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Title: SU-F-BRD-13: A Phenomenological Relative Biological Effectiveness (RBE) Model for Proton Therapy Based On All Published in Vitro Cell Survival Data

Abstract

Purpose: Proton therapy treatments are currently planned and delivered using the assumption that the proton relative biological effectiveness (RBE) relative to photons is 1.1. This assumption ignores strong experimental evidence that suggests the RBE varies. A recent review study (Paganetti 2014), collected over 72 experimental reports on proton RBE, providing a comprehensive dataset for predicting proton RBE. Using this dataset we develop a model to predict RBE based on dose, linear energy transfer (LET) and the tissue specific parameter (α/β)x. Methods: The relationship of the RBE on dose, dose average LET (LETd) and (α/β)x was explored using 290 experimental data points. The RBE was calculated for each experimental point for doses ranging from 1 to 10 Gy. An RBE model, based on the linear-quadratic model, was derived using a nonlinear regression fit to the experimental data. Results: The proposed RBE model predicts that the RBE increases with LET and decreases with (α/β)x. The model additionally predicts a decrease in RBE with increasing dose for low (α/β)x values (< 3 Gy). However the model predicts an increase in RBE with increasing dose for large (α/β)x (> 4 Gy). Previous phenomenological models were based on a small subset of experimental data andmore » deviate significantly from our findings. Conclusion: The proposed RBE model is derived using the most comprehensive collection of proton RBE experimental data to date. The model agrees with previous theoretical predictions on the relationship between RBE, LETd and (α/β)x and also makes predictions on the relationship between RBE and dose. The proposed model shows a relationship between α and LETd but no significant relationship between β and LETd. Previously published phenomenological models based on a limited data set might have to be revised.« less

Authors:
; ;  [1]
  1. Massachusetts General Hospital, Boston, MA (United States)
Publication Date:
OSTI Identifier:
22555191
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 42; Journal Issue: 6; Other Information: (c) 2015 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; DATASETS; IN VITRO; LET; PROTON BEAMS; RADIATION DOSES; RADIOTHERAPY; RBE

