CTNI-55. THE CDK4/6 INHIBITOR ABEMACICLIB IN PATIENTS WITH RECURRENT MENINGIOMA AND OTHER PRIMARY CNS TUMORS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi72-vi73
Author(s):  
Elizabeth Coffee ◽  
Katherine Panageas ◽  
Robert Young ◽  
Tara Morrison ◽  
Ahmad Daher ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Single Agent ◽  
Pituitary Tumors ◽  
Molecular Characteristics ◽  
Multiple Cancer ◽  
Who Grade ◽  
Multiple Tumor ◽  
Primary Brain Tumors ◽  
Basket Trial ◽  
Tumor Types

Abstract BACKGROUND Medical therapies for recurrent brain tumors are limited. Abemaciclib is a small molecule CDK4/6 inhibitor that has demonstrated antitumor activity in multiple cancer types and crosses the blood-brain barrier. METHODS We conducted a phase II trial of single-agent abemaciclib in patients with recurrent primary brain tumors utilizing a novel CNS basket trial design with multiple tumor types accrued to separate cohorts including patients with recurrent IDH-wildtype gliomas (Cohort A), any recurrent gliomas requiring cytoreductive surgery (Cohort B), and any other recurrent primary brain tumors (Cohort C) including IDH-mutant gliomas, meningiomas, and other tumor types. In all patients, abemaciclib was administered orally at 200mg twice daily for each 28-day cycle. In cohort B abemaciclib was administered 4-7 days prior to surgery then resumed after recovery. Neuroimaging disease assessments were performed every two cycles. Cohorts were individually assessed for efficacy, tumoral molecular characteristics, and exploratory biomarker analyses. Next generation sequencing was performed on patients who had prior surgery. RESULTS To date, a total of 61 patients have enrolled and initiated treatment with abemaciclib. Cohort A enrolled 9 patients with IDH-wildtype WHO grade II and III astrocytomas. Cohort B enrolled 10 patients with astrocytomas of varying IDH-status. Cohort C is a diverse group of 42 patients including 22 treatment-refractory meningiomas, 10 IDH-mutant gliomas (5 astrocytomas, 5 oligodendrogliomas), 3 ependymomas, 3 primary CNS lymphomas, 2 pituitary tumors, 1 glioneuronal rosette forming tumor, and 1 diffuse midline glioma. A total of 7 grade 3 toxicities occurred in 6 patients: fatigue (3), neutropenia (2), colitis (1) and seizure (1); no grade 4 toxicities occurred. CONCLUSIONS We present the results of a novel CNS basket trial looking at the efficacy of abemaciclib across multiple recurrent primary brain tumors. Efficacy results will be presented, highlighting an update on promising results in the 22 patients with recurrent meningiomas.

scholarly journals Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors

2021 ◽  
Author(s):  
Hyunhee Kim ◽  
Ka Young Lim ◽  
Jin Woo Park ◽  
Jeongwan Kang ◽  
Jae Kyung Won ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Statistical Significance ◽  
Biological Behavior ◽  
Molecular Characteristics ◽  
Genetic Profile ◽  
Who Grade ◽  
Primary Brain Tumors

