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Prediction of Recurrence in Parasagittal and Parafalcine Meningiomas: Added Value of Diffusion-Weighted Magnetic Resonance Imaging
Original Article
Prediction of Recurrence in Parasagittal and Parafalcine Meningiomas: Added Value of Diffusion-Weighted Magnetic Resonance Imaging Ching-Chung Ko1, Tai-Yuan Chen1,2, Sher-Wei Lim3,4, Yu-Ting Kuo1,5, Te-Chang Wu1,6, Jeon-Hor Chen7,8
BACKGROUND: Parasagittal and parafalcine (PSPF) meningiomas recur more frequently than other intracranial meningiomas owing to the difficulty in achieving gross total resection. The present study investigated the preoperative magnetic resonance imaging (MRI) features for the prediction of progression/recurrence (P/R) in benign PSPF meningiomas with an emphasis on the apparent diffusion coefficient (ADC) values.
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METHODS: We retrospectively investigated the preoperative MRI features for the prediction of P/R in benign (World Health Organization grade I) PSPF meningiomas. Only patients who had undergone preoperative and postoperative MRI follow-up studies for ‡1 year were included. From October 2006 to December 2015, 48 patients with a diagnosis of benign PSPF meningioma were included (median followup period, 42.5 months). Of these 48 patients, 12 (25%) developed P/R (median time to P/R, 23 months).
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RESULTS: PSPF meningiomas in male patients, subtotal resection, large tumor diameter, high diffusion-weighted imaging signal, and lower ADC values or ratios were significantly associated with P/R (P < 0.05). The cutoff points of the ADC value and ADC ratio for the prediction of
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Key words ADC - DWI - Meningioma - Parafalcine - Parasagittal - Recurrence -
Abbreviations and Acronyms ADC: Apparent diffusion coefficient CE: Contrast-enhanced DWI: Diffusion-weighted magnetic resonance imaging FLAIR: Fluid-attenuated inversion recovery FOV: Field of view GRE: Gradient-recalled echo GTR: Gross total resection ICC: Intraclass correlation coefficient NAWM: Normal-appearing cerebral white matter P/R: Progression/recurrence PSPF: Parasagittal and parafalcine ROI: Region of interest RT: Radiotherapy SSS: Superior sagittal sinus STR: Subtotal resection
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P/R were 0.83 3 10e3 mm2/second and 0.99, with an area under the curve of 0.82 and 0.83, respectively (P [ 0.001). On multivariate Cox proportional hazards analysis, male sex and low ADC values (<0.83 3 10e3 mm2/second) were high-risk factors for P/R, with a hazard ratio of 12.37 and 30.2, respectively (P < 0.05). Kaplan-Meier analysis showed that lower ADC values and ratios predicted for significantly shorter progression-free survival (P < 0.05). CONCLUSIONS: The preoperative ADC values and ratios for the prediction of P/R offer additional valuable information for the treatment planning for PSPF meningiomas.
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INTRODUCTION
M
eningiomas are the most commonly diagnosed primary brain tumors.1 Although most meningiomas will be benign tumors (World Health Organization [WHO] grade I) using the 2016 WHO classification system,2 a subset of WHO grade I meningiomas will show early progression/ recurrence (P/R) in the first years after surgical resection.3-5 It has been reported that parasagittal and parafalcine (PSPF) meningiomas recur more frequently than other intracranial
T1WI: T1-weighted imaging T2WI: T2-weighted imaging TR/TE: Repetition time/echo time WHO: World Health Organization From the 1Section of Neuroradiology, Department of Medical Imaging, Chi-Mei Medical Center, Tainan, Taiwan; 2Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan; 3Department of Neurosurgery, Chi-Mei Medical Center, Chiali, Tainan, Taiwan; 4Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan; 5Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; 7Department of Radiology, E-DA Hospital, E-DA Cancer Hospital, I-Shou University, Kaohsiung, Taiwan; and 8 Center for Functional Onco-Imaging of Radiological Sciences, School of Medicine, University of California, Irvine, California, USA To whom correspondence should be addressed: Ching-Chung Ko, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2018.12.117 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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meningiomas, and investigators have demonstrated that the relatively high recurrence rates are related to incomplete tumor removal.6,7 In addition, the surgical outcome of PSPF meningiomas has remained poor owing to the frequent involvement of the superior sagittal sinus (SSS) and deep draining veins.8,9 Postoperative complications will occur in 34.8% of patients.10 Patients can develop mutism and hemiparesis due to injury of the supplementary motor cortex, cingulated cortex, and corpus callosum.11,12 Although postoperative adjuvant radiotherapy (RT) can be implemented for the prevention of P/R, it has been reported that seizures, focal deficits, and intracranial hypertension caused by symptomatic post-RT edema will occur mostly in PSPF meningiomas.13,14 Therefore, the main challenge in the treatment of PSPF meningiomas is to determine the factors that correlate with P/R. Conventional magnetic resonance imaging (MRI) findings such as tumor size, proximity to major sinuses, and bone osteolysis have been reported as important variables related to P/R in PSPF meningiomas.3,15 Although apparent diffusion