Table 3. Open in new tab Univariate and...

	Time to distant metastatic disease (n = 120)	Disease-specific survival (n = 174)	Overall survival (n = 174)
Age	1.02	1.00–1.04	.016	1.05	1.02–1.07	<.001	1.05	1.02–1.08	<.001	1.06	1.03–1.08	<.001	1.06	1.03–1.08	<.001
Female	0.80	0.48–1.34	.39	0.57	0.30–1.08	0.085	—	—	—	0.52	0.28–0.96	.066	—	—	—
T category at diagnosis			.82			.99	—	—	—			.99	—	—	—
T1	Reference	Reference				Reference
T2	0.79	0.34–1.79		0.78	0.28–2.15					0.80	0.31–2.07
T3	1.00	0.49–2.04		0.98	0.42–2.27					0.97	0.44–2.16
T4	1.06	0.49–2.04		0.89	0.31–2.58					0.93	0.34–2.50
N category at diagnosis			.30			.71	—	—	—			.60
N0	Reference	Reference				Reference
N1a	1.60	0.45–5.74		0.66	0.12–3.64					0.53	0.10–2.76
N1b	1.96	0.83–4.61		1.19	0.42–3.38					1.08	0.42–2.76
M category at diagnosis		—				<.001			.001			<.001			.001
M0				Reference	Reference	Reference	Reference
M1				3.70	1.92–7.15		3.17	1.59–6.32		3.63	1.95–6.74		2.98	1.56–5.69
Systemic therapy		—		2.39	1.15–4.96	0.019	2.04	0.96–4.37	.066	2.45	1.22–4.89	.011	2.06	1.00–4.24	0.049
Mutation cohort			.24			.45			.11			.74			.17
RET/RAS WT	Reference	Reference	Reference	Reference	Reference
RAS	1.86	0.42–8.31		4.42	0.57–34.12		6.69	0.86–51.99		2.22	0.49–9.94		3.43	0.76–15.54
RET-other	3.72	0.81–17.04		2.59	0.29–23.23		2.15	0.24–19.60		1.62	0.21–8.38		1.26	0.75–15.51
RET M918T	2.36	0.57–9.89		3.21	0.43–23.93		4.38	0.58–32.79		1.84	0.49–9.94		2.56	0.60–10.92

Time to distant metastatic disease (n = 120)

Disease-specific survival (n = 174)

Overall survival (n = 174)

