Analysis Of Risk Factors And The Effect Of ¹³¹I Therapy Of Lung Metastases In Patients With Differentiated Thyroid Carcinoma

Part 1 Analysis of risk factors of lung metastases in patients with differentiated thyroid carcinomaObjectiveBe aimed to analyze risk factors for lung metastasis in patients with differentiated thyroid carcinoma (DTC) for early diagnosis, treatment and follow-up.Materials and MethodsWe performed a retrospective review of patients with DTC (n=222) who were treated in our department from April 2013 to December 2013, including 37 cases of lung metastases, lung metastases were diagnosed by 131Ⅰ whole body scan, Tg> 2μg/l, PET/CT, chest X-ray, CT or histopathology of pulmonary nodules. Patients pathologically confirmed DTC after thyroidectomy according to the NCCN guidelines for thyroid cancer were included, with the exclusion of other distant metastasis and lung metastasis of unknown origin, and finally 199 cases were performed. All patients included age, gender, primary tumor pathological data [type, maximum diameter of the lesion, single or multiple lesions, thyroid capsular invasion, extrathyroidal extension, vascular thrombosis, thyroid associated disease(for example, nodular goiter, Hashimoto’s thyroiditis and simple goiter), the number of cervical lymph node metastasis, mediastinal lymph node metastasis], using SPSS 13.0 software for data χ2 test,t test, and logistic regression analysis, filtering out risk factors of lung metastases in patients with DTC, using SPSS 13.0 software for data χ2 test,t test, and logistic regression analysis, filtering out risk factors of lung metastases in patients with DTC.Results199 cases of patients, male 56 cases, female 143 cases (male:female=1:2.6), aged 6 to 83 years, mean (41.1±13.6) years old, there were 29 cases with lung metastasis,184 cases with papillary thyroid carcinoma,15 cases with follicular thyroid cancer. By Pearson’s chi-square test, gender, primary tumor type, maximum diameter, multifocal, thyroid capsular invasion, extrathyroidal extension, mediastinal lymph node metastasis and the number of cervical lymph node metastasis were significant factors(x2=4.106,5.045,31.452,16.516,18.503,31.774,21.997,25.728, respectively and all P<0.05), unexpectedly, age, thyroid associated disease and thrombosis were not significantly correlated with lung metastasis(x2=0.436,4.831,0.105, respectively and all.P>0.05). On multivariate logistic regression, primary tumor maximum diameter greater than 20 mm [odds ratio (OR),4.574,8.841; P=0.050], multifocal (OR,7.894; P=0.016), thyroid capsular invasion (OR,4.940; P=0.018), more than 10 involved lymph node metastasis (OR,11.303; P=0.034) and mediastinal lymph node metastasis (OR,5.121; P=0.021) denoted risks of lung metastasis.ConclutionDTC patients with maximum diameter greater than 20mm, multifocal, thyroid capsular invasion, mediastinal lymph node metastasis and the number of cervical lymph node metastasis more than 10 were higher risk for lung metastasis. Therefore, physicians should carefully read the patients information, especially the pathology report, if the presence of these risk factors, the relevant examination should be performed, such as CT, 18F-FDG imaging and so on.Part 2 The evaluation of effect and analyse of influencing factors of 131Ⅰ therapy in lung metastases of differentiated thyroid carcinomaObjectiveBe aimed to analyze evaluate the efficacy and influencing factors of 131Ⅰ therapy for lung metastases of DTC.Materials and MethodsWe performed a retrospective review of patients with DTC (n=850) who were treated in our department from October 2008 to October 2014, including 101 cases of lung metastases. Patients pathologically confirmed DTC and diagnosed pulmonary metastasis were included by 131Ⅰ whole body scan, Tg> 2μg/l, PET/CT, chest X-ray, CT or histopathology of pulmonary nodules, and the exclusions were that lung metastases origin was not clear (associated with other cancers, lung primary cancer and so on), lung uptake of false positives in 131Ⅰ-WBS, such as bronchiectasis, pulmonary aspergilloma and pneumonia, and TgAb was positive. All patients included the diagnosed age, gender, surgical method, the interval time from postoperative to the first 131Ⅰ therapy, sTg and sTg/TSH before 131Ⅰ therapy, primary tumor pathological data [type, maximum diameter of the lesion, single or multiple lesions, thyroid capsular invasion, extrathyroidal extension, vascular thrombosis, thyroid associated disease(for example, nodular goiter, Hashimoto’s thyroiditis and simple goiter), cervical lymph node metastasis, mediastinal lymph node metastasis], other distant metastasis, MACIS score [a score of 3.1 (if age<39 years old) or 0.08 x age (if age≥40 years old),+0.3×tumor size (in cm),+1 (if incompletely resected), +1 (if locally invasive), and+3 (if distant metastases present)], pulmonary metastasis characteristics such as size,131Ⅰ uptake. Using SPSS 13.0 software and receiver operating characteristic curve(ROC) to assess predictive value of sTg, sTg/TSH ratio for the efficacy of lung metastases in patients with DTC after 131Ⅰ therapy, respectively, compare their area under the ROC curve (AUC), and take the cutoff level of sTg, sTg/TSH ratio, MACIS score.χ2 test,t test, and logistic regression analysis to filter out the factors for the efficacy of lung metastases in patients with DTC after 131Ⅰ therapy.Results101 cases of patients,35 males and 66 females (M:F=1:1.9), the diagnosed aged 6 to 80 years, mean (42.9±17.0) years. Among the patients, with cumulative doses of 131Ⅰ 275-2241mci, treatment times 2 to 10 times, follow-up from 3 to 78 months, mean (32.7±21.2) months,15 were clinically cured (14.9%),46 were improved (45.5%),20 were steady (19.8%) and 20 (19.8%) were progressed, and 61(60.4%) patients showed a good prognosis and 40 (39.6%) showed a poor prognosis at last follow-up. sTg, sTg/TSH and MACIS score AUC values respectively were 0.666,0.675,0.887, with efficacy prediction cut-off for lung metastases with DTC respectively were 53.25,3.74,8.52. Univariate analysis showed the diagnosed age, primary tumor size, extrathyroidal extension, MACIS score, sTg/TSH, sTg and lung nodule size, iodine-131 uptake were significant factors(all P<0.05), but sex, primary tumor type, multifocal, thyroid capsule invasion, thyroid associated disease, thrombus, mediastinal lymph node metastasis and lymph node metastasis were no significant difference (all P>0.05). On multivariate logistic regression, age, primary tumor size, size and 131Ⅰ uptake of lung lesions were statistically difference (all P<0.05).ConclutionIn summary,131Ⅰ treatment is an effective method for pulmonary metastasis with DTC, impacted by many factors. Patients with older diagnosed age, sTg≥53.25, sTg/ TSH≥3.74, MACIS score≥8.52, the primary size more than 4cm with extrathyroidal extension, lung nodules and no or poor 131Ⅰ uptake suggested poor efficacy, what’s the more, age, primary tumor size, 131Ⅰ uptake and size of lung lesions were independent factors affecting the efficacy for pulmonary metastasis with DTC.Part 3 Effect of 131I therapy on pulmonary function, peripheral blood and salivary gland function from pulmonary metastases with differentiated thyroid cancerObjectiveAssessment the safety of 131Ⅰ therapy lung metastases with DTC from peripheral blood, lung function and salivary gland, for better understanding of the risks of radioactive iodine therapy (RIT) to better treatment and management of acute and chronic side effects.Materials and MethodsSection 1:We observed pulmonary function of DTC patients with lung metastases who were treated in our department from October 2008 to October 2014 by pulmonary function test, according to the inclusion criteria:diagnosed lung metastases; no history of smoking or no smoking at least six months, and the exclusion criteria:previous history of any acute or chronic respiratory diseases; lung function during treatment were not monitored. By inclusion and exclusion criteria, a total of 63 cases of DTC lung metastases were enrolled, including 23 males and 40 females, aged 13 to 72 years, mean age (38.84±14.74) years. At the end of follow-up the cumulative dose of 131Ⅰ was 100-1905mci, and treatment times of 2 to 9 times. Using SPSS 13.0 software for before and after 6 months of the last treatment, three different groups of different 131Ⅰ cumulative dose of pulmonary function testing indicators, including FVC, FEV1, FEV1/FVC, FEF25-75%, FEF50% and