coefficient (ADC) values acquired in diffusion-weighted MRI (DWI) have been used to differentiate between benign and atypical/malignant (WHO grade II or III) meningiomas,16-22 the association between the ADC and clinical outcomes in benign meningiomas has rarely be studied. In the present study, we investigated the preoperative MRI features for the prediction of P/R in benign PSPF meningiomas, with an emphasis on the quantitative ADC values. METHODS Ethics Statement Our institutional review board approved the present retrospective study. The requirement for written informed consent was waived because our retrospective study would not affect or alter the healthcare of the included individuals. All patient records were anonymized and de-identified before analysis. Patient Selection The inclusion criteria for the present study preoperative brain MRI studies, including DWI and corresponding ADC imaging, sequential diagnosis of benign PSPF meningioma (WHO grade I) by MRI findings, and pathological confirmation. Only patients with postoperative MRI follow-up studies for >1 year (at least every 6e12 months) were included, in accordance with previous studies.3,23,24 From October 2006 to December 2015, 409 patients had a diagnosis of pathologically confirmed meningioma. Of these 409 patients, 107 had a diagnosis of PSPF meningioma by MRI and were selected for further evaluation. Eleven patients with a diagnosis of high-grade (WHO grade II or III) meningioma pathologically were excluded. In addition, 8 patients were excluded because of incomplete preoperative MRI studies or poor imaging quality of the DWI/ADC due to severe susceptibility artifacts resulting from skull bone or intratumoral calcification. Another 25 patients were excluded owing to a postoperative MRI follow-up duration of <1 year. Also, 14 patients who had received postoperative adjuvant RT before the development of P/R were excluded. Finally, 1 patient with a diagnosis of neurofibromatosis type 2 was also excluded. Thus, 48 patients (16 men and 32 women; age 26e84 years; median age, 56 years) with a diagnosis of PSPF meningiomas (WHO grade I) were included in the present
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study. None had undergone previous cranial RT. The median follow-up time was 42.5 months (range, 12e118). In 12 patients with P/R, the median interval to P/R was 23 months (range, 7e92). Clinical Data The clinical data of the study subjects were obtained from the clinical records. The degree of SSS invasion and Simpson grade of surgical resection were determined by a review of the surgical operative notes and preoperative and postoperative MRI findings. For equivocal cases, judgment was made in consensus by the neuroradiologist (C.C.K.) and neurosurgeon (S.W.L.). Using the classification of Sindou et al.,25 the degree of SSS invasion was grouped into 6 types: type 1, meningioma attached to the lateral wall of the sinus; type 2, invasion of 1 lateral recess; type 3, invasion of 1 lateral wall; type 4, invasion of 1 lateral wall and roof; and types 5 and 6, total sinus occlusion, with the contralateral wall free of tumor in type 5. The tumors were also divided into anterior, middle, and posterior types according to their origin in the falx. The anterior third extends from the floor of the frontal fossa to the coronal suture, the middle third from the coronal suture to the lambdoid suture, and the posterior third from the lambdoid suture to the torcula.26 Simpson grade IeIII resections were considered gross total resection (GTR), and Simpson grade IV and V resections were considered subtotal resection (STR).27 Imaging Acquisition The MRI scans were acquired using a 1.5T MRI scanner (MAGNETOM Avanto [Siemens, Munich, Germany]) for 22, 1.5T MRI scanner (Signa HDxt [GE Healthcare, Chicago, Illinois, USA]) for 19, or 3T MRI scanner (Discovery MR750 [GE Healthcare]) for 7. All were equipped with 8-channel head coils. The MRI protocols were as follows: axial and sagittal spin echo T1-weighted imaging (T1WI), axial and coronal fast spin-echo T2-weighted imaging (T2WI), axial fluid-attenuated inversion recovery (FLAIR), and axial T2*-weighted gradient-recalled echo (GRE). DWI was performed by sequential application in the x, y, and z directions, and ADC maps (b ¼ 1000 seconds/mm2) were obtained from these imaging data. Analysis of the diffusion changes was performed by “in-line” calculation of the ADC values using the Stejskal and Tanner equation.28 Contrast-enhanced (CE) images obtained on axial and coronal T1WI were performed after intravenous administration of 0.1 mmol/kg of body weight of gadobutrol or gadoterate meglumine. Details of the imaging parameters for the MRI scanners have been provided in Supplemental Appendix 1. Image Analysis and Interpretation The preoperative MRI features were evaluated by 2 neuroradiologists (C.C.K., with 5 years’ experience; and T.Y.C., with 17 years’ experience). Both were kept unware of the clinical and radiologic outcomes of the studied patients. P/R was defined as tumor recurrence after GTR (Simpson grade IeIII resection) or enlargement of residual tumor after STR (Simpson grade IV and V resection) on CE-T1WI. For the patients who had undergone STR, the threshold for P/R was defined as a 10% increase in the tumor volume compared with the postoperative brain MRI studies. The tumor volume measurements were the sum of the tumor area multiplied by the slice thickness on axial CE-T1WI using the
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ORIGINAL ARTICLE CHING-CHUNG KO ET AL.
PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
Table 1. Continued
Table 1. Clinical Data and Magnetic Resonance Imaging Features Stratified by Progression/Recurrence
P/R
P/R Characteristic
Yes
No
Patients (n)
12
36
8 (66.7)
8 (22.2)
Sex
P Value
0.01*
Male Female
4 (33.3)
28 (77.8)
Age (years)
56 (49e64.3)
56 (49.3e65.8)
Parasagittal or parafalcine 7 (58.3)
27 (75)
Parafalcine
5 (41.7)
9 (25)
Histological subtype 8 (66.7)
24 (66.7)
Transitional (mixed)
1 (8.3)
8 (22.2%)
Fibroblastic (fibrous)
2 (16.7)
2 (5.6%)
Angiomatous
1 (8.3)
2 (5.6%)
Degree of SSS invasion (Sindou classification)
0.19
None
15 (41.7)
3 (25)
Type 1e3
15 (41.7)
4 (33.3)
Type 4e6
6 (16.7)
5 (41.7)
Location
0.48
Anterior third
8 (22.2)
4 (33.3)
Middle third
25 (69.4)
8 (66.7)
3 (8.3)
0 (0)
Posterior third Simpson grade resection Grade IeIII (GTR)
0.03* 7 (58.3)
32 (88.9)
Grade IVeV (STR)
5 (41.7)
4 (11.1)
Maximum diameter (cm)
5.9 (4.1e7.3)
4 (2.9e5.4)
3
Tumor volume (cm ) Peritumoral edema
54.8 (13.7e139.9) 21.8 (10.2e41.7)
0.009* 0.07
8 (66.7)
21 (58.3)
0.74
Edema size (cm)
3.9 (1.9e4.3)
2.9 (1.4e5.4)
0.65
Heterogeneous enhancement
6 (50)
12 (33.3)
0.33
Irregular margin
2 (16.7)
0 (0)
0.06
Calcification
2 (16.7)
12 (33.3)
0.47
Necrosis
1 (8.3)
4 (11.1)
1
Hemorrhage
0 (0)
2 (5.6)
1
Cystic change
2 (16.7)
4 (11.1)
0.63
Adjacent bone invasion
4 (33.3)
3 (8.3)
0.06
0 (0)
4 (11.1)
0.56
Reactive hyperostosis
Continues
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No
P Value
Dural tail sign
4 (33.3)
12 (33.3)
1.00
Multiplicity
2 (16.7)
1 (2.8)
0.15
1 (8.33)
2 (5.6)
0 (0)
15 (41.7)
11 (91.7)
19 (52.8)
DWI
0.03*
Isointensity 0.89
0.5
Meningothelial (syncytial)
Yes
Hypointensity
0.29
Parasagittal
Characteristic
Hyperintensity ADC (10e3 mm2/second)
0.76 (0.67e0.81) 0.88 (0.79e0.96)
0.001*
ADC ratio
0.95 (0.88e1.04) 1.17 (1.04e1.24)
0.001*
Data presented as n (%) or median (interquartile range) for continuous variables. P/R, progression/recurrence; SSS, superior sagittal sinus; GTR, gross total resection; STR, subtotal resection; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient. *Statistically significant (P < 0.05).
