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Original Article

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Blood Res 2020; 55(2):

Published online June 30, 2020

https://doi.org/10.5045/br.2020.2020032

© The Korean Society of Hematology

Apparent diffusion coefficient as a valuable quantitative parameter for predicting clinical outcomes in patients with newly diagnosed primary CNS lymphoma

Dong Won Baek1, Hee Jeong Cho1, Jae Heung Bae2, Sang Kyun Sohn1, Joon Ho Moon1

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1Department of Hematology/Oncology, 2Department of Radiology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea

Correspondence to : Joon Ho Moon, M.D., Ph.D.
Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea
E-mail: jhmoon@knu.ac.kr

Received: February 24, 2020; Revised: March 27, 2020; Accepted: April 16, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background
This study attempted to identify novel prognostic factors in patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using magnetic resonance imaging (MRI).
Methods
We retrospectively evaluated 67 patients diagnosed with central nervous system (CNS) tumors. The enrollment criteria were as follows: i) pathologic diagnosis of CNS lymphoma, ii) no evidence of systemic involvement, iii) no evidence of human immunodeficiency virus-1 infection or other immunodeficiencies, and iv) MRI scans available at diagnosis. Fifty-two patients met these criteria and were enrolled.
Results
The 3-year overall survival (OS) and failure-free survival rates were 69.7% and 45.6%, respectively, with a median follow-up duration of 36.2 months. OS of patients with low apparent diffusion coefficient (ADC) was lower than those with higher ADC. Multivariate analysis revealed that old age (>60 yr) [hazard ratio (HR), 20.372; P=0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR, 10.429; P < 0.001), higher lactate dehydrogenase (LDH) levels (HR, 7.408; P =0.001), and low ADC (HR, 0.273; P=0.009) were associated with lower OS. We modified the conventional prognostic scoring system using low ADC, old age (>60 yr), ECOG PS ≥2, and higher LDH. The risk of death was categorized as high (score 3-4), intermediate-2 (score 2), intermediate- 1 (score 1), and low (score 0), with three-year OS rates of 33.5%, 55.4%, 88.9%, and 100%, respectively.
Conclusion
ADC demonstrated significant prognostic value for long-term survival in patients with newly diagnosed PCNSL. Low ADC was an independent unfavorable prognostic factor, suggesting that ADC obtained from MRI can improve the current prognostic scoring system.

Keywords Lymphoma, Central nervous system, Prognosis, Magnetic resonance imaging

Article

Original Article

Blood Res 2020; 55(2): 99-106

Published online June 30, 2020 https://doi.org/10.5045/br.2020.2020032

Copyright © The Korean Society of Hematology.

Apparent diffusion coefficient as a valuable quantitative parameter for predicting clinical outcomes in patients with newly diagnosed primary CNS lymphoma

Dong Won Baek1, Hee Jeong Cho1, Jae Heung Bae2, Sang Kyun Sohn1, Joon Ho Moon1

1Department of Hematology/Oncology, 2Department of Radiology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea

Correspondence to:Joon Ho Moon, M.D., Ph.D.
Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea
E-mail: jhmoon@knu.ac.kr

Received: February 24, 2020; Revised: March 27, 2020; Accepted: April 16, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
This study attempted to identify novel prognostic factors in patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using magnetic resonance imaging (MRI).
Methods
We retrospectively evaluated 67 patients diagnosed with central nervous system (CNS) tumors. The enrollment criteria were as follows: i) pathologic diagnosis of CNS lymphoma, ii) no evidence of systemic involvement, iii) no evidence of human immunodeficiency virus-1 infection or other immunodeficiencies, and iv) MRI scans available at diagnosis. Fifty-two patients met these criteria and were enrolled.
Results
The 3-year overall survival (OS) and failure-free survival rates were 69.7% and 45.6%, respectively, with a median follow-up duration of 36.2 months. OS of patients with low apparent diffusion coefficient (ADC) was lower than those with higher ADC. Multivariate analysis revealed that old age (>60 yr) [hazard ratio (HR), 20.372; P=0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR, 10.429; P < 0.001), higher lactate dehydrogenase (LDH) levels (HR, 7.408; P =0.001), and low ADC (HR, 0.273; P=0.009) were associated with lower OS. We modified the conventional prognostic scoring system using low ADC, old age (>60 yr), ECOG PS ≥2, and higher LDH. The risk of death was categorized as high (score 3-4), intermediate-2 (score 2), intermediate- 1 (score 1), and low (score 0), with three-year OS rates of 33.5%, 55.4%, 88.9%, and 100%, respectively.
Conclusion
ADC demonstrated significant prognostic value for long-term survival in patients with newly diagnosed PCNSL. Low ADC was an independent unfavorable prognostic factor, suggesting that ADC obtained from MRI can improve the current prognostic scoring system.

Keywords: Lymphoma, Central nervous system, Prognosis, Magnetic resonance imaging

Fig 1.

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Figure 1.Kaplan-Meier curves for overall survival (OS). Patients with low ADC had lower OS (P=0.005) (A), while patients with tumors measuring less than 5 cm exhibited a tendency toward better OS (P=0.055) (B). Abbreviation: ADC, apparent diffusion coefficient.
Blood Research 2020; 55: 99-106https://doi.org/10.5045/br.2020.2020032

Fig 2.

