The following is a summary of “Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas,” published in the March 2023 issue of Oncology by Mutter, et al.

Although the clinical outcomes of patients with CNS lymphomas (CNSLs) are astonishingly diverse, it can be difficult to identify those at high risk of not responding to treatment. Because invasive stereotactic biopsies are only sometimes warranted, the diagnosis of CNSL frequently goes untested. Therefore, improved biomarkers were required to predict treatment outcomes, effectively stratify patients into risk categories, and noninvasively identify CNSL.

By utilizing ultrasensitive targeted next-generation sequencing on a total of 306 tumor, plasma, and CSF specimens from 136 patients with brain cancer, including 92 patients with CNSL, we investigated the value of circulating tumor DNA (ctDNA) for early outcome prediction, measurable residual disease monitoring, and surgery-free CNSL identification.

78% of the plasma and 100% of CSF samples had ctDNA that could be found before treatment. The progression-free survival (PFS, P< .0001, log-rank test) and overall survival (OS, P =.0001, log-rank test) were considerably shorter in patients with positive ctDNA in pretreatment plasma. In addition, pretreatment plasma ctDNA concentrations were independently predictive of clinical outcomes (PFS HR, 1.4; 95% CI, 1.0 to 1.9; P =.03; OS HR, 1.6; 95% CI, 1.1 to 2.2; P =.006) in multivariate analyses that included established clinical and radiographic risk variables. 

Furthermore, individuals with particularly poor prognoses following curative-intent immunochemotherapy were identified by measuring the presence of residual illness in plasma using ctDNA monitoring during treatment (PFS, P =.0002; OS, P =.004, log-rank test). Last, researchers created a proof-of-concept machine learning method for biopsy-free CNSL identification from ctDNA, demonstrating 59% (CSF) and 25% (plasma) sensitivities with strong positive predictive values.

At multiple illness stages in CNSL, they showed robust and ultrasensitive ctDNA detection. The findings demonstrated the utility of ctDNA as a noninvasive biomarker for individualized risk assessment and therapy recommendation in CNSL patients.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.00826