Epilepsy in CNS Metastases

2019 ◽  
pp. 117-125
Author(s):  
Roberta Rudà ◽  
Alessia Pellerino ◽  
Riccardo Soffietti
Keyword(s):  
Cns Metastases

A simple treatment planning strategy for patients with multiple metastases treated with Gamma Knife surgery

2006 ◽  
Vol 105 (Supplement) ◽  
pp. 2-4 ◽  
Author(s):  
James G. Douglas ◽  
Robert Goodkin
Keyword(s):  
Mr Imaging ◽  
Treatment Planning ◽  
Gamma Knife ◽  
Gamma Knife Surgery ◽  
Planning Method ◽  
Cns Metastases ◽  
Cell Lung Carcinoma ◽  
Dose Volume Histograms ◽  
Number Of Patients ◽  
The Brain

ObjectIn a substantial number of patients treated at the authors' facility for brain metastases, additional lesions are identified at the time of Gamma Knife surgery (GKS). These lesions are often widely dispersed and may number over 10, which is the maximal number of matrices that can be currently placed for treatment with Leksell Gamma-Plan 4C. The authors describe a simple planning method for GKS in patients with multiple, widely dispersed central nervous system (CNS) metastases.MethodsTwo patients presented with three to five identified recurrent metastases from non–small cell lung carcinoma and breast carcinoma after having received whole-brain radiotherapy. At the time of treatment with GKS in each patient, spoiled-gradient Gd-enhanced magnetic resonance (MR) imaging revealed substantially more metastases than originally thought, which were widely scattered throughout all regions of the brain. The authors simplified the treatment planning approach by dividing the entire CNS contents into six contiguous, nonoverlapping matrices, which allowed for the planning, calculation, and treatment of all lesions.Two patients were successfully treated with GKS for more than 10 CNS metastases by using this simple planning method. Differing peripheral doses to varied-size lesions were delivered by prescribing to different isodose curves within any given matrix when required. Dose–volume histograms showed brain doses as follows: 10% of the total brain volume received 5 to 6.4 Gy; 25% received 3.8 to 4.8 Gy; 50% received 2.7 to 3.1 Gy; and 75% received 2.2 to 2.5 Gy.Conclusions The delineation of more metastases than appreciated on the diagnostic MR imaging is a common occurrence at the time of GKS at the authors' institution. The treatment of multiple (>10), widely dispersed CNS metastases can be simplified by the placement of multiple, contiguous, non-overlapping matrices, which can be employed to treat lesions in all areas of the brain when separate matrices cannot be utilized.

scholarly journals Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Yang ◽  
Qilong Liu ◽  
Lei Cao ◽  
Wei Sun ◽  
Xiaowei Gu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cns Metastases ◽  
Tki Treatment ◽  
Egfr Tki

Abstract Background The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. Methods Consecutive patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were retrospectively identified from our medical institution during 2016–2018 and underwent either oral 80 daily OSI or oral 40 daily AFA every 3 weeks for up to 6 cycles, until disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). Results The cohort consisted of 124 patients (OSI: n = 60, mean age = 64.24 years [SD: 12.33]; AFA: n = 64, mean age = 64.13 years [SD: 13.72]). After a median follow-up of 24 months (range, 3 to 28), a significant improvement in OS was detected (hazard ratio [HR] 0.59, 95% confidence interval [CI], 0.39–0.91; p = 0.0160; median, 13.7 months [95% CI, 11.1–14.8] for OSI vs 9.6 months [95% CI, 8.4–10.2] for AFA). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.62; 95% CI, 0.41–0.91; p = 0.014; median, 4.5 months [95% CI, 3.5–5.7] vs 3.9 months [95% CI, 3.1–4.8]). The proportion of grade 3 or higher adverse events (AEs) was lower with OSI (22.4%) than with AFA (39.4%). Conclusions In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI may be associated with significantly improved survival benefit compared with AFA, with a controllable tolerability profile.

Oral Targeted Therapies and Central Nervous System (CNS) Metastases

CNS Drugs ◽  
2015 ◽  
Vol 29 (11) ◽  
pp. 935-952 ◽  
Author(s):  
Michael P. Gabay ◽  
Scott M. Wirth ◽  
Joan M. Stachnik ◽  
Colleen L. Overley ◽  
Katie E. Long ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapies ◽  
Cns Metastases

AZD3759 for CNS metastases in EGFR-mutant lung cancer

2017 ◽  
Vol 5 (11) ◽  
pp. 841-842 ◽  
Author(s):  
David Planchard
Keyword(s):  
Lung Cancer ◽  
Cns Metastases ◽  
Egfr Mutant

scholarly journals A case of metastatic adenocarcinoma of the prostate arising in a meningioma

