Radiation induced contrast enhancement after proton beam therapy in patients with low grade glioma – How safe are protons?

Harrabi, Semi; Nettelbladt, Bastian von; Gudden, C.; Adeberg, Sebastian; Seidensaal, Katharina; Bauer, J.; Bahn, Emanuel; Mairani, A.; Alber, M.; Haberer, Thomas; Debus, Jürgen; Herfarth, Klaus

doi:10.1016/j.radonc.2021.12.035

Cited by 39 publications

(17 citation statements)

References 38 publications

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“…However, several trials showed that PT was associated with signi cantly higher rates of MRI sequences T1c+T2 changes compared with photon therapy for brain tumors but the rates of symptomatic RN following PT was as uncommon as conventional photon-based group. [18,19]. In our series we reported a rate of RN of 14% (8.5% for RN grade 2 or more), with a median cumulative EQD2 brain dose of 122 GyRBE (range 111.7-123.2), in line with trials previously published, despite signi cant large irradiated volume (median GTV 43 cc, range 1.2-225.5 cc).…”

Section: Discussionsupporting

confidence: 88%

Proton therapy re-irradiation provides promising clinical results in recurrent brain meningioma

Scartoni¹,

Giacomelli²,

Pertile³

et al. 2023

Preprint

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Purpose To evaluate the clinical outcomes, toxicity and prognostic factors conditioning survival of reirradiation with Proton therapy for recurrent meningiomas. Methods Recurrent meningioma who failed after radiotherapy were re-irradiated with active scanning proton therapy with a median dose of 54 GyRBE (range 50.4-60 GyRBE). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The log rank test was performed to compare the entire survival experience between groups (significant p-value ≤ 0.05). Associations between qualitative variables were analyzed with the Fisher exact test (significant p-value ≤ 0.05). Results Thirty-two patients were re-irradiated with Proton therapy (10 grade I, 22 grade II-III). Median tumor volume at the time of re-irradiation was 43 cc (range 1.2-225.5) and median time from prior RT to reirradiation was 66 months (range 4-288). At a median follow-up of 27 months, 1-yr and 2-yr PFS were 89.4% and 74.5% (1-yr and 2-yr PFS were 100% for grade I, 100% and 76% for grade II, 66% and 50% for grade III). 1-yr and 2-yr OS were 86.6% and 83.0% (2-yr OS were 87% for grade I, 86% for grade II, 66% for grade III). Local recurrence rate was 34% with a median time of recurrence of 13.4 months. Five patients (14%) developed radionecrosis with a median time of 3.4 months from the end of PT (range 3-8.8). Conclusions Re-irradiation with proton therapy seems to be a safe and effective treatment in patients with recurrent meningioma, also for large volume and aggressive lesions (grade II-III).

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Section: Discussionsupporting

confidence: 88%

Proton therapy re-irradiation provides promising clinical results in recurrent brain meningioma

Scartoni¹,

Giacomelli²,

Pertile³

et al. 2023

Preprint

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“…However, in-vitro and invivo studies show that RBE varies within a treatment field as a function of physical and biological parameters [3,4]. While emerging clinical studies showed that RBE varies with the linear energy transfer (LET) and tissue-specific radiosensitivity [5][6][7][8][9][10][11], some studies did not find correlations between LET and toxicity with the interpatient variability being a potential obscuring effect [12,13]. The uncertainty in RBE already affects daily clinical proton therapy treatment planning strategies [14,15] and urges the exploration and development of treatment planning strategies beyond absorbed dose optimization [16,17].…”

