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Title: Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

Purpose: The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate the RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials: Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results: We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictormore » of proton biological effectiveness. Data were also used to validate a parameterized RBE model. Conclusions: The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.« less
Authors:
;  [1] ; ;  [2] ; ;  [3] ; ;  [1] ; ;  [4] ;  [1] ;  [1] ;  [5]
  1. Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast (United Kingdom)
  2. Department of Physics, University of Naples Federico II and INFN Naples Section University of Naples, Naples (Italy)
  3. Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, Belfast (United Kingdom)
  4. Istituto Nazionale di Fisica Nucleare, LNS, Catania (Italy)
  5. (United Kingdom)
Publication Date:
OSTI Identifier:
22420405
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 90; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BRAGG CURVE; CELL KILLING; COMPUTERIZED SIMULATION; FIBROBLASTS; GLIOMAS; LET; MEV RANGE 10-100; MONTE CARLO METHOD; OPTIMIZATION; PLANNING; PROTON BEAMS; RADIATION DOSES; RADIOSENSITIVITY; RADIOTHERAPY; RBE