Abstract
BackgroundTumour volume at therapy initiation, Vi, is rarely available in cancer patients, and the last pre-treatment tumour volume available is from previous diagnostic imaging (Vd). Therapeutic efficacy is thus evaluated by comparing tumour volume after treatment with Vd, instead of Vi, which results in underestimation of treatment efficacy. Vi, together with Vd, can also be used for estimation of the natural growth rate of tumour valuable for, e.g., screening programs, prognostication and individualised treatment planning such as chemotherapy scheduling. The aim of this work was to study the feasibility of estimating Vi by back-extrapolating the post-therapy regression of tumour volume, based on data from animal model.MethodsNude mice bearing human neuroendocrine GOT1 tumour cell line were treated with 177Lu-DOTA-TATE. Tumour volumes were measured regularly after therapy and Vi was estimated by back-extrapolation of (a) linear and (b) exponential regression lines of the two earliest post-therapy tumour volumes and (c) the long-term exponential regression of tumour volume. The estimated Vi values (Vest) were compared with the measured volume of tumour at therapy initiation.ResultsThe linear regression of the two earliest post-therapy tumour volumes gave the best estimate for Vi (Vest = 0.91 Vi, p < 0.00001), compared with the exponential regression models either on short-term (Vest = 2.30 Vi, p < 0.01), or long-term (Vest = 0.93 Vi, non-significant) follow up of tumour volume after therapy.ConclusionBack-extrapolation of the early linear regression of tumour volume after therapy gave the best estimate for tumour volume at time of therapy initiation. This estimate can be used as baseline for treatment efficacy evaluation or for estimation of the natural growth rate of tumour (together with the measured tumour volume at pre-treatment diagnostic imaging).
Highlights
Tumour volume at therapy initiation, Vi, is rarely available in cancer patients, and the last pre-treatment tumour volume available is from previous diagnostic imaging (Vd)
Correlation between the estimated and the true Vi was statistically significant for Lin model (p < 0.00001) with and without forcing intercept = 0 and slope of the regression line was close to the ideal model with unity value, i.e. Vest = Vi
Residual sum of squares (RSS) were 66, 4718, 6416 for the Lin, Exp, and EXP models, respectively. These results show that back-extrapolation of the early linear regression equation of tumour volume after therapy, i.e. the Lin model, gives the best estimate for tumour volume at therapy initiation
Summary
Tumour volume at therapy initiation, Vi, is rarely available in cancer patients, and the last pre-treatment tumour volume available is from previous diagnostic imaging (Vd). Together with Vd, can be used for estimation of the natural growth rate of tumour valuable for, e.g., screening programs, prognostication and individualised treatment planning such as chemotherapy scheduling. The estimated Vi values (Vest) were compared with the measured volume of tumour at therapy initiation. Knowledge of the natural growth rate of tumours is valuable for, e.g., optimization of screening programs, and individualised treatment planning, such as scheduling chemotherapy. SGR is by definition equal to the limit of relative growth rate of tumour when the measurement time interval, i.e. t2-t1, approaches zero and it is usually given in %/d (percent per day). Eq 1 shows that estimation of tumour growth rate needs at least two tumour volume measurements before the start of therapy. Mathematical methods must, be used for indirect estimation of tumour growth rate prior to treatment
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