freehand region of interest (ROI) tool on the Picture Archiving and Communication System (INFINITT PACS [INFINITT Healthcare, Seoul, Republic of Korea]) workstations. The degree of SSS invasion (Sindou classification) was determined from the coronal T2WI and CE-T1WI scans.25 The anterior, middle, and posterior third locations of the tumors were determined from the sagittal CE-T1WI scans. The size of peritumoral edema was determined by the maximum diameter between the tumor border and edematous edge on axial T2WI and FLAIR scans. Smooth or irregular tumor margins were determined from the T2WI and CE-T1WI studies. Adjacent bone invasion was determined from the coronal and sagittal CE-T1WI scans. Intratumoral calcifications were identified as the presence of susceptibility artifacts on T2*weighted GRE and hypointensity on T1WI and T2WI studies. Intratumoral calcification, adjacent bone invasion, and reactive hyperostosis were also confirmed on preoperative brain computed tomography scans, which were performed routinely for navigation (stereotactic surgery) in our hospital. DWI Signals and Quantitative ADC Value For the DWI signals, each lesion was evaluated as predominantly hyperintense, isointense, or hypointense relative to the contralateral normal-appearing cerebral white matter (NAWM). For ADC measurement, the ROI was placed to avoid volume averaging with the inclusion of calcified foci, necrosis, and cystic regions that might influence the ADC values in PSPF meningiomas. A circular ROI with area from 38 to 84 mm2 (mean, 72.4 4.6) was placed within the tumor area to obtaining the measurements for all patients. For normalization of individual variance, an equal ROI was placed in the contralateral NAWM for each patient. Next, the ADC ratio was calculated by dividing the ADC value of the tumor by the ADC value of the contralateral NAWM in the same patient in accordance with the recommendations documented in previously reported studies.24,29,30
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Figure 1. Imaging studies of a 58-year-old man with pathologically proven right parietal parasagittal and parafalcine meningioma (World Health Organization grade I). (A) Axial contrast-enhanced T1-weighted magnetic resonance image showing an enhancing tumor (arrow) arising from the right parietal falx and superior sagittal sinus, with poorly enhancing central necrotic components in the tumor observed. (B) Diffusion-weighted image showing hyperintensity in the solid part of the tumor (arrow). (C) Measured apparent diffusion coefficient value (circular region of interest) and
Statistical Analysis Statistical analyses were performed using the statistical package SPSS for Windows, version 24.0 (IBM Corp., Armonk, New York, USA). The c2 test or Fisher exact test and the Mann-Whitney U test were used to evaluate the categorical and continuous data, respectively. Receiver operating characteristic analysis of the ADC value and ratio was performed to discriminate between patients with and without P/ R. Kaplan-Meier analysis was used to assess the progression-free survival. The log-rank test was used to assess the significance in the recurrence rates. Univariate and multivariate Cox proportional hazard regression analyses were performed to determine the hazard ratio of each parameter. P < 0.05 was considered statistically significant. The interobserver reliabilities in the categorical and continuous data were determined using the Cohen k coefficient and intraclass correlation
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apparent diffusion coefficient ratio were 0.62 10e3 mm2/second and 0. 75, respectively. (D) Gross total resection was performed, and World Health Organization grade I meningioma was confirmed pathologically. (E) Recurrent tumor (arrowheads) was observed 12 months after surgical resection. (F) The proliferation rate determined from the immunohistochemical Ki-67 labeling index was 8%. Only the dark brown stained nuclei were considered immunopositive (original magnification 400).
coefficient (ICC), respectively. The Cohen k coefficient and ICC were interpreted using the methods described by Landis and Koch.31 Cohen k coefficient values of 0.8e0.96 were obtained for categorical MRI, indicating almost perfect reproducibility. An ICC of 0.79e0.94 were obtained for the continuous data. Owing to the substantial to almost perfect reproducibility in the ICC, the subsequent statistical evaluation of continuous data was performed using the mean value calculated from both raters. RESULTS Clinical Data and MRI Findings The clinical data and MRI features of the PSPF meningiomas with and without P/R are summarized in Table 1. Of the 48
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.117
ORIGINAL ARTICLE CHING-CHUNG KO ET AL.
PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
Figure 2. Box plot of (A) apparent diffusion coefficient (ADC) values and (B) ADC ratios in parasagittal and parafalcine meningiomas with and without progression/recurrence (P/R). Lower (A) ADC values and (B) ADC ratios in the P/R group (median ADC value, 0.76 10e3 mm2/second; median ADC ratio, 0.95) compared with the non-P/R group (median ADC value,
patients, 12 (25%) had developed P/R. Male sex, STR, and a larger maximum diameter were more frequent in the P/R group than in those without P/R (P < 0.05). Most of the 12 PSPF meningiomas with P/R (n ¼ 11; 91.7%) exhibited hyperintense DWI signals compared with the contralateral NAWM (P ¼ 0.03; Figure 1). The median ADC values and ADC ratios were lower in the P/R group than in those without P/R (P ¼ 0.001; Figure 2). Receiver Operating Characteristic Curve Analysis of ADC The sensitivity, specificity, area under curve (AUC), and optimal cutoff points for the ADC values and ratios for differentiation between the P/R and non-P/R groups are summarized in Table 2. The cutoff points for the ADC value and ADC ratio were 0.83 10e3 mm2/second and 0.99, respectively. An AUC of 0.82 and 0.83 were obtained for the ADC value and ADC ratio, respectively. Recurrence Rate and Cox Proportional Hazards Regression Analysis The median follow-up duration for all patients was 42.5 months. In the 12 patients with P/R, the median time to P/R was 23
0.88 10e3 mm2/second; median ADC ratio, 1.17; P ¼ 0.001, Mann-Whitney U test) were observed. Boxes indicate the interquartile range, and whiskers indicate the range. The horizontal line represents the median in each box. Circles represent outliers, defined as distances >1.5 times the interquartile range less than the first quartile or greater than the third quartile.
