The online version of this article (doi: https://doi.org/10.1186/s13014-018-0952-y) contains supplementary material, which is available to authorized users.
Tumor immune-evasion and associated failure of immunotherapy can potentially be overcome by radiotherapy, which however also has detrimental effects on tumor-infiltrating and circulating lymphocytes (CL). We therefore established a model to simulate the radiation-dose delivered to CL.
A MATLAB-model was established to quantify the CL-dose during SBRT of liver metastases by considering the factors: hepatic blood-flow, −velocity and transition-time of individual hepatic segments, as well as probability-based recirculation. The effects of intra-hepatic tumor-location and size, fractionation and treatment planning parameters (VMAT, 3DCRT, photon-energy, dose-rate and beam-on-time) were analyzed. A threshold dose ≥0.5Gy was considered inactivating CL and CL0.5 (%) is the proportion of inactivated CL.
Mean liver dose was mostly influenced by treatment-modality, whereas CL0.5 was mostly influenced by beam-on-time. 3DCRT and VMAT (10MV-FFF) resulted in lowest CL0.5 values of 16 and 19%. Metastasis location influenced CL0.5, with a mean of 19% for both apical and basal and 31% for the central location. PTV-volume significantly increased CL0.5 from 27 to 67% (10MV-FFF) and from 31 to 98% (6MV-FFF) for PTV-volumes ranging from 14cm3 to 268cm3.
A simulation-model was established, quantifying the strong effects of treatment-technique, tumor-location and tumor-volume on dose to CL with potential implications for immune-optimized treatment-planning in the future.
Additional file 1: Segment volume. Volume and blood flow per segment. Calculated absolute and relative volume and blood flow of the individual liver segments. (PDF 129 kb)13014_2018_952_MOESM1_ESM.pdf
Additional file 2: Segment distance. Distance to geometric center and mean hepatic transition time per segment. 2D Distance from arterial blood supply/venous drainage to geometric center of individual segments. 3D Pythagorean distance calculation for estimation of mean hepatic transition time per segment (in seconds). (PDF 148 kb)13014_2018_952_MOESM2_ESM.pdf
Additional file 3: DVH convulution algorithm. DVH convolution algorithm. For every treatment fraction, the current Blood DVH is multiplied by a new convolution DVH consisting of individual liver segments & the blood fraction outside the liver. As a result, a new Blood DVH is generated. (PDF 726 kb)13014_2018_952_MOESM3_ESM.pdf
Additional file 4: Fractionation effect on CL (3D CRT). Fractionation effect on CL (3DCRT). There is no significant fractionation effect on circulating lymphocytes with 3DCRT for the apical tumor location. (PDF 26 kb)13014_2018_952_MOESM4_ESM.pdf
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- Modelling the immunosuppressive effect of liver SBRT by simulating the dose to circulating lymphocytes: an in-silico planning study
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