AbstractMismatch repair-deficient (MMRD) brain tumors are rare among primary brain tumors and can be induced by germline or sporadic mutations. Here, we report 13 MMRD-associated (9 sporadic and 4 Lynch syndrome) primary brain tumors to determine clinicopathological and molecular characteristics and biological behavior. Our 13 MMRD brain tumors included glioblastoma (GBM) IDH-wildtype (n = 9) including 1 gliosarcoma, astrocytoma IDH-mutant WHO grade 4 (n = 2), diffuse midline glioma (DMG) H3 K27M-mutant (n = 1), and pleomorphic xanthoastrocytoma (PXA) (n = 1). Next-generation sequencing using a brain tumor-targeted gene panel, microsatellite instability (MSI) testing, Sanger sequencing for germline MMR gene mutation, immunohistochemistry of MMR proteins, and clinicopathological and survival analysis were performed. There were many accompanying mutations, suggesting a high tumor mutational burden (TMB) in 77%, but TMB was absent in one case of GBM, IDH-wildtype, DMG, and PXA, respectively. MSH2, MLH1, MSH6, and PMS2 mutations were found in 31%, 31%, 31% and 7% of patients, respectively. MSI-high and MSI-low were found in 50% and 8% of these gliomas, respectively and 34% was MSI-stable. All Lynch syndrome-associated GBMs had MSI-high. In addition, 77% (10/13) had histopathologically multinucleated giant cells. The progression-free survival tended to be poorer than the patients with no MMRD gliomas, but the number and follow-up duration of our patients were insufficient to get statistical significance. In the present study, we found that the most common MMRD primary brain tumor was GBM IDH-wildtype. The genetic profile of MMRD GBM was different from that of conventional GBM. MMRD gliomas with TMB and MSI-H may be sensitive to immunotherapy but resistant to temozolomide. Our findings can help develop better treatment options.

scholarly journals Apolipoprotein D Expression in Primary Brain Tumors: Analysis by Quantitative RT-PCR in Formalin-fixed, Paraffin-embedded Tissue

2005 ◽  
Vol 53 (8) ◽  
pp. 963-969 ◽  
Author(s):  
Stephen B. Hunter ◽  
Vijay Varma ◽  
Bahig Shehata ◽  
J.D.L. Nolen ◽  
Cynthia Cohen ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Type ◽  
Rt Pcr ◽  
Who Grade ◽  
Primary Brain Tumors ◽  
Formalin Fixed Paraffin ◽  
Pilocytic Astrocytomas ◽  
Formalin Fixed Paraffin Embedded ◽  
Apolipoprotein D ◽  
Formalin Fixed

Apolipoprotein D (apoD) expression has been shown to correlate both with cell cycle arrest and with prognosis in several types of malignancy, including central nervous system astrocytomas and medulloblastomas. ApoD expression was investigated by real-time quantitative RT-PCR using RNA extracted from 68 formalin-fixed, paraffin-embedded brain specimens. Glyceraldehyde phosphate dehydrogenase was used as an internal control. Quantitation was achieved on all specimens. Sixteen poorly infiltrating WHO grade I glial neoplasms (i.e., pilocytic astrocytomas and gangliogliomas) showed an average 20-fold higher apoD expression level compared with the 20 diffusely infiltrating glial neoplasms (i.e., glioblastoma, anaplastic astrocytoma, oligodendrogliomas; p=0.00004). A small number of exceptions (i.e., two high-expressing glioblastomas and three low-expressing gangliogliomas) were identified. Analyzed as individual tumor groups, poorly infiltrating grade I pilocytic astrocytomas and gangliogliomas differed significantly from each tumor type within the diffusely infiltrating higher-grade category ( p<0.05 for each comparison) but not from each other ( p>0.05). Conversely, each individual tumor type within the diffusely infiltrating category differed significantly from both pilocytic astrocytomas and gangliogliomas ( p<0.05) but did not vary from other infiltrating tumors ( p>0.05). Ependymomas, non-infiltrating grade II neoplasms, expressed levels of apoD similar to or lower than levels expressed by the diffusely infiltrating gliomas. Ten medulloblastomas with survival longer than 3 years averaged slightly higher apoD expression than four fatal medulloblastomas; however, this result was not statistically significant and individual exceptions were notable. In 17 of the medulloblastomas, MIB-1 proliferation rates quantitated by image cytometry did not correlate with apoD expression. In addition, apoD expression was 5-fold higher in the slowly proliferating grade I glial neoplasms compared with non-proliferating normal brain tissue ( p=0.01), suggesting that apoD expression is not simply an inverse measure of proliferation. ApoD expression measured by quantitative RT-PCR may be useful in the differential diagnosis of primary brain tumors, particularly pilocytic astrocytomas and gangliogliomas.

