ESTRO 2021 Abstract Book

S777

ESTRO 2021

PD-0934 Spatial modulation enhances the effects of radiation on cancer cells. L. Rogers 1,2 , B. Chen 3 , K. Liu 3 , D. McKenzie 1,2 , N. Suchowerska 1,2 , A. Kwan 3

1 Chris O'Brien Lifehouse, Radiation Oncology, Camperdown, Australia; 2 University of Sydney, School of Physics, Camperdown, Australia; 3 University of Sydney, School of Life and Environmental Sciences, Camperdown, Australia Purpose or Objective Spatially modulated fields deliver radiation with high and low dose regions and have been shown to achieve cancer cell death, while reducing damage to normal tissue for treatments. Spatial modulation of radiation is achieved using synchrotron or clinical photon beams. However, the mechanisms for the beneficial effects of modulated fields are not known and are addressed here using metabolomic analysis. Materials and Methods An androgen-sensitive prostate cancer (LNCaP) cell line and a normal prostate (PNT1A) cell line were exposed to a 6MV photon beam, either to a modulated field with a period of 5 mm, or to a uniform field with a dose equal to the valley, peak or the mean dose of the modulated field (Figure 1). A clonogenic assay was performed to quantify survival. The metabolic profiles of cell extracts and extracellular media following exposure were obtained using Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. For both cell lines, three separate experiments were performed. The irradiated groups were normalized to unirradiated controls and the data combined. A Principal Component Analysis (PCA) was performed to characterize the metabolite expression. A MANOVA was performed to compare the mean metabolite concentrations of the non-irradiated and irradiated groups, as well as between different irradiation regimes.

Results The clonogenic assay revealed that a modulated dose increases the therapeutic ratio, defined as the survival fraction of a normal cell line PNT1A relative to a prostate cancer cell line LNCaP. The PCA showed a dose response in the uniformly irradiated cancer cells (Figure 2A). It also showed that cancer cells irradiated with modulated fields were separated from those irradiated with a uniform field of the same total dose, but overlapped with those irradiated to a higher uniform dose. For cancer cells, metabolites that drive the separation in the metabolic profiles are highly correlated with aminoacyl-tRNA biosynthesis, providing evidence for cancer cells being more stressed by modulated irradiation. For normal cells, the PCA did not reveal a significant separation in response between uniform and modulated irradiation, providing evidence that normal cells are not sensitive to the modulation of the field (Figure 2B).

Conclusion This study presents new evidence that cancer cells exposed to spatially modulated fields, have similar biological responses to those arising from uniform radiation fields of a higher dose. Normal cells appear insensitive to the modulation, creating an opportunity to increase the therapeutic effect for a given prescribed dose.