Effects of Charged Particles on Human Tumor Cells

Abstract

The use of charged particle therapy in cancer treatment is growing rapidly, in large part because the exquisite dose localization of charged particles allows for higher radiation doses to be given to tumor tissue while normal tissues are exposed to lower doses and decreased volumes of normal tissues are irradiated. In addition, charged particles heavier than protons have substantial potential clinical advantages because of their additional biological effects, including greater cell killing effectiveness, decreased radiation resistance of hypoxic cells in tumors, and reduced cell cycle dependence of radiation response. These biological advantages depend on many factors, such as endpoint, cell or tissue type, dose, dose rate or fractionation, charged particle type and energy, and oxygen concentration. This review summarizes the unique biological advantages of charged particle therapy and highlights recent research and areas of particular research needs, such as quantification of relative biological effectiveness (RBE) for various tumor types and radiation qualities, role of genetic background of tumor cells in determining response to charged particles, sensitivity of cancer stem-like cells to charged particles, role of charged particles in tumors with hypoxic fractions, and importance of fractionation, including use of hypofractionation, with charged particles.

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness

“…This impairs cellular ability for correct repair 25 and decreases the dependence of radiosensitization upon the presence of oxygen, desirable features for eradication of resilient, hypoxic tumors 5,26 . Further potential radiobiological advantages include greater RBE for killing putatively radioresistant cancer stem cells 27 and counteracting cancer invasiveness 28,29 , albeit the latter remains controversial 30 . Finally, low doses of high-LET radiation appear to elicit stronger immunological responses compared to low-LET radiation 16 .…”

Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

“…However, it is increasingly appreciated that not only the physical characteristics of the beam but also the microscopic pattern of energy deposition differs between photons and protons, particularly at the distal edge of the Bragg-peak, with a potential impact on the resulting biological effects [14,20]. In fact, depending on the tissue, the measured endpoint, dose and LET of the beam, the RBE values reported for protons vary between~1.1-1.7, with increasing RBE values for protons along the distal edge of the Bragg peak [18,21,[25][26][27]. Moreover, first in vitro studies implicated that cancer-associated genetic defects in DNA repair-homologous recombination repair (HRR) or the Fanconi Anemia (FA) pathway-are associated with an increase in the RBE values for irradiation with proton beams compared to irradiation with gamma-ray photons or X-ray photons [28][29][30][31].…”

Influence of Therapeutic Proton Beam on Glioblastoma Multiforme Proliferation Index — A Preliminary Study

“…Numerous in vitro radiobiological studies for various cells using protons and photons have been carried out resulting in controversial data [21]. Authors showed that results are strongly influenced by the type of cells, culture condition, dose, dose rate, fractionation, and other physical features (i.e., LET, RBE) [22]. S.A. Amundson et al published that proton irradiation compared to X or gamma irradiation increases gene expression level in both their number and strength of response [23].…”