CSF Analysis for Non-Small Cell Lung Cancer

Overseen by Cheryl Ho, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: British Columbia Cancer Agency

Disqualifiers: Thrombocytopenia, Bleeding disorders, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Leptomeningeal disease is malignant seeding of the leptomeninges and presents with a variety of symptoms frequently impacting quality of life. With improvement in treatment options, rates of leptomeningeal disease are increasing and currently found in up to 9% of EGFR mutant NSCLC. Systemic therapy may be more effective if it can target the correct molecular aberration. The molecular characterization of central nervous system disease may differ from disease outside of the central nervous system. The aim of this pilot trial is to evaluate for molecular differences between cerebral spinal fluid (CSF) and blood circulating tumor DNA (ctDNA) through the use of ddPCR and BC Cancer NGS panel molecular testing.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Lumbar puncture and Phlebotomy for non-small cell lung cancer?

The research suggests that analyzing cerebrospinal fluid (CSF) through lumbar puncture can help identify genetic mutations and guide treatment decisions for non-small cell lung cancer (NSCLC) patients with central nervous system metastases. This approach can potentially improve treatment strategies and outcomes by providing valuable information about the cancer's genetic profile. ^{1 2 3 4 5}

Is cerebrospinal fluid analysis safe for humans?

The research articles do not provide specific safety data for cerebrospinal fluid analysis, but this procedure, often involving a lumbar puncture (a needle inserted into the lower back to collect fluid), is generally considered safe with common side effects like headache or back pain. ^{1 4 5 6 7}

How does the treatment involving lumbar puncture and phlebotomy differ from other treatments for non-small cell lung cancer?

This treatment is unique because it uses cerebrospinal fluid (CSF) obtained through lumbar puncture as a liquid biopsy to detect genetic mutations and tumor DNA in non-small cell lung cancer, especially in cases with leptomeningeal metastases. This approach provides a more comprehensive analysis of tumor genetics compared to traditional blood tests, offering a novel way to monitor and diagnose cancer spread to the central nervous system. ^{1 2 3 8 9}

Research Team

Cheryl Ho, MD

Principal Investigator

BC Cancer

Eligibility Criteria

This trial is for adults over 18 with a specific lung cancer (EGFR mutant NSCLC) that has spread to the lining of the brain and spinal cord. They must be able to consent, have a life expectancy of at least 8 weeks, and their body should be functioning well enough for testing. People can't join if they have bleeding issues or conditions preventing safe lumbar puncture.

Inclusion Criteria

I am 18 years old or older.

My lung cancer has a specific EGFR mutation and has spread.

Ability to give informed consent for the study procedures defined in this protocol.

Exclusion Criteria

Subjects who are otherwise felt by the treating clinician to be unfit to proceed with this protocol.

I cannot have a lumbar puncture due to low platelets, bleeding issues, or cannot consent.

My MRI shows a condition in my spine that makes lumbar puncture unsafe.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Baseline MRI brain and spine must be completed, and baseline quality of life questionnaires are collected

1-2 weeks

1 visit (in-person)

Molecular Testing

ddPCR and BC Cancer NGS panel completed on cerebral spinal fluid and blood circulating tumor DNA

Ongoing

Every 12 weeks +/- 2 weeks

Follow-up

Participants are monitored for overall survival and quality of life, with assessments every 12 weeks

36 months

Every 12 weeks +/- 2 weeks

Treatment Details

Interventions

• Lumbar puncture and Phlebotomy (Diagnostic Test)

Trial Overview The study aims to find molecular differences between tumor DNA in cerebral spinal fluid (CSF) and blood in patients with leptomeningeal disease from lung cancer. It involves comparing CSF obtained by lumbar puncture with blood samples using advanced molecular tests.

Participant Groups

Group I: Experimental arm Experimental Treatment 1 Intervention

ddPCR and BC Cancer NGS panel completed on cerebral spinal fluid and blood circulating tumor DNA

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Dr. Kim Nguyen Chi

British Columbia Cancer Agency

Chief Executive Officer since 2023

MD

Dr. Kim Nguyen Chi

British Columbia Cancer Agency

Chief Medical Officer since 2023

MD

Findings from Research

In a study of 30 patients with advanced non-small-cell lung cancer (NSCLC), those diagnosed with cerebrospinal fluid (CSF) metastasis showed significantly higher frequencies of EGFR mutations (80%) and ALK fusions (50%) compared to a control group without CSF metastasis.

Patients with CSF metastasis had a median survival time of only 4.8 months, which is notably shorter than the 9.2 months median survival for those without CSF metastasis, indicating that gene mutations may not only increase the incidence of CSF metastasis but also worsen prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between cerebrospinal fluid metastasis and gene mutations in non-small-cell lung cancer patients. Ji, X., Du, Y., Liu, Y., et al.[2020]

Cerebrospinal fluid (CSF) cell-free DNA (cfDNA) was found to be a highly effective source for detecting genetic mutations in patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC), with 100% detection of driver genes in CSF cfDNA samples.

