Compact and very high dose-rate plasma focus radiation sources for medical applications

A Dense Plasma Focus (DPF) is a pulsed device able to produce a hot and dense short-lived plasma that could become a fast radiation source for diagnostic applications, external radiotherapy, or intra-operative radiation therapy. The plasma confinement phase, identified as “pinch”, lasts few tens of nanoseconds, during which thermonuclear temperatures and densities could be reached. When the DPF vacuum chamber is filled with gases such as nitrogen, the only significant output are self-collimated charged particle beams (electrons and ions in opposite direction). Using that electron beam, it is possible to devise an ultra-high dose-rate source, with applications for direct irradiation of a tumor bed or for photon conversion after the interaction with a suitable target. The ultra-high dose rate could have potential benefits in mitigating the intrinsic or acquired malignant cell radio-resistance, which can be considered the main obstacle to the long-term survival of a patient, also sparing healthy tissues. This is due as the faster the dose deposition, the more relevant is the radiobiological efficacy (as the tumor cells do not have the time to activate the sub-lethal damage repair mechanisms responsible of the radio-resistance). Due to the novelty of the fast source, the usual models cannot easily describe the biological outcomes, therefore new numerical approaches are needed for predicting the RBE outlined in these regimens. A parametric investigation through the Monte Carlo Damage Simulation Software (MCDS), coupled with the Monte Carlo N-Particle (MCNP) code, has been performed for supporting the experimental results previously obtained by irradiating melanoma cell lines with the Plasma Focus Device for Medical Applications #3 (PFMA-3) as UHDR source and a conventional XRT as standard of comparison. The experimental data were benchmarked with MCNP-MCDS, properly fitting the XRT curves. The validation of the MCDS-MCNP coupling was performed by comparing literature data for conventional XRT, with less than 4% of differences. Next, the experimentally evaluated RBE highlighted that for high doses the RBE calculated on the basis of the surviving fraction (RBE(SF)), is the same of the one from double strand break damages (RBE(DSB)), making coherent the application of the Repair Misrepair Fixation theory (RMF) and providing a basis for a reliable comparison between the two devices. The DPF irradiation outcome has been numerically investigated correlating the experimental experiences with a wide range of code parameter variations to find numerical conditions able to reproduce the data. A recipe based on a combination of more than one SF curves to fit the clonogenic assay in UHDR regimen has also been proposed. The results suggested that the UHDR regimen obtained from the DPF source could change the environmental conditions (e.g., oxygen concentration) while cumulating the dose. This implies that a combination of data and MCDS-MCNP analysis could be applied as a strategy for quantifying biological effects.