11C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET).

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.

Adjuvant radiotherapy after brain metastasectomy: analysis of consecutive cohort of 118 patients from real world practice.

Background: The aim of this retrospective study is to analyze a consecutive cohort of brain metastasis (BM) patients treated off clinical trials through combination of surgery and radiotherapy over the last 15 years in a tertiary neurooncology center. Materials and methods: All BM patients operated between 2007-2019 received adjuvant linac-based radiotherapy categorized to whole brain radiotherapy (WBRT) and tumor bed stereotactic radiotherapy. Survival outcomes and local control was analyzed. Results: In total, 118 patients were enrolled, those with stereotactic radiotherapy (41%) had better baseline characteristics mirrored in longer overall survival (OS) [18 vs. 7.1 months, p < 0.001; hazard ratio (HR) 0.47, p = 0.004] with median follow-up of 58 months. Cumulative incidence for local, distant, and extracranial control was not significantly different between groups, with 12-month cumulative control of 22% vs. 18%, 44% vs. 29%, and 35% vs. 32% for stereotactic and WBRT group, respectively. WBRT was an independent factor for better distal brain control. Conclusions: Real world data demonstrating significantly better overall survival in patients treated with postoperative targeted radiotherapy compared with postoperative WBRT is presented, with no significant difference in cumulative incidence for local or distant brain control. The majority of patients with targeted radiotherapy had a fractionated dose schedule with outcomes comparable to single-dose radiation trials of postoperative targeted radiotherapy.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue.

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as 'chemo fog'. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning.This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The main findings of the reviewed studies were summarized, providing also the risk of bias of each study assessed using a modified QUADAS-2 tool. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research.

Impact of analgesic regimen on patient outcome following subarachnoid hemorrhage: positive adjuvant effects of metamizole.

INTRODUCTION: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects. METHODS: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes. RESULTS: Although the administration of non-opioids, in general, had no effect on the development of delayed cerebral ischemia or hydrocephalus, the use of metamizole as the main analgesic was associated with a significantly lower chance of poor outcome at both 2-weeks and 6-months, as well as the development of delayed cerebral ischemia. As opioids were indicated primarily for analgosedation in mechanically ventilated patients with poor clinical status, their usage was associated with a significantly higher chance of poor outcome, delayed cerebral ischemia, and hydrocephalus. CONCLUSION: Our results suggest that the prescription of metamizole may be associated with better outcomes and a lower chance of delayed cerebral ischemia development in patients after subarachnoid hemorrhage. Considering the retrospective nature of our study and the limited worldwide availability of metamizole due to its prohibition in some countries, our results do not demonstrate a clear benefit but rather justify the need for subsequent prospective studies.

The Open Brain Consent: Informing research participants and obtaining consent to share brain imaging data.

Having the means to share research data openly is essential to modern science. For human research, a key aspect in this endeavor is obtaining consent from participants, not just to take part in a study, which is a basic ethical principle, but also to share their data with the scientific community. To ensure that the participants' privacy is respected, national and/or supranational regulations and laws are in place. It is, however, not always clear to researchers what the implications of those are, nor how to comply with them. The Open Brain Consent (https://open-brain-consent.readthedocs.io) is an international initiative that aims to provide researchers in the brain imaging community with information about data sharing options and tools. We present here a short history of this project and its latest developments, and share pointers to consent forms, including a template consent form that is compliant with the EU general data protection regulation. We also share pointers to an associated data user agreement that is not only useful in the EU context, but also for any researchers dealing with personal (clinical) data elsewhere.

Non-steroidal anti-inflammatory drugs in the pathophysiology of vasospasms and delayed cerebral ischemia following subarachnoid hemorrhage: a critical review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm. It appears that NSAIDs (especially coxibs) are even more effective in reducing vasospasm than nimodipine. Other beneficial effects of NSAIDs include reduction in mortality, improved functional outcome and increased hypoaggregability. However, despite these positive effects, there is only one randomized, double-blind, placebo-controlled trial showing a tendency towards a better outcome with lower incidence of vasospasm or mortality in patients following aSAH.

Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes.

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1ß, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1ß, and other known IL-1ß-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1ß, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1ß and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

GliMR: Cross-Border Collaborations to Promote Advanced MRI Biomarkers for Glioma.

