Tag: liquid biopsy

Posted on

Multi-Institutional Assessment of Circulating Cell-Free DNA in Cerebrospinal Fluid Facilitates Central Nervous System Lymphoma Diagnosis and Treatment Initiation

Neurosurgery 99:40–49, 2026

This multi-institutional clinical study evaluates a CLIA-certified rapid PCR assay detecting the MYD88 L265P variant in cell-free DNA from cerebrospinal fluid to diagnose central nervous system (CNS) lymphoma. The assay demonstrated 100% specificity, 40% sensitivity, and facilitated earlier treatment initiation, sometimes obviating the need for risky CNS tissue biopsy.

The report details prospective implementation across 19 hospitals, methods for CSF processing and qPCR, diagnostic performance metrics, clinical trajectories of MYD88-positive patients, and implications for using CSF liquid biopsy to accelerate safe, targeted CNS lymphoma therapy.

Clinical need CNS lymphoma diagnosis has historically relied on CNS tissue biopsy, which can delay treatment and carries neurological morbidity risk.

Assay approach A CLIA-certified rapid PCR test was implemented to detect the MYD88 L265P variant in cell-free DNA (cfDNA) from CSF as a minimally invasive diagnostic method.

Deployment scale Prospective testing was conducted over 16 months across 19 hospitals: 201 samples from 184 patients; 19 samples (18 patients) were MYD88 L265P positive, with 2 test failures from inadequate DNA.

Performance characteristics In patients with available records, the assay showed specificity 100%, sensitivity 40%, PPV 100%, NPV 83% (positive LR ∞; negative LR 0.6).

Clinical utility Positive MYD88 results enabled CNS lymphoma–directed treatment initiation, including cases treated without CNS tissue confirmation, with 100% concordance between CSF and CNS tissue biopsy among contemporaneous paired cases (N=8).

Time impact MYD88-positive results often returned before biopsy (median 5.5 vs 10.5 days from admission), and time to treatment was shorter when LP/CSF testing avoided CNS biopsy (7 vs 9 days, P=.048).

Predictors/limitations Detection was more likely with leptomeningeal disease (multivariable P=.017) and DLBCL histology (multivariable P=.027); sensitivity remained modest, implying negative tests still require further workup such as biopsy.

Practice caveat (annotation) Because of modest sensitivity and concerns about spectrum bias/loss to follow-up, MYD88 CSF testing can supplement or obviate biopsy in selected cases, but generally does not replace the need for tissue-based molecular profiling.

Posted on

Strategies, considerations, and recent advancements in the development of liquid biopsy for glioblastoma

Neurosurg Focus 53 (6):E14, 2022

Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle–based liquid biopsy targeting nonneoplastic extracellular vesicles.

METHODS The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance.

RESULTS Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM.

CONCLUSIONS Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon’s arsenal in the near future for the treatment and management of GBM patients.

Proudly powered by WordPress