title: Key clinical beam parameters for nanoparticle-mediated radiation dose amplification.
abstract: As nanoparticle solutions move towards human clinical trials in radiation therapy, the influence of key clinical beam parameters on therapeutic efficacy must be considered. In this study, we have investigated the clinical radiation therapy delivery variables that may significantly affect nanoparticle-mediated radiation dose amplification. We found a benefit for situations which increased the proportion of low energy photons in the incident beam. Most notably, "unflattened" photon beams from a clinical linear accelerator results in improved outcomes relative to conventional "flat" beams. This is measured by significant DNA damage, tumor growth suppression, and overall improvement in survival in a pancreatic tumor model. These results, obtained in a clinical setting, clearly demonstrate the influence and importance of radiation therapy parameters that will impact clinical radiation dose amplification with nanoparticles.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.|Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Detappe
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.
authors.forename: Sijumon
authors.initials: S
authors.lastname: Kunjachan
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.
authors.forename: Pascal
authors.initials: P
authors.lastname: Drané
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.|Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Shady
authors.initials: S
authors.lastname: Kotb
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.
authors.forename: Marios
authors.initials: M
authors.lastname: Myronakis
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Biancur
authors.affiliation: LA-ICP-MS and ICP-ES Laboratories, Boston University, Boston, MA 02215, US.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ireland
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wagar
authors.affiliation: Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Lux
authors.affiliation: Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, US.
authors.forename: Ross
authors.initials: R
authors.lastname: Berbeco