1.Preliminary study of 131I adjuvant therapy in BRAF V600E mutant patients with non-distant metastatic papillary thyroid cancer
Juanjuan SONG ; Zhuanzhuan MU ; Tao LU ; Xin ZHANG ; Yansong LIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(4):212-217
Objective:To evaluate 131I adjuvant therapy in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutant patients with non-distant metastatic papillary thyroid cancer (PTC). Methods:From January 2008 to January 2019, a total of 181 PTC patients (65 males, 116 females, age: (38.9±11.8) years) with non-distant metastases from Peking Union Medical College Hospital were retrospectively enrolled. All patients received only one time 131I therapy with complete clinicopathological information, data of follow-up (median time: 63 months) and assessment of response to therapy. Patients were divided into mutant and wild type group in terms of BRAF V600E status or ablation group (1.1 GBq) and adjuvant therapy group (3.7-5.5 GBq) in terms of different 131I dosage. Clinicopathological features and the response to therapy were compared between different groups by using independent-sample t test, Mann-Whitney U test and χ2 test. Results:The levels of preablative stimulated thyroglobulin (ps-Tg) in the BRAF V600E mutant type group ( n=150) was significantly higher than that in the wild type group ( n=31; 6.32(0.90, 8.70) vs 3.92(0.40, 4.40) μg/L; z=-2.413, P=0.016), however, there were no significant differences in other clinicopathological characteristics (including age, sex, tumor size, multifocality, capsule invasion and N staging) between the two groups ( t=-0.663, z=-1.151, χ2 values: 0.003-1.491, all P>0.05) and the therapeutic response was also not different between the two groups( χ2=1.094, P=0.778). Of 81 patients who received 131I adjuvant therapy, the ps-Tg level of BRAF V600E mutant type group ( n=69) was higher than that of the wild type group( n=12; 8.70(1.30, 11.80) vs 3.40(0.30, 4.50) μg/L; z=-2.194, P=0.028), while the therapeutic response was not different between the two groups ( χ2=1.792, P=0.617). Compared with BRAF V600E mutant patients received 131I ablation ( n=81), BRAF V600E mutant patients received 131I adjuvant therapy ( n=69) had larger tumors (1.52(0.95, 2.00) vs 1.21(0.60, 1.50) cm; z=-2.728, P=0.006), more advanced N staging ( χ2=11.460, P=0.003) and higher ps-Tg level (8.70(1.30, 11.80) vs 4.34(0.50, 5.30) μg/L; z=-3.314, P=0.001), but the therapeutic response was not different between the two groups ( χ2=6.478, P=0.091). Conclusion:131I adjuvant therapy may improve the longer-term response to therapy in BRAF V600E mutant PTC patients with lager tumors, more advanced N staging and higher ps-Tg level.
2.Serum thyroglobulin in evaluating the response to 131I treatment in patients with distant metastatic differentiated thyroid cancer
Zhuanzhuan MU ; Jierui LIU ; Tao LU ; Libo CHEN ; Yansong LIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2020;40(6):329-333
Objective:To explore the significance of serum thyroglobulin (Tg) in the decision-making of response to 131I therapy and subsequent treatment for distant metastatic differentiated thyroid cancer (DM-DTC). Methods:Between January 2018 and December 2019, a total of 62 papillary thyroid cancer (PTC) patients (20 males and 42 females, age: (38.1±15.9) years) with pulmonary metastasis from Peking Union Medical College Hospital were retrospectively analyzed. Patients were divided into two groups (non-radioactive iodine (RAI)-avid group and RAI-avid group) according to the post-treatment whole body scan (Rx-WBS). The serum Tg response to 131I therapy including Tg change and Tg change speed was compared between two groups, and the relationship between serum Tg change speed and structural progression was explored by binary logistic regression analysis. The Tg response to different treatment schemes ( 131I treatment or follow-up) was compared in non-RAI-avid group. χ2 test and Mann-Whitney U test were used to compare data between different groups. Receiver operating characteristic (ROC) curve analysis was used to find the best threshold of Tg change speed to predict the structural progress. Results:After 131I treatment, increased Tg level was found in 60.0% (15/25) patients in non-RAI-avid group ( n=25), while only 21.6%(8/37) patients in RAI-avid group ( n=37; χ2=9.417, P=0.002). Non-RAI-avid group showed an overall increased Tg trend, with a speed of 0.05(-0.16, 0.15) μg·L -1·month -1, while RAI-avid group showed a general decreased Tg trend, with a speed of -0.18(-1.95, 0.01) μg·L -1·month -1 ( U=265.000, P=0.005). A significant correlation between Tg change speed and structural response (odds ratio ( OR)=53.005, P<0.001) was found. When Tg change speed was more than 0.135 μg·L -1·month -1, structural progression could be well predicted with the sensitivity of 87.5% and specificity of 97.1%. In comparison to non-RAI-avid patients with merely follow-up, further 131I treatment for such patients did not yield significant benefit in terms of Tg change and Tg change speed ( χ2=0.071, U=394.000; both P>0.05). Conclusions:The serum Tg monitoring can be more sensitive in evaluating the therapeutic response to 131I for DM-DTC patients in whom response evaluation criteria in solid tumors (RECIST) might not be sensitive enough to reflect the minor change. For patients with non-RAI-avidity, Tg evaluation will offer more sensitive evidence to tailor the necessity of further 131I treatment.
