All Major Solid Tumors with Brain Metastases

Cancer Type

Cerebrospinal Fluid (CSF)

Specimen Requirements

8 Working Days

Turnaround Time ¹

ACTCerebra™ sequences 40 druggable genes from Cerebrospinal Fluid (CSF) to identify the most effective targeted therapies based on medical history.

Crossing The Barrier To Determine Your Options

40

Specially Curated Genes

1

Test For Brain Metastases Genomic Profiling

Hallmarks

High Sensitivity

Uses Next-generation sequencing (NGS) for microscale specimens.

Tailored Drug Options

Analyses single nucleotide variation (SNV) and small insertion/deletions (InDels) to provide tailored drug options.

Pioneering Bioinformatics

Integrates cancer biology, medical informatics, molecular biology, cell biology, immunology, bioinformatics, data science and pharmaceutical biology to provide insightful interpretation of the data analyses.

Report Consultation

Complements every report with a consultation with an expert from our medical team.

Short Turnaround Time

Provides professional solutions within 8 working days (starting from the date of receipt of approved samples at our CAP-accredited laboratory).

Drug-Target-Based Panel

Sequences 40 actionable genes.

Summary

Precision Treatment Guidance for Patients with Brain Metastases

Tumors that metastasize to the brain affect nearly one in four patients diagnosed with cancer, with the highest frequencies of brain metastases observed in patients with lung cancer(35–50%), breast cancer (10–20%) and melanoma (8–10%)2(Table1). The outcome for patients diagnosed with these tumors has been very poor, with a typically low survival rate.3

Brain metastases are usually treated with surgery, radiation and chemotherapy – either as a separate modality or in various combinations. Importantly, increasing evidence has shown that the status of genomic alterations has revealed the possibility for the treatment of brain metastases with targeted therapies.

Clinical Use of Cerebrospinal Fluid Genomic Analysis

Owing to the blood brain barrier (BBB), only a limited amount of circulating tumor DNA (ctDNA)from the central nervous system (CNS) can be released to plasma, which suggests that plasma-based liquid biopsy might provide incomplete information of brain metastases. Numerous studies have shown that a liquid biopsy using cerebrospinal fluid (CSF) is more sensitive than plasma to detect targetable genomic alterations, characterize resistance mechanisms and monitor treatment response in brain metastases4-8. Specifically, a non-small cell lung cancer (NSCLC) cohort study showed that in patients with brain metastases, actionable genomic alterations could be found in the CSF of all patients. However, 26.9% of the patients exhibited no genomic changes in the plasma (Table 2). Therefore, the use of CSF analysis may be more beneficial for a patient with brain metastases.

Real-World Case: The Benefit of CSF Genomic Profiling

A 56-year-old female, with stage II NSCLC and harboring two EGFR-sensitive mutations, G719S and E709K, had been treated with targeted therapy according to the official guidelines. Simultaneous genomic testing of peripheral blood was performed with no genomic alterations detected until two years later when brain metastases occurred. At that instant, genomic alterations were detected in the CSF but not in the blood samples, which demonstrates the advantages of genetic profiling of the CSF rather than peripheral blood in patients with brain metastases.

Advantages of CSF Genomic Profiling

  1. BBB permits only small amounts of tumor DNA and cells to reach the plasma, which limits the value of plasma ctDNA or circulating tumor cells in evaluating intracranial lesions.
  2. Tumor-derived ctDNA in plasma is susceptible to background interference, which is less of an issue for tumor-derived DNA in the CSF owing to the relatively higher amounts of tumor DNA.
  3. Liquid biopsy of the CSF could potentially be used to dynamically monitor the burden of brain metastases or novel mutations.

For All Solid Tumors

Selects the most suitable treatment for brain metastases patients based on actionable genetic mutations.

Precise Reporting

Considers targeted therapies approved by US FDA or in global clinical trials.

Technical Specifications

Next-Generation Sequencing (NGS)

Mutational analysis of 40 actionable genes

Specimen Requirements9

4-8ml cerebrospinal fluid (CSF)

Sequencing Mean Depth

> 800 x

Hotspots

> 3800

Documentation

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Disclaimers / Footnotes

  1. Turnaround time starts from the date of receipt of approved samples at our CAP-accredited laboratory.
  2. Bindal RK, et al. (1993) J Neurosurg. 79(2):210–6.
  3. Lin J, et al. (2015) Oncology. 29(4):250–7.
  4. Pentsova EI, et al. (2016) JCO Precis Oncol. 34(20):2404–2415.
  5. Wang Y, et al. (2015) Proc Natl Acad Sci USA. 112(31):9704–9709.
  6. De Mattos-Arruda L, et al. (2015) Nat Commun. 6:8839.
  7. Yang H, et al. (2014) J Mol Diagn. 16(5):558–563.
  8. Hannigan B, et al. (2018) Ann Oncol. 29:945–952.
  9. Please refer to our specimen instructions.

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