Risk factors and outcomes of metastatic poorly differentiated thyroid carcinoma

Table 1 Characteristics of 39 poorly differentiated thyroid carcinoma patients, n (%)

	M0 (n = 18)	M1 (n = 16)	M2 (n = 5)	P value
Age, median (years, IQR)	41 (26-59)	52 (49-63)	58 (51-62)	0.042
Age				0.060
< 45 years	10 (55.6)	3 (18.8)	1 (20.0)
≥ 45 years	8 (44.4)	13 (81.2)	4 (80.0)
Sex				0.045
Female	13 (72.2)	7 (43.8)	5 (100)
Male	5 (27.8)	9 (56.2)	0
Tumor size (cm)				0.222
≤ 2	3 (16.7)	0	0
> 2-4	6 (33.3)	6 (37.5)	3 (75.0)
> 4	9 (50.0)	10 (62.5)	1 (25.0)
T stage				0.536
T1	3 (16.7)	0	0
T2	4 (22.2)	5 (31.2)	1 (20.0)
T3	5 (27.8)	3 (18.8)	1 (20.0)
T4	6 (33.3)	8 (50.0)	3 (60.0)
N stage				0.323
N0	17 (94.4)	13 (81.2)	5 (100)
N1	4 (10.3)	3 (18.8)	0
Extrathyroidal invasion	6 (33.3)	8 (50.0)	4 (80.0)	0.166
Initial metastatic sites
Lung	0	9 (56.3)	3 (60.0)
Bone	0	3 (18.8)	0
Lung, bone	0	2 (12.5)	2 (40.0)
Lung, brain	0	1 (6.3)	0
Bone, brain	0	1 (6.3)	0
Type of thyroid surgery				0.041
Lobectomy or subtotal thyroidectomy	0	4 (25.0)	0
Total thyroidectomy	18 (100)	12 (75.0)	5 (100)
131I therapy	11 (61.1)	12 (75.0)	5 (100)	0.217
131I cumulative dose, median (mCi, IQR)	75 (15-100)	100 (97-162)	580 (100-835)	0.005
External beam radiation therapy	3 (16.7)	7 (43.8)	3 (60.0)	0.099
External beam radiation therapy, median (cGy, IQR)	5600 (3950-6200)	3720 (1725-5310)	5000 (4750-5500)	0.634
Targeted therapy	0	3 (18.8)	1 (20.0)	-
Lenvatinib	0	1 (6.25)	0
Lenvatinib, sorafenib	0	2 (12.5)	0
Lenvatinib, sorafenib, cabozantinib	0	0	1 (20.0)
Cancer-specific mortality	1 (5.6)	10 (62.5)	5 (100)	0.001
Overall mortality	2 (11.1)	12 (75.0)	5 (100)	0.001
Follow-up, median (years, IQR)	8.0 (2.4-14.3)	2.0 (1.4-5.2)	4.2 (2.8-8.1)	0.156

IQR: Interquartile range.

Table 2 Risk factors associated with cancer-specific mortality in poorly differentiated thyroid carcinoma patients, n (%)

	Survival (n = 23)	Mortality (n = 16)	Univariate HR (95%CI)	P value	Multivariate HR (95%CI)1	P value
Age
< 45 years	11 (47.8)	3 (18.8)	Reference
≥ 45 years	12 (52.2)	13 (81.2)	3.47 (0.95–12.6)	0.060
Sex
Female	14 (60.9)	11 (68.8)	Reference
Male	9 (39.1)	5 (31.2)	1.58 (0.52–4.81)	0.416
Tumor size
≤ 2 cm	3 (13.0)	0	Reference
> 2-4 cm	7 (30.4)	8 (53.3)
> 4 cm	13 (56.5)	7 (46.7)	1.39 (0.62–3.12)	0.423
T stage
T1/T2	8 (34.8)	5 (31.2)	Reference
T3/T4	15 (65.2)	11 (68.8)	1.31 (0.44–3.85)	0.627
N stage
N0	23 (100)	12 (75.0)	Reference		Reference
N1	0	4 (25.0)	6.86 (1.82–25.8)	0.004	10.1 (2.34–43.3)	0.002
M stage
M0	17 (73.9)	1 (37.5)	Reference		Reference
M1	6 (26.1)	10 (62.5)
M2	0	5 (31.2)	2.96 (1.53–5.74)	0.001	2.41 (1.07–5.39)	0.033
Extrathyroidal invasion
No	14 (60.9)	7 (43.8)	Reference
Yes	9 (39.1)	9 (56.2)	1.64 (0.61–4.43)	0.329
Type of thyroid surgery
Total thyroidectomy	21 (91.3)	14 (87.5)	Reference
Lobectomy or subtotal thyroidectomy	2 (4.3)	2 (6.2)	3.48 (0.71–17.0)	0.124
131I cumulative dose
< 100 mCi	14 (60.9)	7 (43.8)	Reference
≥ 100 mCi	9 (39.1)	9 (56.2)	1.42 (0.52–3.83)	0.493
External beam radiation therapy
No	20 (87.0)	6 (37.5)	Reference		Reference
Yes	3 (13.0)	10 (62.5)	4.42 (1.50–13.0)	0.007	3.07 (0.86–11.0)	0.084

¹Adjusted for N stage, M stage, and external beam radiation therapy.

Table 3 Clinical features of five patients who developed metastatic disease during follow-up

Patient number	Age/Sex	TNM at diagnosis	Type of thyroid surgery	Time from PDTC diagnosis to metastasis (years)	Cumulative dose of RAI before metastasis (mCi)	Positive finding at detection	Sites of metastasis	Time from metastasis to death (years)	Cumulative dose of RAI (mCi)	External beam radiation therapy, dose (cGy)	Targeted therapy
1	44/F	T4N0M0	Total thyroidectomy	11.9	0	CT	Lung, bone	5.9	980	6000
2	51/F	T4N0M0	Total thyroidectomy	1.7	100	PET/CT	Lung	2.5	100	0	Lenvatinib, sorafenib, cabozantinib
3	58/F	T4N0M0	Total thyroidectomy	0.7	30	RAI scan	Lung	2.1	580	5000
4	62/F	T2N0M0	Total thyroidectomy	4.9	160	Chest X-ray	Lung, bone	3.2	835	4500
5	77/F	T3N0M0	Total thyroidectomy	0.9	30	Chest X-ray	Lung	0.6	60	0

CT: Computed tomography; PET: Positron emission tomography; RAI: Radioactive iodine; PDTC: Poorly differentiated thyroid carcinoma.

Table 4 Risk factors associated with distant metastasis in poorly differentiated thyroid carcinoma patients, n (%)

	M0 (n = 18)	M1 + M2 (n = 21)	Univariate OR (95%CI)	P value
Age
< 45 years	10 (55.6)	4 ((19.0)	Reference
≥ 45 years	8 (44.4)	17 (81.0)	5.31 (1.27–22.2)	0.018
Sex
Female	13 (72.2)	12 (57.1)	Reference
Male	5 (27.8)	9 (42.9)	1.95 (0.51–7.49)	0.328
Tumor size
≤ 2 cm	3 (16.7)	0	Reference
> 2-4 cm	6 (33.3)	9 (45.0)
> 4 cm	9 (50.0)	11 (55.0)	1.72 (0.62–4.83)	0.301
T stage
T1/T2	7 (38.9)	6 (28.6)	Reference
T3/T4	11 (61.1)	15 (71.4)	1.59 (0.42–6.07)	0.496
N stage
N0	17 (94.4)	18 (85.7)	Reference
N1	1 (5.6)	3 (14.3)	2.83 (0.27–29.9)	0.370