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Modelling the immunosuppressive effect of liver SBRT by simulating the dose to circulating lymphocytes: an in-silico planning study


Basler, L; Andratschke, N; Ehrbar, S; Guckenberger, M; Tanadini-Lang, S (2018). Modelling the immunosuppressive effect of liver SBRT by simulating the dose to circulating lymphocytes: an in-silico planning study. Radiation Oncology, 13(1):10.

Abstract

BACKGROUND 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.
METHODS 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.
RESULTS 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.
CONCLUSION 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.

Abstract

BACKGROUND 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.
METHODS 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.
RESULTS 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.
CONCLUSION 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:22 January 2018
Deposited On:15 Feb 2018 11:40
Last Modified:01 Mar 2018 01:57
Publisher:BioMed Central
ISSN:1748-717X
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13014-018-0952-y
PubMed ID:29357886

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