Linear Energy Transfer and Relative Biological Effectiveness Investigation of Various Structures for a Cohort of Proton Patients With Brain Tumors

Vaniqui, Ana; Vaassen, Femke; Perri, Dario Di; Eekers, Daniëlle; Compter, Inge; Rinaldi, I.; Elmpt, Wouter van; Unipan, Mirko

doi:10.1016/j.adro.2022.101128

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…However, clear relationships between RBE and LET can be hard to establish. 44,45 Furthermore, LET calculation and reporting is not yet standardised, 46–48 and in our clinical practice, the dose distributions are still exclusively used to judge the quality of the treatment plan. We calculated the LET distribution for a few of the patients (data not shown) but did not observe any large changes in LET distribution between the 3%-plan and 2%-plan.…”

Section: Discussionmentioning

confidence: 99%

Clinical benefit of range uncertainty reduction in proton treatment planning based on dual-energy CT for neuro-oncological patients

Taasti,

Decabooter,

Eekers

et al. 2023

The British Journal of Radiology

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Objective: Several studies have shown that dual-energy CT (DECT) can lead to improved accuracy for proton range estimation. This study investigated the clinical benefit of reduced range uncertainty, enabled by DECT, in robust optimisation for neuro-oncological patients. Methods: DECT scans for 27 neuro-oncological patients were included. Commercial software was applied to create stopping-power ratio (SPR) maps based on the DECT scan. Two plans were robustly optimised on the SPR map, keeping the beam and plan settings identical to the clinical plan. One plan was robustly optimised and evaluated with a range uncertainty of 3% (as used clinically; denoted 3%-plan); the second plan applied a range uncertainty of 2% (2%-plan). Both plans were clinical acceptable and optimal. The dose–volume histogram parameters were compared between the two plans. Two experienced neuro-radiation oncologists determined the relevant dose difference for each organ-at-risk (OAR). Moreover, the OAR toxicity levels were assessed. Results: For 24 patients, a dose reduction >0.5/1 Gy (relevant dose difference depending on the OAR) was seen in one or more OARs for the 2%-plan; e.g. for brainstem D0.03cc in 10 patients, and hippocampus D40% in 6 patients. Furthermore, 12 patients had a reduction in toxicity level for one or two OARs, showing a clear benefit for the patient. Conclusion: Robust optimisation with reduced range uncertainty allows for reduction of OAR toxicity, providing a rationale for clinical implementation. Based on these results, we have clinically introduced DECT-based proton treatment planning for neuro-oncological patients, accompanied with a reduced range uncertainty of 2%. Advances in knowledge: This study shows the clinical benefit of range uncertainty reduction from 3% to 2% in robustly optimised proton plans. A dose reduction to one or more OARs was seen for 89% of the patients, and 44% of the patients had an expected toxicity level decrease.

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Section: Discussionmentioning

confidence: 99%

Clinical benefit of range uncertainty reduction in proton treatment planning based on dual-energy CT for neuro-oncological patients

Taasti,

Decabooter,

Eekers

et al. 2023

The British Journal of Radiology

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“…When LET objectives are used, dose threshold limits can be imposed to ensure only clinically relevant LET voxels are optimised. By considering all LET voxels with no dose threshold, we steer the overall LET distribution toward higher values [82]. Hahn et al [60] proposed an alternative 2-step method wherein only voxels with a dose exceeding the threshold are included in the LET optimisation.…”

Section: Managing the Dose-let Trade-offmentioning

confidence: 99%

A Systematic Review of LET-Guided Treatment Plan Optimisation in Proton Therapy: Identifying the Current State and Future Needs

McIntyre,

Wilson,

Gorayski

et al. 2023

Cancers

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The well-known clinical benefits of proton therapy are achieved through higher target-conformality and normal tissue sparing than conventional radiotherapy. However, there is an increased sensitivity to uncertainties in patient motion/setup, proton range and radiobiological effect. Although recent efforts have mitigated some uncertainties, radiobiological effect remains unresolved due to a lack of clinical data for relevant endpoints. Therefore, RBE optimisations may be currently unsuitable for clinical treatment planning. LET optimisation is a novel method that substitutes RBE with LET, shifting LET hotspots outside critical structures. This review outlines the current status of LET optimisation in proton therapy, highlighting knowledge gaps and possible future research. Following the PRISMA 2020 guidelines, a search of the MEDLINE® and Scopus databases was performed in July 2023, identifying 70 relevant articles. Generally, LET optimisation methods achieved their treatment objectives; however, clinical benefit is patient-dependent. Inconsistencies in the reported data suggest further testing is required to identify therapeutically favourable methods. We discuss the methods which are suitable for near-future clinical deployment, with fast computation times and compatibility with existing treatment protocols. Although there is some clinical evidence of a correlation between high LET and adverse effects, further developments are needed to inform future patient selection protocols for widespread application of LET optimisation in proton therapy.

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“…All LQ-based models are developed from subsets of the available in vitro data in the literature. The model proposed by McNamara et al (2015) is based on the largest dataset with 285 data entries, and has been frequently applied in studies (Marteinsdottir et al 2021, Garbacz et al 2022, Henjum et al 2023, Rechner et al 2023, Vaniqui et al 2023. Since the development of this model, the amount of in vitro data available in the literature has almost doubled.…”

Section: Introductionmentioning

confidence: 99%

An updated variable RBE model for proton therapy

Lyngholm,

Stokkevåg,

Lühr

et al. 2024

Phys. Med. Biol.

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Objective. While a constant relative biological effectiveness (RBE) of 1.1 forms the basis for clinical proton therapy, variable RBE models are increasingly being used in plan evaluation. However, there is substantial variation across RBE models, and several new in vitro datasets have not yet been included in the existing models. In this study, an updated in vitro proton RBE database was collected and used to examine current RBE model assumptions, and to propose an up-to-date RBE model as a tool for evaluating RBE effects in clinical settings. Approach. A proton database (471 data points) was collected from the literature, almost twice the size of the previously largest model database. Each data point included linear-quadratic model parameters and linear energy transfer (LET). Statistical analyses were performed to test the validity of commonly applied assumptions of phenomenological RBE models, and new model functions were proposed for RBEmax and RBEmin (RBE at the lower and upper dose limits). Previously published models were refitted to the database and compared to the new model in terms of model performance and RBE estimates. Main results. The statistical analysis indicated that the intercept of the RBEmax function should be a free fitting parameter and RBE estimates were clearly higher for models with free intercept. RBEmin increased with increasing LET, while a dependency of RBEmin on the reference radiation fractionation sensitivity ((α/β)x) did not significantly improve model performance. Evaluating the models, the new model gave overall lowest RMSE and highest R2 score. RBE estimates in the distal part of a Spread-Out-Bragg-Peak in water ((α/β)x=2.1Gy) were 1.24-1.51 for original models, 1.25-1.49 for refits and 1.42 for the new model. Significance. An updated RBE model based on the currently largest database among published phenomenological models was proposed. Overall, the new model showed better performance compared to refitted published RBE models.

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Linear Energy Transfer and Relative Biological Effectiveness Investigation of Various Structures for a Cohort of Proton Patients With Brain Tumors

Cited by 5 publications

References 54 publications

Clinical benefit of range uncertainty reduction in proton treatment planning based on dual-energy CT for neuro-oncological patients

Clinical benefit of range uncertainty reduction in proton treatment planning based on dual-energy CT for neuro-oncological patients

A Systematic Review of LET-Guided Treatment Plan Optimisation in Proton Therapy: Identifying the Current State and Future Needs

An updated variable RBE model for proton therapy

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