Predicting late magnetic resonance image changes in glioma patients after proton therapy

Eulitz, J.; Troost, Esther G.C.; Raschke, Felix; Schulz, E; Lutz, B.; Dutz, Almut; Löck, Steffen; Wohlfahrt, Patrick; Enghardt, W.; Karpowitz, C.; Krause, Mechthild; Lühr, Armin

doi:10.1080/0284186x.2019.1631477

Cited by 69 publications

(92 citation statements)

References 13 publications

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“…The observed small absolute uncertainties in P IC both in the additional brain tumor patient and in brain tumor cases I and II may indicate a limited impact of range deviations on the estimated absolute voxel-wise image change probability for robust-dose optimized treatment plans. This exemplary analysis suggests that range deviations alone may not explain the disagreement in studies where some authors found correlations between radiation-induced toxicity and an elevated biological effectiveness 11,14,15,18 while others did not. 43 However, the current findings may be limited to the applied model and endpoint in brain patients.…”

Section: Discussionmentioning

confidence: 83%

“…The potentially increased radiosensitivity of the PVR 14,15 was taken into account in P IC estimation by incorporating the PVR as model predictor in addition to physical dose and physical dose times LET d , using the logistic regression model M X from Ref. [14] and its corresponding model coefficients. In this way, the interaction between spatial variations of LET d and dose distributions with local changes in brain radiosensitivity is considered.…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the impact of LET d and range uncertainties on a voxel-by-voxel basis and for a clinical endpoint, a radiation response model was applied. 14 The model correlates a combination of dose and LET d with late radiation-induced brain injury observed in follow-up T1-weighted contrast-enhanced (T1w-CE) MRI in six patients treated with (adjuvant) proton (chemo)therapy at UPTD. The radiological diagnosis was confirmed using either histology (5/6 patients) or methionine positron emission tomography (PET, 1/6).…”

Section: C Linear Energy Transfer Relative Biological Effectivenementioning

confidence: 99%

“…Similarly, two studies on the spatial distribution of late radiation-induced brain toxicity after proton therapy demonstrated a strong correlation with dose and both LET t and LET d in glioma patients. 14,15 This underlines the need to explicitly consider the LET (doseor track-averaged) in clinical proton treatment planning as a parameter affecting the biological effectiveness.…”

Section: Introductionmentioning

confidence: 99%

“…This would support studies on the spatial variability of clinical RBE that test the correlation with dose and LET d as it has been done for glioma patients. 14,15 Here, we set up a study quantifying the LET d in clinically relevant treatment scenarios and, in particular, the effect of range uncertainties on LET d distributions in different patient groups. Additionally, we assess the impact of LET d and its uncertainties on biological effect in tumor and in normal tissues also using clinically derived NTCP models for protons.…”

Section: Introductionmentioning

confidence: 99%

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Impact of range uncertainty on clinical distributions of linear energy transfer and biological effectiveness in proton therapy

et al. 2020

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tumor patients was smaller than 5% and occurred adjacent to the CTV. Range deviations induced absolute differences in P IC up to 1.2%. Conclusions: Robust dose optimization generates LET d distributions in the target volume robust against range deviations. The current findings support using a constant RBE within the CTV. The impact of range deviations on the considered probability of late radiation-induced toxicity in brain tissue was limited for robust dose-optimized treatment plans. Incorporation of LET d in robust optimization frameworks may further reduce uncertainty related to the RBE-weighted dose estimation in normal tissues.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: C Linear Energy Transfer Relative Biological Effectivenementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of range uncertainty on clinical distributions of linear energy transfer and biological effectiveness in proton therapy

et al. 2020

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Treatment‐planning approaches to intensity modulated proton therapy and the impact on dose‐weighted linear energy transfer