Univariate

Multivariate

Univariate

Multivariate

Hazard ratio

95% CI

P value

Hazard ratio

95% CI

P value

Hazard ratio

95% CI

P value

Hazard ratio

95% CI

P value

Hazard ratio

95% CI

P value

Age

1.02

1.00–1.04

.016

1.05

1.02–1.07

<.001

1.05

1.02–1.08

<.001

1.06

1.03–1.08

<.001

1.06

1.03–1.08

<.001

Female

0.80

0.48–1.34

.39

0.57

0.30–1.08

0.085

—

0.52

0.28–0.96

.066

—

T category at diagnosis

.82

.99

—

.99

—

Reference

0.79

0.34–1.79

0.78

0.28–2.15

0.80

0.31–2.07

1.00

0.49–2.04

0.98

0.42–2.27

0.97

0.44–2.16

1.06

0.49–2.04

0.89

0.31–2.58

0.93

0.34–2.50

N category at diagnosis

.30

.71

—

.60

Reference

N1a

1.60

0.45–5.74

0.66

0.12–3.64

0.53

0.10–2.76

N1b

1.96

0.83–4.61

1.19

0.42–3.38

1.08

0.42–2.76

M category at diagnosis

—

<.001

.001

<.001

.001

Reference

3.70

1.92–7.15

3.17

1.59–6.32

3.63

1.95–6.74

2.98

1.56–5.69

Systemic therapy

—

2.39

1.15–4.96

0.019

2.04

0.96–4.37

.066

2.45

1.22–4.89

.011

2.06

1.00–4.24

0.049

Mutation cohort

.24

.45

.11

.74

.17

RET/RAS WT

Reference

RAS

1.86

0.42–8.31

4.42

0.57–34.12

6.69

0.86–51.99

2.22

0.49–9.94

3.43

0.76–15.54

RET-other

3.72

0.81–17.04

2.59

0.29–23.23

2.15

0.24–19.60

1.62

0.21–8.38

1.26

0.75–15.51

RET M918T

2.36

0.57–9.89

3.21

0.43–23.93

4.38

0.58–32.79

1.84

0.49–9.94

2.56

0.60–10.92

	Time to distant metastatic disease (n = 120)	Disease-specific survival (n = 174)	Overall survival (n = 174)
Age	1.02	1.00–1.04	.016	1.05	1.02–1.07	<.001	1.05	1.02–1.08	<.001	1.06	1.03–1.08	<.001	1.06	1.03–1.08	<.001
Female	0.80	0.48–1.34	.39	0.57	0.30–1.08	0.085	—	—	—	0.52	0.28–0.96	.066	—	—	—
T category at diagnosis			.82			.99	—	—	—			.99	—	—	—
T1	Reference	Reference				Reference
T2	0.79	0.34–1.79		0.78	0.28–2.15					0.80	0.31–2.07
T3	1.00	0.49–2.04		0.98	0.42–2.27					0.97	0.44–2.16
T4	1.06	0.49–2.04		0.89	0.31–2.58					0.93	0.34–2.50
N category at diagnosis			.30			.71	—	—	—			.60
N0	Reference	Reference				Reference
N1a	1.60	0.45–5.74		0.66	0.12–3.64					0.53	0.10–2.76
N1b	1.96	0.83–4.61		1.19	0.42–3.38					1.08	0.42–2.76
M category at diagnosis		—				<.001			.001			<.001			.001
M0				Reference	Reference	Reference	Reference
M1				3.70	1.92–7.15		3.17	1.59–6.32		3.63	1.95–6.74		2.98	1.56–5.69
Systemic therapy		—		2.39	1.15–4.96	0.019	2.04	0.96–4.37	.066	2.45	1.22–4.89	.011	2.06	1.00–4.24	0.049
Mutation cohort			.24			.45			.11			.74			.17
RET/RAS WT	Reference	Reference	Reference	Reference	Reference
RAS	1.86	0.42–8.31		4.42	0.57–34.12		6.69	0.86–51.99		2.22	0.49–9.94		3.43	0.76–15.54
RET-other	3.72	0.81–17.04		2.59	0.29–23.23		2.15	0.24–19.60		1.62	0.21–8.38		1.26	0.75–15.51
RET M918T	2.36	0.57–9.89		3.21	0.43–23.93		4.38	0.58–32.79		1.84	0.49–9.94		2.56	0.60–10.92

Table 3.

Open in new tab

Univariate and multivariate analysis of time to distant metastatic disease, disease-specific survival, and overall survival of somatic mutations in sMTC

