in relation to this finding, there are also publications reporting low response rates (although contradictory findings have been described) to RAIT in pulmonary lesions defined as focal on PT-WBS [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Overall, the \u003csup\u003e131\u003c/sup\u003eI uptake pattern and the pulmonary nodule size parameters can be considered as two important parameters that have an impact on disease progression. However, it should be remembered that both parameters come from an intersection set, considering the significant relationship we observed between them (p:0.004), and also that the \u003csup\u003e131\u003c/sup\u003eI uptake model should be considered with some limitations. At this point, we would like to highlight some important points that may be related to misinterpretation of the \u003csup\u003e131\u003c/sup\u003eI uptake pattern on PT-WBS; i) PMs below scintigraphy resolution, although identified by serum Tg and/or imaging modalities, may be classified as non-RAI-avid; ii) misinterpretation of treatment response/survival is possible in cases with a mixed pattern. It is thought that the miliary pattern and macronodular metastasis in some cases in our group may be explained by these conditions. Although we defined the presence of at least 1 focal uptake as a focal \u003csup\u003e131\u003c/sup\u003eI pattern to ensure uniformity in the evaluation of the \u003csup\u003e131\u003c/sup\u003eI uptake pattern, a change between miliary/focal subgroups was found in 14.7% of cases during follow-up, the significance of which has not been previously reported in the literature. It should be considered that these findings may cause differences in the results between previous studies and the current study in determining the \u003csup\u003e131\u003c/sup\u003eI uptake criterion (scintigraphy and radiological findings were defined as a single parameter in some studies) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In this respect, we conclude that anatomical findings will be more significant than \u003csup\u003e131\u003c/sup\u003eI uptake pattern in evaluating the efficacy of PMs on treatment response/survival in adult patients (different from childhood where miliary pattern is frequently observed), contrary to the report of Cho et al [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRepeated RAIT in RAI-avid patients is highly effective in controlling DTC and is predictive of clinical outcome. However, there is no consensus on the number of treatment cycles and the cumulative dose to be administered. There were a few publications in the literature presenting data on cumulative dose in response to treatment [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In these studies, the evaluation was mainly based on descriptive data. In our study, in the effective treatment group (ER\u0026thinsp;+\u0026thinsp;IR), response rate was 94.1% (16 of 17 patients) in \u0026le;\u0026thinsp;3 treatment cycles and at a cumulative dose of \u0026le;\u0026thinsp;21.27 GBq. In this direction, the descriptive data we reported were largely consistent with the literature. Furthermore, when comparing the cumulative responses after each treatment in our cohort of patients who received at least 3 treatments, no significant change in treatment response was observed in the 1st and 2nd treatment cycles, i.e. 6.47 GBq and 13.87 GBq cumulative doses, whereas after the 3rd cycle (21.27 GBq), the number of patients in the effective treatment group was significantly higher than in the 1st (p:0.016). In this regard, when the patients who achieved ER in \u0026le;\u0026thinsp;2 cycles are excluded, we think that it would be appropriate to apply at least 3 treatment cycles \u0026ndash; 21.27 GBq RAIT to achieve IR, which constitutes another pillar of the good prognostic group, and in cases where no treatment response is observed after the first 3 treatments, the decision of treatment non-response and discontinuation of it could be thougt in accordance with individualised management in the light of clinical/prognostic data.