Evaluation Of Short-term Efficacy And Safety Of Anlotinib Hydrochloride In The Treatment Of Iodine-resistant Differentiated Thyroid Cancer

Background&objective:Thyroid cancer is the most common malignant tumor of endocrine system,of which differentiated thyroid cancer（DTC）accounts for the majority.DTC cancer cells are well differentiated.After surgical resection and postoperative ¹³¹I treatment,the prognosis of patients is good.A small number of DTC cancer cells undergo dedifferentiation,the ability to absorb iodine is reduced,and the effect of radioiodine therapy is not good.They progress to iodine-refractory differentiated thyroid cancer（RAIR-DTC）,and the prognosis of RAIR-DTC patients is poor,which has become a difficult and hot spot in clinical diagnosis and treatment.A variety of molecular targeted drugs have been proved to have clinical effects on RAIR-DTC,such as sorafenib,vandetanib,lenvatinib,etc.However,in their long-term clinical application,their slow effect and serious drug-related adverse events have significantly limited their clinical application to a certain extent.Anlotinib hydrochloride is a multi-target molecular targeted drug independently developed in China.It is used in the first-line and second-line treatment of various advanced tumors,such as medullary thyroid carcinoma and renal cell carcinoma,and shows good efficacy and safety.There are few studies on the efficacy and safety evaluation of RAIR-DTC.The purpose of this study is to report the early efficacy and safety evaluation of the targeted drug,anlotinib hydrochloride,with independent intellectual property rights,on RAIR-DTC.Methods:From September 2021 to September 2022,18 patients with RAIR-DTC who were treated with anlotinib（12 mg,once a day,oral）in the East Hospital of Qingdao Municipal Hospital were collected.Thyroglobulin（Tg）was re-examined every 3 weeks,CT was re-examined every 3 weeks,and target lesions（TL）were monitored.The curative effect was evaluated according to the changes of Tg level and imaging changes of serological tumor markers of thyroid cancer（response evaluation criteria in solid tumors,RECIST1.1）.The safety was initially evaluated according to the incidence and severity of adverse events（AEs）after drug treatment.Before treatment,the patient underwent PET/CT examination to obtain TL metabolic indicators（maximum standardized uptake value（SUVmax）,average standardized uptake value（SUVmean）,tumor metabolic volume（MTV）,total glycolysis（TLG））,which were included in the study variables for univariate analysis.Tg was used as the efficacy evaluation standard to observe whether there was a correlation between TL’s PET/CT metabolic indicators and the decline ratio of Tg.Before and after treatment,SPECT iodine whole-body imaging was performed to obtain the iodine uptake of TL,and the iodine uptake of TL was observed before and after treatment.Results:The level of Tg in 17 of the 18 patients decreased after one course of treatment.After three courses of treatment,the average decrease of Tg from baseline reached 74.8%,reaching the standard of"biochemical partial remission".Fifteen patients had 38 TLs in total.After five courses of treatment,the average reduction rate from baseline was 31.5%,66.7%（10/15）of patients reached partial response（PR）,33.3%（5/15）of patients reached stable disease（SD）,and the objective response rate and disease control rate reached 66.7%（10/15）and100%（15/15）respectively.According to the results of changes in serological and imaging indicators,50.0%（9/18）of patients met the PR standard,44.4%（8/18）of patients met the SD standard,and the objective remission rate and disease control rate were 50%（9/18）and 94.4%（17/18）,respectively.After three courses of treatment,the average decrease rate of Tg in the high metabolism group was significantly higher than that in the low metabolism group（73.63%vs 16.11%,χ²=4.860,ν=1,P=0.027<0.05）。Single factor analysis showed that TL SUVmean was correlated with the decrease of Tg（r=0.531,P=0.023）,while other metabolic indicators（TLG,MTV）of PET/CT were not significantly correlated with the decrease of Tg.The comparison results of iodine whole-body imaging before and after treatment showed that there was no significant increase in iodine uptake in TL after 3 courses of treatment.The AEs in the treatment process of the patients with drugs mainly include hand-food-skin reaction（HFSR）,diarrhea and hypertension,accounting for 55.6%（10/18）,33.3%（6/18）and 33.3%（6/18）respectively.Conclusion:Anlotinib hydrochloride can be safely used in the treatment of RAIR-DTC,and its curative effect is confirmed by the serology of three courses of treatment and imaging after five courses of treatment.The objective remission rate and disease control rate of patients are high.PET/CT metabolic parameters（SUVmax and SUVmean）may become the indicators for the preliminary evaluation of the efficacy of the patients with RAIR-DTC after the treatment of anlotinib.