	Time to distant metastatic disease (n = 120)			Disease-specific survival (n = 174)						Overall survival (n = 174)
	Univariate			Univariate			Multivariate			Univariate			Multivariate
	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value
Age	1.02	1.00–1.04	.016	1.05	1.02–1.07	<.001	1.05	1.02–1.08	<.001	1.06	1.03–1.08	<.001	1.06	1.03–1.08	<.001
Female	0.80	0.48–1.34	.39	0.57	0.30–1.08	0.085	—	—	—	0.52	0.28–0.96	.066	—	—	—
T category at diagnosis			.82			.99	—	—	—			.99	—	—	—
T1	Reference			Reference						Reference
T2	0.79	0.34–1.79		0.78	0.28–2.15					0.80	0.31–2.07
T3	1.00	0.49–2.04		0.98	0.42–2.27					0.97	0.44–2.16
T4	1.06	0.49–2.04		0.89	0.31–2.58					0.93	0.34–2.50
N category at diagnosis			.30			.71	—	—	—			.60
N0	Reference			Reference						Reference
N1a	1.60	0.45–5.74		0.66	0.12–3.64					0.53	0.10–2.76
N1b	1.96	0.83–4.61		1.19	0.42–3.38					1.08	0.42–2.76
M category at diagnosis		—				<.001			.001			<.001			.001
M0				Reference			Reference			Reference			Reference
M1				3.70	1.92–7.15		3.17	1.59–6.32		3.63	1.95–6.74		2.98	1.56–5.69
Systemic therapy		—		2.39	1.15–4.96	0.019	2.04	0.96–4.37	.066	2.45	1.22–4.89	.011	2.06	1.00–4.24	0.049
Mutation cohort			.24			.45			.11			.74			.17
RET/RAS WT	Reference			Reference			Reference			Reference			Reference
RAS	1.86	0.42–8.31		4.42	0.57–34.12		6.69	0.86–51.99		2.22	0.49–9.94		3.43	0.76–15.54
RET-other	3.72	0.81–17.04		2.59	0.29–23.23		2.15	0.24–19.60		1.62	0.21–8.38		1.26	0.75–15.51
RET M918T	2.36	0.57–9.89		3.21	0.43–23.93		4.38	0.58–32.79		1.84	0.49–9.94		2.56	0.60–10.92

	Time to distant metastatic disease (n = 120)			Disease-specific survival (n = 174)						Overall survival (n = 174)
	Univariate			Univariate			Multivariate			Univariate			Multivariate
	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value	Hazard ratio	95% CI	P value
Age	1.02	1.00–1.04	.016	1.05	1.02–1.07	<.001	1.05	1.02–1.08	<.001	1.06	1.03–1.08	<.001	1.06	1.03–1.08	<.001
Female	0.80	0.48–1.34	.39	0.57	0.30–1.08	0.085	—	—	—	0.52	0.28–0.96	.066	—	—	—
T category at diagnosis			.82			.99	—	—	—			.99	—	—	—
T1	Reference			Reference						Reference
T2	0.79	0.34–1.79		0.78	0.28–2.15					0.80	0.31–2.07
T3	1.00	0.49–2.04		0.98	0.42–2.27					0.97	0.44–2.16
T4	1.06	0.49–2.04		0.89	0.31–2.58					0.93	0.34–2.50
N category at diagnosis			.30			.71	—	—	—			.60
N0	Reference			Reference						Reference
N1a	1.60	0.45–5.74		0.66	0.12–3.64					0.53	0.10–2.76
N1b	1.96	0.83–4.61		1.19	0.42–3.38					1.08	0.42–2.76
M category at diagnosis		—				<.001			.001			<.001			.001
M0				Reference			Reference			Reference			Reference
M1				3.70	1.92–7.15		3.17	1.59–6.32		3.63	1.95–6.74		2.98	1.56–5.69
Systemic therapy		—		2.39	1.15–4.96	0.019	2.04	0.96–4.37	.066	2.45	1.22–4.89	.011	2.06	1.00–4.24	0.049
Mutation cohort			.24			.45			.11			.74			.17
RET/RAS WT	Reference			Reference			Reference			Reference			Reference
RAS	1.86	0.42–8.31		4.42	0.57–34.12		6.69	0.86–51.99		2.22	0.49–9.94		3.43	0.76–15.54
RET-other	3.72	0.81–17.04		2.59	0.29–23.23		2.15	0.24–19.60		1.62	0.21–8.38		1.26	0.75–15.51
RET M918T	2.36	0.57–9.89		3.21	0.43–23.93		4.38	0.58–32.79		1.84	0.49–9.94		2.56	0.60–10.92

M category at diagnosis and use of systemic therapy were not included in the time to distant metastatic disease analysis as patients were all M0 at diagnosis and use of systemic therapy would largely be driven by the development of distant metastatic disease. Patients with RET indel were not included in either regression analysis.

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