FEF75% were analysis by paired t-test and ANOVA. P<0.05 was considered statistically significant.Section 2:We performed a retrospective review of patients treated in lung metastases with DTC (n=78) who were treated in our department from October 2008 to October 2014, with the exclusion of the ones with drug treatment to increase WBC before 131Ⅰ treatment, anomalous peripheral blood, recent infection and DTC with bone metastasis. By inclusion and exclusion criteria, a total of 78 cases of DTC lung metastases were enrolled, including 26 males and 52 females, aged 6 to 80 years, mean age (39.75±17.29) years. At the end of follow-up the cumulative dose of 131Ⅰwas 150-1740mci, and treatment times of 2 to 7 times. The levels of white blood cells(WBC), lymphocytes(LY), neutrophils(NE), red blood cell (RBC), hemoglobin (Hb) and platelet (PLT) were measured by automatic hemocyte analyzer in all enrolled patients before 131Ⅰ therapy,6 month after the last 131Ⅰ therapy. SPSS 13.0 software for before and after treatment, three different groups of different 131Ⅰ cumulative dose of peripheral blood, including WBC, LY, GR, RBC, Hb and PLT were analysis by paired t-test and ANOVA. P<0.05 was considered statistically significant.Section 3:We observed salivary gland of DTC patients with lung metastases who were treated in our department from October 2008 to October 2014, according to the inclusion criteria:diagnosed lung metastases of DTC, and the exclusion criteria:no history of external radiotherapy, diabetes, Sjogren’s syndrome; no long-term using of anti-cholinergic, anti-anxiety drug history and other relevant impact of dry mouth during treatment and six months after treatment. By inclusion and exclusion criteria, a total of 101 cases of DTC lung metastases were enrolled, including 35 males and 66 females (M:F=1:1.9), the diagnosed aged 6 to 80 years, mean (42.9±17.0) years.Among the patients, with cumulative doses of 131Ⅰ 275-2241mci, treatment times 2 to 10 times. Performed 99mTcO4- salivary gland scintigraphy, drew regions of interest glands, and finally got the parotid and submandibular glands time-activity curve and functional parameters:uptake index (UI), maximum gland secretion rate (SR) after acid stimulation gland. Using SPSS 13.0 software for three different groups of different 131Ⅰ cumulative dose of including UI and SR of bilateral parotid and submandibular glands were analysis by ANOVA. P<0.05 was considered statistically significant.ResultsNot found radiation pneumonitis or pulmonary fibrosis during follow-up. Pulmonary function testing indicators, including FVC, FEV1, FEV1/FVC, FEF25-75%, FEF50% and FEF75% before 131Ⅰ treatment and 6 months after the last treatment, were not statistically significant (all P> 0.05), so were in the three groups of different 131Ⅰ cumulative dose (all P> 0.05).19.2%(15/78) of patients’ peripheral blood were lower than normal level after 131Ⅰ therapy, most of them returned to normal in the short term, and only 1.3%(1/78) of patients encountered long-term bone marrow suppression.WBC, LY, GR and PLT before 131Ⅰ treatment and 6 months after the last treatment, were statistically significant (all P<0.05), however, RBC and Hb were not statistically significant (both P>0.05). LY, GR among the three groups of different 131Ⅰ cumulative dose was statistically significant (both P<0.05), however, WBC, RBC, Hb and PLT were no significant difference (all P>0.05).20% of patients encountered acute sialadenitis, including 11 cases of parotid gland swelling and pain, seven cases of dry mouth, two cases of altered taste, etc, and 3.0% (3/101) of chronic sialadenitis. SR, UI of bilateral parotid among the three groups of different 131Ⅰ cumulative dose were statistically significant (both P<0.05), however, SR, UI of bilateral submandibular glands were not statistically significant (both P>0.05).ConclutionIn summary,131Ⅰ treatment in pulmonary metastasis of DTC had no influence on lung function, had definite influence on peripheral blood, especially WBC, and salivary glands, with a positive correlation with cumulative dose of 131Ⅰ. If 131Ⅰ cumulative dose reaches a certain level, serious bone marrow suppression, salivary gland damage may occur, although rare, can’t be ignored.