rhTSH Preparation for Radioiodine Ablation in Thyroid Cancer

Abstract and Introduction

Abstract

Objective: Recombinant human TSH (rhTSH) is commonly used to prepare patients for postoperative radioiodine (I-131) ablation after surgery for differentiated thyroid cancer (DTC). In adults, rhTSH is associated with equivalent oncologic efficacy in comparison to thyroid hormone withdrawal (THW), but its use has not been well studied in children.

We aimed to measure time to disease progression after rhTSH stimulation vs. THW in paediatric patients under the age of 21 with DTC following total thyroidectomy.

Design: Retrospective cohort study (March 2001–July 2018).

Patients: Sixteen children and adolescents (75% female, median age, 17.4 years) who received rhTSH were compared to 29 historical controls (72% female, median age, 18.5 years) prepared with THW, followed for a median of 2.4 years (range, 0.5–14).

Measurements: Stimulated serum TSH concentrations prior to I-131 ablation and time to disease progression, as determined by a component outcome variable encompassing both structural and biochemical disease persistence/recurrence.

Results: No differences were observed in tumour characteristics and I-131 dose (median 2.3 [1.8–2.90] mCi/kg rhTSH) between groups. Patients who received rhTSH achieved a similar median stimulated TSH level (163 [127–184] mU/L), compared to those who underwent THW (136 [94.5–197] mU/L; p = .20). Both groups exhibited similar time to progression (p = .13) and disease persistence/recurrence rates (rhTSH 31% vs. THW 59%, p = .14).

Conclusion: In this cohort of children and adolescents with DTC, we observed similar time to disease progression among those who received rhTSH or underwent THW prior to postoperative I-131 ablation.

Introduction

Paediatric differentiated thyroid carcinoma (DTC) is a rare disease that affects between 0.6 and 1.2 per 100,000 patients,^[1] but similar to adult thyroid cancer, it has been increasing in incidence over the past several decades.^[2] Paediatric patients commonly present with advanced disease, and the standard of care involves total thyroidectomy and adjuvant radioiodine (I-131) ablation.^[3] Thyroid hormone withdrawal (THW) for 2–4 weeks prior to I-131 has historically been used to achieve sufficiently elevated serum thyrotropin (TSH) levels necessary to maximum I-131 uptake in residual thyroid tissue and tumour cells. This can be associated with significant hypothyroid morbidity and may acutely exacerbate concurrent medical or psychiatric conditions.^[4] Due to the rarity of paediatric DTC, treatment options are often derived from experiences in the adult population.^[5] In adults, exogenous stimulation with recombinant human TSH (rhTSH) 1 and 2 days prior to I-131 has been demonstrated to have equivalent oncologic efficacy and clinical safety, while lowering systemic radioactivity and improving quality of life (QOL) outcomes relative to THW.^[6–8]

Data supporting the safety and efficacy of rhTSH preparation in the paediatric DTC population are limited, and the optimal approach to I-131 ablation in this group remains unclear. A recent study demonstrated similar rates of biochemical recurrence, structural recurrence and I-131 retreatment after rhTSH preparation in children with DTC, although only patients without evidence of persistent disease during I-131 were selected limiting the generalizability to patients with more advanced disease.^[9] Furthermore, this previous study^[9] was conducted in Poland, a historically iodine-deficient region^[10,11] until recently.^[12] Endemic iodine deficiency may exaggerate I-131 uptake and tumoricidal potency.

This study is a retrospective cohort study of our experience using rhTSH stimulation, compared to THW, prior to I-131 ablation in paediatric patients with DTC. The primary outcomes were time to disease progression and biochemical and structural disease persistence/recurrence. The efficacy of achieving sufficiently stimulated serum thyroid-stimulating hormone (TSH) levels in paediatric DTC patients with the rhTSH dose standardly used in adults was also examined.