scholarly journals BRAF Mutations and the Utility of RAF and MEK Inhibitors in Primary Brain Tumors

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1262 ◽  
Author(s):  
Karisa C. Schreck ◽  
Stuart A. Grossman ◽  
Christine A. Pratilas
Keyword(s):  
Brain Tumors ◽  
Poor Prognosis ◽  
Primary Brain Tumor ◽  
High Grade ◽  
Braf Mutations ◽  
Mek Inhibitors ◽  
Primary Brain Tumors ◽  
The Poor ◽  
Oncogenic Mutations ◽  
Tumor Types

BRAF mutations have been identified as targetable, oncogenic mutations in many cancers. Given the paucity of treatments for primary brain tumors and the poor prognosis associated with high-grade gliomas, BRAF mutations in glioma are of considerable interest. In this review, we present the spectrum of BRAF mutations and fusion alterations present in each class of primary brain tumor based on publicly available databases and publications. We also summarize clinical experience with RAF and MEK inhibitors in patients with primary brain tumors and describe ongoing clinical trials of RAF inhibitors in glioma. Sensitivity to RAF and MEK inhibitors varies among BRAF mutations and between tumor types as only class I BRAF V600 mutations are sensitive to clinically available RAF inhibitors. While class II and III BRAF mutations are found in primary brain tumors, further research is necessary to determine their sensitivity to third-generation RAF inhibitors and/or MEK inhibitors. We recommend that the neuro-oncologist consider using these drugs primarily in the setting of a clinical trial for patients with BRAF-altered glioma in order to advance our knowledge of their efficacy in this patient population.

Acral Lentiginous Melanoma Harboring a ROS1 Gene Fusion With Clinical Response to Entrectinib

2017 ◽  
pp. 1-7 ◽  
Author(s):  
Kasey L. Couts ◽  
Caroline E. McCoach ◽  
Danielle Murphy ◽  
Jason Christiansen ◽  
Jacqueline Turner ◽  
...  
Keyword(s):  
Clinical Response ◽  
Cutaneous Melanoma ◽  
Gene Fusions ◽  
Small Cell Lung ◽  
Durable Response ◽  
Acral Lentiginous Melanoma ◽  
Multiple Tumor ◽  
Alk Inhibitor ◽  
Basket Trial ◽  
Tumor Types

Purpose ROS1 gene fusions demonstrate oncogenic activity, and patients with non–small-cell lung cancer (NSCLC) harboring a ROS1 fusion benefit from the use of a ROS1 inhibitor; however, clinical response to ROS1 inhibitors remains largely uncharacterized outside of NSCLC. ROS1 fusions have been identified in multiple tumor types but have not been reported in cutaneous melanoma. Patients and Methods Tumors from 22 patients with acral lentiginous melanoma (ALM) were analyzed with targeted RNA sequencing to detect fusions in ROS1, NTRK1, NTRK2, NTRK3, and ALK genes. A patient harboring a ROS1 fusion was enrolled in a phase I basket trial of a ROS1/TRK/ALK inhibitor (entrectinib). An additional 78 tumors with different subtypes of melanoma were screened by ROS1 immunohistochemistry. Results Targeted sequencing identified a GOPC- ROS1 fusion in a patient with ALM. The patient underwent a dramatic and durable response to entrectinib, with a RECIST (version 1.1) partial response of −38% at 3 months and −55% at 11 months. The response is ongoing, and the patient has not developed any new lesions. No additional ROS1 fusions were identified by immunohistochemistry, resulting in a frequency of 3.0% in ALM and 1.3% in all melanomas. Conclusion ROS1 fusions occur and can respond to targeted therapy in cutaneous melanoma; however, they may be specific to ALM subtype. This report expands knowledge of ROS1 inhibitor response outside of NSCLC and identifies new therapeutic options for a subset of patients with ALM.

