**Tumour marker as a function of time**

Illustration of simulated data for steady-state concentrations (-●-), with a mean concentration 50 U/L, CVB = 24.5% and CVA = 8.5%, and tumours with exponential growth λ = 0.0132 (-■-)), according to 0.95\* eλ\*t U/L. Baseline (starting) concentration 50 U/L and the cut-off concentration, 95 U/L, (- - - -). Sampling frequency every two months (61 days).

Fig. 1B. *Steady-state* and tumour growth graphs.

298 Biomarker

Three consecutive measurements. The last and middle concentrations are both above the

At least three measurements. The last concentration is higher than the penultimate concentration and both are above the cut-off. The penultimate concentration is significantly

Three consecutive measurements. The first concentration is below twice the cut-off (doubling) and the last two are both above twice the cut-off (doubling) (Molina et al., 1995).

Three consecutive measurements. The first measured concentration is below the cut-off. The middle concentration is above the cut-off and the last measured concentration is >30 %

The basic principles and methods have been presented previously (Petersen et al., 2011; Söletormos et al., 2000b), and the basic model and the additional calculations of results for the varying start concentrations of TPA between the cut-off and these initial concentrations

> 0 100 200 300 400 500 600 **Time (days)**

Illustration of simulated data for steady-state concentrations (-●-), with a mean concentration 50 U/L, CVB = 24.5% and CVA = 8.5%. Baseline (starting) concentration 50 U/L and the cut-off concentration, 95

**Tumour marker as a function of time**

higher than any previous measurement below the cut-off (Söletormos et al., 1996).

higher than the middle measured concentration (Nicolini et al., 1991).

cut-off and the first is below the cut-off (Chan et al., 1997).

Chan et al. {4}:

Söletormos et al. B {5}:

Molina et al. {6}:

Nicolini et al. {7}:

**2.1.5 Methods** 

are described in detail below.

0

U/L, (- - - -). Sampling frequency every two months (61 days).

50

100

150

**Concentration**

Fig. 1A. *Steady-state* graph

200

250

300
