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Published on: October 23, 2019
MRI Features Associated with Plasma ctDNA Positivity in Central Nervous System Lymphoma
Yulan Li1, Bing Xiu2, Wei Wang1
1Department of Medical Imaging, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China (Y.L., W.W., Y.J., Y.X., Y.L., D.C., Z.H., A.S.); Institute of Medical Imaging Artificial Intelligence, Tongji University School of Medicine, Shanghai, China (Y.L., W.W., Y.J., Y.X., Y.L., D.C., Z.H., A.S.).
Reproducible MRI features, like midline edema, are inversely associated with circulating tumor DNA (ctDNA) positivity in central nervous system lymphoma (CNSL). This finding may improve interpretation of negative ctDNA tests in CNSL patients.
Area of Science:
- Neuro-oncology
- Medical imaging
- Molecular diagnostics
Background:
- Plasma circulating tumor DNA (ctDNA) detectability in central nervous system lymphoma (CNSL) is inconsistent, complicating interpretation of negative results.
- Multiparametric Magnetic Resonance Imaging (MRI) offers reproducible features that may correlate with molecular markers.
- Understanding associations between imaging and ctDNA can enhance diagnostic and prognostic capabilities in CNSL.
Purpose of the Study:
- To investigate the association between reproducible, multiparametric MRI features and plasma ctDNA positivity in CNSL patients.
- To determine if specific MRI characteristics can predict or correlate with the presence of detectable ctDNA in peripheral blood.
- To explore the utility of MRI features in interpreting non-detectable ctDNA results in CNSL.
Main Methods:
- Retrospective analysis of 25 CNSL patients with 46 paired plasma ctDNA and contrast-enhanced brain MRI evaluations.
- Prospective definition and independent annotation of MRI features by two blinded radiologists, ensuring inter-reader reliability (kappa/ICC ≥0.60/0.75).
- Logistic generalized estimating equations (GEEs) and L1-penalized logistic regression with patient-level bootstrap were used to assess associations with ctDNA positivity (variant allele frequency ≥0.5%), adjusting for age and disease type.
Main Results:
- Of 31 reproducible MRI features, edema crossing the midline was most frequent (55.8%) and inversely associated with ctDNA positivity (Firth-penalized OR 0.068).
- Patient-level cluster bootstrap (B=1000) confirmed the robustness of the inverse association (95% CI: 0.00031-0.236; Pr[OR < 1] = 1.000).
- Sensitivity analyses suggested high non-contrast-enhancing tumor (nCET) burden (≥34%) correlated with higher ctDNA positivity, while mass effect correlated with lower positivity.
Conclusions:
- Reproducible MRI features, particularly edema crossing the midline, demonstrate a significant inverse association with plasma ctDNA positivity in CNSL.
- These imaging findings provide a potential tool for interpreting negative ctDNA results and understanding tumor biology in CNSL.
- External validation in larger cohorts is recommended prior to clinical implementation.
