Management Of Leptomeningeal Metastases Research Articles

Real-world use of a CSF circulating tumor cell assay in the diagnosis and management of leptomeningeal metastasis.

2029 Background: The diagnosis of leptomeningeal metastasis (LM) can be challenging due to variability in clinical symptoms, radiographic, and cerebrospinal fluid (CSF) findings. The National Comprehensive Cancer Network (NCCN) guidelines recommend assessment of circulating tumor DNA (ctDNA) to increase sensitivity of tumor cell detection and assess the response to treatment. We hypothesize that the real-world use of an assay for the direct detection and enumeration of circulating tumor cells (CTCs) in the CSF is clinically useful for accurate diagnosis of LM, particularly in an early stage of disease. Methods: We report a series of 55 patients treated at our institution with a cancer diagnosis and either neurological symptoms or radiographic findings that suggested LM. All patients underwent a lumbar puncture, assessment for CSF CTCs, and conventional hospital-based cytology testing between 6/1/2020 and 8/1/2023. Survival data cutoff was 12/31/2023. Patient outcomes are reported. Results: 55 patients were tested, and 30 patients were found to be positive for CTCs and diagnosed with LM. Only 10 patients were concurrently positive for CTCs and cytology at our institution, whereas 20 patients with positive CTCs had a negative or ambiguous cytology. No patients with a negative CTC result (25 patients) were subsequently diagnosed with LM, whereas 4 patients with a positive CTC result remained without progressive neurological symptoms. 5 patients diagnosed with LM were alive at the time of data cutoff. The histologic breakdown for LM was: breast (11), non-small cell lung cancer (NSCLC) (16), gastrointestinal (GI) (3). Median overall survival (OS) was longer in patients with a positive CTC and negative cytology result compared to patients with concurrent positive CTC and cytology (172 vs. 63 days, p = 0.06). Median OS was also longer in breast cancer LM compared to NSCLC LM (235 vs. 63 days, p = 0.008). Most patients diagnosed with LM received therapies including Ommaya reservoir placement, intrathecal chemotherapy, and/or radiation. Conclusions: The use of a CSF circulating tumor cell assay aided the diagnosis of LM and led to timely initiation of treatment. A negative result of the CTC assay was associated with ruling out LM. Diagnosis of LM with the CTC assay and negative cytology was associated with longer survival, possibly due to earlier treatment initiation, and not solely a lead time bias. Breast cancer LM patients had improved survival compared to NSCLC and GI cancer patients, possibly due to more effective treatment options.

New strategies for the treatment of breast cancer with leptomeningeal metastasis.

Leptomeningeal metastasis is a complication of metastatic breast cancer that has a rising incidence likely due to the increased availability of novel systemic therapies, which have improved survival with better extracranial disease control but with limited intracranial efficacy. A poor prognosis of less than 6 months has historically been associated with leptomeningeal metastasis and it is often an exclusion factor for enrollment in clinical trials. There are limited evidence-based data supporting use of therapeutics in leptomeningeal metastasis patients and recommendations are largely derived from retrospective reports and small prospective studies. However, in recent years, there has been a surge in effective modern therapeutics with promising intracranial activity. The study aims to review the most recent updates in the management of leptomeningeal metastasis in breast cancer. We discuss the effectiveness and limitations of intrathecal administration, predictive biomarkers in the cerebrospinal fluid, proton radiation therapy and promising new systemic therapies such as antibody drug conjugates. Ongoing development of clinical trials that allow inclusion of leptomeningeal metastasis are essential for establishing efficacy potential and discovering new treatment options in this population of great unmet need.

Real-world data of osimertinib in the management of leptomeningeal metastases in EGFR mutant NSCLC: Light at the end of the tunnel?

