Vienna, Austria

ESTRO 2023

Session Item

Saturday
May 13
10:30 - 11:30
Business Suite 3-4
Radiomics and modelling
Tiziana Rancati, Italy
Poster Discussion
Physics
NTCP model prediction considering RBE variability in proton therapy of primary brain tumors
Fabian Hennings, Germany
PD-0172

Abstract

NTCP model prediction considering RBE variability in proton therapy of primary brain tumors
Authors:

Fabian Hennings1,2, Martina Palkowitsch3,2, Jan Eulitz3, Annekatrin Seidlitz3,4,5,7, Esther G.C. Troost6,2,7,4,5, Mechthild Krause3,2,7,4,5, Jona Bensberg8, Christian Hahn6,7,8, Feline Heinzelmann9,10,11, Christian Bäumer9,10,11, Armin Lühr8, Beate Timmermann9,10,11, Steffen Löck3,7,4,5

1OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden–Rossendorf , Dresden, Germany; 2Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology – OncoRay, Dresden, Germany; 3OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden–Rossendorf, Dresden, Germany; 4German Cancer Consortium (DKTK), partner site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; 6OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden–Rossendorf, Dresden, Germany; 7Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 8TU Dortmund University, Department of Physics, Dortmund, Germany; 9West German Proton Therapy Center Essen (WPE), University Hospital Essen, Essen, Germany; 10Clinic for Particle Therapy, University Hospital Essen, Essen, Germany; 11German Cancer Consortium (DKTK), partner site Essen, German Cancer Research Center (DKFZ), Heidelberg, Germany

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Purpose or Objective

The variable relative biological effectiveness (RBE) of protons can lead to an increased risk of complications in normal tissue compared to the estimated risk based on the clinically applied RBE of 1.1. To demonstrate how accounting for variability in RBE affects the expected probability of side effects, we evaluated normal tissue complication probability (NTCP) models following proton beam therapy (PBT) of patients with primary brain tumors.

Material and Methods

We retrospectively evaluated clinically applied PBT plans of 51 patients with primary brain tumors. The median prescribed dose was 60 Gy(RBE) [42.5–60 Gy(RBE)] administered in fractions of 2 Gy(RBE) [1.8–2.5 Gy(RBE)]. Dose and dose-averaged linear energy transfer were recalculated for these treatment plans using an in-house developed Monte-Carlo simulation framework [1] or the Monte-Carlo scoring extension of a research version of the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden). For each patient, the absorbed dose distribution was converted into two RBE-weighted absorbed dose distributions: one using a constant RBE of 1.1 (DconstRBE) and one using a variable RBE obtained from the Wedenberg et al. model [2] (DvarRBE) with an α/β ratio of 2 Gy and 10 Gy for organs at risk (OARs) and tumor, respectively. An example is presented in the Figure. Dose-volume parameters were extracted for different OARs and inserted into eleven published NTCP models for various radiation-induced side effects of the central nervous system [3]. For each patient and all adverse events, NTCPs were calculated based on DconstRBE and DvarRBE leading to NTCPconstRBE and NTCPvarRBE, respectively. Patient-specific differences were calculated using ∆NTCP=NTCPvarRBE-NTCPconstRBE.


Results

Consideration of RBE variability resulted in similar or slightly higher median NTCP values for all endpoints (Table). Pronounced relative changes were observed for blindness and necrosis. For individual patients, an increase in NTCP of more than 30% was observed, in particular for endocrine dysfunction, delayed recall, hearing loss and ocular toxicity when considering a variable RBE. The OARs related to these side effects are small in volume, underlining the local effect of an increased DvarRBE. For 34 patients (66.6%), the change in NTCP was greater than 5% for at least one of the considered endpoints.


Conclusion

Considering the cohort median, the observed NTCP differences due to variability in the RBE of protons remained small. However, for some patients, large ∆NTCP values were observed, especially for OARs of small volume. Accurate modelling of proton RBE is needed to identify these patients before treatment and to consider the reduction of the individual toxicity risk during treatment planning.

[1] Eulitz J et al. Phys Med Biol 2019; 64:225020.
[2] Wedenberg M et al. Acta Oncol. 2013; 52:580–588.
[3] Dutz A et al. Radiother Oncol. 2021; 160:69-77.