Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors

M. Garbacz; F.G. Cordoni; M. Durante; J. Gajewski; K. Kisielewicz; N. Krah; R. Kopec; P. Olko; V. Patera; I. Rinaldi; M. Rydygier; A. Schiavi; E. Scifoni; T. Skora; F. Tommasino; A. Rucinski

doi:10.1016/j.radonc.2021.08.015

Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors

M. Garbacz^*, F.G. Cordoni, M. Durante, J. Gajewski, K. Kisielewicz, N. Krah, R. Kopec, P. Olko, V. Patera, I. Rinaldi, M. Rydygier, A. Schiavi, E. Scifoni, T. Skora, F. Tommasino, A. Rucinski

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Purpose: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons. Methods: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis. Results: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values. Conclusions: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd. (c) 2021 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 163 (2021) 143-149 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Original language	English
Pages (from-to)	143-149
Number of pages	7
Journal	Radiotherapy and Oncology
Volume	163
DOIs	https://doi.org/10.1016/j.radonc.2021.08.015
Publication status	Published - 1 Oct 2021

Keywords

Brain necrosis
Linear energy transfer
Monte Carlo
Proton therapy
Variable RBE
RELATIVE BIOLOGICAL EFFECTIVENESS
EFFECTIVENESS RBE VALUES
TEMPORAL-LOBE NECROSIS
CLINICAL-EVIDENCE
CANCER-PATIENTS
NORMAL TISSUE
RADIOTHERAPY

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Garbacz, M., Cordoni, F. G., Durante, M., Gajewski, J., Kisielewicz, K., Krah, N., Kopec, R., Olko, P., Patera, V., Rinaldi, I., Rydygier, M., Schiavi, A., Scifoni, E., Skora, T., Tommasino, F., & Rucinski, A. (2021). Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors. Radiotherapy and Oncology, 163, 143-149. https://doi.org/10.1016/j.radonc.2021.08.015

@article{27ef18560b264e3ca6eb8d689753935b,

title = "Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors",

abstract = "Purpose: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons. Methods: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis. Results: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values. Conclusions: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd. (c) 2021 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 163 (2021) 143-149 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).",

keywords = "Brain necrosis, Linear energy transfer, Monte Carlo, Proton therapy, Variable RBE, RELATIVE BIOLOGICAL EFFECTIVENESS, EFFECTIVENESS RBE VALUES, TEMPORAL-LOBE NECROSIS, CLINICAL-EVIDENCE, CANCER-PATIENTS, NORMAL TISSUE, RADIOTHERAPY",

author = "M. Garbacz and F.G. Cordoni and M. Durante and J. Gajewski and K. Kisielewicz and N. Krah and R. Kopec and P. Olko and V. Patera and I. Rinaldi and M. Rydygier and A. Schiavi and E. Scifoni and T. Skora and F. Tommasino and A. Rucinski",

note = "Funding Information: This project was carried out within the Reintegration programme of the Foundation for Polish Science co-financed by the EU under the European Regional Development Fund - grant no. POIR.04.04.00-00-2475/16-00 . MG acknowledges the support of InterDokMed project no. POWR.03.02.00-00-I013/16. INFN Call MoVe-IT is also acknowledged. We acknowledge Prof. Jan Swako{\'n} from the Department of Radiation Research and Proton Radiotherapy Institute of Nuclear Physics in Krakow for valuable support and sharing knowledge on proton therapy. We acknowledge the support of NVIDIA Corporation with the donation of the GPU used for this research. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = oct,

day = "1",

doi = "10.1016/j.radonc.2021.08.015",

language = "English",

volume = "163",

pages = "143--149",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Garbacz, M, Cordoni, FG, Durante, M, Gajewski, J, Kisielewicz, K, Krah, N, Kopec, R, Olko, P, Patera, V, Rinaldi, I, Rydygier, M, Schiavi, A, Scifoni, E, Skora, T, Tommasino, F & Rucinski, A 2021, 'Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors', Radiotherapy and Oncology, vol. 163, pp. 143-149. https://doi.org/10.1016/j.radonc.2021.08.015

TY - JOUR

T1 - Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors

AU - Garbacz, M.

AU - Cordoni, F.G.

AU - Durante, M.

AU - Gajewski, J.

AU - Kisielewicz, K.

AU - Krah, N.

AU - Kopec, R.

AU - Olko, P.

AU - Patera, V.

AU - Rinaldi, I.

AU - Rydygier, M.

AU - Schiavi, A.

AU - Scifoni, E.

AU - Skora, T.

AU - Tommasino, F.

AU - Rucinski, A.

N1 - Funding Information: This project was carried out within the Reintegration programme of the Foundation for Polish Science co-financed by the EU under the European Regional Development Fund - grant no. POIR.04.04.00-00-2475/16-00 . MG acknowledges the support of InterDokMed project no. POWR.03.02.00-00-I013/16. INFN Call MoVe-IT is also acknowledged. We acknowledge Prof. Jan Swakoń from the Department of Radiation Research and Proton Radiotherapy Institute of Nuclear Physics in Krakow for valuable support and sharing knowledge on proton therapy. We acknowledge the support of NVIDIA Corporation with the donation of the GPU used for this research. Publisher Copyright: © 2021 The Authors

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Purpose: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons. Methods: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis. Results: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values. Conclusions: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd. (c) 2021 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 163 (2021) 143-149 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

AB - Purpose: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons. Methods: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis. Results: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values. Conclusions: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd. (c) 2021 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 163 (2021) 143-149 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

KW - Brain necrosis

KW - Linear energy transfer

KW - Monte Carlo

KW - Proton therapy

KW - Variable RBE

KW - RELATIVE BIOLOGICAL EFFECTIVENESS

KW - EFFECTIVENESS RBE VALUES

KW - TEMPORAL-LOBE NECROSIS

KW - CLINICAL-EVIDENCE

KW - CANCER-PATIENTS

KW - NORMAL TISSUE

KW - RADIOTHERAPY

U2 - 10.1016/j.radonc.2021.08.015

DO - 10.1016/j.radonc.2021.08.015

M3 - Article

C2 - 34461183

SN - 0167-8140

VL - 163

SP - 143

EP - 149

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

ER -

Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors

Abstract

Keywords

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