The existence of cranial bone flap displacement during brain radiotherapy.

This retrospective study examined bone flap displacement during radiotherapy in 25 post-operative brain tumour patients. Though never exceeding 2.5 mm, the sheer frequency of displacement highlights the need for future research on larger populations to validate its presence and assess the potential clinical impact on planning tumour volume margins.

Improved reliability of perfusion estimation in dynamic susceptibility contrast MRI by using the arterial input function from dynamic contrast enhanced MRI.

The arterial input function (AIF) plays a crucial role in estimating quantitative perfusion properties from dynamic susceptibility contrast (DSC) MRI. An important issue, however, is that measuring the AIF in absolute contrast-agent concentrations is challenging, due to uncertainty in relation to the measured R 2 ∗ -weighted signal, signal depletion at high concentration, and partial-volume effects. A potential solution could be to derive the AIF from separately acquired dynamic contrast enhanced (DCE) MRI data. We aim to compare the AIF determined from DCE MRI with the AIF from DSC MRI, and estimated perfusion coefficients derived from DSC data using a DCE-driven AIF with perfusion coefficients determined using a DSC-based AIF. AIFs were manually selected in branches of the middle cerebral artery (MCA) in both DCE and DSC data in each patient. In addition, a semi-automatic AIF-selection algorithm was applied to the DSC data. The amplitude and full width at half-maximum of the AIFs were compared statistically using the Wilcoxon rank-sum test, applying a 0.05 significance level. Cerebral blood flow (CBF) was derived with different AIF approaches and compared further. The results showed that the AIFs extracted from DSC scans yielded highly variable peaks across arteries within the same patient. The semi-automatic DSC-AIF had significantly narrower width compared with the manual AIFs, and a significantly larger peak than the manual DSC-AIF. Additionally, the DCE-based AIF provided a more stable measurement of relative CBF and absolute CBF values estimated with DCE-AIFs that were compatible with previously reported values. In conclusion, DCE-based AIFs were reproduced significantly better across vessels, showed more realistic profiles, and delivered more stable and reasonable CBF measurements. The DCE-AIF can, therefore, be considered as an alternative AIF source for quantitative perfusion estimations in DSC MRI.

Anatomical changes in resection cavity during brain radiotherapy.

BACKGROUND AND PURPOSE: Brain tumors are in general treated with a maximal safe resection followed by radiotherapy of remaining tumor including the resection cavity (RC) and chemotherapy. Anatomical changes of the RC during radiotherapy can have impact on the coverage of the target volume. The aim of the current study was to quantify the potential changes of the RC and to identify risk factors for RC changes. MATERIALS AND METHODS: Sixteen patients treated with pencil beam scanning proton therapy between October 2019 and April 2020 were retrospectively analyzed. The RC was delineated on pre-treatment computed tomography (CT) and magnetic resonance imaging, and weekly CT-scans during treatment. Isotropic expansions were applied to the pre-treatment RC (1-5 mm). The percentage of volume of the RC during treatment within the expanded pre-treatment volumes was quantified. Potential risk factors (volume of RC, time interval surgery-radiotherapy and relationship of RC to the ventricles) were evaluated using Spearman's rank correlation coefficient. RESULTS: The average variation in relative RC volume during treatment was 26.1% (SD 34.6%). An expansion of 4 mm was required to cover > 95% of the RC volume in > 90% of patients. There was a significant relationship between the absolute volume of the pre-treatment RC and the volume changes during treatment (Spearman's ρ = - 0.644; p = 0.007). CONCLUSION: RCs are dynamic after surgery. Potentially, an additional margin in brain cancer patients with an RC should be considered, to avoid insufficient target coverage. Future research on local recurrence patterns is recommended.

Early and late contrast enhancing lesions after photon radiotherapy for IDH mutated grade 2 diffuse glioma.