months. When comparing the tumor progression trends, patients with lower ADC values (less than cutoff value of 0.83 10e3 mm2/ second) and lower ADC ratios (less than cutoff value of 0.99) exhibited shorter progression-free survival (P < 0.05; Figure 3). The results of the Cox proportional hazards analyses are summarized in Table 3. On univariate analysis, a statistically significance difference (P < 0.05) was found in sex, STR, maximum diameter, tumor size, and low ADC values (less than cutoff value of 0.83 10e3 mm2/second) between these 2 groups. Furthermore, male sex and low ADC values predicted for a high risk of P/R (P < 0.05) on multivariate analysis with a hazard ratio of 12.37 and 30.2, respectively. DISCUSSION The purpose of the present study was to analyze the preoperative clinical and MRI features for the prediction of P/R in benign PSPF meningiomas. Our results have shown that male sex, STR, large maximum diameter, high DWI signal, and lower ADC values and ratios are significantly more likely to be associated with P/R. Although the risk factors for the recurrence of PSPF meningiomas have been previously reported,15,32,33 to the best of our knowledge,
Table 2. Results of Receiver Operating Characteristic Analysis of Apparent Diffusion Coefficient Value and Ratio for Differentiating Parasagittal and Parafalcine Meningiomas Stratified by Progression/Recurrence Variable
Sensitivity
Specificity
AUC
Cutoff Value
P Value
ADC (10e3 mm2/second)
0.67
0.92
0.82
0.83
0.001*
ADC ratio
0.89
0.75
0.83
0.99
0.001*
AUC, area under the curve; ADC, apparent diffusion coefficient. *Statistically significant (P < 0.05).
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PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
Figure 3. Kaplan-Meier curves showing overall trends of progression-free survival using cutoff points of (A)
the present results are the first to offer quantitative cutoff points for ADC for the prediction of P/R in PSPF meningiomas. Although w90% meningiomas will be classified as WHO grade I benign tumors, 21% of these tumors will recur within 5 years.4,5 DWI has been widely used as a imaging biomarker to evaluate
apparent diffusion coefficient (ADC) value and (B) ADC ratio.
various intracranial tumors and predict their grade of differentiation.34,35 DWI provides biomedical information related to the tissues of interest using measurement of thermally induced diffusion of water molecules (Brownian motion) shown by ADC.36,37 Therefore, unusual ADC values could be an early
Table 3. Results of Cox Proportional Hazards Analysis of Progression/Recurrence Univariate Analysis Variable
Multivariate Analysis
HR (95% CI) for P/R
P Value
HR (95% CI) for P/R
P Value
Sex (fraction male)
6.58 (1.95e22.16)
0.002*
12.37 (2e76.4)
0.007*
Age (years)
0.99 (0.95e1.04)
0.81
NS
NA
SSS invasion (Sindou type 4e6)
2.17 (0.68e6.89)
0.19
NS
NA
Location (middle or posterior third)
1.11 (0.32e3.86)
0.87
NS
NA
STR
4.58 (1.44e14.57)
0.01*
0.86 (0.19e3.87)
0.85
1.5 (1.12e2)
0.007*
1.78 (0.57e5.54)
0.32
Maximum diameter (cm) 3
Tumor volume (cm )
1.01 (1e1.02)
0.02*
0.98 (0.94e1.02)
0.37
Peritumoral edema
1.39 (0.42e4.66)
0.59
NS
NA
Heterogeneous enhancement
1.66 (0.53e5.14)
0.38
NS
NA
Calcification
0.49 (0.11e2.24)
0.36
NS
NA
Necrosis
0.48 (0.06e3.79)
0.48
NS
NA
Cystic change
1.06 (0.23e4.88)
0.94
NS
NA
Adjacent bone invasion
3.1 (0.9e10.62)
0.07
NS
NA
Dural tail sign
1.96 (0.53e7.28)
0.32
NS
NA
Multiplicity
2.16 (0.46e10.19)
0.33
NS
NA
DWI (hyperintensity)
5.86 (0.75e45.89)
0.09
NS
NA
15.27 (1.97e118.59)
0.009*
30.2 (2.4e380.69)
0.008*
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ADC <0.83 10
2
mm /second (cutoff value)
HR, hazard ratio; CI, confidence interval; P/R, progression/recurrence; NS, not significant; NA, not applicable; SSS, superior sagittal sinus; STR, subtotal resection; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient. *Statistically significant (P < 0.05).
