Estimation Of Bone Marrow Absorbed Dose,Guided And Analyzed ¹³¹I Treatment Of Differentiated Thyroid Cancer

Purpose: The aim of the study was to evaluate the methodology of radio-iodine(¹³¹I)bone marrow absorbed dose estimation,to explore the feasibility of personalized guidance for 131 I therapy of differentiated thyroid carcinoma?DTC?patients and to analyze the efficacy of 131 I therapy for thyroid ablation guided by 131 I bone marrow absorbed dose estimation.Methods:1 A total of sixty-six DTC patients after surgical thyroid resection?21males,45 females,age range: 24 y to70y,average age: 46.89±12.07y?were enrolled from March 2014 to December 2015 in this prospective study.2 All DTC patients did not take or stoped taking thyroid hormone drugs for 3⁴ weeks after operation.Their thyroid stimulating hormone?TSH?was greater than 30mU/L.Low iodine diet was for at least 1² weeks.Avoid using iodine contrast agents and drugs.Measure the index of T3,T4,TSH,Tg,TgAb,blood routine examination,liver and kidney function,neck ultrasonography,electrocardiogram,chest X-ray or CT examination.3 Five consecutive whole-body planar images at 2,4,6,8,24 h and a two-field-of-view hybrid SPECT/CT images at 4h were acquired after trace activity of ¹³¹I?185MBq,5mCi?administration.Automatic extract volume of interest?VOI?of bone marrow by Dosimetry Toolkit software?GE company?,and calculate time distribution,retention time and other pharmacokinetic information of 131 I in bone marrow,at the same time remove the effect of high131 I uptaking organs' VOI such as the thyroid,stomach and bladder.The maximum tolerated 131 I activity in bone marrow was calculated using 2 Gy as a threshold.The 131 I treatment activity was individual modified within the scope of empiric 131 I treatment guidelines for each patient,according to pre-therapeutic results of bone marrow absorbed dose estimation and clinicalcharacteristics of patients.4 Monitor patients with the index of T3,T4,TSH,Tg,Tg Ab,blood routine examination,liver and kidney function,neck ultrasonography,131 I Dx-WBS,et al.5 The criteria for successful remnant ablation: at 4 months?±1 month?after 131 I treatment,diagnostic whole body scan?Dx-WBS?showed that the thyroid bed had no radioactivity concentration or stimulus-induced Tg < 1ng/ml.6 Analyze the factors influencing the efficacy of thyroid ablation,such as gender,age,clinical stage,mode of operation,Tg level,the ratio D of residual thyroid bed radioactivity counts and mediastinal radioactivity,the treatment dosage,pre-therapeutic TSH value,the time between 131 I treatment and operation.7 Statistical analyses were performed by SPSS 21.0.All measurement data were expressed by Mean ± SD and paired sample t-test or paired samples Wilcoxon signed-rank test or Mann-Whitney U test or Kruskal-Wallis H test were used to analyze the data.Count data were analyzed using chi-square test or Fisher exact probability method.P value of less than 0.05 was considered statistically significant.Results:1 Of 66 patiens,the follow-up data of 56 patients?16 males,40 females,age range: 24 y to70y,average age: 46.02±11.58y?were complete.And the rate of missed follow-up was 15.15%?10/66?.56 cases were papillary thyroid carcinoma.54 patients were with total resection or subtotal thyroidectomy and2 cases were with thyroid lobectomy plus isthmus resection.2 Of 56 patients who used pre-therapeutic 131 I bone marrow absorbed dose estimation,131 I “effective doses” per unit dose of bone marrow was2.48E-02±1.46E-02mSv/MBq?0.69E-02⁷.13E-02mSv/MBq?,131 I bone marrow absorbed dose per unit dose was 2.07E-04±1.21E-04Gy/MBq?0.58E-04⁵.94E-04Gy/MBq?,the corresponding 131 I maximum tolerated activity was 13.07±7.03GBq?3.37³4.56GBq?[ 353.14±190.09mCi?91.00⁹34.00mCi?].3 Of 56 patients,the 131 I treatment dose was 4.06±0.99GBq?2.96⁷.40GBq?[109.82±26.66mCi?80²00mCi?].The 131 I treatment doses of 11 patients increased by 59.09%±20.23%?50%¹00%?than the fixed empiric dose 3.70GBq?100mCi?within the scope of empiric 131 I treatment guidelines,according to pre-therapeutic results of bone marrow absorbed dose estimation,including 9 patients with 131 I treatment dose up to 5.55GBq?150mCi?,the other 2 patients with 131 I treatment dose up to 7.40GBq?200mCi?.The 131 I treatment doses of 6 patients decreased by 20% than the fixed empiric dose 3.70GBq?100mCi?and their treatment doses were reduced to 2.96GBq?80mCi?,including 5 patients with therapeutic doses according to the clinical characteristics,the other 1 patient according to pre-therapeutic results of bone marrow absorbed dose estimation[this patient's maximum tolerated activity was 3.37GBq?91mCi?].39 patients were treated with fixed empiric dose 3.70GBq?100mCi?.Of 56 patients,the maximum tolerated activity of 11 patients whose treatment doses were increased was 16.33±5.87GBq?8.77²7.79 GBq,237⁷51mCi?.The maximum tolerated activity of 6 patients whose treatment doses were decreased was 10.44±7.38GBq?3.37²1.61 GBq,91⁵84mCi?.The maximum tolerated activity of 39 patients whose treatment dose were fixed empiric dose was 12.55±7.13GBq?4.22³4.56 GBq,114⁹34mCi?.4 Of 56 patients,the white blood cell counts at 1 month?