imri Investigative Magnetic Resonance Imaging iMRI 2384-1095 2384-1109 Korean Society of Magnetic Resonance in Medicine 10.13104/imri.2018.22.3.158 imri-22-158 Original Article Dynamic Susceptibility Contrast (DSC) Perfusion MR in the Prediction of Long-Term Survival of Glioblastomas (GBM): Correlation with MGMT Promoter Methylation and 1p/19q Deletions KwonYong Wonn 1 MoonWon-Jin 1 ParkMina 1 3 RohHong Gee KohYoung Cho 2 SongSang Woo 2 ChoiJin Woo 1 Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea Department of Neurosurgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Correspondence to: Jin Woo Choi, M.D., Ph.D. Department of Radiology, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea. Tel. +82-2-2030-5512 Fax. +82-2-2030-5549 E-mail: cardijin@kuh.ac.kr 01 2018 12 01 2018 22 3 158 167 04042018 15052018 28062018 Copyright © 2018 Korean Society of Magnetic Resonance in Medicine 2018 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Purpose

To investigate the surgical, perfusion, and molecular characteristics of glioblastomas which influence long-term survival after treatment, and to explore the association between MR perfusion parameters and the presence of MGMT methylation and 1p/19q deletions.

 Materials and Methods

This retrospective study was approved by our institutional review board. A total 43 patients were included, all with pathologic diagnosis of glioblastoma with known MGMT methylation and 1p/19q deletion statuses. We divided these patients into longterm (≥ 60 months, n = 7) and short-term (< 60 months, n = 36) survivors, then compared surgical extent, molecular status, and rCBV parameters between the two groups using Fisher's exact test or Mann-Whitney test. The rCBV parameters were analyzed according to the presence of MGMT methylation and 1p/19q deletions. We investigated the relationship between the mean rCBV and overall survival using linear correlation. Multivariable linear regression was performed in order to find the variables related to overall survival.

 Results

Long-term survivors (100% [7 of 7]) demonstrated a greater percentage of gross total or near total resection than short-term survivors (54.5% [18 of 33]). A higher prevalence of 1p/19q deletions was also noted among the long-term survivors (42.9% [3 of 7]) than the short-term survivors (0.0% [0 of 36]). The rCBV parameters did not differ between the longterm and short-term survivors. The rCBV values were marginally lower in patients with MGMT methylation and 1p/19q deletions. Despite no correlation found between overall survival and rCBV in the whole group, the short-term survivor group showed negative correlation (R2 = 0.181, P = 0.025). Multivariable linear regression revealed that surgical extent and 1p/19q deletions, but not rCBV values, were associated with prolonged overall survival.

 Conclusion

While preoperative rCBV and 1p/19q deletion status are related to each other, only surgical extent and the presence of 1p/19q deletion in GBM patients may predict longterm survival.

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Study design diagram.

Scatter plot of mean rCBV versus overall survival (in months) in GBM patients, including both long-term and short-term survivors. Although the scatter plot demonstrates a decreasing trend towards lower mean rCBV values with greater overall survival, the linear regression analysis did not demonstrate a statistically significant linear correlation (P = 0.186, R2 = 0.029).

Scatter plot of mean rCBV versus overall survival (in months) in short-term GBM survivors. Linear regression analysis demonstrated the presence of a statistically significant negative linear correlation between mean rCBV and overall survival (P = 0.025, R2 = 0.181).

A 47-year-old male with glioblastoma in the right frontal lobe. (a) T2-weighted image, (b) T1-weighted contrast-enhanced image, and (c) rCBV map are shown. The mean rCBV value measured from the enhanced part of the tumor was 1.95. Molecular analysis revealed both MGMT promoter methylation and 1p19q codeletion. The overall survival was 81 months.

A 73-year-old male with glioblastoma in the left temporal lobe. (a) T2-weighted image, (b) T1-weighted contrast-enhanced image, and (c) rCBV map are shown. The mean rCBV value measured from the enhanced part of the tumor was 2.70. Molecular analysis revealed that both MGMT promoter and 1p19q were intact. The overall survival was 13 months.

A 43-year-old female with glioblastoma in the right frontal lobe. (a) T2-weighted image, (b) T1-weighted contrast-enhanced image, and (c) rCBV map are shown. The mean rCBV value measured from the enhanced part of the tumor was 3.48. The molecular analysis revealed that both MGMT promoter and 1p19q were intact. The overall survival was 106 months.