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harbinger of a biologic abnormality.34 Several studies have reported that high DWI signals and lower ADC values (more restricted diffusion) are related to atypical or malignant meningiomas.16-22 However, the correlation between ADC values and recurrence in benign meningiomas has rarely been studied. According to the 2016 WHO guidelines, benign meningiomas will be characterized by a count of <4 mitotic cells/10 high power fields and <3 of the atypical features. These atypia features include increased cellularity, small cells (high nuclear/cytoplasmic ratio), spontaneous necrosis, sheeting, and prominent nucleoli.2 Hwang et al.23 was the first to report that lower ADC values were found in benign meningiomas with 1e2 histopathologic atypia features compared with those without atypia. Thus, lower ADC values could represent more histopathologic features of atypia in benign meningiomas even if they are all classified as WHO grade I. In addition, Hwang et al.23 reported that the ADC value and extent of surgical resection can predict for P/R of meningioma better than using the WHO histopathologic grade.23 Furthermore, that low ADC values will predict for a high rate of recurrence in skull base meningiomas was first reported in our previous study.24 However, it is known that the genetic mechanisms between PSPF meningiomas and skull base meningiomas are different.38-40 Therefore, specific ADC data for the prediction of P/R in PSPF meningiomas are essential because of the difficulty in achieving GTR and the high rate of P/R in this anatomic location.6,7 Although we were unable to correlate the ADC values with Ki-67 because of the lack of complete Ki-67 data in the present retrospective study, some investigators have reported that the ADC values correlated inversely with the Ki-67 proliferation index in meningiomas and are helpful in differentiating low-grade and aggressive meningiomas.17,22,41 Baskan et al.41 reported an ADC value of 0.81 10e3 mm2/second and Ki-67 of 2.19% in low-grade meningiomas compared with an ADC of 0.66 10e3 mm2/second and Ki-67 of 11.2% in high-grade meningiomas. Surov et al.22 reported a threshold ADC value of 0. 85 10e3 mm2/second for detecting meningiomas with a high proliferation potential (Ki-67 5%). Therefore, ADC values that lead to a high rate of P/R in PSPF meningiomas could be explained by a high Ki-67 proliferation index. It is known that some differences could exist in the DWI and ADC between 1.5T and 3T MRI scanners. However, the association between a low ADC and a high rate of P/R was similar for both 1.5T (n ¼ 41) and 3T (n ¼ 7) MRI scanners in our study. With the 1.5T MRI scanner, the median ADC value was 0.77 10e3 mm2/ second and the ADC ratio was 0.96 for patients with P/R (n ¼ 11). Similarly, a lower ADC value (0.65 10e3 mm2/second) and lower ADC ratio (0.9) were observed for the patient with recurrence who had undergone MRI with the 3T MRI scanner. Although the extent of tumor resection is an important key factor in determining the rate of recurrence in PSPF meningiomas,26,42,43 the surgical outcome of PSPF meningiomas has remained poor.8,9 The postoperative complications have included deterioration of motor function and/or consciousness level and death from intracranial hematoma, brain edema, venous thrombosis or infarction, and air embolism.8,9 It is known that adjuvant
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RT will improve local tumor control and disease-free survival in those with high-grade meningiomas.44 However, the role of postoperative adjuvant RT for benign PSPF meningiomas is still unclear, resulting in inconsistent practice in each institution.45 Whether adjuvant RT will be beneficial for patients without evidence of tumor growth is controversial, because it could increase the risk of complications such as symptomatic peritumoral edema, venous occlusion, cranial nerve deficits, internal carotid artery stenosis, and neurologic deficits.13,46-49 Furthermore, the incidence of post-RT complications has been greater with PSPF meningiomas than with other tumors.13,14 The preoperative prediction of P/R would, thus, offer vital information for determining the extent of surgical resection and the necessity for adjuvant RT. For benign PSPF meningiomas with high-risk factors for P/R, aggressive tumor resection during primary surgery, combined with postoperative adjuvant RT and close imaging follow-up, should be considered. In contrast, for patients with a lower possibility of P/R, the aim of surgery might be the relief of the mass effect and clinical symptoms to avoid postoperative neurological deficits. Adjuvant RT should be used more conservatively because all radiotherapeutic procedures have long-term side effects and might affect future treatment.46-49 Therefore, our results have provided added valuable information for the planning of treatment of benign PSPF meningiomas. In contrast, patients with postoperative adjuvant RT before P/R were excluded from our study because adjuvant RT could have affected the independent predictive value of ADC for P/R. Recently, application of ADC to differentiate low-grade (WHO grade I) and high-grade (WHO grade II/III) PSPF meningiomas has been reported.19-21 Compared with the reported data, we offer the new concept that preoperative ADC could also be used to evaluate the clinical outcomes for WHO grade I PSPF meningiomas. This concept is clinically significant and useful regarding the treatment choices, because most PSPF meningiomas will be classified as WHO grade I. However, the present study still had limitations. The retrospective nature of the present study could have resulted in bias. Just as in other ROI-based studies, the subjective placement of the ROIs could have influenced the accuracy of the ADC measurements. Furthermore, the ADC values could have differed among the different MRI systems, although similar parameters were used with each scanner. The relatively small sample size and short follow-up time could have limited our statistical power to detect potential associations between some of the imaging features and P/R. Finally, our retrospective study lacked complete histopathologic findings, including Ki-67, for correlation with the ADC values. CONCLUSIONS Our results showed that PSPF meningiomas in male patients, STR, a large maximum diameter, a high DWI signal, and lower ADC values and/or ADC ratios were all associated with P/R. The preoperative ADC values and ratios for the prediction of P/R offer clinically vital information for the planning of PSPF meningioma treatment, including the extent of tumor resection, implementation of postoperative adjuvant RT, and the imaging follow-up strategy.