Preclinical efficacy evaluation of ixabepilone (BMS-247550) in combination with cetuximab or capecitabine in human colon and lung carcinoma xenografts

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12017-12017 ◽  
Author(s):  
F. Y. Lee ◽  
A. Camuso ◽  
S. Castenada ◽  
C. Flefleh ◽  
I. Ingio ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Lung Carcinoma ◽  
Therapeutic Potential ◽  
Single Agent ◽  
Human Colon ◽  
Maximum Tolerated Dose ◽  
Antitumor Efficacy ◽  
Efficacy Evaluation ◽  
Multiple Tumor ◽  
Tumor Types

12017 Background: Ixabepilone belongs to a class of structurally novel, microtubule-stabilizing agents that exert their antimitotic action by binding to tubulin with a binding mode that is distinct from the taxanes. Preclinical findings that ixabepilone has antitumor activity in a broad spectrum of tumor types, including taxane-resistant tumors, is borne out by Phase II clinical trials where ixabepilone has demonstrated activities in multiple tumor types including breast, renal, pancreatic, prostate and lymphoma. The aim of this series of studies was to further characterize the therapeutic potential of ixabepilone in combination with currently approved chemotherapy agents. Methods: Antitumor activity was evaluated in the GEO human colon and L2987 human lung carcinoma xenografts. Therapeutic synergism of the combination was defined as the attainment of efficacy that was significantly better than the best response of the individual single agents administered at their maximum-tolerated dose (MTD) or optimal dose (OD). Results: In the GEO tumors, single-agent ixabepilone produced 1.1 log cell kill (LCK) at its MTD. Cetuximab at its OD yielded 0.8 LCK. The combination of ixabepilone and cetuximab produced 1.7 LCK which was significantly superior to ixabepilone alone (P=0.0173) and cetuximab alone (P=0.0002). Similar synergistic efficacy was observed in the L2987 tumors. The combined efficacy of capecitabine plus ixabepilone was evaluated in the GEO tumors. In this tumor, single-agent ixabepilone was modestly active (LCK = 0.8) at its MTD. Single-agent capecitabine was not effective (LCK = 0.4) at its MTD. However, the combination of the two agents produced therapeutic synergism, yielding antitumor efficacy (1.9 LCK) that was superior to either of the agents alone at their MTDs (P=0.035 and 0.0004, respectively). Conclusions: Ixabepilone demonstrates robust synergistic antitumor efficacy when used in combination with cetuximab or capecitabine in human xenografts providing a biologic rationale for these combinations in the treatment of cancer. [Table: see text]

Assessment of safety with abbreviated, weight-based bevacizumab infusions in a variety of solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19674-19674
Author(s):  
J. W. Hart ◽  
J. R. Murillo ◽  
M. S. Oholendt ◽  
H. A. Preti
Keyword(s):  
Solid Tumors ◽  
Single Agent ◽  
Central Nervous System Involvement ◽  
Minimal Risk ◽  
Phase I Clinical Trials ◽  
Multiple Tumor ◽  
Humanized Monoclonal Antibody ◽  
Number Of Patients ◽  
Infusion Schedule ◽  
Tumor Types

