Inter-patient variations in relative biological effectiveness for cranio-spinal irradiation with protons

Abstract

cranio-spinal irradiation (cSi) using protons has dosimetric advantages compared to photons and isexpected to reduce risk of adverse effects. The proton relative biological effectiveness (RBE) varies with linear energy transfer (LET), tissue type and dose, but a variable RBE has not replaced the constant RBE of 1.1 in clinical treatment planning. We examined inter-patient variations in RBE for ten proton CSI patients. Variable RBE models were used to obtain RBE and RBE-weighted doses. RBE was quantified in terms of dose weighted organ-mean RBE (RBE d = mean RBE-weighted dose/mean physical dose) and effective RBE of the near maximum dose (D 2% ), i.e., where subscripts RBE and phys indicate that the D 2% is calculated based on an RBE model and the physical dose, respectively. compared to the median RBE d of the patient population, differences up to 15% were observed for the individual RBE d values found for the thyroid, while more modest variations were seen for the heart (6%), lungs (2%) and brainstem (<1%). Large inter-patient variation in RBE could be correlated to large spread in LET and dose for these organs at risk (OARs). For OARs with small inter-patient variations, the results show that applying a population based RBE in treatment planning may be a step forward compared to using RBE of 1.1. OARs with large inter-patient RBE variations should ideally be selected for patient-specific biological or RBE robustness analysis if the physical doses are close to known dose thresholds.Proton therapy has been established as an important radiation treatment modality for cancer, offering improved sparing of normal tissue compared to conventional radiation therapy with photons 1 . The dosimetric advantages of protons have already been shown for medulloblastoma patients receiving cranio-spinal irradiation (CSI) 2,3 , and early clinical outcomes suggest that similar disease control can be achieved with reduced toxicity compared to photon therapy 4-6 . Longer follow-up and more clinical data are awaited to draw firm conclusions on the clinical benefits of proton CSI 7 .Dosimetric benefits of proton CSI include a significant dose reduction to organs anterior to the spinal column, including the cochlea, transverse colon, stomach, kidney, heart, and lungs 8 . Besides the different spatial patterns in physical dose deposition, protons also have an increased biological effect compared to photons, i.e. protons produce more damage than photons from the same physical dose. This difference is currently accounted for by a dose scaling factor; the relative biological effectiveness (RBE). Although contemporary clinical proton treatment planning is based on a constant RBE of 1.1 (RBE 1.1 ), the proton RBE is known to vary with linear energy transfer (LET), tissue type and physical dose 9-11 . In particular, the RBE increases due to the increase in LET towards the end of the proton beam range. The need to investigate the RBE further and to and to provide clinical solutions accounting for variations in the RBE has therefore recently bee...

Variation in relative biological effectiveness for cognitive structures in proton therapy of pediatric brain tumors

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Dosimetric analysis of six whole-breast irradiation techniques in supine and prone positions

“…In addition, the impact of the variable RBE on secondary cancer risk was not considered in the current model. Consequently, generalizing the results of this study www.nature.com/scientificreports/ may be challenging due to inherent biological uncertainties, model limitations in accounting for RBE in tumor initiation, and the presence of significant inter-patient variation 68,69 . Nevertheless, these findings are expected to provide valuable insights for clinicians and patients in their decision-making processes, particularly in the context of reducing the secondary cancer risk when considering PBT.…”

A Critical Review of LET-Based Intensity-Modulated Proton Therapy Plan Evaluation and Optimization for Head and Neck Cancer Management

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