OBJECTIVE: The interpretation of new enhancing lesions after radiotherapy for diffuse glioma remains a clinical challenge. We sought to characterize and classify new contrast enhancing lesions in a historical multicenter cohort of patients with IDH mutated grade 2 diffuse glioma treated with photon therapy. METHODS: We reviewed all follow-up MRI's of all patients treated with radiotherapy for histologically confirmed, IDH mutated diffuse grade 2 glioma between 1-1-2007 and 31-12-2018 in two tertiary referral centers. Disease progression (PD) was defined in accordance with the RANO criteria for progressive disease in low grade glioma. Pseudoprogression (psPD) was defined as any transient contrast-enhancing lesion between the end of radiotherapy and PD, or any new contrast-enhancing lesion that remained stable over a period of 12 months in patients who did not exhibit PD. RESULTS: A total of 860 MRI's of 106 patients were reviewed. psPD was identified in 24 patients (23%) on 76 MRI's. The cumulative incidence of psPD was 13% at 1 year, 22% at 5 years, and 28% at 10 years. The mean of the observed maximal volume of psPD was 2.4 cc. The median Dmin in psPD lesions was 50.1 Gy. The presence of an 1p/19q codeletion was associated with an increased risk of psPD (subhazard ratio 2.34, p = 0.048). psPD was asymptomatic in 83% of patients. CONCLUSION: The cumulative incidence of psPD in grade 2 diffuse glioma increases over time. Consensus regarding event definition and statistical analysis is needed for comparisons between series investigating psPD.

Pre-contrast MAGiC in treated gliomas: a pilot study of quantitative MRI.

Quantitative MR imaging is becoming more feasible to be used in clinical work since new approaches have been proposed in order to substantially accelerate the acquisition and due to the possibility of synthetically deriving weighted images from the parametric maps. However, their applicability has to be thoroughly validated in order to be included in clinical practice. In this pilot study, we acquired Magnetic Resonance Image Compilation scans to obtain T1, T2 and PD maps in 14 glioma patients. Abnormal tissue was segmented based on conventional images and using a deep learning segmentation technique to define regions of interest (ROIs). The quantitative T1, T2 and PD values inside ROIs were analyzed using the mean, the standard deviation, the skewness and the kurtosis and compared to the quantitative T1, T2 and PD values found in normal white matter. We found significant differences in pre-contrast T1 and T2 values between abnormal tissue and healthy tissue, as well as between T1w-enhancing and non-enhancing regions. ROC analysis was used to evaluate the potential of quantitative T1 and T2 values for voxel-wise classification of abnormal/normal tissue (AUC = 0.95) and of T1w enhancement/non-enhancement (AUC = 0.85). A cross-validated ROC analysis found high sensitivity (73%) and specificity (73%) with AUCs up to 0.68 on the a priori distinction between abnormal tissue with and without T1w-enhancement. These results suggest that normal tissue, abnormal tissue, and tissue with T1w-enhancement are distinguishable by their pre-contrast quantitative values but further investigation is needed.

The potential of advanced MR techniques for precision radiotherapy of glioblastoma.

As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1-2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.

Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675).

INTRODUCTION: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). METHODS: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. RESULTS: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm. CONCLUSIONS: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm.

Evaluation of the Hippocampal Normal Tissue Complication Model in a Prospective Cohort of Low Grade Glioma Patients-An Analysis Within the EORTC 22033 Clinical Trial.

Purpose: To evaluate the performance of the hippocampal normal tissue complication model that relates dose to the bilateral hippocampus to memory impairment at 18 months post-treatment in a population of low-grade glioma (LGG) patients. Methods: LGG patients treated within the radiotherapy-only arm of the EORTC 22033-26033 trial were analyzed. Hippocampal dose parameters were calculated from the original radiotherapy plans. Difference in Rey Verbal Auditory Learning test delayed recall (AVLT-DR) performance pre-and 18 (±4) months post-treatment was compared to reference data from the Maastricht Aging study. The NTCP model published by Gondi et al. was applied to the dosimetric data and model predictions were compared to actual neurocognitive outcome. Results: A total of 29 patients met inclusion criteria. Mean dose in EQD2 Gy to the bilateral hippocampus was 39.8 Gy (95% CI 34.3-44.4 Gy), the median dose to 40% of the bilateral hippocampus was 47.2 EQD2 Gy. The model predicted a risk of memory impairment exceeding 99% in 22 patients. However, only seven patients were found to have a significant decline in AVLT-dr score. Conclusions: In this dataset of only LGG patients treated with radiotherapy the hippocampus NTCP model did not perform as expected to predict cognitive decline based on dose to 40% of the bilateral hippocampus. Caution should be taken when extrapolating this model outside of the range of dose-volume parameters in which it was developed.