Irradiation of the subventricular zone and subgranular zone in high- and low-grade glioma patients: an atlas-based analysis on overall survival.

BACKGROUND: Neural stem cells in the subventricular zone (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. METHODS: We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBrA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. RESULTS: Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, P < .001; multivariate: 1.103/Gy, P = .002) and SGZ dose (univariate: 1.023/Gy, P < .001; multivariate: 1.055/Gy, P < .001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high-/low-dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS, P = .011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS, P < .001). No correlations between dose and OS were found for LGG patients. CONCLUSION: Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

The Impact of Stereotactic or Whole Brain Radiotherapy on Neurocognitive Functioning in Adult Patients with Brain Metastases: A Systematic Review and Meta-Analysis.

Background & Objectives: Radiotherapy is standard treatment for patients with brain metastases (BMs), although it may lead to radiation-induced cognitive impairment. This review explores the impact of whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) on cognition. METHODS: The PRISMA guidelines were used to identify articles on PubMed and EmBase reporting on objective assessment of cognition before, and at least once after radiotherapy, in adult patients with nonresected BMs. RESULTS: Of the 867 records screened, twenty articles (14 unique studies) were included. WBRT lead to decline in cognitive performance, which stabilized or returned to baseline in patients with survival of at least 9-15 months. For SRS, a decline in cognitive performance was sometimes observed shortly after treatment, but the majority of patients returned to or remained at baseline until a year after treatment. CONCLUSIONS: These findings suggest that after WBRT, patients can experience deterioration over a longer period of time. The cognitive side effects of SRS are transient. Therefore, this review advices to choose SRS as this will result in lowest risks for cognitive adverse side effects, irrespective of predicted survival. In an already cognitively vulnerable patient population with limited survival, this information can be used in communicating risks and aid in making educated decisions.

Dose-dependent volume loss in subcortical deep grey matter structures after cranial radiotherapy.

BACKGROUND AND PURPOSE: The relation between radiotherapy (RT) dose to the brain and morphological changes in healthy tissue has seen recent increased interest. There already is evidence for changes in the cerebral cortex and white matter, as well as selected subcortical grey matter (GM) structures. We studied this relation in all deep GM structures, to help understand the aetiology of post-RT neurocognitive symptoms. MATERIALS AND METHODS: We selected 31 patients treated with RT for grade II-IV glioma. Pre-RT and 1 year post-RT 3D T1-weighted MRIs were automatically segmented, and the changes in volume of the following structures were assessed: amygdala, nucleus accumbens, caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus. The volumetric changes were related to the mean RT dose received by each structure. Hippocampal volumes were entered into a population-based nomogram to estimate hippocampal age. RESULTS: A significant relation between RT dose and volume loss was seen in all examined structures, except the caudate nucleus. The volume loss rates ranged from 0.16 to 1.37%/Gy, corresponding to 4.9-41.2% per 30 Gy. Hippocampal age, as derived from the nomogram, was seen to increase by a median of 11 years. CONCLUSION: Almost all subcortical GM structures are susceptible to radiation-induced volume loss, with higher volume loss being observed with increasing dose. Volume loss of these structures is associated with neurological deterioration, including cognitive decline, in neurodegenerative diseases. To support a causal relationship between radiation-induced deep GM loss and neurocognitive functioning in glioma patients, future studies are needed that directly correlate volumetrics to clinical outcomes.

Effect of radiation therapy on cerebral cortical thickness in glioma patients: Treatment-induced thinning of the healthy cortex.

BACKGROUND: With overall survival of brain tumors improving, radiation induced brain injury is becoming an increasing issue. One of the effects of radiation therapy (RT) is thinning of the cerebral cortex, which could be one of the factors contributing to cognitive impairments after treatment. In healthy brain, cortex thickness varies between 1 and 4.5 mm. In this study, we assess the effect of RT on the thickness of the cerebral cortex and relate the changes to the local dose. METHODS: We identified 28 glioma patients with optimal scan quality. Clinical CTs and MRIs at baseline and 1 year post-RT were collected and coregistered. The scans were processed via an automated image processing pipeline, which enabled measuring changes of the cortical thickness, which were related to local dose. RESULTS: Three areas were identified where significant dose-dependent thinning occurred, with thinning rates of 5, 6, and 26 µm/Gy after 1 year, which corresponds to losses of 5.4%, 7.2%, and 21.6% per 30 Gy per year. The first area was largely located in the right inferior parietal, supramarginal, and superior parietal regions, the second in the right posterior cingulate and paracentral regions, and the third almost completely in the right lateral orbital frontal region. CONCLUSIONS: We have identified three areas susceptible to dose-dependent cortical thinning after radiation therapy. Should future prospective studies conclude that irradiation of these areas lead to cognitive decline, they need to be spared in order to prevent this debilitating consequence of treatment.

Programmed Death Receptor Ligand One Expression May Independently Predict Survival in Patients With Non-Small Cell Lung Carcinoma Brain Metastases Receiving Immunotherapy.

