Use of Fluorescence to Guide Resection or Biopsy of Primary Brain Tumors and Brain Metastases

Author(s):  
S. Marbacher ◽  
E. Klinger ◽  
L. Schwzer ◽  
I. Fischer ◽  
E. Nevzati ◽  
...  
2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi98-vi98
Author(s):  
Radim Jancalek ◽  
Martin Smrcka ◽  
Alena Kopkova ◽  
Jiri Sana ◽  
Marek Vecera ◽  
...  

Abstract Cerebrospinal fluid (CSF) baths extracellular environment of the central nervous system, and thus, it is ideal source of tumor diagnostic biomarkers like microRNAs (miRNAs), short non-coding RNAs involved in the pathogenesis of many cancers. As dysregulated levels of brain tumor specific miRNAs have been already observed in CSF, analysis of CSF miRNAs in brain tumor patients might help to develop new diagnostic platform. Next-Generation sequencing (NGS) was performed for analysis of small RNAs in 89 CSF samples taken from 32 glioblastomas (GBM), 14 low-grade gliomas (LGG), 11 meningiomas, 13 brain metastases and 19 non-tumor donors. Subsequently, according to NGS results levels of 10 miRNAs were measured in independent set of CSF samples (41 GBM, 44 meningiomas, 12 brain metastases and 20 non-tumor donors) using TaqMan Advanced miRNA Assays. NGS analysis revealed 22, 12 and 35 CSF miRNAs with significantly different levels in GBM, meningiomas, and brain metastases (adj.p < 0.0005, adj.p < 0.01, and adj.p < 0.005) respectively, in comparison with non-tumor CSF samples. Subsequent validation of selected CSF miRNAs has confirmed different levels of 7 miRNAs in GBM, 2 in meningiomas, and 2 in brain metastases compared to non-tumors. Panel of miR-30e-5p and miR-140-5p was able to distinguish brain metastases with 65% sensitivity and 100% specificity compared to non-tumor samples (AUC = 0.8167); panel of miR-21-3p and miR-196-5p classified metastatic patients with 78% sensitivity and 92 % specificity in comparison to GBM (AUC = 0.90854) and with 75% sensitivity and 83% specificity compared to meningiomas (AUC = 0.84848). We have observed that CSFs from patients with various primary brain tumors and metastases are characterized by specific miRNA signatures. This work was supported by the Ministry of Health, Czech Republic grant nr. NV18-03-00398 and the Ministry of Education, Youth and Sports, Czech Republic under the project CEITEC 2020 (LQ1601).


2014 ◽  
Vol 36 (2) ◽  
pp. E10 ◽  
Author(s):  
Serge Marbacher ◽  
Elisabeth Klinger ◽  
Lucia Schwyzer ◽  
Ingeborg Fischer ◽  
Edin Nevzati ◽  
...  

Object The accurate discrimination between tumor and normal tissue is crucial for determining how much to resect and therefore for the clinical outcome of patients with brain tumors. In recent years, guidance with 5-aminolevulinic acid (5-ALA)–induced intraoperative fluorescence has proven to be a useful surgical adjunct for gross-total resection of high-grade gliomas. The clinical utility of 5-ALA in resection of brain tumors other than glioblastomas has not yet been established. The authors assessed the frequency of positive 5-ALA fluorescence in a cohort of patients with primary brain tumors and metastases. Methods The authors conducted a single-center retrospective analysis of 531 patients with intracranial tumors treated by 5-ALA–guided resection or biopsy. They analyzed patient characteristics, preoperative and postoperative liver function test results, intraoperative tumor fluorescence, and histological data. They also screened discharge summaries for clinical adverse effects resulting from the administration of 5-ALA. Intraoperative qualitative 5-ALA fluorescence (none, mild, moderate, and strong) was documented by the surgeon and dichotomized into negative and positive fluorescence. Results A total of 458 cases qualified for final analysis. The highest percentage of 5-ALA–positive fluorescence in open resection was found in glioblastomas (96%, n = 99/103). Among other tumors, 5-ALA–positive fluorescence was detected in 88% (n = 21/32) of anaplastic gliomas (WHO Grade III), 40% (n = 8/19) of low-grade gliomas (WHO Grade II), no (n = 0/3) WHO Grade I gliomas, and 77% (n = 85/110) of meningiomas. Among metastases, the highest percentage of 5-ALA–positive fluorescence was detected in adenocarcinomas (48%, n = 13/27). Low rates or absence of positive fluorescence was found among pituitary adenomas (8%, n = 1/12) and schwannomas (0%, n = 0/7). Biopsies of high-grade primary brain tumors showed positive rates of fluorescence similar to those recorded for open resection. No clinical adverse effects associated with use of 5-ALA were observed. Only 1 patient had clinically silent transient elevation of liver enzymes. Conclusions Study findings suggest that the administration of 5-ALA as a surgical adjunct for resection and biopsy of primary brain tumors and brain metastases is safe. In light of the high rate of positive fluorescence in high-grade gliomas other than glioblastomas, meningiomas, and a variety of metastatic cancers, 5-ALA seems to be a promising tool for enhancing intraoperative identification of neoplastic tissue and optimizing the extent of resection.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2521-2521
Author(s):  
Brian J. Carney ◽  
Erik J. Uhlmann ◽  
Maneka Puligandla ◽  
Charlene Mantia ◽  
Griffin M. Weber ◽  
...  