e21197 Background: Presence of leptomeningeal metastases (LM) in NSCLC is indicative of aggressive disease and the incidence is as high as 9%-16% in the EGFR mutant subgroup. Traditionally, these patients had a dismal outcome with WBRT and intrathecal chemotherapy. Osimertinib crosses the blood brain barrier and is efficacious in the second line setting, as seen in BLOOM trial (LM ORR of 62%) and AURA program (LM ORR 55%). Osimertinib has also demonstrated CNS efficacy in the first line (FLAURA trial). This study is a retrospective review of cases with LM treated with osimertinib, and their response outcomes. Methods: 16 patients of EGFR mutant NSCLC developed LM at some point in their disease course and were treated with osimertinib. Clinical features and response outcomes were retrieved from medical record archives. Descriptive statistics were done using SPSS v23 software. LM PFS was defined as the time between 1st dose of osimertinib and date of progression in LM. LM OS was defined as the time between the first dose of osimertinib to the date of last follow up/death. ORR was defined as the percentage of cases showing CR/PR to osimertinib. Results: Median age was 61 years (range: 33-79) with 9 males and 7 females. Del19 mutations were seen in 9 patients and L858R in 7 patients. Only one patient was given WBRT prior to TKI. 6 patients with LM at diagnosis were given 1st line osimertinib. 3 (50%) progressed in LM and 3 (50%) showed partial response. Median LM PFS and median LM OS was not reached. ORR for osimertinib in the first line was 83.3%. 10 patients developed LM later in the course of the disease and median time to onset of LM was 12.47 months. Median LM PFS for osimertinib was 7.9 months (95% CI:3.2-8.3). Median LM OS was 8.2 months (95% CI: 2.6-19.8 months). ORR for osimertinib in the later line was 60%. Conclusions: This early experience reveals superior efficacy of osimertinib in LM with an excellent LM ORR in the first line setting and concordant results with second line BLOOM Study. Despite the small numbers in this study, this report becomes clinically relevant owing to the rarity of LM occurrence and paucity of available data. Efficacy of osimertinib in EGFR treatment-naive patients with LM requires further investigation and a larger prospective trial with a longer follow up may help confirm our preliminary findings.

1446P - Management of leptomeningeal metastases in EGFR mutated non-small cell lung cancer: Analysis of tyrosine kinase inhibitors sequence

1446P - Management of leptomeningeal metastases in EGFR mutated non-small cell lung cancer: Analysis of tyrosine kinase inhibitors sequence

Experimental Treatments for Leptomeningeal Metastases From Solid Malignancies.

Leptomeningeal metastasis is a consequence of advanced solid malignancies and has limited treatment options. It is possible that it is becoming more common as the leptomeninges act as a sanctuary site for recurrence from systemic cancer. Potential targeted and immunotherapy agents for the most common types of solid-tumor leptomeningeal metastasis are reviewed, as are their dosing/delivery strategies and novel, immunological approaches. Historically, patients with leptomeningeal metastasis have been excluded from clinical trials, and data on the management of leptomeningeal metastasis come from single case reports and retrospective analyses. For the first time ever, published reports suggest the tide may be turning in this challenging disease.

P13.04 Practice patterns of diagnosis and management of leptomeningeal metastasis in Europe: results from a web-based survey

AbstractLeptomeningeal metastases are typically a late manifestation of systemic cancer affecting up to 10% of patients with solid tumors. Depending on the pattern of spread within the central nervous system, a broad variety of clinical symptoms and signs may occur, but cranial nerve palsies and multifocal deficits are particularly common. The incidence is highest in lung cancer, malignant melanoma and breast cancer. Survival is a only a few weeks without treatment, but is approximately 10% across the spectrum of patients. The diagnosis is typically triggered by clinical suspicion followed by neuroimaging and cerebrospinal fluid analysis. Management is often individualized and depends on primary tumor and pattern of metastasis, in particular concurrent systemic or solid brain metastases.Here we set out to characterize current practice patterns of diagnosing and treating leptomeningeal metastasis in Europe. To this end, we prepared a web-based survey including multiple choice questions on best practice supplemented by some case vignettes. This survey was sent to members of the European Association of Neuro-Oncology (EANO) and the Brain Tumor Group of the European Organisation for Research and Treatment of Cancer (EORTC) in April 2016.We will present the results of this survey and illustrate patterns of care by profession and country or region. Results from this survey shall inform on the design of future EANO recommendations for the diagnosis and management of leptomeningeal metastasis from solid tumors.