19674 Background: Bevacizumab (BEV), a humanized monoclonal antibody that neutralizes vascular endothelial growth factor, has shown improved responses in patients with colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) while displaying activity in a variety of other solid tumors. Phase I clinical trials with BEV utilized standard 90- 60-, and 30-minute infusions for 1st, 2nd, and subsequent infusions, as tolerated; initial doses reported less than 3% incidence of infusion-related adverse events (AEs), with 0.2% grade III/IV reactions. Recommended infusion rates for BEV remain unchanged despite the minimal risk of infusion-related AEs. Saltz and colleagues recently reported novel data supporting the safety and tolerability of abbreviated BEV infusions in CRC patients within a single institution. Our objective was to replicate previously reported safety profiles while utilizing abbreviated infusions of BEV in multiple tumor types. Methods: An internal retrospective analysis revealing minimal infusion AEs with standard infusions facilitated this current study. BEV- naïve and previously-treated patients were consented for the study utilizing the following weight-based infusion times: 5, 10, and 15 mg/kg doses over 10, 20, or 30 minutes, respectively, for all doses. Patients were assessed throughout and immediately following the infusion for any infusion-related AE. Results: A variety of tumor types are represented in 26 enrolled patients including CRC, NSCLC, breast, ovarian, pancreatic, and brain. Central nervous system involvement accounted for 35% of patients [primary brain (23%) and metastatic disease (12%)]. A considerable number of patients (19%) were treated with single-agent BEV. Nine BEV-naïve patients were initiated on abbreviated infusions, while 16 were converted from the standard infusion schedule. Seventy-seven total doses utilizing the abbreviated infusions failed to produce infusion-related AEs. Conclusion: These results support previous data affirming the safety and tolerability of abbreviated BEV infusions in CRC patients, while also reporting promising safety of abbreviated infusions in a variety of additionally unreported solid tumors types. No significant financial relationships to disclose.

Association of LRP1B pathogenic genomic alterations with favorable outcomes with immune checkpoint inhibitors across multiple tumor types.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3007-3007 ◽  
Author(s):  
Landon Carter Brown ◽  
Ramy Sedhom ◽  
Eric B Schwartz ◽  
Jason Zhu ◽  
Chester Kao ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Density Lipoprotein ◽  
Primary Objective ◽  
Missense Mutations ◽  
Multiple Tumor ◽  
Tumor Types

3007 Background: Low-density lipoprotein receptor-related protein 1b (LRP1b) is a putative tumor suppressor and one of the most frequently altered genes in cancer. Our prior single-center work suggested that LRP1B alterations may enrich for responses to immune checkpoint inhibitors (ICI) in solid tumors including prostate cancer; however, validation of these findings is needed. Methods: We conducted a multicenter, retrospective analysis of patients with LRP1B alterations (on tissue-based next-generation sequencing panels) treated with ICI at Duke, Johns Hopkins (JHU), and University of Michigan (UM). The primary objective was to assess the association between objective response rate (ORR) to ICI and pathogenic LRP1B alterations, defined as deletions or truncating alterations, when compared with LRP1B variants of undetermined significance (VUS), defined as missense mutations not predicted to be pathogenic in COSMIC. Missense changes with a COSCMIC FATHMM score of > 0.8 were categorized separately as likely pathogenic. Summary statistics, ORR, progression free survival (PFS), and overall survival (OS) were calculated. Results: 101 patients (44 Duke, 35 JHU, 22 UM) with LRP1B alterations were treated with ICI. Median age was 61 (range 32-82). The most common tumor types by alteration (pathogenic or likely pathogenic/VUS%) were lung (33/47%), GI (17/13%), prostate (11/7%), sarcoma (2/9%), melanoma (11/0%), and others (26/24%). 93% of patients received single-agent PD-(L)1 inhibition. The ORR for patients with either pathogenic/likely pathogenic alterations, or VUS alterations was 57% and 18%, respectively. After excluding MSI-high or TMB-high ( > 10 mut/Mb) tumors, ORR was 14/25 (56%) and 6/36 (17%), respectively. Pathogenic or likely pathogenic LRP1B alterations were associated with longer PFS (HR 0.39, 95% CI 0.24-0.63) and OS (HR 0.58, 95% CI 0.36-0.95). Conclusions: This multicenter study shows impressive and durable objective response rates to ICI for patients harboring pathogenic LRP1B alterations when compared to those with LRP1B VUS, independent of TMB/MSI status. Further mechanistic insights and prospective validation studies are warranted. [Table: see text]

scholarly journals Driver safety in patients with primary brain tumors

2019 ◽  
Vol 6 (6) ◽  
pp. 490-498
Author(s):  
Eduardo Estevis ◽  
Kyle R Noll ◽  
Mariana E Bradshaw ◽  
Jeffrey S Wefel
Keyword(s):  
Brain Tumors ◽  
Visual Attention ◽  
Neuropsychological Tests ◽  
Motor Vehicle ◽  
Patient Characteristics ◽  
Driving Safety ◽  
Dominant Hand ◽  
Visual Scanning ◽  
Who Grade ◽  
Primary Brain Tumors

