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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.).
Rationale And Objectives:
Peripheral-blood circulating tumor DNA (ctDNA) detectability is inconsistent in central nervous system lymphoma (CNSL), so negative plasma findings are hard to interpret. This exploratory, hypothesis-generating study tested whether routinely available, reproducible multiparametric Magnetic resonance imaging (MRI) features are associated with plasma ctDNA positivity across repeated paired MRI-plasma assessments.
Materials And Methods:
In this retrospective single-center study, 25 patients with diffuse large B-cell lymphoma involving the CNS (primary or secondary) contributed 46 paired plasma ctDNA and contrast-enhanced brain MRI evaluations. MRI features were prospectively defined and independently annotated by two blinded radiologists; features were retained only with substantial inter-reader agreement (kappa/weighted kappa ≥0.60) or good ICC (≥0.75). Associations with ctDNA positivity (variant allele frequency ≥0.5%) were screened using logistic generalized estimating equations (GEEs) for within-patient correlation, prioritized by patient-level bootstrap stability selection with L1-penalized logistic regression, and summarized in adjusted multivariable models (age at CNS diagnosis and disease type).
Results:
Among 31 reproducible MRI-derived features, edema crossing the midline had the highest selection frequency (55.8%). In the primary adjusted multivariable model, edema crossing the midline was linked to markedly lower odds of plasma ctDNA positivity (Firth-penalized OR 0.068). To address within-patient correlation from repeated evaluations, uncertainty was estimated by patient-level cluster bootstrap (B = 1000; percentile method), giving a 95% confidence interval of 0.00031-0.236 with complete directional consistency across resamples (Pr[OR < 1] = 1.000; bootstrap failure rate 0.3%). Sensitivity analyses indicated that high non-contrast-enhancing tumor (nCET) burden (≥34%) was associated with higher ctDNA positivity odds, while mass effect was associated with lower odds, though both showed sparse-data patterns.
Conclusion:
Reproducible MRI features, especially edema crossing the midline, were inversely associated with plasma ctDNA positivity across repeated evaluations. Patient-level cluster-bootstrap inference supported the robustness of the observed association. External validation in larger cohorts is needed before clinical implementation.