\u003c/p\u003e \u003cp\u003eWe would like to emphasise that our study has several limitations. Firstly, due to the retrospective nature of our study, it may be associated with possible bias in patient selection. Again, it is thought that a larger number of patients may be more meaningful in terms of making the evaluation stronger, especially in subcategories. Another limitation in the patient group, in which the follow-up period is relatively long, is that we could not report and interpret the difference, relationship and effect analyses between Tg values, which constitute an important pillar of disease follow-up, and other parameters, especially due to the changes observed in Tg measurement methods (upper limit, dilution, measurement method).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, advanced age, presence of \u0026gt;\u0026thinsp;2 cm primary tumor, macronodular metastases and non-RAI avidity were found to be effective independent prognostic factors for treatment response in patients with PMs diagnosed with DTC. Also, advanced age, presence of extrapulmonary metastases and macronodular PMs were found to be effective in predicting OS. We thought that, when the patients who achieved ER in \u0026le;\u0026thinsp;2 cycles are excluded, it would be appropriate to apply at least 3 treatment cycles (21.27 GBq) RAIT to achieve IR, which constitutes another pillar of the good prognostic group. In this context, we concluded that even if RAI uptake is observed in pulmonary lesions, in cases where no response is observed after the first 3 treatments, it would be appropriate to reconsider discontinuation of RAIT due to treatment non-response.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor(s\u0026rsquo;) disclosure \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChen DW, Lang BHH, McLeod DSA, Newbold K, Haymart MR. Thyroid cancer. \u003cem\u003eLancet\u003c/em\u003e. 2023;401:1531-44.\u003c/li\u003e\n\u003cli\u003eBoucai L, Zafereo M, Cabanillas ME. Thyroid Cancer: A Review. \u003cem\u003eJAMA\u003c/em\u003e. 2024;331:425-35.\u003c/li\u003e\n\u003cli\u003eHaugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1-133.\u003c/li\u003e\n\u003cli\u003eFugazzola L, Elisei R, Fuhrer D, Jarzab B, Leboulleux S, Newbold K, et al. 2019 European Thyroid Association Guidelines for the Treatment and Follow-Up of Advanced Radioiodine-Refractory Thyroid Cancer. Eur Thyroid J. 2019;8:227-45.\u003c/li\u003e\n\u003cli\u003eLi C, Wu Q, Sun S. Radioactive Iodine Therapy in Patients With Thyroid Carcinoma With Distant Metastases: A SEER-Based Study. Cancer Control. 2020;27. \u003c/li\u003e\n\u003cli\u003eNixon IJ, Whitcher MM, Palmer FL, Tuttle RM, Shaha AR, Shah JP, et al. The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland. Thyroid. 2012;22:884-9.\u003c/li\u003e\n\u003cli\u003eLiu Y, Wang J, Hu X, Pan Z, Xu T, Xu J, et al. Radioiodine therapy in advanced differentiated thyroid cancer: Resistance and overcoming strategy. Drug Resist Updat. 2023;68:100939.\u003c/li\u003e\n\u003cli\u003eGoodsell K, Ermer J, Amjad W, Swisher-McClure S, Wachtel H. External beam radiotherapy for thyroid cancer: Patients, complications, and survival. Am J Surg. 2023;225:994-9.\u003c/li\u003e\n\u003cli\u003eWang H, Shi L, Huang R, Liu B, Tian R. The association between the interval of radioiodine treatment and treatment response, and side effects in patients with lung metastases from differentiated thyroid cancer. Front Endocrinol (Lausanne). 2023;14:1117001.\u003c/li\u003e\n\u003cli\u003eMaciel J, Cavaco D, Silvestre C, Sim\u0026otilde;es Pereira J, Vilar H, Leite V. Clinical outcomes of a cohort of 271 patients with lung metastases from differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2022;97:814-21.\u003c/li\u003e\n\u003cli\u003eWang R, Zhang Y, Tan J, Zhang G, Zhang R, Zheng W, et al. Analysis of radioiodine therapy and prognostic factors of differentiated thyroid cancer patients with pulmonary metastasis: An 8-year retrospective study. Medicine. 2017;96.