Purpose: There is an annual incidence of 50,000 glioma cases in Europe. The optimal treatment strategy is highly personalised, depending on tumour type, grade, spatial localization, and the degree of tissue infiltration. In research settings, advanced magnetic resonance imaging (MRI) has shown great promise as a tool to inform personalised treatment decisions. However, the use of advanced MRI in clinical practice remains scarce due to the downstream effects of siloed glioma imaging research with limited representation of MRI specialists in established consortia; and the associated lack of available tools and expertise in clinical settings. These shortcomings delay the translation of scientific breakthroughs into novel treatment strategy. As a response we have developed the network "Glioma MR Imaging 2.0" (GliMR) which we present in this article. Methods: GliMR aims to build a pan-European and multidisciplinary network of experts and accelerate the use of advanced MRI in glioma beyond the current "state-of-the-art" in glioma imaging. The Action Glioma MR Imaging 2.0 (GliMR) was granted funding by the European Cooperation in Science and Technology (COST) in June 2019. Results: GliMR's first grant period ran from September 2019 to April 2020, during which several meetings were held and projects were initiated, such as reviewing the current knowledge on advanced MRI; developing a General Data Protection Regulation (GDPR) compliant consent form; and setting up the website. Conclusion: The Action overcomes the pre-existing limitations of glioma research and is funded until September 2023. New members will be accepted during its entire duration.

Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections.

PURPOSE: The presence of Propionibacterium acnes in a substantial component of resected disc specimens obtained from patients undergoing discectomy or microdiscectomy has led to the suggestion that this prominent human skin and oral commensal may exacerbate the pathology of degenerative disc disease. This hypothesis, therefore, raises the exciting possibility that antibiotics could play an important role in treating this debilitating condition. To date, however, little information about antibiotic penetration into the intervertebral disc is available. METHODS: Intervertebral disc tissue obtained from 54 microdiscectomy patients given prophylactic cefazolin (n = 25), clindamycin (n = 17) or vancomycin (n = 12) was assayed by high-performance liquid chromatography, with cefaclor as an internal standard, to determine the concentration of antibiotic penetrating into the disc tissue. RESULTS: Intervertebral disc tissues from patients receiving the positively charged antibiotic clindamycin contained a significantly greater percentage of the antibacterial dose than the tissue from patients receiving negatively charged cefazolin (P < 0.0001) and vancomycin, which has a slight positive charge (P < 0.0001). CONCLUSION: Positively charged antibiotics appear more appropriate for future studies investigating potential options for the treatment of low-virulence disc infections. These slides can be retrieved under Electronic Supplementary Material.

Correction to: Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections.

Unfortunately, the complete conflict of interest statement was missed out in the original publication. The same is given below.

Radiotherapy of Glioblastoma 15 Years after the Landmark Stupp's Trial: More Controversies than Standards?

BACKGROUND: The current standard of care of glioblastoma, the most common primary brain tumor in adults, has remained unchanged for over a decade. Nevertheless, some improvements in patient outcomes have occurred as a consequence of modern surgery, improved radiotherapy and up-to-date management of toxicity. Patients from control arms (receiving standard concurrent chemoradiotherapy and adjuvant chemotherapy with temozolomide) of recent clinical trials achieve better outcomes compared to the median survival of 14.6 months reported in Stupp's landmark clinical trial in 2005. The approach to radiotherapy that emerged from Stupp's trial, which continues to be a basis for the current standard of care, is no longer applicable and there is a need to develop updated guidelines for radiotherapy within the daily clinical practice that address or at least acknowledge existing controversies in the planning of radiotherapy.The goal of this review is to provoke critical thinking about potentially controversial aspects in the radiotherapy of glioblastoma, including among others the issue of target definitions, simultaneously integrated boost technique, and hippocampal sparing. CONCLUSIONS: In conjunction with new treatment approaches such as tumor-treating fields (TTF) and immunotherapy, the role of adjuvant radiotherapy will be further defined. The personalized approach in daily radiotherapy practice is enabled with modern radiotherapy systems.

MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response.

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.

[Surgeons and Neurosurgeons as Nobel Prize Winners]. / Chirurgové a neurochirurgové jako laureáti Nobelovy ceny.

