Background/Aim: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We Metastatic tumors present one of the most challenging issues in modern oncology as they are very detrimental to patients' 18

Brain metastases are the most frequent intracranial tumors in adults and the cause of death in almost one-fourth of cases. The incidence of brain metastases is steadily increasing. The main reason for this increase could be the introduction of new and more efficient therapeutic strategies that lead to longer survival but, at the same time, cause a higher risk of brain parenchyma infiltration. In addition, the advances in imaging methodology, which provide earlier identification of brain metastases, may also be a reason for the higher recorded number of patients with these tumors. Metastasis is a complex biological process that is still largely unexplored, influenced by many factors and involving many molecules. A deeper understanding of the process will allow the discovery of more effective diagnostic and therapeutic approaches that could improve the quality and length of patient survival. Recent studies have shown that microRNAs (miRNAs) are essential molecules that are involved in specific steps of the metastatic cascade. MiRNAs are endogenously expressed small non-coding RNAs that act as post-transcriptional regulators of gene expression and thus regulate most cellular processes. The dysregulation of these molecules has been implicated in many cancers, including brain metastases. Therefore, miRNAs represent promising diagnostic molecules and therapeutic targets in brain metastases. This review summarizes the current knowledge on the importance of miRNAs in brain metastasis, focusing on their involvement in the metastatic cascade and their potential clinical implications.

Background Despite current advances in systemic therapy for brain metastases, neurosurgery remains the preferred method of choice in patients with limited brain metastases. Postoperative radiotherapy indicated to reduce the risk of local recurrence is recommended in all patients after surgery. The aim of this retrospective study is to describe clinical characteristics and survival outcomes in consecutive cohorts of patients treated by this combined local treatment. Material and Methods Clinical data were retrieved from electronic medical records for consecutive patients who underwent surgery for brain metastases between 2007 and 2019. All patients underwent postsurgery radiotherapy. Local progression free survival (localPFS) evaluated the local control at the operated site. DistalPFS at the other parts of the brain. Univariable and multivariable analysis of survival characteristics was performed. The Median follow-up was 49 months. Results A total of 118 patients were included (54% women, median age 60 years, median Karnofsky index 80% at the time of radiotherapy). Single metastasis was treated in 66%, while 11% presented with more than 3 metastases. The most common primary diagnosis was lung cancer (33%) and breast (20%). Radical surgery was achieved in 92/117 (79 % of patients). In total, only 48/118 (41%) of patients underwent targeted radiotherapy (mostly fractionated stereotactic radiotherapy of 25Gy in 5 fractions). Significantly more patients (p<0.001) underwent targeted radiotherapy during 2016-2019 (45/48) compared to 2007-2015 period (3/48). A total of 20% of those who underwent postsurgery whole brain radiotherapy (WBRT) had a special technic of hippocampal sparing WBRT of WBRT with simultaneous integrated boost to remaining brain metastases. Median overall survival (OS) for all patients was 9 months (6.2 - 12), median localPFS 22 months (14 - not reached), median distalPFS 11 months (6.8 - 27) and median extracranialPFS 11 months (5.9 - 15). A significant (p=0.00017) difference in OS was while grouping patients according to Graded prognostic assessment (brainmetgpa.com). Significantly better OS was in the cohort of patients with targeted stereotactic radiotherapy (17months) vs. WBRT (5.6 months; p=0.00069) with no difference in local PFS, distal PFS or extracranialPFS. Multivariable analysis revealed type or radiotherapy, control of primary tumor, number of brain metastases 1-2 and the possibility to discontinue corticosteroids to be independent variables for OS. Conclusion Targeted fractionated stereotactic radiotherapy to tumor bed after metastasectomy was associated with improved survival compared to postsurgery WBRT in our cohort. Stereotactic radiotherapy should be preferred in all workplaces with adequate radiotherapy technology. Supported by Ministry of Health of the Czech Republic AZV, NV18-03-00469 and NV18-03-00398.

Background The positive effects of goal-directed hemodynamic therapy (GDHT) on patient-orientated outcomes have been demonstrated in various clinical scenarios; however, the effects of fluid management in neurosurgery remain unclear. Therefore, this study was aimed at assessing the safety and feasibility of GDHT using non-invasive hemodynamic monitoring in elective neurosurgery. The incidence of postoperative complications was compared between GDHT and control groups. Methods We conducted a single-center randomized pilot study with an enrollment target of 34 adult patients scheduled for elective neurosurgery. We randomly assigned the patients equally into control and GDHT groups. The control group received standard therapy during surgery and postoperatively, whereas the GDHT group received therapy guided by an algorithm based on non-invasive hemodynamic monitoring. In the GDHT group, we aimed to achieve and sustain an optimal cardiac index by using non-invasive hemodynamic monitoring and bolus administration of colloids and vasoactive drugs. The number of patients with adverse events, feasibility criteria, perioperative parameters, and incidence of postoperative complications was compared between groups. Results We successfully achieved all feasibility criteria. The GDHT protocol was safe, because no patients in either group had unsatisfactory brain tissue relaxation after surgery or brain edema requiring therapy during surgery or 24 h after surgery. Major complications occurred in two (11.8%) patients in the GDHT group and six (35.3%) patients in the control group (p = 0.105). Conclusions Our results suggested that a large randomized trial evaluating the effects of GDHT on the incidence of postoperative complications in elective neurosurgery should be safe and feasible. The rate of postoperative complications was comparable between groups. Trial registration Trial registration: ClininalTrials.gov, registration number: NCT04754295, date of registration: February 15, 2021.

