title: Examining recombinant human TSH primed ¹³¹I therapy protocol in patients with metastatic differentiated thyroid carcinoma: comparison with the traditional thyroid hormone withdrawal protocol.
abstract: OBJECTIVE
  Recombinant human thyroid-stimulating hormone (rhTSH)-based protocol is a promising recent development in the management of differentiated thyroid carcinoma (DTC). The objectives of this prospective study were: (1) to assess the feasibility and efficacy of the rhTSH primed (131)I therapy protocol in patients with DTC with distant metastatic disease, (2) to perform lesional dosimetry in this group of patients compared to the traditional protocol, (3) to document the practical advantages (patient symptoms and hospital stay) of the rhTSH protocol compared to the traditional thyroid hormone withdrawal protocol, (4) to document and record any adverse effect of this strategy, (5) to compare the renal function parameters, and (6) to compare the serum TSH values achieved in either of the protocols in this group of patients.
  
  
  METHODS
  The study included 37 patients with metastatic DTC having lung or skeletal metastases or both. A comparison of lesional radiation absorbed dose, hospital stay, renal function tests, and symptom profile was undertaken between the traditional thyroid hormone withdrawal protocol and rhTSH-based therapy protocol. Dosimetric calculations of metastatic lesions were performed using lesion uptake and survey meter readings for calculation of effective half-life. Non-contrast-enhanced CT was used for assessment of tumor volume. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL forms. A comparison of pretreatment withdrawal thyroglobulin (TG) was done with the withdrawal TG level 3 months after treatment.
  
  
  RESULTS
  The mean effective half-life of (131)I in metastatic lesions was less during the rhTSH protocol (29.49 h) compared to the thyroid hormone withdrawal protocol (35.48 h), but the difference was not statistically significant (p = 0.056). The mean 24-h % uptake of the lesions during the traditional protocol (4.84 %) was slightly higher than the 24-h % uptake during the rhTSH protocol (3.56 %), but the difference was not found to be statistically significant (p = 0.301). The mean tumor radiation absorbed dose per mCi was less during the rhTSH protocol (6.04 rad/mCi) than during the thyroid hormone withdrawal protocol (8.68 rad/mCi), and the difference was statistically significant (p = 0.049), though visual analysis of the rhTSH posttherapy scans showed avid concentration of (131)I in the metastatic sites and revealed more lesions in 30 % of the patients compared to the traditional large dose scan and equal number of lesions in 65 % of the patients. Visual analysis of the traditional large dose scan, rhTSH pretreatment scan, and rhTSH posttherapy scans showed that the traditional large dose scan is better compared to the rhTSH 1 mCi scan as it showed more lesions in 19 of 37 patients (51.35 %). rhTSH posttherapy scans were better compared to the traditional large dose scans and rhTSH pretreatment scans. More lesions were seen on rhTSH posttherapy scans in 11 of 37 patients (29.7 %) compared to the traditional large dose scans and in 24 of 37 (64.86 %) patients compared to the rhTSH 1 mCi scans. Our findings demonstrate that the rhTSH primed pretreatment scan undertaken at 24 h after diagnostic dose is suboptimal to evaluate whether a metastatic lesion concentrates (131)I. The majority of these lesions demonstrated radioiodine accumulation in the posttreatment scan. Quality of life as assessed using EORTC QOL-3 forms clearly showed that rhTSH improved the quality of life of patients compared to the thyroid hormone withdrawal protocol. Functional scale and global health status were significantly better in the rhTSH protocol compared to the thyroid hormone withdrawal protocol (p < 0.001). The mean symptom scale score was significantly higher in the thyroid hormone withdrawal protocol (45.25) compared to the rhTSH protocol (13.59) (p < 0.001). Of the 20 patients, 4 (20 %) had more than 25 % increase in the TG value on follow-up. The median hospital stay of patients receiving (131)I therapy with the rhTSH protocol was shorter (2 days, range 2-8 days) compared to the thyroid hormone withdrawal protocol (3 days, range 1-8 days) and the difference was found to be statistically significant (p = 0.007). The mean serum creatinine level was significantly lower in the rhTSH protocol (0.826 mg/dl) than the thyroid hormone withdrawal protocol (0.95 mg/dl) (p = 0.013), though the mean blood urea level of patients during the rhTSH therapy protocol was slightly higher (22.81 mg/dl) than during the thyroid hormone withdrawal protocol (21.91 mg/dl) without statistical significance (p = 0.55). The mean serum TSH on day 2 of the rhTSH protocol was 140.99 μIU/ml (range 71-176 μIU/ml) compared to 72.62 μIU/ml (range 2.05-154 μIU/ml) in the traditional protocol after around 4-6 weeks of thyroid hormone withdrawal (p < 0.05).
  
  
  CONCLUSIONS
  Overall, the rhTSH primed (131)I therapy protocol was found to be feasible and a good alternative to the thyroid hormone withdrawal protocol in patients with metastatic DTC. The lesional dosimetry findings need to be further examined in subsequent studies. The rhTSH primed pretreatment scan at 24 h after diagnostic dose is suboptimal to determine whether a metastatic lesion concentrates (131)I and the posttreatment scan is important for the correct impression.
authors.affiliation: Radiation Medicine Centre, Bhabha Atomic Research Centre (BARC), Tata Memorial Hospital Annexe, Jerbai Wadia Road, Parel, Mumbai, 400012, India.
authors.forename: Deepa
authors.initials: D
authors.lastname: Rani
authors.forename: Sushma
authors.initials: S
authors.lastname: Kaisar
authors.forename: Sushma
authors.initials: S
authors.lastname: Awasare
authors.lastname: Kamaldeep
authors.forename: Amit
authors.initials: A
authors.lastname: Abhyankar
authors.forename: Sandip
authors.initials: S
authors.lastname: Basu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000556:secondary*; D008875:Middle Aged; D013963:Thyroid Hormones / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D057073:Thyrotropin Alfa / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D007457:Iodine Radioisotopes; D013963:Thyroid Hormones; D057073:Thyrotropin Alfa