\u003c/li\u003e\n\u003cli\u003eZhang X, Liu DS, Luan ZS, Zhang F, Liu XH, Zhou W, et al. Efficacy of radioiodine therapy for treating 20 patients with pulmonary metastases from differentiated thyroid cancer and a meta-analysis of the current literature. Clin Transl Oncol. 2018;20:928-35.\u003c/li\u003e\n\u003cli\u003eQutbi M, Shafeie B, Amoui M, Tabeie F, Azizmohammadi Z, Mahmoud-Pashazadeh A, et al. Evaluation of Prognostic Factors Associated With Differentiated Thyroid Carcinoma With Pulmonary Metastasis. Clin Nucl Med. 2016;41:917-21. \u003c/li\u003e\n\u003cli\u003eSohn SY, Kim HI, Kim YN, Kim TH, Kim SW, Chung JH. Prognostic indicators of outcomes in patients with lung metastases from differentiated thyroid carcinoma during long-term follow-up. Clin Endocrinol (Oxf). 2018;88:318-26.\u003c/li\u003e\n\u003cli\u003eCucanic O, Farnsworth RH, Stacker SA. The cellular and molecular mediators of metastasis to the lung. Growth Factors. 2022;40:119-52.\u003c/li\u003e\n\u003cli\u003eWu XY, Li B, Zhang J, Duan LL, Hu BX, Gao YJ. Analysis of the clinical factors affecting excellent response of Iodine-131 treatment for pulmonary metastases from differentiated thyroid cancer. Heliyon. 2023;9:e20853.\u003c/li\u003e\n\u003cli\u003eAkatani N, Wakabayashi H, Kayano D, Inaki A, Takata A, Hiromasa T, et al. Long-term outcomes and prognostic factors of patients with lung metastases from differentiated thyroid cancer after radioiodine therapy in Japan. Endocr J. 2023;70:315-22.\u003c/li\u003e\n\u003cli\u003eSabra MM, Ghossein R, Tuttle RM. Time Course and Predictors of Structural Disease Progression in Pulmonary Metastases Arising from Follicular Cell-Derived Thyroid Cancer. Thyroid. 2016;26:518-24.\u003c/li\u003e\n\u003cli\u003eChopra S, Garg A, Ballal S, Bal CS. Lung metastases from differentiated thyroid carcinoma: prognostic factors related to remission and disease-free survival. Clin Endocrinol (Oxf). 2015;82:445-52.\u003c/li\u003e\n\u003cli\u003eLong B, Yang M, Yang Z, Yi H, Li L. Assessment of radioiodine therapy efficacy for treatment of differentiated thyroid cancer patients with pulmonary metastasis undetected by chest computed tomography. Oncol Lett. 2016;11:965-8. \u003c/li\u003e\n\u003cli\u003eCho SW, Choi HS, Yeom GJ, Lim JA, Moon JH, Park DJ, et al. Long-term prognosis of differentiated thyroid cancer with lung metastasis in Korea and its prognostic factors. Thyroid. 2014;24:277-86.\u003c/li\u003e\n\u003cli\u003eSunny SS, Hephzibah J, Shanthly N, Oommen R, Cherian AJ, Mathew D. Treatment Response following Radioactive Iodine Therapy in Miliary versus Macronodular Pulmonary Metastases in Papillary Thyroid Carcinoma. World J Nucl Med. 2022;21:52-8.\u003c/li\u003e\n\u003cli\u003eChen P, Feng HJ, Ouyang W, Wu JQ, Wang J, Sun YG, Xian JL, et al. RISK FACTORS FOR NONREMISSION AND PROGRESSION-FREE SURVIVAL AFTER I-131 THERAPY IN PATIENTS WITH LUNG METASTASIS FROM DIFFERENTIATED THYROID CANCER: A SINGLE-INSTITUTE, RETROSPECTIVE ANALYSIS IN SOUTHERN CHINA. Endocr Pract. 2016;22:1048-56. doi:10.4158/EP151139.OR\u003c/li\u003e\n\u003cli\u003eRonga G, Filesi M, Montesano T, Di Nicola AD, Pace C, Travascio L, et al. Lung metastases from differentiated thyroid carcinoma. A 40 years\u0026rsquo;experience. Q J Nucl Med Mol Imaging. 2024;48:12-9.\u003c/li\u003e\n\u003cli\u003eZhao H, Liu CH, Cao Y, Zhang LY, Zhao Y, Liu YW, et al. Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis. Front Oncol. 2022;12:990154.\u003c/li\u003e\n\u003cli\u003ePitoia F, Bueno F, Cross G. Long-term survival and low effective cumulative radioiodine doses to achieve remission in patients with 131Iodine-avid lung metastasis from differentiated thyroid cancer. Clin Nucl Med. 2014;39:784-90.\u003c/li\u003e\n\u003cli\u003eDurante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91:2892-9.\u003c/li\u003e\n\u003cli\u003eHuang IC, Chou FF, Liu RT, Tung SC, Chen JF, Kuo MC, et al. Long-term outcomes of distant metastasis from differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2012;76:439-47.\u003c/li\u003e\n\u003cli\u003eWang C, Zhang X, Li H, Li X, Lin Y. Quantitative thyroglobulin response to radioactive iodine treatment in predicting radioactive iodine-refractory thyroid cancer with pulmonary metastasis. PLoS One. 2017;12: e0179664.