To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA).
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.
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.
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.
•In this cohort, the cumulative incidence of psPD increases from 13% in the first year to 28% at 10 years.•psPD is asymptomatic in 83% of patients.•1p/19q codeletion and biopsy are associated with an ...increased risk of psPD.•When analyzed as a time-dependent covariate, psPD is not associated with overall survival.•An uniform definition and analysis method for psPD in diffuse glioma is needed for comparisons between photon - and proton beam radiotherapy.
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.
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.
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.
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.
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 (CMRO
2
), 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 CMRO
2
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.
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.
•Retrospective study of 25-post-operative brain tumour patients.•First documented literature recording the displacement of cranial bone flaps over the course of radiation treatment.•Displacement, ...though never exceeding 2.5 mm, was found to have a high frequency in all patients.•Bone flaps found not to remain a fixed entity as is assumed when cropping the CTV to the bone.•Provides insight for future research to focus on determining the impact of displacement on planning treatment margins.
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.
Both inflow and the partial volume effect (PVE) are sources of error when measuring the arterial input function (AIF) in dynamic contrast‐enhanced (DCE) MRI. This is relevant, as errors in the AIF ...can propagate into pharmacokinetic parameter estimations from the DCE data. A method was introduced for flow correction by estimating and compensating the number of the perceived pulse of spins during inflow. We hypothesized that the PVE has an impact on concentration–time curves similar to inflow. Therefore, we aimed to study the efficiency of this method to compensate for both effects simultaneously. We first simulated an AIF with different levels of inflow and PVE contamination. The peak, full width at half‐maximum (FWHM), and area under curve (AUC) of the reconstructed AIFs were compared with the true (simulated) AIF. In clinical data, the PVE was included in AIFs artificially by averaging the signal in voxels surrounding a manually selected point in an artery. Subsequently, the artificial partial volume AIFs were corrected and compared with the AIF from the selected point. Additionally, corrected AIFs from the internal carotid artery (ICA), the middle cerebral artery (MCA), and the venous output function (VOF) estimated from the superior sagittal sinus (SSS) were compared. As such, we aimed to investigate the effectiveness of the correction method with different levels of inflow and PVE in clinical data. The simulation data demonstrated that the corrected AIFs had only marginal bias in peak value, FWHM, and AUC. Also, the algorithm yielded highly correlated reconstructed curves over increasingly larger neighbourhoods surrounding selected arterial points in clinical data. Furthermore, AIFs measured from the ICA and MCA produced similar peak height and FWHM, whereas a significantly larger peak and lower FWHM was found compared with the VOF. Our findings indicate that the proposed method has high potential to compensate for PVE and inflow simultaneously. The corrected AIFs could thereby provide a stable input source for DCE analysis.
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