Table 3 Open in new tab Univariate and...

Analysis	Predictor	HR (95% CI)	p value
Univariate
Age		1.00 (0.97–1.03)	.928
Sex		1.19 (0.57–2.49)	.639
Smoking		1.32 (0.60–3.06)	.506
Stage of disease at sample collection		2.08 (0.77–6.64)	.173
ECOG for patients Treated with immune checkpoint blockade		2.30 (0.74–9.30)	.182
TMB (continuous): method 3		1.00 (0.98–1.03)	.699
TMB (high vs. low): method 3		1.45 (0.666–3.19)	.350
TMB (continuous): method 3 including 0 TMB scores		1.01 (1.00–1.03)	.135
TMB (high vs. low): method 3 including 0 TMB scores		2.00 (0.96–4.19)	.065
MAF (continuous)		1.02 (1.00–1.06)	.074
MAF (high vs. low)		3.82 (1.80–8.52)	.001^a
Multivariate
Age + sex + smoking + stage + TMB (high vs. low, method 3)	TMB	1.40 (0.62–3.21)	.420
Age + sex + smoking + stage + TMB (high vs. low, method 3 including 0 TMB scores)	TMB	2.01 (0.93–4.38)	.075
Age + sex + smoking + stage + ECOG + MAF (high vs. low)	MAF	3.70 (1.70–8.44)	.001^a
Age + sex + smoking + stage + TMB (high vs. low, method 3) + MAF (high vs. low)	TMB	0.62 (0.08–3.15)	.592
MAF	2.35 (0.73–7.92)	.157
TMB* MAF	1.82 (0.27–16.86)	.560
TMB (high vs. low, method 3) + MAF (high vs. low) + TMB* MAF	TMB	0.91 (0.13–4.26)	.911
MAF	3.28 (1.12–9.83)	.031^a
TMB* MAF	1.29 (0.20–11.49)	.798

Analysis

Predictor

HR (95% CI)

p value

Univariate

Age

1.00 (0.97–1.03)

.928

Sex

1.19 (0.57–2.49)

.639

Smoking

1.32 (0.60–3.06)

.506

Stage of disease at sample collection

2.08 (0.77–6.64)

.173

ECOG for patients Treated with immune checkpoint blockade

2.30 (0.74–9.30)

.182

TMB (continuous): method 3

1.00 (0.98–1.03)

.699

TMB (high vs. low): method 3

1.45 (0.666–3.19)

.350

TMB (continuous): method 3 including 0 TMB scores

1.01 (1.00–1.03)

.135

TMB (high vs. low): method 3 including 0 TMB scores

2.00 (0.96–4.19)

.065

MAF (continuous)

1.02 (1.00–1.06)

.074

MAF (high vs. low)

3.82 (1.80–8.52)

.001^a

Multivariate

Age + sex + smoking + stage + TMB (high vs. low, method 3)

TMB

1.40 (0.62–3.21)

.420

Age + sex + smoking + stage + TMB (high vs. low, method 3 including 0 TMB scores)

TMB

2.01 (0.93–4.38)

.075

Age + sex + smoking + stage + ECOG + MAF (high vs. low)

MAF

3.70 (1.70–8.44)

.001^a

Age + sex + smoking + stage + TMB (high vs. low, method 3) + MAF (high vs. low)

TMB

0.62 (0.08–3.15)

.592

MAF

2.35 (0.73–7.92)

.157

TMB* MAF

1.82 (0.27–16.86)

.560

TMB (high vs. low, method 3) + MAF (high vs. low) + TMB* MAF

TMB

0.91 (0.13–4.26)

.911

MAF

3.28 (1.12–9.83)

.031^a

TMB* MAF

1.29 (0.20–11.49)

.798

Analysis	Predictor	HR (95% CI)	p value
Univariate
Age		1.00 (0.97–1.03)	.928
Sex		1.19 (0.57–2.49)	.639
Smoking		1.32 (0.60–3.06)	.506
Stage of disease at sample collection		2.08 (0.77–6.64)	.173
ECOG for patients Treated with immune checkpoint blockade		2.30 (0.74–9.30)	.182
TMB (continuous): method 3		1.00 (0.98–1.03)	.699
TMB (high vs. low): method 3		1.45 (0.666–3.19)	.350
TMB (continuous): method 3 including 0 TMB scores		1.01 (1.00–1.03)	.135
TMB (high vs. low): method 3 including 0 TMB scores		2.00 (0.96–4.19)	.065
MAF (continuous)		1.02 (1.00–1.06)	.074
MAF (high vs. low)		3.82 (1.80–8.52)	.001^a
Multivariate
Age + sex + smoking + stage + TMB (high vs. low, method 3)	TMB	1.40 (0.62–3.21)	.420
Age + sex + smoking + stage + TMB (high vs. low, method 3 including 0 TMB scores)	TMB	2.01 (0.93–4.38)	.075
Age + sex + smoking + stage + ECOG + MAF (high vs. low)	MAF	3.70 (1.70–8.44)	.001^a
Age + sex + smoking + stage + TMB (high vs. low, method 3) + MAF (high vs. low)	TMB	0.62 (0.08–3.15)	.592
MAF	2.35 (0.73–7.92)	.157
TMB* MAF	1.82 (0.27–16.86)	.560
TMB (high vs. low, method 3) + MAF (high vs. low) + TMB* MAF	TMB	0.91 (0.13–4.26)	.911
MAF	3.28 (1.12–9.83)	.031^a
TMB* MAF	1.29 (0.20–11.49)	.798

