Minimally invasive local ablative therapies in combination with radioiodine therapy in benign thyroid disease: preparation, feasibility and efficiency – preliminary results

Figures & data

Figure 1. The individual total thyroid reduction of every included patient in both subgroups.

Figure 2. A comparison of the relative thyroid volume reduction due to combined therapy (RFA + RIT) in both subgroups.

Table 1. An overview of the data evaluated in this study.

	Sex		Total thyroid volume (ml)		Volume reduction Thyroid	Volume reduction Thyroid
Patient	M/F	Age	Enrolment (T0)	3MFU (T3)	ΔΤ0;Τ3 (ml)	ΔΤ0;Τ3 (%)
RFA + RIT (subgroup 1)
1	F	53	102	83.1	18.9	18.53
2	M	59	62	46	16	25.81
3	F	53	100	83	17	17
4	F	48	24	19	5	20.83
5	F	55	40	22.8	17.2	43
6	M	53	170	120	50	29.41
7	M	48	90	31	59	65.56
8	F	55	88	53	35	39.77
9	M	52	32	22	10	31.25
10	F	56	12	5.9	6.1	50.83
11	F	56	38	20	18	47.37
12	M	42	86	58.2	27.8	32.33
13	F	61	60	40	20	33.33
14	M	34	120	111.2	8.8	7.33
15	M	49	73	47	26	35.62
Mean		51.4	73.13	50.81	22.32	33.20
Max		61	170	120	59	65.56
Min		34	12	5.9	5	7.33
RIT mono (subgroup 2)
16	F	71	135	90	45	33.33
17	F	74	110	76	34	30.91
18	F	65	90	85.9	4.1	4.56
19	F	53	30	16	14	46.67
20	F	77	136	103.5	32.5	23.9
21	F	66	63	37	26	41.27
22	M	49	40	27	13	32.5
23	M	66	126.3	90	36.3	28.74
24	F	76	44.2	31.5	12.7	28.73
25	M	80	40	34	6	15
26	F	69	39.6	31	86	21.72
27	F	75	30.3	19.1	11.2	36.96
28	F	40	32	18.5	13.5	42.19
29	M	62	86	58.2	27.8	32.33
30	F	72	75.5	57	18.5	24.5
Mean		66.3	71.86	51.65	20.21	29.55
Max		80	136	103.5	45	46.67
Min		40	30	16	4.1	4.56

Table 2. A complete overview of the combined therapy approaches in the current literature. It evaluates the essential parameters in order to make the different studies comparable.