Abstract Introduction Venous thromboembolism (VTE) is a common complication of cancer. Patients with primary brain tumors and brain metastases are at particularly high risk, with about 20-30% suffering a VTE event. The administration of enoxaparin appears to be safe in patients with brain metastases but confers an increased risk of intracranial hemorrhage (ICH) in patients with primary brain tumors. Direct-acting oral anticoagulants (DOACs) have demonstrated efficacy in the treatment of cancer-associated thrombosis with an increased risk of hemorrhage compared to low molecular weight heparin (LMWH). There are limited data on the safety of DOACs in patients with brain tumors. As the risk of ICH associated with parenteral anticoagulants differs for primary versus secondary brain tumors, we analyzed ICH outcomes for patients with VTE receiving enoxaparin or a DOAC. Methods A retrospective cohort study was performed using a hospital-based online medical record database (CQ2) linking ICD-9 and ICD-10 codes with prescription medication records. Cases were identified based on coding for primary brain tumors or brain metastases and prescription of either a DOAC or enoxaparin. A blinded review of radiographic imaging was performed, and intracranial hemorrhages were categorized as either trace, measurable, and major. Measurable intracranial hemorrhages were those defined as greater than 1 mL in volume and major intracranial hemorrhages were defined as greater than 10 mL in volume, symptomatic (defined as focal deficit, headache, nausea, or a change in cognitive function), or required surgical intervention. Gray's test was used to compare the cumulative incidence of ICH between the groups, with death as a competing risk. Results A total of 170 patients with primary brain tumors and brain metastases were included in the study. In the primary brain tumor cohort (N=65), 18 patients received a DOAC while 47 received enoxaparin. The cumulative incidence of any ICH at 12 months was 0% in patients receiving a DOAC compared to 36.8% (95% confidence interval 22.3-51.3%) in those receiving enoxaparin (P=0.012). There were no major ICH events in the DOAC group and 8 and in the LMWH group (12-month cumulative incidence of 0% versus 18.2%, 95% CI 8.4-31.0, P=0.062). In the brain metastases cohort (N=105), 21 patients received a DOAC while 84 received enoxaparin. The DOAC and enoxaparin groups were well-matched for tumor diagnosis (non-small lung cancer 52% and 51%, respectively) including those tumor types with a high incidence of ICH (i.e. melanoma 5% and 7% and renal cell carcinoma 14% and 11%, respectively). In patients with brain metastases, DOACs did not increase the risk of any ICH relative to enoxaparin (12-month cumulative incidence 27.8% versus 52.9%, P=0.15) nor major ICH (12-month cumulative incidence 11.1% vs 17.8%, P=0.38). Conclusions DOACs can be safely administered to patients with brain tumors. In patients with primary brain tumors (i.e. glioma), DOACs appear to be safer than LMWH and should be considered for this indication. Figure. Figure. Disclosures Zwicker: Incyte: Research Funding; Parexel: Consultancy; Quercegen: Research Funding; Daiichi: Honoraria.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6 ◽  
Author(s):  
Angela Lee ◽  
Frank Oley ◽  
Mimi Lo ◽  
Richard Fong ◽  
Mary McGann ◽  
...  