Citation Formats

McNamara, A, Schuemann, J, and Paganetti, H. SU-F-BRD-13: A Phenomenological Relative Biological Effectiveness (RBE) Model for Proton Therapy Based On All Published in Vitro Cell Survival Data. United States: N. p., 2015. Web. doi:10.1118/1.4925192.
McNamara, A, Schuemann, J, & Paganetti, H. SU-F-BRD-13: A Phenomenological Relative Biological Effectiveness (RBE) Model for Proton Therapy Based On All Published in Vitro Cell Survival Data. United States. doi:10.1118/1.4925192.
McNamara, A, Schuemann, J, and Paganetti, H. 2015. "SU-F-BRD-13: A Phenomenological Relative Biological Effectiveness (RBE) Model for Proton Therapy Based On All Published in Vitro Cell Survival Data". United States. doi:10.1118/1.4925192.
@article{osti_22555191,
title = {SU-F-BRD-13: A Phenomenological Relative Biological Effectiveness (RBE) Model for Proton Therapy Based On All Published in Vitro Cell Survival Data},
author = {McNamara, A and Schuemann, J and Paganetti, H},
abstractNote = {Purpose: Proton therapy treatments are currently planned and delivered using the assumption that the proton relative biological effectiveness (RBE) relative to photons is 1.1. This assumption ignores strong experimental evidence that suggests the RBE varies. A recent review study (Paganetti 2014), collected over 72 experimental reports on proton RBE, providing a comprehensive dataset for predicting proton RBE. Using this dataset we develop a model to predict RBE based on dose, linear energy transfer (LET) and the tissue specific parameter (α/β)x. Methods: The relationship of the RBE on dose, dose average LET (LETd) and (α/β)x was explored using 290 experimental data points. The RBE was calculated for each experimental point for doses ranging from 1 to 10 Gy. An RBE model, based on the linear-quadratic model, was derived using a nonlinear regression fit to the experimental data. Results: The proposed RBE model predicts that the RBE increases with LET and decreases with (α/β)x. The model additionally predicts a decrease in RBE with increasing dose for low (α/β)x values (< 3 Gy). However the model predicts an increase in RBE with increasing dose for large (α/β)x (> 4 Gy). Previous phenomenological models were based on a small subset of experimental data and deviate significantly from our findings. Conclusion: The proposed RBE model is derived using the most comprehensive collection of proton RBE experimental data to date. The model agrees with previous theoretical predictions on the relationship between RBE, LETd and (α/β)x and also makes predictions on the relationship between RBE and dose. The proposed model shows a relationship between α and LETd but no significant relationship between β and LETd. Previously published phenomenological models based on a limited data set might have to be revised.},
doi = {10.1118/1.4925192},
journal = {Medical Physics},
number = 6,
volume = 42,
place = {United States},
year = 2015,
month = 6
}
  • Purpose: High throughput in vitro experiments assessing cell survival following proton radiation indicate that both the alpha and the beta parameters of the linear quadratic model increase with increasing proton linear energy transfer (LET). We investigated the relative biological effectiveness (RBE) of double-strand break (DSB) induction as a means of explaining the experimental results. Methods: Experiments were performed with two lung cancer cell lines and a range of proton LET values (0.94 – 19.4 keV/µm) using an experimental apparatus designed to irradiate cells in a 96 well plate such that each column encounters protons of different dose-averaged LET (LETd). Traditionalmore » linear quadratic survival curve fitting was performed, and alpha, beta, and RBE values obtained. Survival curves were also fit with a model incorporating RBE of DSB induction as the sole fit parameter. Fitted values of the RBE of DSB induction were then compared to values obtained using Monte Carlo Damage Simulation (MCDS) software and energy spectra calculated with Geant4. Other parameters including alpha, beta, and number of DSBs were compared to those obtained from traditional fitting. Results: Survival curve fitting with RBE of DSB induction yielded alpha and beta parameters that increase with proton LETd, which follows from the standard method of fitting; however, relying on a single fit parameter provided more consistent trends. The fitted values of RBE of DSB induction increased beyond what is predicted from MCDS data above proton LETd of approximately 10 keV/µm. Conclusion: In order to accurately model in vitro proton irradiation experiments performed with high throughput methods, the RBE of DSB induction must increase more rapidly than predicted by MCDS above LETd of 10 keV/µm. This can be explained by considering the increased complexity of DSBs or the nature of intra-track pairwise DSB interactions in this range of LETd values. NIH Grant 2U19CA021239-35.« less
  • Purpose: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and Materials: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions weremore » simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.« less
  • Purpose: To investigate in a simulation study whether using a variable relative biological effectiveness (RBE) in calculation and optimization of intensity-modulated proton therapy (IMPT) instead of using an RBE of 1.1 would result in significant changes in the RBE-weighted dose (RWD) distributions. Methods and Materials: For 4 patients with head-and-neck tumors, three IMPT plans were prepared respectively. The first plan was physically optimized (IMPT-PO plan), and the RWD was calculated with a constant RBE of 1.1. Then the plan's RWD was recalculated (IMPT-R plan) using a variable RBE model taking into account the linear energy transfer (LET) and tissue-specific radiobiologicalmore » parameters. The third IMPT plan was optimized using a biological optimization routine (IMPT-BO plan). Results: Comparing the IMPT-PO and IMPT-R plans, we observed that the RWD in radioresistant tissues was more sensitive to the LET than in radiosensitive tissues. The IMPT-R plans were in general more inhomogeneous than the IMPT-PO plans. The differences of RWD distributions for all volumes between IMPT-PO and IMPT-BO plans complied with predefined dose-volume constraints. The average LET was significantly lower in IMPT-BO plans than in IMPT-R plans. Conclusion: In radioresistant normal tissues caution has to be used regarding the LET distribution because these are most sensitive to changes in the LET. Biological optimization of IMPT plans based on the organ-specific biological parameters and LET distributions is feasible.« less
  • Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine themore » LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.« less