Section: Introductionmentioning

confidence: 99%

Comparing biological effectiveness guided plan optimization strategies for cranial proton therapy: potential and challenges

et al. 2022

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Background To introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies minimizing variable relative biological effectiveness (RBE) induced dose burden in organs at risk (OAR) while maintaining plan quality with a constant RBE. Methods Dose-optimized (DOSEopt) proton pencil beam scanning reference treatment plans were generated for ten cranial patients with prescription doses ≥ 54 Gy(RBE) and ≥ 1 OAR close to the clinical target volume (CTV). For each patient, four additional BG plans were created. BG objectives minimized either proton track-ends, dose-averaged linear energy transfer (LETd), energy depositions from high-LET protons or variable RBE-weighted dose (DRBE) in adjacent serially structured OARs. Plan quality (RBE = 1.1) was assessed by CTV dose coverage and robustness (2 mm setup, 3.5% density), dose homogeneity and conformity in the planning target volumes and adherence to OAR tolerance doses. LETd, DRBE (Wedenberg model, α/βCTV = 10 Gy, α/βOAR = 2 Gy) and resulting normal tissue complication probabilities (NTCPs) for blindness and brainstem necrosis were derived. Differences between DOSEopt and BG optimized plans were assessed and statistically tested (Wilcoxon signed rank, α = 0.05). Results All plans were clinically acceptable. DOSEopt and BG optimized plans were comparable in target volume coverage, homogeneity and conformity. For recalculated DRBE in all patients, all BG plans significantly reduced near-maximum DRBE to critical OARs with differences up to 8.2 Gy(RBE) (p < 0.05). Direct DRBE optimization primarily reduced absorbed dose in OARs (average ΔDmean = 2.0 Gy; average ΔLETd,mean = 0.1 keV/µm), while the other strategies reduced LETd (average ΔDmean < 0.3 Gy; average ΔLETd,mean = 0.5 keV/µm). LET-optimizing strategies were more robust against range and setup uncertaintes for high-dose CTVs than DRBE optimization. All BG strategies reduced NTCP for brainstem necrosis and blindness on average by 47% with average and maximum reductions of 5.4 and 18.4 percentage points, respectively. Conclusions All BG strategies reduced variable RBE-induced NTCPs to OARs. Reducing LETd in high-dose voxels may be favourable due to its adherence to current dose reporting and maintenance of clinical plan quality and the availability of reported LETd and dose levels from clinical toxicity reports after cranial proton therapy. These optimization strategies beyond dose may be a first step towards safely translating variable RBE optimization in the clinics.

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“…This may be due to the location of neural stem cells in the ventricular subependymal region [ 67 , 68 ] that are probably more sensitive to irradiation. In particle therapy, according to the beam arrangement, on the marginal treatment field where an increased RBE (and therefore higher dose with exceedance of the TD5/5) due to the distal edge of Bragg peak is expected, BBD occur more frequently [ 69 – 71 ]. This can often be seen in the temporal lobes and also near the ventricular system.…”

Section: Resultsmentioning

confidence: 99%

DEGRO practical guideline for central nervous system radiation necrosis part 1: classification and a multistep approach for diagnosis

et al. 2022

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Purpose The Working Group for Neuro-Oncology of the German Society for Radiation Oncology in cooperation with members of the Neuro-Oncology Working Group of the German Cancer Society aimed to define a practical guideline for the diagnosis and treatment of radiation-induced necrosis (RN) of the central nervous system (CNS). Methods Panel members of the DEGRO working group invited experts, participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for medical treatment of RN including bevacizumab in clinical routine. Conclusion Diagnosis and treatment of RN requires multidisciplinary structures of care and defined processes. Diagnosis has to be made on an interdisciplinary level with the joint knowledge of a neuroradiologist, radiation oncologist, neurosurgeon, neuropathologist, and neuro-oncologist. A multistep approach as an opportunity to review as many characteristics as possible to improve diagnostic confidence is recommended. Additional information about radiotherapy (RT) techniques is crucial for the diagnosis of RN. Misdiagnosis of untreated and progressive RN can lead to severe neurological deficits. In this practice guideline, we propose a detailed nomenclature of treatment-related changes and a multistep approach for their diagnosis.

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Radiation induced contrast enhancement after proton beam therapy in patients with low grade glioma – How safe are protons?

Cited by 39 publications

References 38 publications

Proton therapy re-irradiation provides promising clinical results in recurrent brain meningioma

Proton therapy re-irradiation provides promising clinical results in recurrent brain meningioma

Comparing biological effectiveness guided plan optimization strategies for cranial proton therapy: potential and challenges

DEGRO practical guideline for central nervous system radiation necrosis part 1: classification and a multistep approach for diagnosis

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