\u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\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":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Differantiated thyroid cancer, Pulmonary metastases, Radioactive iodine treatment, Cumulative dose","lastPublishedDoi":"10.21203/rs.3.rs-5841558/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5841558/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eOur primary objective in this study was to analyse clinical-prognostic factors, to evaluate their effects on response to RAIT and survival in pulmonary metastatic differantiated thyroid cancer. Another aim was to evaluate the treatment cycles/doses to achive effective treatment at the end of the follow-up.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e68 patients with pulmonary metastatic differentiated thyroid cancer who met all inclusion criteria were included. Clinical-pathological features and imaging findings of patients were collected and analysed retrospectively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAdvanced age (p 0.037, OR 1.045), \u0026gt;\u0026thinsp;2 cm primary tumor (p: 0.009, OR 8), macronodular pulmonary metastases (p: 0.024, OR 3.7) and non-RAI-avidity (p: 0.045, OR 4.5) were independent factors associated with non-response to RAIT. When cumulative RAIT responses in the first 3 cycles were compared, no significant change was observed until the 3rd cycle (up to a cumulative dose of 21.27 GBq). That is, excluding patients who achieved excellent response in \u0026le;\u0026thinsp;2 cycles, it would be appropriate to administer at least 3 cycles (21.27 GBq) to achieve indeterminate resonse, which constitutes another pillar of the good prognostic group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCollectively, it would be appropriate to consider that response and survival to RAIT decreases in advanced age and in the presence of macronodular pulmonary metastases. In addition to this, it was concluded that at least 3 cycles of RAIT (21.27 GBq) may be appropriate in the determination of treatment-resistant cases, in other words, in the determination of cases in which biochemical-structural incomplete response can be obtained during follow-up.\u003c/p\u003e","manuscriptTitle":"Which factors affect treatment success/prognosis in thyroid cancers with pulmonary metastases and what is/how should be the effective cumulative cure/dose as a current approach; A retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 06:36:00","doi":"10.21203/rs.3.rs-5841558/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-04-17T06:48:07+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-14T14:16:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-09T00:14:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Nuclear Medicine","date":"2025-04-08T06:54:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-nuclear-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anme","sideBox":"Learn more about [Annals of Nuclear Medicine](http://link.springer.com/journal/12149)","snPcode":"12149","submissionUrl":"https://www.editorialmanager.com/anme/default2.aspx","title":"Annals of Nuclear Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"77de18d7-6c0f-4071-92c9-9bd009f86503","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T15:59:17+00:00","versionOfRecord":{"articleIdentity":"rs-5841558","link":"https://doi.org/10.1007/s12149-025-02060-5","journal":{"identity":"annals-of-nuclear-medicine","isVorOnly":false,"title":"Annals of Nuclear Medicine"},"publishedOn":"2025-05-19 15:56:57","publishedOnDateReadable":"May 19th, 2025"},"versionCreatedAt":"2025-04-17 06:36:00","video":"","vorDoi":"10.1007/s12149-025-02060-5","vorDoiUrl":"https://doi.org/10.1007/s12149-025-02060-5","workflowStages":[]},"version":"v1","identity":"rs-5841558","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5841558","identity":"rs-5841558","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}