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Figure 2.Kaplan-Meier curves for failure-free survival (FFS). Patients with hyperintense signal on T2-weighted imaging (P=0.001) (A) and homogenous enhancement (P=0.011) (B) had better FFS, while patients with low ADC (P=0.018) (C) and necrosis had poor FFS (P<0.001) (D). Abbreviation: ADC, apparent diffusion coefficient.
Blood Research 2020; 55: 99-106https://doi.org/10.5045/br.2020.2020032

Fig 3.

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Figure 3.Modified prognostic scoring system. The prognostic scoring system comprising old age, ECOG PS, and LDH (A) and the modified scoring system comprising old age, ECOG PS, LDH, and ADC (B). Abbreviations: ADC, apparent diffusion coefficient; ECOG PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase.
Blood Research 2020; 55: 99-106https://doi.org/10.5045/br.2020.2020032

Table 1 . Patient characteristics..

VariableN (%)
N52
Age, median yr (range)56 (42–82)
Age>60 yr24 (46.2)
Sex
Male30 (57.7)
Female22 (42.3)
ECOG performance status
≤146 (88.5)
>16 (11.5)
Raised LDH16 (30.8)
Elevated CSF protein7 (13.5)
Involvement of deep structuresa)34 (65.4)
Lymphoma subtype
DLBCL52 (100)
First-line treatment
MVP44 (84.6)
R-MVP8 (15.4)
Response to first-line therapy
CR40 (76.9)
PR8 (15.4)
Refractory4 (7.7)
Auto-SCT10 (19.2)
Relapse26 (50.0)
Death20 (34.6)

a)Involvement of deep structures, basal ganglia and/or corpus callosum and/or brain stem and/or cerebellum..

Abbreviations: Auto-SCT, autologous stem cell transplantation; CR, complete response; CSF, cerebrospinal fluid; DLBCL, diffuse large B cell lymphoma; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; MVP, methotrexate, vincristine, procarbazine; PR, partial response; R-MVP, rituximab, methotrexate, vincristine, procarbazine..

Table 2 . MRI features of the 52 patients..

VariableN (%)
Location
Supratentorial38 (73.1)
Infratentorial2 (3.8)
Both12 (23.1)
N of lesions
One20 (38.5)
Two or more32 (61.5)
Corpus callosum involvement18 (34.6)
Basal ganglia involvement30 (57.7)
Cerebral cortex involvement22 (42.3)
Enhancement
Homogenous30 (57.7)
Heterogenous22 (42.3)
Necrosis22 (42.3)
Ependymal infiltration26 (50.0)
Low ADC values36 (69.2)
Mass effect36 (69.2)
Size
≥5.0 cm5 (9.6)
<5.0 cm47 (90.4)
Signal T1
Isointense18 (34.6)
Hypointense34 (65.4)
Signal T2
Isointense26 (50.0)
Hyperintense26 (50.0)

Abbreviations: ADC, apparent diffusion coefficient; MRI, magnetic resonance imaging..

Table 3 . Factors affecting long-term clinical outcomes..

(A) Factors affecting overall survival (OS)
UnivariateMultivariate
HR95% CIPHR95% CIP
Age>60 vs. ≤60 yr20.3723.466–119.7240.00161.9455.675–676.2010.001
ECOG PS>1 vs. ≤110.4292.851–38.155<0.00121.3842.851–160.3690.003
LDH, increased vs. normal7.4082.381–23.0490.0016.5761.655–26.1390.007
High ADC vs. low ADC0.2730.103–0.7210.0090.3920.155–0.8540.012
Size≥5 cm vs. <5 cm2.6940.931–7.7940.067
(B) Factors affecting failure-free survival (FFS)
UnivariateMultivariate
HR95% CIPHR95% CIP
Age>60 vs. ≤60 yr4.2271.597–11.1920.004
ECOG PS>1 vs. ≤14.2781.305–14.0170.01610.3191.428–74.5510.021
LDH, increased vs. normal1.8390.882–3.8310.099
Enhancement, homogenous vs. non-homogenous0.4010.193–0.8340.014
Necrosis, presence vs. absence4.6102.151–9.876<0.0016.3721.609–25.2350.008
High ADC vs. low ADC0.4320.210–0.8880.0220.2260.065–0.7920.020
T2-weighted imaging, hyperintense signal vs. isointense signal0.2890.128–0.6500.003

Abbreviations: ADC, apparent diffusion coefficient; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; LDH, lactate dehydrogenase..

Table 4 . Modified prognostic scoring system..

Prognostic factora)
Age>60 yr
ECOG PS>1
Raised LDH
Low ADC
Scores (risk)2-yr overall survival (%)
0 (low)100
1 (intermediate-1)88.9
2 (intermediate-2)55.4
3–4 (high)33.5

a)Each factor was assigned a value of 1, if is present. The score was the sum of each value..

Abbreviations: ADC, apparent diffusion coefficient; ECOG PS, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase..
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