Does the uncertainty in relative biological effectiveness affect patient treatment in proton therapy?

A case-control study of linear energy transfer and relative biological effectiveness related to symptomatic brainstem toxicity following pediatric proton therapy

“…While the low incidence is fortunate, the serious nature of these side effects calls for investigation. Nevertheless, clinically applied efforts to reduce LET in vital organs [2] coupled with low incidence of symptomatic brainstem necrosis as well as the difficulty of distinguishing between symptomatic toxicity and disease progression [22], complicates the task of acquiring a sufficient amount of patients to draw definitive conclusions regarding the clinical effects of the RBE variability [40], particularly for this clinical endpoint. For instance, in a recently published study, a power analysis was conducted for head and neck cancer patients treated with intensity-modulated proton therapy.…”

Towards harmonizing clinical linear energy transfer (LET) reporting in proton radiotherapy: a European multi-centric study

“…This further complicates the direct application of many available in vitro-based RBE models for patient cases. To overcome this limitation and to allow for an application in patient treatment, it is recommended to update the current parameters of empirical models based on a consistent analysis of patient instead of preclinical response dataas recently requested by the EPTN [18]. In the current situation, harmonized LET supports intercenter comparability when used as input parameter for existing phenomenological RBE models and when analyzing the radiation response to dose and LET after PT without changing center-specific procedures in MC frameworks.…”

“…Six out of eight centers were able to convert their LET simulation data to DICOM format for both non-TPS MC engines and non-clinical research versions of commercially available TPS. Firstly, this enables consistent archiving of both dose and LET d data for upcoming patient outcome analysis on clinical RBE [18]. Secondly, making LET distributions accessible in a clinical setting further informs clinicians on treatment plan safety in view of a variable RBE [1].…”

“…The influence of these parameters on averaged LET, hereafter denoted as LET, has been investigated in monocentric research works [11][12][13][14][15][16], where their effects can be isolated and investigated systematically. However, despite of their evident impact on LET, so far, no standard has been established for calculating and reporting LET in experiments, in clinical practice or for evaluating patient follow-up data [17,18]. Therefore, it must be evaluated whether the calculation and reporting of LET at different PT centers are coherent for the same treatment planning situation and whether LET distributions can currently be exchanged between centers in addition to dose.…”

Clinical use and future requirements of relative biological effectiveness: Survey among all European proton therapy centres

“…At the same time, the growing awareness of uncertainties in proton therapy caused by possible RBE effects [3,23,24] lets proton therapy centres already apply various methods during treatment planning to mitigate uncertainties in RBE weighted dose, including the avoidance of certain beam angles or consideration of LET distributions in patient plans. The impact of RBE uncertainty on everyday clinical practice was discussed at a workshop by the European Particle Therapy Network (EPTN) work package 6 (WP6) on radiobiology [25]. The discussions emphasized the inevitable insecurity of proton clinics on how to effectively account for RBE variability, which urges a deeper insight into this issue and, particularly, a robust review examining the current clinically applied RBE strategies at a large number of centres.…”