Cellular Damage in the Target and Out-Of-Field Peripheral Organs during VMAT SBRT Prostate Radiotherapy: An In Vitro Phantom-Based Study

Abstract

Hypo-fractionated stereotactic body radiation therapy (SBRT) is an effective treatment for prostate cancer (PCa). Although many studies have investigated the effects of SBRT on the prostate and adjacent organs, little is known about the effects further out-of-field. The aim of this study was to investigate, both in vitro and in a quasi-humanoid phantom, the biological effects (using a dose-scaling approach) of radiation in the out-of-field peripheral organs delivered by 6 MV volumetric modulated arc therapy (VMAT) SBRT in a prostate cancer model. Healthy prostate cells were irradiated in a phantom at locations corresponding to the prostate, intestine, lung, thyroid, and brain. Seven 10 Gy fractions of VMAT SBRT were delivered to the target in a single session without intermission (scaled-up method). Radiochromic films were used to measure the doses. The radiobiological response was assessed by measuring DNA breaks, the cell survival fraction, and differences in gene expression profile. Our results showed a strong, multiparametric radiobiological response of the cells in the prostate. Outside of the radiation field, the highest doses were observed in the intestine and lung. A small increase (not statistically significant) in DNA damage and cell death was observed in the intestines. Several gene groups (cell cycle, DNA replication) were depleted in the lung and thyroid (DNA replication, endocytosis), but further analysis revealed no changes in the relevant biological processes. This study provides extensive evidence of the types and extent of radiobiological responses during VMAT SBRT in a prostate cancer model. Additional research is needed to determine whether the radiobiological effects observed in the peripheral organs are validated in a clinical context.