title: Targeted dose enhancement in radiotherapy for breast cancer using gold nanoparticles, part 2: A treatment planning study.
abstract: OBJECTIVE
  In recent years, there has been growing interest in the use of gold nanoparticles (GNPs) combined with radiotherapy to improve tumor control. However, the complex interplay between GNP uptake and dose distribution in realistic clinical treatment are still somewhat unknown.
  
  
  METHODS
  The effects of different concentrations of 2 nm diameter GNP, ranging from 0 to 5×105 nanoparticles per tumoral cell, were theoretically investigated. A parametrization of the GNP distribution outside the target was carried out using a Gaussian standard deviation σ, from a zero value, relative to a selective concentration of GNPs inside the tumor volume alone, to 50mm, when GNPs are spatially distributed also in the healthy tissues surrounding the tumor. Treatment simulations of five patients with breast cancer were performed with 6 and 15 MV photons assuming a partial breast irradiation. A closed analytical reformulation of the Local Effect Model coupled with the estimation of local dose deposited around a GNP was validated using an in vitro study for MDA-MB-231 tumoral cells. The expected treatment outcome was quantified in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP) as a function of the spatially varying gold uptake.
  
  
  RESULTS
  Breast cancer treatment planning simulations show improved treatment outcomes when GNPs are selectively concentrated in the tumor volume (i.e., σ = 0 mm). In particular, the TCP increases up to 18% for 5×105 nanoparticles per cell in the tumor region depending on the treatment schedules, whereas an improvement of the therapeutic index is observed only for concentrations of about 105 GNPs per tumoral cell and limited spatial distribution in the normal tissue.
  
  
  CONCLUSIONS
  The model provides a useful framework to estimate the nanoparticle-driven radiosensitivity in breast cancer treatment irradiation, accounting for the complex interplay between dose and GNP uptake distributions.
authors.affiliation: Laboratory of Medical Physics and Expert Systems, National Cancer Institute Regina Elena, Roma, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Strigari
authors.affiliation: Physics Department, Università degli Studi di Torino, Torino, Italy.|Istituto Nazionale di Fisica Nucleare (INFN), Torino, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Ferrero
authors.affiliation: Physics Department, Università degli Studi di Torino, Torino, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Visonà
authors.affiliation: Physics Department, Università degli Studi di Torino, Torino, Italy.|Istituto Nazionale di Fisica Nucleare (INFN), Torino, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Dalmasso
authors.affiliation: Physics Department, Università degli Studi di Torino, Torino, Italy.|Istituto Nazionale di Fisica Nucleare (INFN), Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gobbato
authors.affiliation: Istituto Nazionale di Fisica Nucleare (INFN), Torino, Italy.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Cerello
authors.affiliation: Istituto Nazionale di Fisica Nucleare (INFN), Torino, Italy.|Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, Torino, Italy.
authors.forename: Sonja
authors.initials: S
authors.lastname: Visentin
authors.affiliation: Istituto Nazionale di Fisica Nucleare (INFN), Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Attili
mesh_terms: D001943:Breast Neoplasms / Q000532:radiotherapy*; D005260:Female; D006046:Gold; D006801:Humans; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D017785:Photons; D011836:Radiation Tolerance
chemical_list: D006046:Gold
keywords: breast cancer; gold nanoparticles; radiosensitization; radiotherapy; treatment planning