Table 1. Demographics and clinical characteristics of recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW)-prepared patients
	rhTSH (n = 16)	THW (n = 29)	p-value
Gender
Female	12 (75%)	21 (72.4%)	1.00
Age at I-131, years
Median (IQR)	17.4 (13.9–18.1)	18.5 (13.3–20.3)	.42
<10 years	1 (6%)	3 (10%)
TNM stage (AJCC 8th Edition)
Stage I	15 (93.75%)	26 (89.7%)	.64
Stage II	1 (6.25%)	3 (10.3%)
DTC T status
T1	–	1 (3%)
T1a	–	4 (14%)
T1b	7 (44%)	6 (21%)
T2	4 (25%)	7 (24%)
T3	–	2 (7%)
T3a	3 (19%)	4 (14%)
T3b	–	2 (7%)
T4a	2 (12%)	3 (10%)
DTC N status
Nx	2 (12%)	4 (14%)
N0	–	3 (10%)
N1	–	1 (3%)
N1a	8 (50%)	5 (17%)
N1b	6 (38%)	16 (55%)
DTC M status
M0	15 (94%)	26 (90%)
M1	1 (6%)	3 (10%)
ATA risk stratification^a
Low	4 (25%)	6 (20.7%)	.25
Intermediate	3 (18.8%)	13 (44.8%)
High	9 (56.3%)	10 (34.5%)
DTC histopathology
Papillary, classical	11 (69%)	20 (69%)	.99
Papillary follicular variant	–	5 (17%)
Papillary (other variants)^b	4 (25%)	4 (14%)
Follicular	1 (6%)	–
Time from thyroidectomy to I-131 therapy, days
Median (IQR)	72 (47–114)	52 (39–86) (n = 24)	.26

Table 1. Demographics and clinical characteristics of recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW)-prepared patients

rhTSH (n = 16)

THW (n = 29)

p-value

Gender

Female

12 (75%)

21 (72.4%)

1.00

Age at I-131, years

Median (IQR)

17.4 (13.9–18.1)

18.5 (13.3–20.3)

.42

<10 years

1 (6%)

3 (10%)

TNM stage (AJCC 8th Edition)

Stage I

15 (93.75%)

26 (89.7%)

.64

Stage II

1 (6.25%)

3 (10.3%)

DTC T status

–

1 (3%)

T1a

–

4 (14%)

T1b

7 (44%)

6 (21%)

4 (25%)

7 (24%)

–

2 (7%)

T3a

3 (19%)

4 (14%)

T3b

–

2 (7%)

T4a

2 (12%)

3 (10%)

DTC N status

2 (12%)

4 (14%)

–

3 (10%)

–

1 (3%)

N1a

8 (50%)

5 (17%)

N1b

6 (38%)

16 (55%)

DTC M status

15 (94%)

26 (90%)

1 (6%)

3 (10%)

ATA risk stratification^a

Low

4 (25%)

6 (20.7%)

.25

Intermediate

3 (18.8%)

13 (44.8%)

High

9 (56.3%)

10 (34.5%)

DTC histopathology

Papillary, classical

11 (69%)

20 (69%)

.99

Papillary follicular variant

–

5 (17%)

Papillary (other variants)^b

4 (25%)

4 (14%)

Follicular

1 (6%)

–

Time from thyroidectomy to I-131 therapy, days

Median (IQR)

72 (47–114)

52 (39–86) (n = 24)

.26

Table 2. Radioactive Iodine (I-131) Treatment Details and Biochemical and Structural Disease Outcomes, recombinant human TSH (rhTSH) vs. thyroid hormone withdrawal (THW) patients
	rhTSH (n = 16)	THW (n = 29)	p-value
Stimulated TSH (mU/L)
Median (IQR)	163 (123.8–187.2)	136 (94.5–197) (n = 17)	.20
Stimulated thyroglobulin (Tg), mg/dl
Median (IQR)	3.3 (0.8–21.6) (n = 13)	73.9 (17–312) (n = 13)	.07
Mean ± SD	28.1 ± 57.5 (n = 13)	230 ± 375 (n = 13)
Stimulated thyroglobulin antibody (Tg Ab)
Positive	2 (12.5%)	6 (33.3%) (n = 18)	.23
I-131 radiation dose (mCi)
Median (IQR)	143.5 (105.8–154.6)	105 (99.0–148.2)	.10
Mean (SD)	129.2 (36.8)	110.6 (34.6)
I-131 radiation dose per weight (mCi/kg)
Median (IQR)	2.3 (1.8–2.9)	1.7 (1.4–2.4)	.08
I-131 scintigraphy results
No uptake	1 (6.3%)	5 (17.3%)	.49
Persistent uptake in thyroid bed/neck	14 (87.7%)	21 (72.4%)
Lung uptake	1 (6.3%)	3 (10.3%)
Biochemical evaluation^a
Suppressed Tg > 2 mg/dl, stimulated Tg > 10 mg/dl or upwardly trending stimulated Tg levels between 2 and 10 mg/dl	2 (14.3%) (n = 14)	7 (30.4%) (n = 23)	–
Suppressed Tg ≥ 0.2 mg/dl or stimulated Tg > 1 mg/dl	5 (35.7%) (n = 14)	12 (52.2%) (n = 23)
Structural evaluation
Lesion on Neck Ultrasound	5 (31.3%)	10 (34.5%)	-
Lung Lesion on CT Thorax	–	1 (3.5%)
Disease progression^b based on ATA risk stratification^c
Low	1 (25%) n = 4	2 (33.3%) n = 6	–
Intermediate	0 (0%) n = 3	7 (53.9%) n = 13
High	4 (44.4%) n = 9	8 (80%) n = 10
I-131 treatment^d
1 dose	13 (81%)	18 (62%)	.18
2 doses	3 (19%)	8 (28%)
3 doses	0 (0%)	3 (10%)
Reoperation
Lymphadenectomy	5 (31%)	8 (28%)	.80
Follow-up, years^e
Median (IQR)	2.8 (1.5–4.3)	2.3 (1.1–8.0)	.22