Demographic Characteristics of the Study Subjects

Characteristics Baseline analysis (n = 43) MR perfusion analysis (n = 29)
Sex    
Male 60.5% (26/43) 55.1% (16/29)
Female 39.5% (17/43) 44.8% (13/29)
Age (years) 56.4 (14–89)* 57.0 (14–89)*
Overall survival (months)    
Long-term survivor (≥ 60 months) 16.3% (7/43) 20.7% (6/29)
Short-term survivor (< 60 months) 83.7% (36/43) 79.3% (23/29)
Genetic markers    
MGMT promoter methylation 48.8% (25/43) 55.1% (16/29)
1p / 19q deletions 7.0% (3/43) 6.9% (2/29)
Surgical extent    
GTR + NTR** 62.5% (25/40***) ) 65.5% (19/29)
STR + PR + Bx** 37.5% (15/40***) ) 34.5% (10/29)

Data are number of patients, and data in parenthesis are percentages except where indicated. *The data is the mean value and the data in parenthesis is range of the values. ** Abbreviations area indicated as follows: GTR = gross total resection; NTR = near total resection; STR = subtotal resection; PR = partial resection; Bx = biopsy *** 40 of 43 patients were evaluated for surgical extent. Three patients who could not undergo immediate postoperative (< 24 hours) MRI were excluded because the surgical extent could not be accurately measured.

Comparison of Various rCBV Parameters between the Long-Term and Short-Term Survivors

rCBV parameter Long-term (n = 6) Short-term (n = 23) P-value
Mean 2.66 [1.95–3.48] 2.98 [1.52–6.48] 0.148
Median 2.32 [1.44–3.59] 2.84 [1.58–6.48] 0.430
5th percentile 2.32 [1.44–3.59] 2.84 [1.48–6.48] 0.964
95th percentile 5.71 [3.60–8.09] 7.78 [2.29–12.64] 0.072
1st quartile 1.52 [0.95–2.50] 1.38 [0.00–4.81] 0.693
3rd quartile 3.71 [2.74–5.49] 4.49 [1.87–8.55] 0.072
Minimum 0.03 [0.00–0.18] 0.00 [0.00–1.00] 0.953
Maximum 5.71 [3.60–8.09] 7.79 [2.29–12.64] 0.072

Majority of the rCBV values were lower in the long-term survivor group. However, Mann-Whitney test failed to reveal any statistically significant difference.

Comparison of Various rCBV Parameters in Terms of MGMT Methylation and 1p/19q Deletions

rCBV parameter Group Group P-value
MGMT methylation With MGMT methylation (n = 16) Without MGMT methylation (n = 13)  
Mean 2.71 [1.52–3.58] 2.99 [1.85–6.48] 0.148
Median 2.63 [1.58–3.68] 2.59 [1.44–6.48] 0.430
5th percentile 0.36 [0.00–1.69] 0.44 [0.00–2.88] 0.964
95th percentile 5.45 [2.29–12.64] 8.09 [3.73–12.52] 0.072
1st quartile 1.37 [0.00–2.95] 1.68 [0.00–4.81] 0.693
3rd quartile 3.74 [1.87–7.07] 5.00 [2.55–8.55] 0.072
Minimum 0.00 [0.00–1.12] 0.00 [0.00–1.07] 0.953
Maximum 5.45 [2.29–12.64] 8.09 [3.73–12.51] 0.072
1p/19q deletion status With 1p/19q deletions (n = 2) Without 1p/19q deletion (n = 27)  
Mean 2.34 [1.95–2.73] 2.92 [1.52–6.48]  
Median 1.71 [1.43–2.00] 2.68 [1.44–6.48]  
5th percentile 0.51 [0.50–0.53] 0.43 [0.00–2.88]  
95th percentile 1st quartile 5.84 [3.60–8.09] 1.16 [0.95–1.37] 6.60 [2.29–12.64] 1.51 [0.00–4.81] N/A**
3rd quartile 4.11 [2.73–5.48] 4.23 [1.87–8.55]  
Minimum 0.08 [0.00–0.15] 0.00 [0.00–1.12]  
Maximum 5.84 [3.60–8.09] 6.60 [2.29–12.64]  

** Mann-Whitney test was inapplicable in terms of 1p/19q deletions due to limited sample size.

Multivariate Analysis of Predicting Overall Survival in Terms of Surgical Extent, 1p/19q Deletion, MGMT Methylation and Mean rCBV

Variables Adjusted R2 P-value, univariate P-value, multivariate
Surgical extent 0.163 0.017 0.042
1p/19q deletions 0.188 0.011 0.039
MGMT methylation –0.035 0.826 0.490
Mean rCBV 0.029 0.186 0.273