Since 1901 Nobel Prize is awarded for exceptional achievements in physics, chemistry, literature, peace, economy (since 1968) and medicine or physiology. The first aim of the paper is to provide an overview of surgeons - winners of Nobel Prize for medicine or physiology. Although the prominent neurosurgeons were frequently nominated as Nobel Prize candidates, surprisingly no neurosurgeon received this prestigious award so far despite that the results of their research transgressed the relatively narrow limits of neurosurgical speciality.The most prominent leaders in the field of neurosurgery, such as Victor Horsley, Otfrid Foerster, Walter Dandy and Harvey Cushing are discussed from the point of their nominations. The overview of the activity of the Portuguese neurologists and Nobel Prize Winter in 1949 Egas Moniz (occasionally erroneously reported as neurosurgeon) is also provided. Although his work on brain angiography has fundamentally changed the diagnostic possibilities in neurology and neurosurgery, he was eventually awarded Nobel Prize for the introduction of the currently outdated frontal lobotomy.The fact that none of the above mentioned prominent neurosurgeons has not been recognised by Nobel Prize, may be attributed to the fact that their extensive work cannot be captured in a short summary pinpointing its groundbreaking character.

Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.

The role of the TP73 gene and its transcripts in neuro-oncology.

Protein p73 is a member of the p53 protein family that can induce cell cycle arrest or apoptosis by the activation of p53-responsive genes as well as p53-independent pathways. Alternative promoter usage, together with differential splicing of the C-terminal exons, forms several distinct mRNAs that are translated into corresponding protein isoforms containing different domains. While TAp73 isoforms respond to genotoxic stress in a manner similar to tumor suppressor p53, ΔTAp73 isoforms inhibit apoptosis during normal development and in cancer cell lines. Thus, the impact of p73 on tumorigenesis depends on a subtle balance between tumor-promoting and -suppressing isoforms. Due to the structural homology between p53 and p73, a subtle balance among p53 family members and their isoforms could influence glioma cell evolution toward malignancy. Thus, the p73 status has to be considered when studying the regulatory role of p53 protein in gliomagenesis. The presented review summarizes recent knowledge about the issue of p73 and its isoforms with respect to neuro-oncology research.

Hippocampal subfield volumetric changes after radiotherapy for brain metastases.

Background: Changes in the hippocampus after brain metastases radiotherapy can significantly impact neurocognitive functions. Numerous studies document hippocampal atrophy correlating with the radiation dose. This study aims to elucidate volumetric changes in patients undergoing whole-brain radiotherapy (WBRT) or targeted stereotactic radiotherapy (SRT) and to explore volumetric changes in the individual subregions of the hippocampus. Method: Ten patients indicated to WBRT and 18 to SRT underwent brain magnetic resonance before radiotherapy and after 4 months. A structural T1-weighted sequence was used for volumetric analysis, and the software FreeSurfer was employed as the tool for the volumetry evaluation of 19 individual hippocampal subregions. Results: The volume of the whole hippocampus, segmented by the software, was larger than the volume outlined by the radiation oncologist. No significant differences in volume changes were observed in the right hippocampus. In the left hippocampus, the only subregion with a smaller volume after WBRT was the granular cells and molecular layers of the dentate gyrus (GC-ML-DG) region (median change -5 mm3, median volume 137 vs. 135 mm3; P = .027), the region of the presumed location of neuronal progenitors. Conclusions: Our study enriches the theory that the loss of neural stem cells is involved in cognitive decline after radiotherapy, contributes to the understanding of cognitive impairment, and advocates for the need for SRT whenever possible to preserve cognitive functions in patients undergoing brain radiotherapy.

Challenges with hippocampal MR spectroscopy as a surrogate for pre-radiotherapy assessment of neurocognitive impairment in patients with brain metastasis.

AIM: Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF). METHODS: 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs. RESULTS: HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051). CONCLUSION: Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.

Whole brain radiotherapy: Consequences for personalized medicine.

Several studies focusing on brain irradiation are in progress. Reflecting updates of relevant outcomes in palliative treatment of patients suffering from brain metastases, the primary objective of these studies is the evaluation of neurocognitive function and quality of life. Improvements of technology in radiation oncology allows us to spare the hippocampal region while appropriately irradiating other parts of brain tissue. Irradiation of the hippocampus region is likely to lead to manifestations of adverse events with a subsequent impact on patient's quality of life, which is in fact an improper approach in palliative medicine. Ongoing studies evaluate results of hippocampus avoiding radiotherapy compared to standard whole brain radiotherapy. Incorporation of neurocognitive function assessment may result in the confirmation of superiority of sparing the region of hippocampus and thus change current style of providing brain irradiation.