title: 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.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Kathryn D
authors.initials: KD
authors.lastname: Held
authors.affiliation: Gunma University Heavy Ion Medical Center, Gunma, Japan; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Kawamura
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Gunma University Heavy Ion Medical Center, Gunma, Japan; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kaminuma
authors.affiliation: Gunma University Heavy Ion Medical Center , Gunma , Japan.
authors.forename: Athena Evalour S
authors.initials: AE
authors.lastname: Paz
authors.affiliation: Gunma University Heavy Ion Medical Center , Gunma , Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
authors.forename: Henning
authors.initials: H
authors.lastname: Willers
authors.affiliation: Gunma University Heavy Ion Medical Center , Gunma , Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takahashi
keywords: altered fractionation; cancer stem cells; carbon-ion therapy; charged particles; clustered DNA damage; hypoxic radioresistance; proton therapy; relative biological effectiveness