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REFERENCES 1. Wiemels J, Wrensch M, Claus EB. Epidemiology and etiology of meningioma. J Neurooncol. 2010;99: 307-314.
PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
15. Escribano Mesa JA, Alonso Morillejo E, Parron Carreno T, et al. Risk of recurrence in operated parasagittal meningiomas: a logistic binary regression model. World Neurosurg. 2018;110: e112-e118.
2. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803-820.
16. Nagar VA, Ye JR, Ng WH, et al. Diffusionweighted MR imaging: diagnosing atypical or malignant meningiomas and detecting tumor dedifferentiation. AJNR Am J Neuroradiol. 2008;29: 1147-1152.
3. Ildan F, Erman T, Gocer AI, et al. Predicting the probability of meningioma recurrence in the preoperative and early postoperative period: a multivariate analysis in the midterm follow-up. Skull Base. 2007;17:157-171.
17. Tang Y, Dundamadappa SK, Thangasamy S, et al. Correlation of apparent diffusion coefficient with Ki-67 proliferation index in grading meningioma. AJR Am J Roentgenol. 2014;202:1303-1308.
4. Maillo A, Orfao A, Espinosa AB, et al. Early recurrences in histologically benign/grade I meningiomas are associated with large tumors and coexistence of monosomy 14 and del(1p36) in the ancestral tumor cell clone. Neuro Oncol. 2007;9: 438-446. 5. Perry A, Stafford SL, Scheithauer BW, Suman VJ, Lohse CM. Meningioma grading: an analysis of histologic parameters. Am J Surg Pathol. 1997;21: 1455-1465. 6. Melamed S, Sahar A, Beller A. The recurrence of intracranial meningiomas. Neurochirurgia. 1979;22: 47-51. 7. Huo WY, Li L, Zhang YF. Resection of recurrent parasagittal meningiomas with complete obstructed superior sagittal sinus. Int Congr Ser. 2004;1259:53-57. 8. Oyama H, Kito A, Maki H, Hattori K, Noda T, Wada K. Surgical results of parasagittal and falx meningioma. Nagoya J Med Sci. 2012;74:211-216. 9. Raza SM, Gallia GL, Brem H, Weingart JD, Long DM, Olivi A. Perioperative and long-term outcomes from the management of parasagittal meningiomas invading the superior sagittal sinus. Neurosurgery. 2010;67:885-893. 10. Skudas G, Tamasauskas A. [Prognosis of the surgical treatment of parasagittal meningioma]. Medicina (Kaunas). 2002;38:1089-1096. 11. Crutchfield JS, Sawaya R, Meyers CA, Moore BD III. Postoperative mutism in neurosurgery: report of two cases. J Neurosurg. 1994;81: 115-121. 12. Tahta K, Cirak B, Pakdemirli E, Suzer T, Tahta F. Postoperative mutism after removal of an anterior falcine meningioma. J Clin Neurosci. 2007;14: 793-796. 13. Conti A, Pontoriero A, Siddi F, et al. Post-treatment edema after meningioma radiosurgery is a predictable complication. Cureus. 2016;8:e605. 14. Kalapurakal JA, Silverman CL, Akhtar N, et al. Intracranial meningiomas: factors that influence the development of cerebral edema after stereotactic radiosurgery and radiation therapy. Radiology. 1997;204:461-465.