Abstract Background Operating a motor vehicle involves multiple cognitive and sensorimotor faculties. Neurological conditions pose driving risk, but this has not been examined in patients with primary brain tumors. Methods Sixty-four patients with primary brain tumors (32 left hemisphere; 69% glioblastoma) completed the Cognitive Behavioral Driver’s Inventory (CBDI). A subset also completed broader cognitive testing. Patient characteristics, CBDI measures, and broader neuropsychological test scores were compared between Passing and Nonpassing groups. Follow-up logistic regression analyses identified patient characteristics and CBDI measures predictive of Pass/Nonpass outcome. Point-biserial correlations determined associations between neuropsychological tests and CBDI outcome. Results Sixty-nine percent of patients were classified as passing the CBDI. Nonpassing patients were older and more likely to have WHO grade IV and temporal lobe tumors. Age was the most salient predictor of CBDI performance. CBDI measures of speeded visual search and set-shifting, speeded response inhibition, vigilance and freedom from distractibility, and basic visual scanning speed were predictive of Pass/Nonpass outcome. Neuropsychological tests of memory in particular, but also speeded visual scanning and discrimination, executive function, basic visual attention, visuoconstruction, and manual dexterity (dominant hand), were associated with CBDI outcome. Conclusions A sizeable proportion of patients with primary brain tumors appear at risk of driving difficulty, particularly those with higher-grade tumors and of older age. Memory, visual attention, and executive difficulties appear to contribute most to driving safety risk as determined by the CBDI. These results highlight the importance of driving safety screening in this population.

Measurement Methodologies for Assessing the Glycolysis Effect in the Discrimination and Therapy of Brain Gliomas

2013 ◽  
Vol 1 (1) ◽  
pp. 34-55 ◽  
Author(s):  
Michalis G Kounelakis ◽  
Ekaterini S Bei ◽  
Michalis E Zervakis ◽  
Georgios C Giakos ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Molecular Classification ◽  
Scientific Basis ◽  
World Health ◽  
Primary Brain Tumors ◽  
Glycolysis Pathway ◽  
Health Organization ◽  
Tumor Types ◽  
Brain Gliomas ◽  
The Brain

Primary brain tumors refer to those developing from the various types of cells that compose the brain. Gliomas represent about 50% of all primary brain tumors and include a variety of different histological tumor types and malignancy grades. The World Health Organization (WHO) classifies gliomas into four histological types and four grades. The goal of molecular classification using advanced pattern recognition tools is to identify subgroups of tumors with distinct biological and clinical features and initiate the challenge of classifying complex gliomas of similar histology and malignancy status into distinct categories. The aim of this paper is to i) present the measurement procedures and analysis methodologies, ii) summarize the currently available knowledge related to the utilization of ’omics’ measurements in the discrimination of brain gliomas, and iii) provide a scientific basis for future medical practice in the discrimination and treatment of brain gliomas based specifically on the metabolic process of glycolysis. In particular, the paper explores the idea of the glycolysis pathway as a critical concept for the development of therapeutic strategies for brain gliomas.

scholarly journals Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases

2014 ◽  
Vol 36 (2) ◽  
pp. E10 ◽  
Author(s):  
Serge Marbacher ◽  
Elisabeth Klinger ◽  
Lucia Schwyzer ◽  
Ingeborg Fischer ◽  
Edin Nevzati ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Brain Tumors ◽  
Brain Metastases ◽  
Low Grade ◽  
High Grade ◽  
Open Resection ◽  
Who Grade ◽  
Primary Brain Tumors ◽  
High Grade Gliomas ◽  
Surgical Adjunct

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.

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