The FLASH enigma

Abstract

We consider physics behind the FLASH modality of cancer radiation treatment where extremely short treatment times are achieved with ultra high dose rates maintaining the conventional antitumor effectiveness and yet substantially reducing damage to normal tissues (sparing effect). The difference in responses between normal and tumor tissues is attributed here to different recombination rates related to their structure morphologies: ordered in normal vs disordered in the tumor tissues. Correspondingly different are their charge densities under ionizing radiation. In normal tissues it is high enough to form electron-hole liquid (EHL). Because of low EHL diffusivities, the chemical reaction and generation of free radicals are suppressed; hence, sparing effect. To the contrary, a disordered tumor tissue renders efficient energy relaxation channels forming antitumor free radicals. We describe the FLASH thresholds for doses and dose rates.

Figures (7)

• Figure 1: Schematics of ordered vs. disordered counterpart structures. (a) Scanning electron microscopy image of polymer cast of normal microvasculature; (b) same for tumor microvasculature showing disorganization and lack of conventional hierarchy of blood vessels. mcdonald2003 (c) Cell structure in healthy vs. that of cancer tissue. kenny2001 (d) Crystalline (c-Si) vs. amorphous (a-Si) silicon structure. Note the dangling bonds which can play the role of recombination centers. si
• Figure 2: Flow chart aimed at answering the FLASH enigma. The top row boxes (following Fig. 1 of the earlier published review chow2024) presents the general physicochemical processes found with both CONV-RT and FLASH-RT modalities. The bottom row discriminates between CONV-RT (left) and FLASH-RT (right), as explained in the text. The insert figure in the left bottom corner presents a graphical illustration of the electronic processes under irradiation in the tumor (left) and healthy tissues (right) regions. Thin arrows show the e-h recombination processes, $RC$ stand for recombination centers (defects). $+$ and $-$ denote holes and electrons respectively.
• Figure 3: Electronic processes related to FLASH enigma. (a) e-h pair with energy gap $G$ recombining in one step; (b) same pair recombining in two consecutive steps through a defect state with energy $G_1$; (c) multilevel defect states forming a recombination staircase; (d) same as in (c) in greater detail, showing that each electronic transition takes place not only in energy but in real space as well. Here, vertical axis represents the energy, while the horizontal one corresponds to spatial coordinates.
• Figure 4: Radiation induced ionization depending on dose rate and energy. Dark circles represent the electrons, white circles represent holes. From right to left: (1) plasma of weakly interacting electrons and holes generated with low dose rates high energy radiation; (2) excitons, i. e. coupled electron - hole pairs generated with higher dose rates and close to the absorption edge radiation; (3) biexcitons which are coupled pairs of excitons forming with increase of exciton concentration; (4) a droplet of electron hole liquid under high dose rate of well absorbed radiation.
• Figure 5: Typical rate dependencies of EHL ($dn(t)/dt$) and RSS ($dR(t)/dt$) on EHL concentration assuming strong enough binding as described in Eqs. (\ref{['eq:kinetics']}) and (\ref{['eq:RSS']})