Treatment initiation by positive liquid biopsy alone in primary central nervous system lymphoma: A retrospective analysis of a multi-institutional study

TL;DR

This study shows that a non-surgical liquid biopsy can reliably detect PCNSL and guide treatment when surgery is not possible.

Contribution

Demonstrates the feasibility of using liquid biopsy alone for PCNSL diagnosis and treatment initiation in non-operable cases.

Findings

MYD88 L265P-mutant droplets were detected in all 10 patients via CSF cfDNA using ddPCR.

Treatment response was observed in all patients diagnosed via liquid biopsy.

Liquid biopsy helped rule out relapse in a patient with chronic renal failure.

Abstract

The gold standard for the diagnosis of primary central nervous system lymphoma (PCNSL) remains surgical biopsy, but it carries the risk of complications, and operability depends on the size and location of the lesion or the patient’s condition. Previously, we have reported the reliable detection of MYD88 L265P-mutant droplets in cerebrospinal fluid (CSF) cell-free DNA (cfDNA) of PCNSL using droplet digital PCR (ddPCR). In the present study, we conducted a multi-institutional study to diagnose and initiate treatment for PCNSL by liquid biopsy alone without a surgical biopsy.

We analyzed 10 patients from 5 institutions who were deemed difficult to biopsy surgically and were subsequently treated based on the detection of MYD88 L265P-mutant droplets in their CSF cfDNA. CSF was obtained by lumbar puncture at each institution, cfDNA was extracted at Niigata University, and ddPCR was performed to detect MYD88 L265P-mutant droplets.

Surgical biopsy was not performed in 8 patients because the lesions were located in deep locations, such as the brainstem, and in 2 patients because of low performance status and/or advanced age. MYD88 L265P-mutant droplets were detected in all cases. Treatment response was observed in all cases. In a patient with chronic renal failure, liquid biopsy was helpful to rule out possible relapse.

Liquid biopsy for the diagnosis of PCNSL has the potential to replace surgical biopsy with a less-invasive method and early diagnosis, leading to early treatment and possibly better outcomes. Further large-scale studies are warranted to establish the reliability of this approach.

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