Ethics
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol was approved by the ethics committee of Nagasaki university hospital (Protocol Number: 19102110). The ethics committee of Nagasaki university hospital waived the need of informed consent from participants because this research was a retrospective and non-invasive, and the identifying information was not included in the collected data.
Patients
We conducted a retrospective study of the cases of 74 patients with DTC who had received RAI treatment in the period between June 2016 and July 2018 at Nagasaki University Hospital. There were 23 males and 51 females, and their mean age was 58.6 years (range, 14-83 years). We included only those patients who had complete information of primary tumor size (PTS) as mentioned in their histopathology reports, TNM staging, serum TSH (uIU/ml), free-T3 (pg/mL), free-T4 (ng/dL), thyroglobulin level (Tg) (ng/ml) (one month before, on the day of the treatment, and one month after receiving RAI), anti-Tg antibodies (IU/mL), dose of Levothyroxine (before and after RAI), as well as renal function (creatinine, BUN, eGFR), exposure rate (µSv/h) and taken dose (mCi). In Japan, the equation to calculate eGFR8 is follow:
Japanese Equation (3 variables): 194 X (SCr)-1.094 X (Age)-0.287 X 0.739 (if female)
SCr: serum creatinine
According to the American Thyroid Association (ATA)3, we stratified DTC patients in three groups (low risk, intermediate risk, high risk). The group of patients planned for rTSH preparation underwent radioactive iodine ablation soon after surgery and received 0.9mg thyrotropin intramuscularly on two days before I-131 administration. The other group of patients were instructed to be on low iodine diet 2 week before RAI treatment and do not take any iodine containing drug (Levothyroxine withdrawal method)9. On the day of RAI administration, patients were instructed to fast 2 hours for food but take at least 1 liter of water to ensure good hydration. Administration is performed on Monday before noon or Wednesday just after noon. Dose of 3700MBq or 5550MBq (100 or 150 mCi) of I-131 capsule is orally taken. Dose is determined by clinical decision (body size, age, volume of metastasis etc). In our hospital fixed dose is used. All patients were hospitalized in an isolated room following RAI administration. In isolation room, patients were consulted by nuclear physician about the purpose of RAI, importance of good hydration and bowel clearance as well as necessary steps after getting RAI to minimize radiation exposure to others. Foods are delivered and patients drink bottled water to avoid unintentional iodine intake and to avoid unnecessary environment contamination. Dose rate was measured (immediately, 12h, 24h, 36h, 48h, 60h) at 1 meter distance from anterior mid trunk using NaI scintillation survey meter (Aloka TGS-172 Survey meter). As per Nagasaki University Hospital requirement, patients were released when their dose rate was <30 µSv/h at 1 meter distance. All dose rate measurements were performed after patients emptied their urinary bladder.
Using these dose rates, the effective half-life (E1/2) of I-131 was calculated. The actual effective half-life is determined by two factors, long physical half-life of I-131 and short biological half-life which determined by the biological washout. Considering the small sample time point number to calculate half-life and much longer and fixed physical half-life than biological half-life, we determined to use simple mono-exponential fitting instead of complex bi-exponential fitting for the effective half-life calculation. The measured dose rates cannot be expressed in µSv/h because each patient has different exposure rate, but expressing as ratio is easier for mathematical calculation. Ratio 1 is equal to 1, because it is initial (first) dose rate at the time of I-131 administration, ratio 2 is relation of exposure rate of 2nd measurement to initial exposure rate, etc.
Statistical analysis
All statistical analyses were performed using the JMP Pro14 software. Univariate correlation analysis was used to compare factors which made influence on clearance of Iodine-131. All factors are expressed as median (1st quartile, 3rd quartile) values. P-values less than 0.05 were considered significant.