PURPOSE: Programmed death receptor ligand 1 (PD-L1) expression is known to predict response to PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC). However, the predictive role of this biomarker in brain metastases (BMs) is unknown. The aim of this study was to assess whether PD-L1 expression predicts survival in patients with NSCLC BMs treated with PD-1/PD-L1 inhibitors, after adjusting for established prognostic models. METHODS AND MATERIALS: In this multi-institutional retrospective cohort study, we identified patients with NSCLC-BM treated with PD-1/PD-L1 inhibitors after local BM treatment (radiation therapy or neurosurgery) but before intracranial progression. Cox proportional hazards models were used to assess the predictive value of PD-L1 expression for overall survival (OS) and intracranial progression-free survival (IC-PFS). RESULTS: Forty-eight patients with BM with available PD-L1 expression were identified. PD-L1 expression was positive in 33 patients (69%). Median survival was 26 months. In univariable analysis, PD-L1 predicted favorable OS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.19-1.02; P = .055). This effect persisted after correcting for lung-graded prognostic assessment and other identified potential confounders (HR, 0.24; 95% CI, 0.10-0.61; P = .002). Moreover, when modeled as a continuous variable, there appeared to be a proportional relationship between percentage of PD-L1 expression and survival (HR, 0.86 per 10% expression; 95% CI, 0.77-0.98; P = .02). In contrast, PD-L1 expression did not predict IC-PFS in uni- or multivariable analysis (adjusted HR, 0.54; 95% CI, 0.26-1.14; P = .11). CONCLUSIONS: In patients with NSCLC-BMs treated with PD-1/PD-L1 checkpoint inhibitors and local treatment, PD-L1 expression may predict OS independent of lung-graded prognostic assessment. IC-PFS did not show association with PD-L1 expression, although the present analysis may lack power to assess this. Larger studies are required to validate these findings.

Does an immobilization mask have added value during planning magnetic resonance imaging for stereotactic radiotherapy of brain tumours?

BACKGROUND AND PURPOSE: When using an immobilization mask, a magnetic resonance imaging (MRI) head receive coil cannot be used and patients may experience discomfort during the examination. We therefore wish to assess the added value of an immobilization mask during all MRI scans intended for cranial stereotactic radiotherapy (SRT) planning. MATERIALS AND METHODS: An MRI was acquired with and without a thermoplastic immobilization mask in ten patients eligible for SRT. A planning computed tomography (CT) scan was also made, to which the two MRIs were independently registered. Additionally, the MRI without immobilization was registered to the MRI in mask. On each sequence, gross tumour volume (GTV), the right eye, brain stem and chiasm were delineated. The absolute differences in centre-of-gravity coordinates and Dice coefficients of the volumes of the delineated structures between the two MRIs were compared. RESULTS: Differences in GTV volume between the two MRIs were low, with median Dice coefficients between 0.88 and 0.91. Similarly, the median absolute differences in centre-of-gravity coordinates between the GTVs, organs at risk and landmarks delineated on the two MRIs were within 0.5 mm. The 95% confidence intervals of the median absolute differences in the three GTV coordinates was within 1 mm, which corresponds to the target volume safety margin used to account for possible errors during the SRT treatment chain. CONCLUSIONS: The effect of scanning a patient without the immobilization mask falls within acceptable bounds of error for the geometrical accuracy of the SRT treatment chain. Consequently, placing the head in treatment position during all MRI scans for patients undergoing radiotherapy of brain metastasis is deemed unnecessary.

Comparing survival predicted by the diagnosis-specific Graded Prognostic Assessment (DS-GPA) to actual survival in patients with 1-10 brain metastases treated with stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Multiple prognostic models for predicting survival after treatment for brain metastases have been developed. One of them, the diagnosis-specific Graded Prognostic Assessment (DS-GPA), has been developed to predict the median survival for brain metastases from the most frequent primary sites: lung carcinoma, breast cancer, melanoma, renal cell cancer and gastrointestinal tumours. In this study we aim to compare the survival predicted by the DS-GPA to actual survival, and to assess this models performance on both population and individual levels. METHODS: We identified a consecutive cohort of patients treated with SRS for brain metastases in our institute. DS-GPA scores were calculated for each patient, and the median survival for each DS-GPA group was calculated. Differences in survival between DS-GPA groups were tested with Wilcoxon Signed Rank tests and log-rank tests. RESULTS: In total 367 patients were included in the analysis. Median survival in our cohort is largely comparable to corresponding DS-GPA cohorts, but some notable differences are present. There was a significantly shorter median survival (15.4 months, compared to 26.5 months) in the adenocarcinoma NSCLC subgroup with a GPA score of 2.3-3. We confirmed the significant differences in survival time for most cancer-specific subgroups. CONCLUSION: DS-GPA seems to be a reliable tool to classify patients with brain metastases treated with SRS into prognostic subgroups. However, we found some aberrations from predicted median survival times, which may be due to specific characteristics of the populations of patients treated with SRS versus other patients.

Changes in cortical thickness and volume after cranial radiation treatment: A systematic review.

Cognitive decline has a clear impact on quality of life in patients who have received cranial radiation treatment. The pathophysiological process is most likely multifactorial, with a possible role for decreased cortical thickness and volume. As radiotherapy treatment systems are becoming more sophisticated, precise sparing of vulnerable regions and tissue is possible. This allows radiation oncologists to make treatment more patient-tailored. A systematic search was performed to collect and review all available evidence regarding the effect of cranial radiation treatment on cortical thickness and volume. We searched the Pubmed, Embase and Cochrane databases, with an additional reference check in the Scopus database. Studies that examined cortical changes on MRI within patients as well as between treated and non-treated patients were included. The quality of the studies was assessed with a checklist specially designed for this review. No meta-analysis was performed due to the lack of randomised trials. Out of 1915 publications twenty-one papers were selected, of which fifteen observed cortical changes after radiation therapy. Two papers reported radiation-dependent decrease in cortical thickness within patients one year after radiation treatment, suggesting a clear relation between the two. However, study quality was considered mostly suboptimal, and there was great inhomogeneity between the included studies. This means that, although there has been increasing interest in the effects of radiation treatment on cortex morphology, no reliable conclusion can be drawn based on the currently available evidence. This calls for more research, preferably with a sufficiently large patient population, and adequate methodology.