Abstract

Introduction: Ki-67 expression, a marker of tumor proliferation, is considered a prognostic factor in primary CNS lymphoma (PCNSL). Apparent diffusion coefficient (ADC) parameters have also been proposed as imaging biomarkers for tumor progression and proliferative activity in various malignancies. The aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival (OS) and progression free survival (PFS) in PCNSL.Materials and Methods: Patients diagnosed with PCNSL at MD Anderson Cancer Center between Mar 2000 and Jul 2016 and at Ben Taub Hospital between Jan 2012 and Dec 2016 were retrospectively studied. Co-registered ADC maps and post-contrast images underwent whole tumor segmentation. Normalized ADC parameters (nADC) were calculated as the ratio to normal white matter. Percentiles of nADC were calculated and were correlated with Ki-67 using Pearson’s correlation coefficient and clinical outcomes (OS and PFS) using Cox proportional hazards models.Results: Selection criteria yielded 90 patients, 23 patients living with HIV (PLWH) and 67 immunocompetent patients. Above median values for nADCmean, nADC15, nADC75 and nADC95 were associated with improved OS in all patients (p < 0.05). Above median values for nADCmin, nADCmean, nADC1, nADC5 and kurtosis were associated with improved PFS in all patients (p < 0.05). In patients with available Ki-67 expression data (n = 22), nADCmean, nADC15 and nADC75 inversely correlated with Ki-67 expression (p < 0.05). For PLWH, there was no correlation between ADC parameters and Ki-67 expression or clinical outcomes.Conclusions: ADC histogram analysis can predict tumor proliferation and survival in immunocompetent patients with PCNSL, but with limited utility in PLWH.

Highlights

  • Ki-67 expression, a marker of tumor proliferation, is considered a prognostic factor in primary CNS lymphoma (PCNSL)

  • Selection criteria yielded 90 patients, 23 patients living with HIV (PLWH) and 67 immunocompetent patients

  • Patients living with HIV (PLWH) represent an important population to include in investigations related to PCNSL, as the association with the Epstein Barr virus highlights PCNSL in PLWH is a distinct entity from sporadic cases [3, 4]

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Summary

Introduction

Ki-67 expression, a marker of tumor proliferation, is considered a prognostic factor in primary CNS lymphoma (PCNSL). The aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival (OS) and progression free survival (PFS) in PCNSL. Expression of tumor Ki-67, a cellular biomarker for proliferative activity, has been shown correlate with overall survival (OS) and progression-free survival (PFS) in PCNSL patients [15,16,17]. These studies, were limited due to the small sample sizes (< 30) or neglected to investigate the effect of immune status, as PLWH represent a wellestablished, clinically distinct, subset of patients with PCNSL. Tumor segmentation was performed using only the ADC sequence with the potential inclusion of intra-tumoral necrosis, hemorrhage or regions outside of the actual solid tumor that would otherwise have been excluded with contrast co-registration, providing a suboptimal representation of true tumor parenchyma

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