title: Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo study.
abstract: OBJECTIVE
  This work explores a new radiation therapy approach which might trigger a renewed use of neon and heavier ions to treat cancers. These ions were shown to be extremely efficient in radioresistant tumor killing. Unfortunately, the efficient region also extends into the normal tissue in front of the tumor. The strategy the authors propose is to profit from the well-established sparing effect of thin spatially fractionated beams, so that the impact on normal tissues might be minimized while a high tumor control is achieved. The main goal of this work is to provide a proof of concept of this new approach. With that aim, a dosimetric study was carried out as a first step to evaluate the interest of further explorations of this avenue.
  
  
  METHODS
  The gate/geant4 v.6.1 Monte Carlo simulation platform was employed to simulate arrays of rectangular minibeams (700 μm × 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed with a 2 cm-long spread-out Bragg peak centered at 7 cm-depth. Dose distributions in a water phantom were scored considering two minibeams center-to-center distances: 1400 and 3500 μm. Peak and valley doses, peak-to-valley dose ratios (PVDRs), beam penumbras, and relative contribution of nuclear fragments and electromagnetic processes were assessed as figures of merit. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions.
  
  
  RESULTS
  Extremely high PVDR values (>100) and low valley doses were obtained. The higher the atomic number (Z) of the primary ion is, the lower the valleys and the narrower the penumbras. Although the yield of secondary nuclear products increases with Z, the actual dose being deposited by the secondary nuclear fragments in the valleys starts to be the dominant contribution at deeper points, helping in the sparing of proximal normal tissues. Additionally, a wider center-to-center distance leads to a minimized contribution of heavier secondary fragments in valleys.
  
  
  CONCLUSIONS
  The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of neon and heavier ions for the treatment of radioresistant tumors, while preserving normal tissues. The authors' results support the further exploration of this avenue. Next steps include the realization of biological experiment to confirm the shifting of normal tissue complication probability curves.
authors.affiliation: IMNC-UMR 8165, CNRS Paris 7 and Paris 11 Universities, 15 rue Georges Clemenceau, Orsay Cedex 91406, France.
authors.forename: C
authors.initials: C
authors.lastname: Peucelle
authors.affiliation: IMNC-UMR 8165, CNRS Paris 7 and Paris 11 Universities, 15 rue Georges Clemenceau, Orsay Cedex 91406, France.
authors.forename: I
authors.initials: I
authors.lastname: Martínez-Rovira
authors.affiliation: IMNC-UMR 8165, CNRS Paris 7 and Paris 11 Universities, 15 rue Georges Clemenceau, Orsay Cedex 91406, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Prezado
mesh_terms: D019583:Dose Fractionation, Radiation; D063193:Heavy Ion Radiotherapy; D020450:Heavy Ions / Q000009:adverse effects; D009010:Monte Carlo Method; D009356:Neon / Q000009:adverse effects / Q000627:therapeutic use*; D059351:Organ Sparing Treatments; D011874:Radiometry
chemical_list: D009356:Neon