Background: Management of venous thromboembolism (VTE) in patients with central nervous system (CNS) malignancies is challenging as there is an increased risk of recurrent VTE and intracranial hemorrhage (ICH). Low molecular weight heparins (LMWH) have historically been the standard of care for treatment of cancer-associated thrombosis (CAT). Current guidelines recommend direct oral anticoagulants (DOACs) for CAT treatment, but patients with CNS malignancies have limited representation in the supporting clinical trials. This multicenter, retrospective cohort study evaluated the safety and efficacy of DOACs compared to LMWH for CAT in patients with primary brain tumors or secondary brain metastases. Patients/Methods: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for CAT were evaluated. The primary outcome was the incidence of any bleeding event within a 6-month period following the initiation of anticoagulation. Secondary outcomes included incidence of recurrent VTE events, major bleeding, clinically relevant non-major bleeding (CRNMB), and minor bleeding, within a 6-month period following the initiation of anticoagulation. Patients were excluded if their indication for anticoagulation was stroke, non-cancer-associated VTE, or VTE prophylaxis, were on LMWH for one week or less while bridging to warfarin, or received a diagnosis of VTE at an outside hospital. All bleeding events were defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Primary and secondary outcomes were analyzed using Fisher's exact test for categorical variables and Wilcoxon rank-sum tests for non-parametric continuous variables. Results: Between January 1, 2012 to October 9, 2019, one-hundred eleven patients met inclusion criteria. Of the patients who met inclusion criteria, 26 (23.4%) patients had primary brain tumors and 85 (76.6%) patients had secondary brain metastases. Bleeding events occurred in 7 of 55 patients (12.7%) in the DOAC group compared to 13 of 56 (23.2%) patients in the LMWH group (RR 0.55, 95% CI 0.24-1.27). Recurrent VTE events occurred in 3 of 55 (5.5%) patients in the DOAC group compared to 3 of 56 (5.4%) patients in the LMWH group (RR 1.02, 95% CI 0.21-4.83). Major bleeding occurred in 3 of 55 (5.5%) patients in the DOAC group, compared to 4 of 56 (7.1%) patients in the LMWH group (RR 0.76, 95% CI 0.18-3.26). There were no differences in the rates of CRNMB and rates of minor bleeding between groups. Conclusion: In this multicenter retrospective cohort study, therapeutic anticoagulation with DOACs showed no significant difference in bleeding events or recurrent VTE events when compared to LMWH, in patients with primary brain tumors or secondary brain metastases. We conclude that DOACs may be potentially safe and efficacious for VTE treatment in patients with primary brain tumors or secondary brain metastases. As prescribing practices are expected to continue to shift towards DOACs, this study provides preliminary evidence of the safety of DOACs in this high-bleeding risk patient population. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Katherine G Holste ◽  
Daniel A Orringer

Abstract Background Laser interstitial thermal therapy (LITT) is becoming an increasingly popular technique for the treatment of brain lesions. More minimally invasive that open craniotomy for lesion resection, LITT may be more appropriate for lesions that are harder to access through an open approach, deeper lesions, and for patients who may not tolerate open surgery. Methods A search of the current primary literature on LITT for brain lesions on PubMed was performed. These studies were reviewed and updates on the radiological, pathological, and long-term outcomes after LITT for brain metastases, primary brain tumors, and radiation necrosis as well as common complications are included. Results Larger extent of ablation and LITT as frontline treatment were potential predictors of favorable progression-free and overall survival for primary brain tumors. In brain metastases, larger extent of ablation was more significantly associated with survival benefit, whereas tumor size was a possible predictor. The most common complications after LITT are transient and permanent weakness, cerebral edema, hemorrhage, seizures, and hyponatremia. Conclusions Although the current literature is limited by small sample sizes and primarily retrospective studies, LITT is a safe and effective treatment for brain lesions in the correct patient population.


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