Brain metastases (BMs) comprise a heterogeneous group of the most frequent intracranial tumors in adults, most originating in lung, breast, renal cell, and colorectal carcinomas and melanomas. Despite the recent improvements in imaging methodology resulting in earlier BM identification and advancements in treatment strategies, BMs are still a significant cause of patient morbidity. Furthermore, BMs frequency increases due to more prolonged survival of cancer patients and population aging. Since the most widely used prognostic scoring systems for BMs require prior knowledge of the primary origin and up to 14% of BMs are classified as BMs of unknown primary, there is an urgent unmet need for accurate biomarkers for identification of BM origin. MiRNAs are non-coding RNAs with an approximate length of 22 nucleotides, functioning as post-transcriptional regulators of gene expression. Dysregulated miRNA expression profile has been observed in many pathological processes, including the complex and not fully understood metastatic cascade. These molecules are very stable and present not only in tissues but also in human body fluids, including blood plasma and cerebrospinal fluid (CSF). Based on these facts, both tissue and circulating miRNAs are extensively studied as potential diagnostic biomarkers. Specific miRNA signatures of BMs were obtained using high-throughput miRNA profiling (Illumina small RNA sequencing) on 3 types of samples (metastatic tissue, blood plasma, CSF) from a cohort of 30 patients with BMs originating in the 5 tumor types – lung, breast, renal cell and colorectal carcinomas and melanomas (6 patients per group, 87 samples in total, only 3 CSF samples from RCC patients available). We identified significantly differentially expressed miRNAs in BM tissues with the ability to differentiate between primary origins. Tissue miRNAs could identify BMs originating from breast, colorectal and renal cell carcinomas and melanomas with high specificity and sensitivity. Interestingly, the heterogeneity of lung carcinomas was also characteristic for the corresponding BMs, making it challenging to distinguish accurately from other BMs. Even though the tissue-specific miRNA signature was the most precise, our results suggest a significant diagnostic potential of circulating miRNAs from CSF for BM patients. Therefore, these short and stable molecules could potentially help identify the origin of BMs of unknown primary. The research is supported by project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU. Citation Format: Dagmar Al Tukmachi, Michaela Ruckova, Marek Vecera, Tana Machackova, Petra Pokorna, Marketa Hermanova, Michal Hendrych, Leos Kren, Ivana Roskova, Vaclav Vybihal, Hana Valekova, Radim Jancalek, Jiri Sana, Martin Smrcka, Ondrej Slaby. Tumor tissue and cerebrospinal fluid microRNA profiles enable the classification of brain metastasis accordingly to their origin. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3758.

INTRODUCTION Modern comprehensive local treatment of BM provides the possibility of adequate local control while maintaining a satisfactory quality of life. METHODS Patients after metastasectomy and postoperative radiotherapy treated between 2007-2020 were evaluated. Local control was assessed separately at the site of the operated MM (localPFS) and separately in other parts of the brain (distalPFS). RESULTS A total of 118 patients were enrolled (70 with WBRT), 54% were women, the median age was 60 years, the median performance status Karnofsky 80%. The most common primary tumor was lung carcinoma (39/118, 33%). Targeted stereotactic radiotherapy was significantly more often indicated in operations performed after 2016 (p < 0.001). In the period 2013-2019, gross total resection was achieved significantly more often (83 vs 64%; p = 0.061). The median follow-up is 49 months. The median overall survival (OS) is 9 months (6.2 - 12), the median localPFS 22 months (14 - unattainable), median distPFS 11 months (6.8 - 27 months), median extracranialPFS 11 months (5.9 - 15). Stratification of patients according to the prognostic index brainmetgpa.com led to significant separation of patients for OS (p = 0.00017). In a multivariate analysis, stereotactic radiotherapy was statistically significant positive prognostic factor for OS compared to WBRT (median OS 17 vs. 5.6 months, HR 0.59, p = 0.018) with no effect on localPFS. CONCLUSION Our results of comprehensive local treatment of BM are comparable with the results presented by important foreign studies from prestigious oncology centers. We described targeted stereotactic postoperative radiotherapy as an independent positive prognostic factor after brain metastasectomy. The study was supported by the programme project of the Ministry of Health of the Czech Republic with reg. no. NV18-03-00398, NV19-03-00501 and NV19-03-00559 and Supported by Ministry of Health, Czech Republic-conceptual development of research organization (FNBr, 65269705).

Introduction: Goal-directed hemodynamic therapy aims to reduce the incidence of postoperative complications in patients undergoing surgical procedures. Optimal preload is mandatory to achieve adequate cardiac output and oxygen supply to organs and tissues. Neurosurgical patients are at risk of inadequate preload, decreased blood flow and reduced oxygen delivery, all of which can lead to organ dysfunction. Current knowledge regarding the effect of fluid management on patient-orientated outcomes in neurosurgery is limited. Therefore, this study aims to compare the safety and feasibility of goal-directed therapy with standard management in patients undergoing neurosurgical procedures. Methods and analysis: Patients undergoing neurosurgical operation will be randomised into two groups. Therapy in the first group of patients will be guided by standard perioperative monitoring. In the second group, perioperative therapy will be guided using non-invasive hemodynamic monitoring in addition to standard monitoring. Administration of fluids and vasoactive drugs will depend on the assessment of stroke volume variation and cardiac index. The safety of goal-directed hemodynamic therapy protocol will be assessed by comparing incidences of adverse events between groups.