2013 ◽  
Vol 3 (3) ◽  
pp. 4 ◽  
Author(s):  
Devin Pugsley ◽  
Greg Bailly ◽  
Rekha Gupta ◽  
Derek Wilke ◽  
Lori Wood
Keyword(s):  
Prostate Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Prostate Carcinoma ◽  
Metastatic Adenocarcinoma ◽  
Cns Metastases ◽  
Diagnostic Uncertainty ◽  
Sont Encore ◽  
Adenocarcinoma Of The Prostate ◽  
Cns Tumours

We present the case of a 70-year-old man who had a prostate adenocarcinomathat metastatized to a previously unknown cranialmeningioma. Central nervous system (CNS) metastases are veryuncommon in patients with prostate cancer, and metastases topre-existing primary CNS tumours are even more uncommon. Rareevents like this can cause diagnostic uncertainty, as shown by thiscase. This case is a reminder for clinicians to consider prostatemetastases in patients with known prostate carcinoma and focalneurological symptoms.Nous décrivons le cas d'un homme de 70 ans présentant un adénocarcinomemétastatique de la prostate secondaire à un méningiomeintra-crânien non diagnostiqué auparavant. Les métastasesau niveau du SNC sont très rares chez les patients atteints de cancerde la prostate et les métastases sont encore plus rares dansle cas de tumeurs primitives pré-existantes au niveau du SNC.La rareté de ces cas peut soulever des incertitudes au niveau dudiagnostic, comme nous le montrerons. Ce cas permet de rappeleraux cliniciens d'envisager la possibilité de métastases chezles patients atteints d'un carcinome prostatique confirmé et présentantdes signes neurologiques focaux.

scholarly journals P2.05-030 WBRT Prior EGFR TKIs is Effective Treatment Option for NSCLC Patients with CNS Metastases Harboring EGFR Mutation

2017 ◽  
Vol 12 (1) ◽  
pp. S1048-S1049
Author(s):  
Pawel Krawczyk ◽  
Marcin Nicoś ◽  
Dariusz Kowalski ◽  
Rodryg Ramlau ◽  
Kinga Winiarczyk ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Treatment Option ◽  
Egfr Mutation ◽  
Cns Metastases ◽  
Effective Treatment Option ◽  
Nsclc Patients ◽  
Egfr Tkis

Clinical outcomes in patients (pts) with a history of central nervous system (CNS) metastases receiving talazoparib (TALA) or physician’s choice of chemotherapy (PCT) in the phase 3 EMBRACA trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1090-1090
Author(s):  
Jennifer Keating Litton ◽  
Johannes Ettl ◽  
Sara A. Hurvitz ◽  
Miguel Martin ◽  
Henri Roche ◽  
...  
Keyword(s):  
Stable Disease ◽  
Subgroup Analysis ◽  
Odds Ratio ◽  
Objective Response ◽  
Locally Advanced ◽  
Cns Metastases ◽  
Intracranial Disease ◽  
Patient Reported ◽  
History Of ◽  
Baseline Characteristics

1090 Background: In the EMBRACA trial (NCT01945775) of pts with germline BRCA1/2-mutated HER2-negative locally advanced/metastatic breast cancer (ABC), the poly(ADP-ribose) polymerase (PARP) inhibitor TALA significantly improved progression-free survival (PFS) vs PCT (8.6 vs 5.6 mo; HR [95% CI] 0.54 [0.41-0.71]; P < 0.0001). Patient-reported outcomes favored TALA, and most common adverse events included anemia, fatigue, and nausea. Previous subgroup analyses found that pts with a history of CNS metastases had improved PFS for TALA vs PCT (HR [95% CI] 0.32 [0.15-0.68]; P = 0.0016) and improved objective response rate (ORR) 63.2% vs 15.8%, respectively (odds ratio [95% CI] 8.95 [1.86-52.26]; P = 0.0013). This retrospective subgroup analysis further explored the clinical characteristics and outcomes in pts with a history of CNS metastases in EMBRACA. Methods: Pts were randomized 2:1 to TALA or PCT. Pts with adequately treated and stable CNS metastases not requiring corticosteroids were included. This analysis assessed intracranial ORR and best overall response (BOR) based on investigator assessment per RECIST 1.1 in pts with intracranial disease at baseline (data cutoff 15-Sep-17), and overall survival (OS; data cutoff 30-Sep-19). Results: In the intent-to-treat (ITT) population, 63 pts (43/287 [15.0%] TALA and 20/144 [13.9%] PCT) had a history of CNS metastases, of which 33 (11.5%) pts (TALA) and 15 (10.4%) pts (PCT) had intracranial disease at baseline. Additional baseline characteristics are shown in the table. Intracranial ORR in pts with intracranial disease at baseline and unconfirmed complete or partial response was 18.2% (TALA) vs 20.0% (PCT) (odds ratio [95% CI] 0.78 [0.13-5.80]; P = 0.765). In pts with intracranial disease at baseline, an intracranial BOR of stable disease was 69.7% for TALA vs 33.3% for PCT. Median OS in pts with a history of CNS metastases was 12.9 mo (95% CI 9.4-15.6) for TALA and 13.4 mo (95% CI 8.8-17.6) for PCT (HR [95% CI] 0.67 [0.37-1.2]; P = 0.1936 [stratified log-rank test]). In the safety population ([n = 43, TALA]; [n = 19, PCT]), median treatment duration (range) with TALA was 5.0 (0.1-36.0) mo compared with 2.1 (0.4-6.9) mo for PCT. Conclusions: In this subgroup analysis, baseline characteristics between pts with a history of CNS metastases treated with TALA or PCT were comparable. More pts with intracranial disease at baseline treated with TALA vs PCT experienced stable disease. Intracranial ORR in pts with intracranial disease was 18.2% for TALA vs 20.0% for PCT. Treatment options for pts with a history of CNS metastases are limited and further investigation in larger data sets is warranted. Clinical trial information: NCT01945775 .[Table: see text]

