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