Biological Efficacy of Quasi-Monoenergetic Convergent Photons
Abstract
Purpose
Recent advancements in x-ray optics have led to the development of a Bragg-reflecting x-ray lens to converge radiation beams into a focus spot (Convergent Radiotherapy and Radiosurgery, CRnR, Haifa, Israel), generating quasi-monoenergetic x-rays (~60 keV) with a sharp localized dose gradient, and a unique depth dose profile that resembles a Bragg peak. This study presents a comprehensive biological characterization of the convergent CRnR x-rays.
Methods
For in vitro experiments, we used human (NCI-H460 and NCI-H2172), or murine (KLN-205 and LKR-13) lung cancer cell lines and a normal human bronchial epithelial cell line (BEAS-2B). Cell lines were irradiated with convergent CRnR, clinical orthovoltage (180 kVp, average energy ~60 keV), or 6 MV x-rays. We assessed clonogenic cell survival, cell cycle, and DNA damage. An NCI-H460 xenograft model was used to assess tumor growth delay and survival for convergent CRnR versus 6 MV x-rays.
Results
Clonogenic survival showed either comparable or higher cell kill for CRnR and orthovoltage compared to 6-MV. CRnR and orthovoltage x-rays were more efficacious than 6 MV in killing NCI-H460 and NCI-H2172 cells, further supported by increased DNA damage response (γ-H2AX and 53BP1 foci) and more pronounced G2/M cell-cycle arrest. Whereas relative biological effectiveness (RBE) for CRnR and orthovoltage (relative to 6 MV) showed variation among cell lines, with some cell lines presenting significant or non-significant RBE>1. In vivo, CRnR and 6 MV produced comparable tumor growth delay and survival benefits.
Conclusion
While low-energy convergent x-rays induce more DNA damage and consequent more G2/M arrest compared to 6 MV, some cell lines can cope with DNA damage, presenting RBE=1, while others present RBE>1. An exciting application of the small focus spot of convergent beams is to deliver spatially fractionated radiotherapy to deep-seated small tumors, which may also be used as a platform to combine radiation with immunotherapy.