Therapeutic Response And Long-term Outcome Of Differentiated Thyroid Cancer With Pulmonary Metastases Treated By Radioiodine Therapy

Objective:Thyroid cancer(TC)is one of the most common endocrine cancers and differentiated thyroid carcinoma(DTC)accounts for about 90%.The course of DTC in most patients develop slowly,which is approximate benign course and the 10 year survival rate was as high as 85%to 90%.However,the overall survival rate of DTC patients with distant metastasis decreased.Distant metastasis,which occur in 2.2-12.4%of patients with known DTC,among which the lungs are the most frequent sites and account for about 7%of DTC patients.The common treatment of lung metastasis in DTC is I-131 treatment,but the exact curative effect of 1-131 treatment is still controversial.The factors that affect the efficacy of 1-131 in the treatment of DTC lung metastasis are still unclear.The research was designed to explore the therapy response and long-term outcomes of 1-131 treatment for DTC with pulmonary metastasis patients,as well as the association of therapy response assessment and long-term outcomes.Methods:This retrospective study included 151 DTC lung metastasis with 1-131 treatment patients in department of nuclear medicine of our hospital from February 1991 to July 2007.The median ages at diagnosis of DTC and pulmonary metastases were 42(range,6-82 years)and 49(range,11-86 years),respectively.Eighty-six were women and 65 were men(male:female ratio= 1:1.32)and the majority of patients had papillary thyroid cancer(73.5%).Only pulmonary metastases were involved in 124 patients while 27 patients also had distant metastases to other organs.1-131-avid pulmonary metastases were observed in 122 patients and non-I-131-avid pulmonary metastases were found in 29 patients.Of the 151 patients who were diagnosed with lung metastasis,77 patients had a cumulative dose over 530 mCi while the others with doses lower than 19.6 GBq(530 mCi).The median follow-up time was 11.2 years(range,0.4-20.5 years).The therapy response was evaluated by the changes in serum thyroglobulin,anatomical images and the iodine uptake in pulmonary nodules.Based on the radiological images,including WBS and serum Tg levels,the disease status was classified as follows:1)Complete response(CR),no clinical symptoms of lung metastases,no abnormal iodine concentrate of lung in I-131-WBS and other imaging examinations,and Tg negativity(serum Tg levels<1 ng/ml with TSH stimulation);2)Partial response(PR),iodine concentrate of lung reduced in 1-131-WBS and lung metastases nodes were smaller in other imaging examinations,with decreased Tg levels(compared with either TSH inhibition or stimulation).3)No response(NR),no improvement or increased in iodine concentrate of lung and no change or get larger of lung metastases nodes in other imaging examinations,with increased Tg levels.The overall response(OR)was the rate combined CR and PR together.The Chi-square or Fisher’s exact test was used to estimate the differences between groups.A binary logistic regression model was fitted to access which factors contributed to the outcome of I-131 treatment response.Kaplan-Meier survival analysis was applied to evaluate the effect of every potential prognostic variable on survival and the differences between the groups were compared using the log-rank test.Multivariate analysis was performed with a Cox proportional hazards model to assess the relationship between survival time and several variables simultaneously.P<0.05 was considered to indicate a statistically significant difference.Data were analyzed using R software(version 3.2.5;R Foundation for Statistical Computing).Results:After 1-131 treatment,17 patients achieved CR.,71 PR,and 63 NR.The age,node size,iodine-concentrating of lung metastasis,extra metastasis,frequency and cumulative dose of 1-131 treatment were significant for therapy response(P values were<0.001,0.032,<0.001,0.016,0.018,and 0.003,respectively).For all 122 I-131-avid patients,the associations between therapy response and age,extra pulmonary metastasis remained significant(P values were<0.001 and 0.022 respectively)while the other factors not significant any more.The overall survival rate was 72.2%at 5 years,55.2%at 10 years and 51.3%at 15 years.The overall survival rates is consistent with those of a published study in Shanghai of China,but higher than those demonstrated in the studies in western countries and lower than other Asian studies.After adjustment for other factors,age,node size,extra metastasis,frequency and cumulative dose of I-131 treatment were significant(P values were<0.001,0.018,0.007 and 0.002,respectively).Age is proven to be a predictable factor,with risk of NR increasing 6.0%per year.After adjustment for the other three factors list of node size,extra pulmonary metastasis and the frequency of I-131 treatment,the risk of death in patients with DTC lung metastases increased by 6.3%per year.The size of lung lesions(macro-or micro-nodules)was a valuable prognostic factor.Macro-nodular metastases show poor iodine concentrate(14/46,30.4%)and poor survival rate.The long-term outcome between the lung only metastasis patient and extra pulmonary metastases patients was significant(P<0.001).For all 151 patients,frequency of 1-131 treatment reached 5 times or cumulative dose reached 530mCi showed better therapy response and long-term outcome.For all 122 I-131-avid patients,the estimate of Cox’s regression model showed a similar pattern to all 151 DTC patients.There were significant differences(P<0.001)in long-term survival among patients with different therapy response assessment.For all 151 DTC lung metastasis patients,patients with CR assessment had an absolutely better prognosis than PR group,while the poorest prognosis were observed in the NR group,the 15 years OS rate for 17 CR patients was 100%.In contrast,the rate were 72.4%for 71 PR patients and 0%for 63 NR patients.As to the 122 I-131-avid patients,the similar pattern was observed.Conclusions:1-131 therapy is a feasible and effective treatment for DTC lung metastases.The older and non-I-131-avid patients were more likely no response to the 1-131 treatment,and greater benefits could be achieved by the 1-131-avid patients who fulfill the treatment.Long-term outcome was related to age,node size,extra metastasis,and the frequency of iodine treatment.The predictive power of therapy response on long-term prognosis was favorable.