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et al. 2022

J Applied Clin Med Phys

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Purpose We quantified the effect of various forward‐based treatment‐planning strategies in proton therapy on dose‐weighted linear energy transfer (LETd). By maintaining the dosimetric quality at a clinically acceptable level, we aimed to evaluate the differences in LETd among various treatment‐planning approaches and their practicality in minimizing biologic uncertainties associated with LETd. Method Eight treatment‐planning strategies that are achievable in commercial treatment‐planning systems were applied on a cylindrical water phantom and four pediatric brain tumor cases. Each planning strategy was compared to either an opposed lateral plan (phantom study) or original clinical plan (patient study). Deviations in mean and maximum LETd from clinically acceptable dose distributions were compared. Results In the phantom study, using a range shifter and altering the robust scenarios during optimization had the largest effect on the mean clinical target volume LETd, which was reduced from 4.5 to 3.9 keV/μm in both cases. Variations in the intersection angle between beams had the largest effect on LETd in a ring defined 3 to 5 mm outside the target. When beam intersection angles were reduced from opposed laterals (180°) to 120°, 90°, and 60°, corresponding maximum LETd increased from 7.9 to 8.9, 10.9, and 12.2 keV/μm, respectively. A clear trend in mean and maximum LETd variations in the clinical cases could not be established, though spatial distribution of LETd suggested a strong dependence on patient anatomy and treatment geometry. Conclusion Changes in LETd from treatment‐plan setup follow intuitive trends in a controlled phantom experiment. Anatomical and other patient‐specific considerations, however, can preclude generalizable strategies in clinical cases. For pediatric cranial radiation therapy, we recommend using opposed lateral treatment fields to treat midline targets.

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How can scanned proton beam treatment planning for low‐grade glioma cope with increased distal RBE and locally increased radiosensitivity for late MR‐detected brain lesions?

et al. 2021

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A novel risk model has recently been proposed for the occurrence of late contrast-enhancing brain lesions (CEBLs) after proton irradiation of low-grade glioma (LGG) patients. It predicts a strong dependence on dose-weighted linear-energy transfer (LET d effect) and an increased radiosensitivity of the ventricular proximity, a 4-mm fringe surrounding the ventricular system (VP 4mm effect). On this basis, we investigated (A) how these two risk factors and patient-specific anatomical and treatment plan (TP) features contribute to normal tissue complication probability (NTCP) and (B) if conventional LET d-reduction techniques like multiple-field TP are able to reduce NTCP. (A) The LGG model cohort (N = 110) was stratified with respect to prescribed dose, tumor grade, and treatment field configuration. NTCP predictions and CEBL occurrence rates per strata were analyzed. (B) The effect of multiple-field TP was investigated in two patient groups: (i) nine high-risk subjects with extended lateral target volumes who had developed CEBLs after single-beam treatments were retrospectively replanned with a clinical standard two-field setting using almost orthogonal fields and strictly opposing fields, (ii) single-field treatments were simulated for seven low-risk patients with small central target volumes clinically treated with two strictly opposing fields. (A) In the model cohort, we identified the exposure of the radiosensitive VP 4mm fringe with proton field components of increased biological effectiveness as dominant NTCP driving factor. We observed that larger target volumes and location lateral to the main ventricles, both being characteristic for WHO°II tumors, presented with the highest complication risks. Among subjects of an equal dose prescription of 54 Gy(RBE), the highest median NTCP was obtained for the WHO°II group treated with two fields using sharp angles. (B) Regarding the effect of multiplefield plans, we found that an NTCP reduction was only achievable in the low-risk group where the LET d effect dominates and the VP 4mm effect is small. NTCP of the single-field plans was 23% higher compared to the clinical opposing field plan. In the high-risk group, where the VP 4mm effect dominates the risk, both two-field scenarios yielded 44% higher NTCP predictions compared to the clinical single-field plans. The interplay of an increased radiosensitivity in the VP 4mm fringe with proton field components of increased biological effectiveness creates a geometric complexity that can hardly be

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Predicting late magnetic resonance image changes in glioma patients after proton therapy

Cited by 69 publications

References 13 publications

Impact of range uncertainty on clinical distributions of linear energy transfer and biological effectiveness in proton therapy

Impact of range uncertainty on clinical distributions of linear energy transfer and biological effectiveness in proton therapy

Treatment‐planning approaches to intensity modulated proton therapy and the impact on dose‐weighted linear energy transfer

How can scanned proton beam treatment planning for low‐grade glioma cope with increased distal RBE and locally increased radiosensitivity for late MR‐detected brain lesions?

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