Metastatic Differentiated Thyroid Cancer Survival is Unaffected by Mode of Preparation for 131I Administration

Cristiane J. Gomes-Lima; Sanjita Chittimoju; Leen Wehbeh; Sunita Dia; Prathyusha Pagadala; Mohammad Al-Jundi; Sakshi Jhawar; Eshetu Tefera; Mihriye Mete; Joanna Klubo-Gwiezdzinska; Douglas Van Nostrand; Jacqueline Jonklaas; Leonard Wartofsky; Kenneth D. Burman


J Endo Soc. 2022;6(5) 

In This Article


From 1996 to 2017 we identified 124 patients with metastatic DTC that were treated with RAI. We excluded 21 patients for lack of relevant follow-up data, 25 patients because of non-RAI avid metastases, 6 patients younger than 18 years at first RAI therapy, and 4 patients for incomplete data from the beginning of their disease. In 13 patients, THW was used as a method of preparation in initial treatments and rhTSH in subsequent ones throughout the follow-up; this group is described separately.

Our final cohort consisted of 55 patients (39 women) who were prepared for RAI therapy exclusively either with rhTSH or with THW. The baseline characteristics of patients are summarized in Table 1. Twenty-seven patients (49%) were prepared exclusively with rhTSH, whereas 28 patients (51%) were prepared exclusively with THW. The median age was 59 years (range, 47.5–65.5 years) for the rhTSH group and 41 years (range, 30.0–63.5 years) for the THW group (P < .05). In the entire cohort, 42 patients (76%) had papillary thyroid cancer, either classic or follicular variant, 6 patients (22%) had follicular thyroid cancer, 1 patient (4%) had Hürthle cell thyroid cancer, and 1 patient (4%) had poorly differentiated thyroid cancer. There was no statistically significant difference in pathologic features between the groups, regarding tumor size, histologic type, and extrathyroidal extension. All patients had distant metastases. The groups were balanced as to metastatic sites, except for macronodular lung metastasis, for which there were 14 patients (52%) in the rhTSH group and 6 patients (21%) in the THW group (P < .05). Metastases to the liver, pleura, skin, or mediastinal lymph nodes were considered atypical.

Thyrotropin levels at the time of therapy were adequately elevated in both groups, with higher levels in the rhTSH group (median of 112.7 mIU/L the day after rhTSH stimulation vs 68.9 mIU/L after THW, P = .01). Mean urine iodine levels were similar between the groups. There was no statistical difference in RAI activity used in the first therapy in both groups, but in the rhTSH group 24 out of 27 patients (89%) received a dosimetry-based therapy, while in the THW group 14 out of 28 patients (50%) were dosimetrically treated (P = .002). There was no statistically significant difference in the mean number of RAI therapies and in the mean cumulative activity between the groups. The median follow-up time for patients prepared with rhTSH was 4.2 years (range, 3.3–5.5 years) and for patients prepared with THW was 6.8 years (range, 4.2–11.6 years) (P = .002).

There was no statistically significant difference in the PFS between the groups of patients prepared with rhTSH or THW (Figure 1). Multivariate analysis adjusting for age, sex, macronodular lung metastases, number of RAI therapies, and cumulative activity of RAI revealed that older age at the time of diagnosis was the only variable significantly associated with a greater risk of progression. The method of thyrotropin stimulation, either rhTSH or THW, was not associated with a difference in PFS (Table 2). Similarly, no statistically significant difference was observed in the OS between the groups (Figure 2). Multivariate analysis adjusting for the same variables demonstrated that both older age at diagnosis and higher total cumulative activity of RAI were associated with a greater risk of death. The method of thyrotropin stimulation was not associated with a difference in the OS of these patients (Table 3).

Figure 1.

Progression-free survival in recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) groups.

Figure 2.

Overall survival in recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) groups.

In the rhTSH group, structural incomplete response was observed in 23 patients (85%), followed by indeterminate response in 2 patients (7%), and biochemical incomplete response and excellent response (1 patient each—4% each). In the THW group, structural incomplete response was seen in 16 patients (57%), excellent response in 6 patients (21%), biochemical incomplete response in 5 patients (18%) and indeterminate response in 1 patient (4%) (Figure 3). The difference between the types of response was statistically significant (P = .039).

Figure 3.

Best overall response.

Regarding target lesion evaluation, no patient achieved CR. PR was observed in 17 out of 27 patients (63%) in the rhTSH group, compared to 3 out of 28 patients (11%) in the THW group (P < .001). PD was found in 15 patients (56%) in the rhTSH group, and in 11 patients (39%) in the THW group (P = .227). SD was more often observed in the THW group (36% vs 11%, P = .032) (Figure 4).

Figure 4.

Target lesion evaluation according to RECIST 1.1.

A third group of patients was composed of patients who had initial RAI therapy with THW but had subsequent therapies prepared with rhTSH. The baseline characteristics of this group are described in Table 4. This group is characterized by more therapies (2.8 ± 1.0) and higher mean cumulative activity of radioiodine (584.6 ± 161.1 mCi). Responses to therapy in this group were biochemical incomplete response in 3 patients (23%) and structural incomplete response in 10 patients (77%).