(1)
Author	Zingrillo, M et al.	Chianelli, M et al.
Intervention	Percutaneous alcohol injection therapy (PEIT) in combination with Radioiodine-131 therapy (RIT)	Laser ablation therapy (LAT) in combination with radioiodine 131-treatment (131I)
Journal	Journal of Nuclear Medicine (J Nucl Med) 2003;44:207–210	Journal of Clinical Endocrinology & Metabolism (J Clin Endocrinol Metab) 2014;9(7):Ε1283–Ε1286
Patients	Total: 22 PEIT + RIT: 11 /∅ 61 (52–75) y/55% female	Total: 32 LAT + RIT: 15/∅ 62 ± 16 years/67% female
Control group	RIT: 11/∅ 61 years (range 48–69)/55% female	RIT: 17/∅ 59 years ±15/65% female
Size: nodules/thyroid	Nodule-PEIT + RIT: ∅ 60.8 ml (range: 33.5–112 ml) Nodule-RIT: ∅ 53.1 ml (range: 34.9–103 ml)	Nodule-LAT + RIT: ∅ 27.7 ml ±17.0 ml Nodule-RIT: ∅ 29.4 ml ±10.6 ml
Indication	Single palpable hot thyroid toxic nodules (TTΝ) > 4 cm	Large hot thyroid toxic nodules (TTN) (solid or with fluid component <20% at US) Volume >10 ml with at least one diameter >30 mm
Assessments	PEIT RAI: I-131 uptake calculation at 2 h, 6 h and 24 h 2-month assessment after PEIT (24-h I-131 uptake) calculation of radioiodine 131 dose, than beginning of RAI	FT3. FT4, TSH, TPOAb and TgAb assessed at baseline, 99mTc scans and US-evaluation were performed before LAT
Chronological sequence	2–4 sessions at weekly intervals 2 months prior to 24 h RIUT and RAI divided into 4–8 ml doses	LAT sessions at monthly interval 1 months prior to RIT
Follow up	2 months, 6 months and 12 months after RAI administration: clinical evaluation, ultrasound evaluation (NV). SYS evaluation, hormone status (FT3, FT4, TSH) A new scintigraphic picture for all patients after 6 months	Hormone status (FT3, FT4, TSH, TPOAb and TgAb): 1, 3, 6, 12 and 24 months after initial LAT and after initial RIT. US: 1, 12, 24 months after LAT and 1, 2, 12, 24 after RIT 99mTc scans 1 and 24 LAT and 12 months after RIT
Volume reduction	PEIT + RAI: ∅ 13.2 ± 12.9 (1.2–49.3) (ml) = 12 months PEIT + RAI: ∅ 79.3 ± 14.7 (56.0–96.5) (%) = 12 months Significantly higher reduction in combined therapy than in RAI p < 0.05 (NODLUE VOLUME)	LAT +131I: ∅ 23.5 ± 14.9 (ml) = 16.6 % (p < 0.001) = 1 month LAT +131I: ∅ 20.6 ± 13.5 (ml) = 27.8 % (p < 0.001) = 2 months LAT +131I: ∅ 10.1 ± 9.3 (ml) = 67.8 % (p < 0.001) = 12 months LAT +131I: ∅ 9.6 ± 8.9 (ml) = 71.3 % (p < 0.001) = 24 months Combined therapy was leading to a faster volume reduction
Hormone status	PEIT + RIT: 1 Pat showed slight TSH increase RIT: 1 pat subclinically hyperthyroid/1 pat clinically hypothyroid/ 2 showed slight increase in TSH	TSH normal in all pat after 12 months. In LAT +131I 60% normal after 1 month Quicker normalisation of TSH value with LAT
Influence on RIT	Significantly lower administered dose of radioiodine-131 in PAIT + RAI than in RAI subgroup p < 0.05	LAT leading to a reduction of 21.1 ± 8.1% in administered dose of radioiodine 131. p = 0.01
Thyroid function	PEIT + RAI (after 12 months): 11 of 11 pat. Clinically euthyroid 1 pat.: slight increase in TSH (4.2 mU/L/norm level =0.2–4.0) RAI (after 12 months): 10 of 11 pat. clinically euthyroid 2 suppressed TSH/2 slightly increased TSH/1 hypothyroid	All treated nodules showed slightly increased uptake at thyroid scintigraphy by the residual vital nodule without inhibition of surrounding normal tissue Late hypothyroidism only in 1 pat (LAT + RIT)
Complications	No major complications occurred/mortality 0%	No complications occurred/mortality 0 %
Author's conclusion	RAI can be used for TTNs larger than 4 cm when surgery is either refused or contraindicated. The combination of PEIT + RAI can be considered when marked shrinkage of the nodule relieve local symptoms or when the reduction of the RAI dose can prevent hospitalisation	Combined LAT/131I treatment permitted lower activities of 131I, allowing outpatient treatment and reduced absorbed dose to pat. and caregivers. This approach was well tolerated and induced faster improvement of local symptoms and of biochemical hyperthyroidism