Table 2. Radioactive Iodine (I-131) Treatment Details and Biochemical and Structural Disease Outcomes, recombinant human TSH (rhTSH) vs. thyroid hormone withdrawal (THW) patients

rhTSH (n = 16)

THW (n = 29)

p-value

Stimulated TSH (mU/L)

Median (IQR)

163 (123.8–187.2)

136 (94.5–197) (n = 17)

.20

Stimulated thyroglobulin (Tg), mg/dl

Median (IQR)

3.3 (0.8–21.6) (n = 13)

73.9 (17–312) (n = 13)

.07

Mean ± SD

28.1 ± 57.5 (n = 13)

230 ± 375 (n = 13)

Stimulated thyroglobulin antibody (Tg Ab)

Positive

2 (12.5%)

6 (33.3%) (n = 18)

.23

I-131 radiation dose (mCi)

Median (IQR)

143.5 (105.8–154.6)

105 (99.0–148.2)

.10

Mean (SD)

129.2 (36.8)

110.6 (34.6)

I-131 radiation dose per weight (mCi/kg)

Median (IQR)

2.3 (1.8–2.9)

1.7 (1.4–2.4)

.08

I-131 scintigraphy results

No uptake

1 (6.3%)

5 (17.3%)

.49

Persistent uptake in thyroid bed/neck

14 (87.7%)

21 (72.4%)

Lung uptake

1 (6.3%)

3 (10.3%)

Biochemical evaluation^a

Suppressed Tg > 2 mg/dl, stimulated Tg > 10 mg/dl or upwardly trending stimulated Tg levels between 2 and 10 mg/dl

2 (14.3%) (n = 14)

7 (30.4%) (n = 23)

–

Suppressed Tg ≥ 0.2 mg/dl or stimulated Tg > 1 mg/dl

5 (35.7%) (n = 14)

12 (52.2%) (n = 23)

Structural evaluation

Lesion on Neck Ultrasound

5 (31.3%)

10 (34.5%)

Lung Lesion on CT Thorax

–

1 (3.5%)

Disease progression^b based on ATA risk stratification^c

Low

1 (25%) n = 4

2 (33.3%) n = 6

–

Intermediate

0 (0%) n = 3

7 (53.9%) n = 13

High

4 (44.4%) n = 9

8 (80%) n = 10

I-131 treatment^d

1 dose

13 (81%)

18 (62%)

.18

2 doses

3 (19%)

8 (28%)

3 doses

0 (0%)

3 (10%)

Reoperation

Lymphadenectomy

5 (31%)

8 (28%)

.80

Follow-up, years^e

Median (IQR)

2.8 (1.5–4.3)

2.3 (1.1–8.0)

.22

Recombinant Human Thyroid-Stimulating Hormone Versus Thyroid Hormone Withdrawal Preparation for Radioiodine Ablation in Differentiated Thyroid Cancer in Children, Adolescents and Young Adults

Abstract and Introduction

Abstract

Introduction

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Tables

References

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