Radiation dose-fractionation effects in spinal cord: comparison of animal and human data

Abstract

Purpose: Recognizing spinal cord dose limits in various fractionations is essential to ensure adequate dose for tumor control while minimizing the chance of radiation-induced myelopathy (RIM). This study aimed to determine the α/β ratio of the spinal cord and the cord dose limit in terms of BED50, the biological equivalent dose (BED) that induces 50 % chance of RIM, by fitting data collected from published animal and patient studies.

Methods: RIM data from five rat studies; three large animal studies on monkeys, dogs, and pigs; and 18 patient studies were included for the investigation. The α/β ratios were derived, respectively, for rat (group A), large animal (group B), patient (group C), and combined data (group D).

Results: The α/β ratio (and its 95 % confidental interval) was 4.1 (3.2, 5.0) or 3.6 (2.6, 4.6) Gy for group A, depending on fitting algorithms. It was 3.9 (3.0, 4.8), 3.7 (2.2, 8.2) and 3.9 (3.0, 4.9) for groups B, C, and D, respectively. BED50 was 111 Gy for the combined data. It corresponds to a D50 of 73.4 Gy in 2 Gy/FX, or 19.0 Gy in single fraction. BED5, which is the BED to induce 5 % of RIM, was calculated to be 83.9 Gy. It corresponds to D5 of 55.4 Gy in 2 Gy/FX, or 16.2 Gy in single fraction.

Conclusion: The study showed that all four groups had similar α/β ratios close to 3.9 Gy, suggesting that the spinal cord has a similar fractionation effect for different species, including human beings.

Keywords: Cord dose tolerance; Dose fractionation effect; Myelopathy; α/β ratio.

Fig. 1

Monte Carlo calculated dose distribution of an AP 20 MeV electron beam to a female patient

Fig. 2

Re-analysis of the α/β ratio for the six data sets from five rat studies specifically designed for studying fractionation effect using linear and non-linear regression. a Original data plotted (1/D50, D50/n) for linear regression. b Original data plotted (D50, n) for non-linear regression. c Normalized data plotted (1/D50, D50/n) and linear regression of the combined data for C- and T/L-spine subgroups. d Normalized data plotted (D50, n) and non-linear regression of combined data sets for the two subgroups

Fig. 3

Fitting the data with a logistic radiation-induced myelopathy (RIM) model. The data are plotted as percentage of RIM versus BED. BED was calculated from dose/fraction and number of fractions using the best fitting α/β ratio. a Large animal data. b Patient data. Data points 1, 2, and 3 before correction were also plotted for comparison

Fig. 4

Fitting the combined (group D) data with a logistic radiation-induced myelopathy (RIM) model. In addition to the 3 patient data points before correction, data from mice and rat studies were also plotted for comparison