Table 2 Summary of baseline biomarker levels and changes during treatment

Biomarker type	Biomarker name	Pre-treatment levels (Median ± SD)	Median change at 14 days with single agent bevacizumab (%)	Biggest median change during treatment (%)	Median change at disease progression (%)
Circulating	Ang1	2.5 ± 2.0 × 10³	102.9	50.8	50.8
Circulating	Ang2	4.9 ± 9.0 × 10²	76.1	65.7	72.5
Circulating	E-selectin	1.5 ± 0.9 × 10⁴	92.8	86.9	96.4
Circulating	FGF2	2.6 ± 13.0 × 10²	86.5	46.9	57.5
Circulating	HGF	4.2 ± 12.2 × 10²	93.1	82.0	95.7
Circulating	IL6	1.1 ± 6.7 × 10¹	104.3	148.3	148.3
Circulating	IL8	5.0 ± 9.6 × 10	88.6	71.7	87.1
Circulating	KGF	7.3 ± 68.4 × 10⁰	92.3	41.1	106.7
Circulating	CK18	1.1 ± 0.6 × 10³	91.5	58.1	86.7
Circulating	PDGFbb	2.4 ± 2.2 × 10²	97.2	70.6	82.5
Circulating	PLGF	3.3 ± 41.0 × 10¹	104.1	92.9	113.3
Circulating	SDF1b	1.8 ± 1.2 × 10³	103.6	114.1	101.3
Circulating	Tie2	1.4 ± 0.8 × 10⁴	84.4	80.8	84.8
Circulating	VCAM1	5.6 ± 1.9 × 10⁵	103.6	186.3	183.6
Circulating	VEGFA	1.9 ± 1.9 × 10²	74.8	56.7	62.0
Circulating	VEGFC	5.8 ± 10.0 × 10²	94.8	64.6	81.4
Circulating	VEGFD	5.6 ± 255.3 × 10²	100.9	87.9	94.2
Circulating	VEGFR1	6.2 ± 78.7 × 10¹	96.0	91.6	115.7
Circulating	VEGFR2	1.1 ± 0.7 × 10⁴	97.6	84.0	84.0
Imaging	ADC	1.0 ± 0.2 × 10⁻³	102.4	91.0	98.8
Imaging	EF	9.7 ± 0.5 × 10¹	96.8	95.9	97.1
Imaging	ETV	3.8 ± 12.8 × 10⁴	84.4	43.6	48.3
Imaging	WTV	3.9 ± 13.9 × 10⁴	89.6	39.9	61.1
Imaging	IAUC	1.7 ± 0.7 × 10¹	72.1	68.0	72.9
Imaging	K ^trans	1.7 ± 1.1 × 10⁻¹	71.7	66.5	74.1
Imaging	T1	1.1 ± 0.2 × 10³	94.0	86.8	90.4
Imaging	Ve	3.1 ± 1.1 × 10⁻¹	88.7	86.5	86.5
Imaging	Vp	1.7 ± 1.6 × 10⁻²	67.8	63.4	63.4

Median pre-treatment levels of circulating and imaging biomarkers are shown, with the standard deviation (SD). Changes through treatment at three time-points are shown, related as a relative percentage (%) to the pre-treatment baseline levels. Values above 100 indicate increased biomarker levels while values below 100 indicate reduced biomarker levels. Plots of biomarker changes are shown in Supplementary Figure 2
The units for circulating biomarkers are pg/ml. The units of ADC are mm2/s; ETV and WTV mm3; IAUC s.mmol/l; Ktrans 1/min; T1 ms. EF, Ve and Vp are all ratios and therefore are unit-less, ± indicates plus and minus around one standard deviation (SD)
Ang1 and 2 angiopoietin 1 and 2, FGFb fibroblast growth factor beta, HGF hepatocyte growth factor, IL6 and 8 interleukins 6 and 8, KGF keratinocyte growth factor, CK18 cytokeratin 18, PDGFbb platelet-derived growth factor bb isoform, PlGF placental growth factor, SDF1b stromal-derived growth factor beta, VCAM1 vascular cell adhesion molecule 1, VEGFA, C, D, R1, and R2 vascular endothelial growth factor A, C, and D and receptors 1 and 2, ADC apparent diffusion coefficient, EF ejection fraction, ETV enhancing tumor volume, WTV whole tumor volume, IAUC initial area under the contrast agent concentration curve, Ktrans endothelial transfer constant, Ve extracellular extravascular space fractional volume, Vp plasma fractional volume

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