Management of leptomeningeal metastases: Prognostic factors and associated outcomes

Limited data are currently available to direct treatment recommendations in the management of leptomeningeal metastases (LM). Here we review treatment modalities clinicians should understand in order to manage patients with LM. We first describe our institution’s experience with the treatment of LM and use this dataset to frame the discussion of LM management. Between 1999 and 2014, 1361 patients with central nervous system metastases were reviewed, 124 (9.1%) had radiographic evidence of LM, and these patients form the cohort for this analysis. Mean age at diagnosis of LM was 52years. Median survival for the entire cohort was 2.3months. The most common primary malignancies were non-small cell lung cancer (25.8%), breast cancer (17.7%), small cell lung cancer (16.9%) and melanoma (8.9%). Univariate analyses demonstrated that greater Karnofsky Performance Status (KPS) (p=0.001) and administration of systemic chemotherapy (p<0.001) resulted in improved median survival. Multivariate Cox analyses revealed that receipt of chemotherapy and a complete course of whole brain radiotherapy (WBRT) (median dose 30Gy in 10 fractions, range 24–40Gy) were predictive of longer survival, (p=0.013 and 0.019, respectively). These data suggest that there is a group of patients with good KPS who may experience significantly longer median survival than expected. Multivariate analysis from this single institution retrospective study demonstrated a benefit for WBRT and chemotherapy in individuals with good KPS. These findings provide contemporary data from a large cohort of LM patients, which may be utilized to guide treatment recommendations, assist in patient counseling and direct future investigations into optimization of treatment regimens.

Leptomeningeal metastasis in solid tumors with a special focus on lung cancer.

Leptomeningeal metastasis is a common problem in advanced solid tumor malignancies. A significant number of patients have underlying lung cancer. With the advent of better therapies, the management of leptomeningeal metastasis is gained more importance to improve survival and quality of live. This review article focuses on the epidemiology, clinical features, diagnostics and the recent management strategies directed towards leotomeningela metastasis from solid tumor, esp lung cancer.

Management of Leptomeningeal Metastasis in Patients with Lung Cancer

445 ISSN 1758-1966 10.2217/LMT.13.55 © 2013 Future Medicine Ltd Lung Cancer Manage. (2013) 2(6), 445–447 Leptomeningeal metastasis (LM) is a rare complication of lung cancer. It occurs in approximately 1–6% of patients with lung cancer and it is most commonly associated with adenocarcinoma (50–56%), followed by squamous cell carcinoma (26–36%) and small cell carcinoma (13–14%) [1]. Lung cancer patients harboring activating mutations in EGFR are associated with prolonged disease control and survival when tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib are used. These improvements may contribute to a relative increase in the prevalence of LM from non-small-cell lung cancer (NSCLC), which is still a devastating complication associated with poor survival. Even with maximal therapy, average survival following the diagnosis of LM is less than 1 year [2]. The optimal therapeutic approach for LM remains challenging. Poor penetration of chemotherapeutic agents beyond the blood–brain barrier (BBB) is in part responsible for the limited therapeutic options for LM patients. LM patients are treated with various treatment methods: whole-brain and/or spinal cord irradiation, intrathecal chemotherapy (ITC), systemic chemotherapy and surgery. Nevertheless due to the small and heterogeneous population of LM patients, the relative benefits of these approaches remain poorly characterized. So in this editorial, recent topics and commentaries are provided regarding the management of LM from lung cancer with an emphasis on the treatment strategy.

Navigation-Guided Ommaya Reservoir Placement: Implications for the Treatment of Leptomeningeal Metastases

Ommaya reservoirs are commonly used in the diagnosis and management of leptomeningeal metastases (LM) from malignant tumors. The present study investigates the utility of an intraoperative navigation-guided technique for Ommaya reservoir placement. Between March 2004 and December 2005, 85 navigation-guided Ommaya reservoir placements were performed in 77 patients with intracranial malignancies at the Komagome Metropolitan Hospital. Anterior horn puncture and posterior horn puncture were used for 59 and 26 procedures, respectively. A slit ventricle was present in 6 cases. All procedures were performed under assistance from the Medtronic STEALTH STATION TRIA navigation system. Computed tomographic (CT) scans were routinely obtained just after completion of the procedure. Patients diagnosed with LM received subsequent treatment. An Ommaya catheter was applied to the ventricular puncture needle registered in the navigation system and was inserted into the lateral ventricle. Using the real-time "Guidance View", the surgeon was able to verify the catheter position continuously during the procedure. Postoperative CT scan revealed an appropriate catheter position in all except for one case. Complications (catheter malposition) occurred in only one case (complication rate, 1.2%). None of the patients experienced hemorrhage or infection. In conclusion, navigation-guided Ommaya reservoir placement was associated with a very low incidence of complications. This method appears to be safe and effective when employed in patients with intracranial malignancy.

Cerebrospinal fluid tumor markers for the diagnosis and management of leptomeningeal metastases

Cerebrospinal fluid tumor markers for the diagnosis and management of leptomeningeal metastases