CTNI-01. A PHASE 1-2 CLINICAL TRIAL OF EO1001 (APL-122), A NOVEL IRREVERSIBLE PAN-ERBB INHIBITOR WITH PROMISING BRAIN PENETRATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi58-vi58
Author(s):  
Sophia Frentzas ◽  
Gary Richardson ◽  
Jeffrey Bacha ◽  
Sarath Kanekal ◽  
Neil Sankar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dose Escalation ◽  
Phase 1 ◽  
Standard Of Care ◽  
Maximum Tolerated Dose ◽  
Cns Metastases ◽  
Once Daily ◽  
Adult Participants ◽  
Xenograft Models ◽  
Cns Penetration

Abstract CNS metastases are a prominent driver of cancer morbidity and mortality, especially as targeted therapies have improved systemic outcomes. Mutations in the ErbB/HER kinase family are known oncodrivers in many cancers. Extensive crosstalk among ErbB/HER receptors suggests that inhibition of multiple family members may benefit treatment and limit drug resistance. There is a desperate need for new agents that are more tolerable and effective in treating CNS metastases. EO1001 (APL-122) is a first-in-class, oral, irreversible pan-ErbB inhibitor targeting ErbB1, ErbB2 and ErbB4 with promising CNS penetration in preclinical models. Preclinical data suggests a favorable pharmacokinetic and safety profile and activity against ErbB-driven cancers in patient-derived xenograft models. We report on a first-in-human Phase 1-2 clinical trial in progress. Adult participants with confirmed ErbB-positive cancer, including patients with CNS involvement, who have progressed after standard-of-care, with adequate bone marrow, renal and liver function are eligible. ESCALATION: One subject per dose cohort is enrolled in an accelerated dose-escalation design until drug-related toxicity (≥G2) is observed in the first cycle, after which dose escalation will revert to a 3 + 3 design to determine the maximum tolerated dose (MTD). Cycle 1: Patients receive a single oral dose of EO1001 on day 1; single-dose pharmacokinetics are measured. Beginning on day 8, EO1001 is administered once daily for 21 days; multi-dose pharmacokinetics are measured. Cycles 2-6: EO1001 is administered once daily in continuous 28-day cycles for up to 20 weeks. EXPANSION: EO1001 will be administered once daily to 20 patients at the MTD in continuous 28-day cycles for up to 6 cycles to determine a recommended Phase 2 dose (RP2D) for further study. Toxicity is assessed based on NCI CTCAEv5 and tumor response is assessed by RECIST 1.1. CNS exposure is evaluated in patients via CSF collection with confirmed CNS disease involvement.

Efficacy of PD-1 or PD-L1 inhibitors and central nervous system metastases in advanced cancer: a meta-analysis

2021 ◽  
Vol 21 ◽  
Author(s):  
Minyong Peng ◽  
Shan Li ◽  
Hui Xiang ◽  
Wen Huang ◽  
Weiling Mao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Cell Death ◽  
Nervous System ◽  
Programmed Cell Death ◽  
Future Research ◽  
Significant Heterogeneity ◽  
Cns Metastases ◽  
Hazard Ratios ◽  
Significant Difference

<P>Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases. <P> Objective: Assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases. <P> Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime. <P> Results: 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (Χ=0.06 P=0.80). <P> Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded from PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PD-L1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.</P>

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