Table 3

Open in new tab

Univariate and multivariate regression analyses

Analysis	Predictor	HR (95% CI)	p value
Univariate
Age		1.00 (0.97–1.03)	.928
Sex		1.19 (0.57–2.49)	.639
Smoking		1.32 (0.60–3.06)	.506
Stage of disease at sample collection		2.08 (0.77–6.64)	.173
ECOG for patients Treated with immune checkpoint blockade		2.30 (0.74–9.30)	.182
TMB (continuous): method 3		1.00 (0.98–1.03)	.699
TMB (high vs. low): method 3		1.45 (0.666–3.19)	.350
TMB (continuous): method 3 including 0 TMB scores		1.01 (1.00–1.03)	.135
TMB (high vs. low): method 3 including 0 TMB scores		2.00 (0.96–4.19)	.065
MAF (continuous)		1.02 (1.00–1.06)	.074
MAF (high vs. low)		3.82 (1.80–8.52)	.001^a
Multivariate
Age + sex + smoking + stage + TMB (high vs. low, method 3)	TMB	1.40 (0.62–3.21)	.420
Age + sex + smoking + stage + TMB (high vs. low, method 3 including 0 TMB scores)	TMB	2.01 (0.93–4.38)	.075
Age + sex + smoking + stage + ECOG + MAF (high vs. low)	MAF	3.70 (1.70–8.44)	.001^a
Age + sex + smoking + stage + TMB (high vs. low, method 3) + MAF (high vs. low)	TMB	0.62 (0.08–3.15)	.592
	MAF	2.35 (0.73–7.92)	.157
	TMB* MAF	1.82 (0.27–16.86)	.560
TMB (high vs. low, method 3) + MAF (high vs. low) + TMB* MAF	TMB	0.91 (0.13–4.26)	.911
	MAF	3.28 (1.12–9.83)	.031^a
	TMB* MAF	1.29 (0.20–11.49)	.798

Analysis	Predictor	HR (95% CI)	p value
Univariate
Age		1.00 (0.97–1.03)	.928
Sex		1.19 (0.57–2.49)	.639
Smoking		1.32 (0.60–3.06)	.506
Stage of disease at sample collection		2.08 (0.77–6.64)	.173
ECOG for patients Treated with immune checkpoint blockade		2.30 (0.74–9.30)	.182
TMB (continuous): method 3		1.00 (0.98–1.03)	.699
TMB (high vs. low): method 3		1.45 (0.666–3.19)	.350
TMB (continuous): method 3 including 0 TMB scores		1.01 (1.00–1.03)	.135
TMB (high vs. low): method 3 including 0 TMB scores		2.00 (0.96–4.19)	.065
MAF (continuous)		1.02 (1.00–1.06)	.074
MAF (high vs. low)		3.82 (1.80–8.52)	.001^a
Multivariate
Age + sex + smoking + stage + TMB (high vs. low, method 3)	TMB	1.40 (0.62–3.21)	.420
Age + sex + smoking + stage + TMB (high vs. low, method 3 including 0 TMB scores)	TMB	2.01 (0.93–4.38)	.075
Age + sex + smoking + stage + ECOG + MAF (high vs. low)	MAF	3.70 (1.70–8.44)	.001^a
Age + sex + smoking + stage + TMB (high vs. low, method 3) + MAF (high vs. low)	TMB	0.62 (0.08–3.15)	.592
	MAF	2.35 (0.73–7.92)	.157
	TMB* MAF	1.82 (0.27–16.86)	.560
TMB (high vs. low, method 3) + MAF (high vs. low) + TMB* MAF	TMB	0.91 (0.13–4.26)	.911
	MAF	3.28 (1.12–9.83)	.031^a
	TMB* MAF	1.29 (0.20–11.49)	.798

Circulating tumor DNA TMB and MAF scores were included based on low (below the median) and high (above the median) and as continuous variables. Samples without detected mutations were excluded from this analysis unless specified.

^aIndicates significance based on p < 0.05.

Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; MAF, mutant allele frequency; TMB, tumor mutational burden.

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