(2)
Author	Korkusuz et al.	Happel et al.
Intervention	Percutaneous microwave ablation (MWA) in combination with radioiodine-131 therapy (RIT)	Radiofrequency ablation (RFA) in combination with radioiodine-131 therapy (RIT)
Journal	RÖFO – Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren (Fortschr Röntgenstr) 2016; 188:60–68	Not yet published
Patients	Total: 15 MWA + RIT: 15/∅ 55 (27–79) years/53% female	Total: 25 RFA + RIT: 10/∅ 53 (48–61 years/50% female)
Control group	No control group established	RIT: 15/∅ 67 (47–91/71% female)
Size: Nodules/Thyroid	Nodule-MWA + RIT: ∅ 22.9 ± 7.2 ml Thyroid-MWA + RIT: ∅ 86.5 ml ±24.2 ml	Thyroid-LAT + RIT: ∅ 87 (29–200) ml Thyroid-RIT: ∅ 76 (22–160) ml
Indication	Symptomatic benign thyroid nodules; hot, cold or indifferent clinical symptoms, contraindications or refusal of surgery	Benign goitres with contingently diffuse hot nodules clinical symptoms, contraindications or refusal of surgery
Assessments	All patients underwent pre- and post-MWA assessments including: ultrasound (US)/thyroid hormone status (T3, T4, TSH, Tg, TPOAb, TgAb and TRAb)/scintigraphic imaging with Tc-99-m/R1UT 2–4 Mbq radioiodine 131 with measurements after 2, 48 and 96 h	All patients underwent pre- and post-MWA assessments including: ultrasound (US)/thyroid hormone status (T3, T4, TSH, Tg, TPOAb, TgAb and TRAb)/scintigraphic imaging with Tc-99-m/RIUT 2–4 Mbq radioiodine 131 with measurements after 2, 48 and 96 h
Chronological sequence	1 session with 24–28 weeks reaching a target temperature of 60–80 °C one day later beginning of RIT	Beginning of RIT one day after thermoablation
Follow up	Complete thyroid hormone status (T3, T4, TSH, Tg) with antibody detection test (TPOAb, TgAb and TRAb) as well as US and Tc-99-m scintigraphic imaging after 3 months (3MFU)	Complete thyroid hormone status (T3, T4, TSH, Tg) with antibody detection test (TPOAb, TgAb and TRAb). as well as US and Tc-99-m scintigraphic imaging after 3 months (3MFU)
Volume reduction	Ablated nodule volume; ∅ 22.9 ± 7.2 (ml) = 3MFU Pretherapy thyroid volume: ∅ 86.5 ± 24.2 (ml) 3MFU thyroid volume: ∅ 60.1 ± 18.3 (ml) Absolute thyroid volume reduction: ∅ 26.4 ± 7.9 ml Relative thyroid volume reduction: ∅ 30.7 ± 10.7 (%) (p < 0.05)	RFA + RIT-thyroid absolute: ∅ 18 (10–70 ml) = 3MFU RFA + RIT-Thyroid relative: ∅ 32 (17–60%) significant reduction (p < 0.05)
Hormone status	No significant changes in T3, T4 and TSH. Improvement of TSH-value in one case	Decrease in T3/T4 decrease at 3MFU after initial increase. TSH increased but remained in normal range
Influence on RIT	MWA leading to a sign reduction of activity and hospitalisation time relative activity reduction due to MWA: ∅ 26.6 ± 4.8%	Significantly reduced dose of radioiodine 131 and hospitalisation time due to RFA (p 0.05). No change in 24 h RIUT
Thyroid function	All patients were euthyroid after 3 months	All patients remained euthyroid after treatment
Complications	No serious complications/mortality 0%	No complications occurred/mortality 0%
Author’s conclusion	Combined therapy of MWA and RIT displays an effective approach for the treatment of large benign nodular goitres. It significantly reduces goitre volume, administered activity and hospitalisation time. Thyroid function is preserved at 3MFU	Combined therapy of RIT + RFA led to a significant reduction of total thyroid volume as well as required radioiodine-131 dose and hospitalisation time without reducing RIT effectiveness