±1 week?and 4months?±1 month?after 131 I treatment were lower than that pre-therapy,and the difference was statistically significant?Z=-4.495,P=0.000;Z=-3.573,P=0.000?.The red blood cell counts at 1 month?±1 week?and 4 months?±1month?after 131 I treatment were slightly higher than that before treatment,and the difference was not statistically significant?t=-1.751,P=0.085;t=-1.170,P=0.247?.The platelet counts at 1 month?±1 week?and 4 months?±1 month?after 131 I treatment were lower than that before treatment,and the difference was statistically significant?t=6.342,P=0.000;t=4.865,P=0.000?.The white blood cells,red blood cells,platelet counts of all 56 patients at 1 month?±1week?and 4 months?±1 month?after 131 I treatment were higher than the low limit value of normal reference,that is,no bone marrow suppression occurred.5 Of 56 patients,Tg was 50.89±121.16 ng/ml?0.2⁴70 ng/ml?before treatment,and Tg decreased to 34.45±101.57 ng/ml?0.2⁴70 ng/ml?at 4months?±1 month?after treatment,and the difference was statistically significant?Z=-4.117,P=0.000?.6 Of 56 patients,Dx-WBS of 46 patients showed that the thyroid bed had no radioactivity concentration at 4 months?±1 month?after 131 I treatment,and thyroid bed of the other 10 patients had radioactivity concentration.Of the 10 patients,5 patients' stimulus-induced Tg were less than 1ng/ml.The successful rate of thyroid ablation was 91.1%?51/56?for the first time,and the unsuccessful rate was 8.9%?5/56?.The successful rate of thyroid ablation of 11 patients whose treatment doses were increased was as high as 100%?11/11?.The successful rate of thyroid ablation of 39 patients whose treatment doses were fixed empiric dose was 92.3%?36/39?.The successful rate of thyroid ablation of 6 patients whose treatment doses were decreased was only 66.7%?4/6?.With the 131 I dose increased,the successful rate was a upward trend,but there were no significant difference between the groups??2=4.170,P=0.130?.7 Analysis of the factors influencing the efficacy of thyroid ablation,statistically significant differences in the successful rate of thyroid ablation between 1?D<10 and 30?D<40 group,10?D<20 and 30?D<40 group were observed.The successful rate of low ratio group of residual thyroid bed radioactivity counts and mediastinal radioactivity?1?D<20?was higher than the high ratio group?30?D<40?,that is,the lower the dose of 131 I of pre-therapeutic thyroid bed uptaked,the higher the successful rate was.The successful rate in group of total resection or subtotal thyroid ectomy was94.4%?51/54?,higher than the thyroid gland and isthmus resection group 0%?0/2?,and the difference was statistically significant?P=0.006?.The successful rate in group of Tg <10ng/ml before treatment was 100%?37/37?,was higher than Tg?10ng/ml group 73.7%?14/19?,and the difference was statisticallysignificant??2=7.700,P=0.003?.No statistically significant differences were found in the successful rate of thyroid ablation between gender,age,clinical stage,1?D<10,10?D<20 and20?D<30 group,20?D<30 and 30?D<40 group,the treatment dosage,pre-therapeutic TSH,the time between 131 I treatment and operation?P>0.05?.Conclusion:1 Sequential whole-body planar and hybrid SPECT/CT images,was feasible for pre-therapeutic quantitative analysis of bone marrow absorbed dose.2 The methodology of 131 I bone marrow absorbed dose estimation may be used for personalized guidance on 131 I DTC internal radiation therapy,and 131 I treatment dose can be increased within the limits of sensitive organs,but the evaluation of treatment effect need a larger samples to be confirmed by further studies.3 In general,the 131 I treatment doses of DTC patients which were in the scope of the guidelines,did not exceed the limit of the bone marrow absorbed dose.4 With the bone marrow maximum absorbed dose permits,increasing 131 I dose,the successful rate was increased after thyroid ablation with 131 I.But in this study,the groups were not statistically significant.5 The lower the dose of 131 I of pre-therapeutic thyroid bed uptaked,the higher the successful rate was.The successful rate was high when the operation was total resection or subtotal thyroidectomy.6 When DTC patients who were treated with total resection or subtotal thyroidectomy were with lymph node metastasis,the treatment of thyroid ablation and metastatic foci could be carried out at the same time.