The study revealed that CSF cfDNA not only captured unique genetic profiles compared to plasma and primary tumor samples but also showed a significantly higher frequency of copy number variations and loss of heterozygosity in key genes like TP53, indicating its potential as a superior liquid biopsy medium for monitoring LM in patients with EGFR mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy. Li, YS., Jiang, BY., Yang, JJ., et al.[2020]

A study analyzing cerebrospinal fluid (CSF) from 46 patients with leptomeningeal metastases from non-small cell lung cancer (NSCLC) identified six potential biomarkers, including tyrosine and phenylalanine, which could help in diagnosing this condition.

The research utilized advanced metabolomic techniques and found that these biomarkers are linked to key metabolic pathways, such as glycolysis and amino acid metabolism, suggesting their role in the disease's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Untargeted metabolomics analysis of cerebrospinal fluid in patients with leptomeningeal metastases from non-small cell lung cancer. Li, H., Lin, Y., Zheng, S., et al.[2023]

In a study of 970 non-small cell lung cancer (NSCLC) patients with CNS metastases, cerebrospinal fluid (CSF) samples showed significantly higher rates of actionable mutations compared to plasma samples, particularly for copy number variants, indicating CSF's superior sensitivity for genomic profiling.

CSF analysis not only identified more mutations but also helped uncover resistance mechanisms to EGFR-targeted therapies in 78.87% of patients, suggesting its potential to guide more effective treatment strategies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic Alterations Identification and Resistance Mechanisms Exploration of NSCLC With Central Nervous System Metastases Using Liquid Biopsy of Cerebrospinal Fluid: A Real-World Study. Shen, F., Liang, N., Fan, Z., et al.[2022]

In a study of 32 EGFR+ non-small cell lung cancer patients with leptomeningeal metastasis, switching to or initiating high-dose EGFR-tyrosine kinase inhibitors (TKIs) resulted in a significantly higher disease control rate (100% vs. 12.5%).

The overall survival for these patients was 27 months, but those with a worse clinical status after leptomeningeal metastasis had a median survival of only 4.2 months, highlighting the importance of treatment strategy and patient status in prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of molecular characteristics of cerebrospinal fluid for non-small cell lung cancer patients with leptomeningeal metastasis. Li, N., Liu, Y., Duan, J., et al.[2020]

Cerebrospinal fluid (CSF) from nonsmall cell lung cancer (NSCLC) patients with leptomeningeal metastasis (LM) shows unique molecular features, indicating it could serve as a more effective liquid biopsy compared to plasma or primary tumor tissue.

In a study of 131 NSCLC patients, high somatic copy number variations (CNV) were found in CSF, and the presence of EGFR mutations was highly consistent across CSF, plasma, and tumor samples, suggesting CSF may provide reliable genetic information for treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unique Genomic Alterations of Cerebrospinal Fluid Cell-Free DNA Are Critical for Targeted Therapy of Non-Small Cell Lung Cancer With Leptomeningeal Metastasis. Wang, Y., Jiang, F., Xia, R., et al.[2021]

This case study highlights the successful use of next-generation sequencing (NGS) of cerebrospinal fluid (CSF) to identify an uncommon EGFR mutation (G719A) in a 34-year-old male patient with non-small cell lung cancer (NSCLC) and leptomeningeal metastases, which was not detected in peripheral blood.

The patient showed significant clinical improvement and a good response to afatinib therapy over 7 months, demonstrating the efficacy of targeted therapy guided by CSF genetic testing, which proved to be more effective than blood testing in this scenario.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afatinib for Advanced Non-small Cell Lung Cancer in a Case With an Uncommon Epidermal Growth Factor Receptor Mutation (G719A) Identified in the Cerebrospinal Fluid. Ma, C., Huang, C., Tang, D., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

The relationship between cerebrospinal fluid metastasis and gene mutations in non-small-cell lung cancer patients. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Untargeted metabolomics analysis of cerebrospinal fluid in patients with leptomeningeal metastases from non-small cell lung cancer. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Genomic Alterations Identification and Resistance Mechanisms Exploration of NSCLC With Central Nervous System Metastases Using Liquid Biopsy of Cerebrospinal Fluid: A Real-World Study. [2022]

5. Singapore pubmed.ncbi.nlm.nih.gov

Prognostic significance of molecular characteristics of cerebrospinal fluid for non-small cell lung cancer patients with leptomeningeal metastasis. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Unique Genomic Alterations of Cerebrospinal Fluid Cell-Free DNA Are Critical for Targeted Therapy of Non-Small Cell Lung Cancer With Leptomeningeal Metastasis. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Afatinib for Advanced Non-small Cell Lung Cancer in a Case With an Uncommon Epidermal Growth Factor Receptor Mutation (G719A) Identified in the Cerebrospinal Fluid. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid-derived circulating tumor DNA is more comprehensive than plasma in NSCLC patients with leptomeningeal metastases regardless of extracranial evolution. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid cytology diagnosis of meningeal carcinomatosis in patients with small-cell carcinoma of the lung. A study of interobserver and intraobserver variability. [2006]