3.Recombinant human thyroid-stimulating hormone for post-operative assessment in patients with low- to intermediate-risk differentiated thyroid cancer: results of phase Ⅰ study
Yansong LIN ; Hui YANG ; Xiaoyi LI ; Liqing WU ; Bin ZHANG ; Yingqiang ZHANG ; Kai CHEN ; Zhuanzhuan MU ; Jianmin JIA ; Na NIU ; Di SUN ; Xin ZHANG ; Baoxia HE
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(2):84-89
Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.
4.Serologically biochemical evaluation for patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid cancer treated by apatinib
Yuqing SUN ; Zhuanzhuan MU ; Xing WEI ; Xin ZHANG ; Xiang WANG ; Yansong LIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(11):644-649
Objective:To analyze the relationship between serologically biochemical response and the disease progression trend and prognosis evaluated by traditional structural imaging in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated by apatinib.Methods:A retrospective study was performed on apatinib-treated (phase Ⅱ) patients ( n=19; 9 males, 10 females; age 46.0 (41.0, 57.5) years) with locally advanced/metastatic RAIR-DTC in Peking Union Medical College Hospital from March 2016 to June 2022. The relationships between serum thyroglobulin (Tg) and response evaluation criteria in solid tumors (RECIST) 1.1 structural imaging efficacy evaluation and disease progression trend were analyzed. The relationships between change of Tg after dose adjustment and the change of maximum diameter of target lesions in structure imaging were also discussed. Mann-Whitney U test and Wilcoxon signed-rank test were used to analyze the data. Results:During the median 49.41 months follow-up, the baseline Tg was 363.20(13.08, 2 490.50) μg/L. The Tg time-to-response was 0.47(0.47, 0.98) months, which was 1.80 (1.30, 1.90) months for RECIST 1.1. After 2, 4 and 8 weeks of initial treatment, the median Tg of the whole cohort decreased by 38.68%, 64.70% and 78.94%, respectively. After 8 weeks, the reducing degree of maximum diameter of target lesions was 33.48%. According to the best response, patients were divided into two groups: partial response (PR) group ( n=15) and stable disease (SD) group ( n=4). The median decreasing degree of Tg in PR group and that in SD group were 87.00% and 28.79%, and the reducing degree of maximum diameter of target lesions in corresponding groups were 45.00% and 21.22%. According to the final efficacy evaluation, patients were further divided into two groups: progressive disease (PD) group ( n=13) and non-PD (including PR and SD) group ( n=5). The median increasing degree of Tg in PD group was higher than that in non-PD group (381.55% vs 175.43%; U=10.00, P=0.037). The increasing degree of Tg and that of the maximum diameter of target lesions were 167.31% and 2.14% after the 1st adjustment, which were 231.06% and 9.73% after the 2nd adjustment. The differences of changes in Tg and maximum diameter of target lesions before and after the 1st dose adjustment were statistically significant ( z values: -3.06 and -2.23, P values: 0.002 and 0.026). Conclusion:During the apatinib treatment of RAIR-DTC, Tg can reflect the therapeutic effect of apatinib earlier than traditional imaging (RECIST 1.1), indicating the disease progression trend more sensitively.
5.Effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer evaluated as indeterminate response after surgery
Ningning ZHAO ; Zhuanzhuan MU ; Wenting GUO ; Xing WEI ; Yansong LIN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(12):736-740
Objective:To investigate the effect of 131I therapy on the clinical outcome of patients with differentiated thyroid cancer (DTC) who were evaluated as indeterminate response (IDR) after surgery and before 131I therapy. Methods:A total of 281 DTC patients (89 males, 192 females, age (38.4±10.2)years ) assessed as IDR before 131I therapy and after total or near-total thyroidectomy in the Department of Nuclear Medicine of Peking Union Medical College Hospital from April 2009 to March 2022 were retrospectively analyzed. Patients were divided into 131I therapy group ( 131I group) and just thyroid stimulating hormone (TSH) suppressive therapy group (TSH group) according to whether receiving 131I therapy, and the efficacies of two groups at the end of follow-up were compared. Subgroup analysis was conducted in different risk stratifications (low-risk, moderate-risk and high-risk), positive thyroglobulin antibody (TgAb) group (TgAb≥115 kU/L) and negative TgAb group (TgAb<115 kU/L). For patients with positive TgAb, the duration and rate for TgAb declining to negative level under the 2 regimens were compared. Independent-sample t test, Mann-Whitney U test, χ2 test and Fisher exact test were performed to compare the differences between groups. Results:Median follow-up time was 39(6-146) months. There was no statistical difference between patients in 131I group and TSH group in baseline characteristics, and the efficacies at the end of follow-up was similar between the 2 groups ( χ2=6.50, P=0.075). For low-, moderate- and high-risk stratification, there were also no statistical differences of response to 2 regimens ( P=0.221; χ2=4.21, P=0.223; χ2=3.01, P=0.274). Similar results were showed for patients with positive and negative TgAb ( n=50, n=231; χ2=4.02, P=0.242; χ2=3.14, P=0.341). For patients with positive TgAb, the duration and rate for TgAb declining to negative level were not statistically different either between 2 regimens (71.0%(22/31) vs 14/19, χ2=0.04, P=0.836; 7.0(5.0, 9.3) vs 7.0(5.0, 7.3) months, z=-0.89, P=0.375). Conclusion:For DTC patients assessed as IDR after surgery, 131I therapy may not provide more benefit than follow-up with TSH suppressive therapy.