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18. Lin L, Bhawana R, Xue Y, et al. Comparative analysis of diffusional kurtosis imaging, diffusion tensor imaging, and diffusion-weighted imaging in grading and assessing cellular proliferation of meningiomas. AJNR Am J Neuroradiol. 2018;39: 1032-1038. 19. Aslan K, Gunbey HP, Tomak L, Incesu L. The diagnostic value of using combined MR diffusion tensor imaging parameters to differentiate between low- and high-grade meningioma. Br J Radiol. 2018;91:20180088. 20. Gihr GA, Horvath-Rizea D, Garnov N, et al. Diffusion profiling via a histogram approach distinguishes low-grade from high-grade meningiomas, can reflect the respective proliferative potential and progesterone receptor status. Mol Imaging Biol. 2018;20:632-640. 21. Surov A, Gottschling S, Mawrin C, et al. Diffusionweighted imaging in meningioma: prediction of tumor grade and association with histopathological parameters. Transl Oncol. 2015;8:517-523. 22. Surov A, Ginat DT, Sanverdi E, et al. Use of diffusion weighted imaging in differentiating between maligant and benign meningiomas: a multicenter analysis. World Neurosurg. 2016;88: 598-602. 23. Hwang WL, Marciscano AE, Niemierko A, et al. Imaging and extent of surgical resection predict risk of meningioma recurrence better than WHO histopathological grade. Neuro Oncol. 2016;18: 863-872. 24. Ko CC, Lim SW, Chen TY, Chen JH, Li CF, Shiue YL. Prediction of progression in skull base meningiomas: additional benefits of apparent diffusion coefficient value. J Neurooncol. 2018;138: 63-71. 25. Sindou MP, Auque J, Jouanneau E. Neurosurgery and the intracranial venous system. Acta Neurochir Suppl. 2005;94:167-175. 26. Chung S-B, Kim C-Y, Park C-K, Kim DG, Jung HW. Falx meningiomas: surgical results and lessons learned from 68 cases. J Korean Neurosurg Soc. 2007;42:276-280. 27. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry. 1957;20:22-39.
28. Stejskal EO, Tanner JE. Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient. J Chem Phys. 1965; 42:288-292. 29. Server A, Kulle B, Maehlen J, et al. Quantitative apparent diffusion coefficients in the characterization of brain tumors and associated peritumoral edema. Acta Radiol. 2009;50:682-689. 30. Toh CH, Castillo M, Wong AM, et al. Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging. AJNR Am J Neuroradiol. 2008;29:471-475. 31. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159-174. 32. Colli BO, Carlotti CG Jr, Assirati JA Jr, Dos Santos MB, Neder L, Dos Santos AC. Parasagittal meningiomas: follow-up review. Surg Neurol. 2006; 66(suppl 3):S20-S27 [discussion: S27-S28]. 33. Nowak A, Marchel A. Surgical treatment of parasagittal and falx meningiomas. Neurol Neurochir Pol. 2007;41:306-314. 34. Padhani AR, Liu G, Mu-Koh D, et al. Diffusionweighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia. 2009;11:102-125. 35. Higano S, Yun X, Kumabe T, et al. Malignant astrocytic tumors: clinical importance of apparent diffusion coefficient in prediction of grade and prognosis. Radiology. 2006;241:839-846. 36. Le Bihan D, Poupon C, Amadon A, Lethimonnier F. Artifacts and pitfalls in diffusion MRI. J Magn Reson Imaging. 2006;24:478-488. 37. Gass A, Niendorf T, Hirsch JG. Acute and chronic changes of the apparent diffusion coefficient in neurological disorders—biophysical mechanisms and possible underlying histopathology. J Neurol Sci. 2001;186(suppl 1):S15-S23. 38. Clark VE, Erson-Omay EZ, Serin A, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science. 2013;339:1077-1080. 39. McGovern SL, Aldape KD, Munsell MF, Mahajan A, DeMonte F, Woo SY. A comparison of World Health Organization tumor grades at recurrence in patients with non-skull base and skull base meningiomas. J Neurosurg. 2010;112: 925-933. 40. Sade B, Chahlavi A, Krishnaney A, Nagel S, Choi E, Lee JH. World Health Organization grades II and III meningiomas are rare in the cranial base and spine. Neurosurgery. 2007;61:1194-1198 [discussion: 1198]. 41. Baskan O, Silav G, Bolukbasi FH, Canoz O, Geyik S, Elmaci I. Relation of apparent diffusion coefficient with Ki-67 proliferation index in meningiomas. Br J Radiol. 2016;89:20140842.
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42. Mansouri A, Klironomos G, Taslimi S, et al. Surgically resected skull base meningiomas demonstrate a divergent postoperative recurrence pattern compared with non-skull base meningiomas. J Neurosurg. 2016;125:431-440. 43. Nanda A, Bir SC, Maiti TK, Konar SK, Missios S, Guthikonda B. Relevance of Simpson grading system and recurrence-free survival after surgery for World Health Organization grade I meningioma. J Neurosurg. 2017;126:201-211. 44. Kaur G, Sayegh ET, Larson A, et al. Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review. Neuro Oncol. 2014;16: 628-636. 45. Maclean J, Fersht N, Short S. Controversies in radiotherapy for meningioma. Clin Oncol (R Coll Radiol). 2014;26:51-64.
PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
46. Girvigian MR, Chen JC, Rahimian J, Miller MJ, Tome M. Comparison of early complications for patients with convexity and parasagittal meningiomas treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy. Neurosurgery. 2008;62:A19-A27 [discussion: A27-A28]. 47. Conti A, Pontoriero A, Salamone I, et al. Protecting venous structures during radiosurgery for parasagittal meningiomas. Neurosurg Focus. 2009;27:E11. 48. Stafford SL, Pollock BE, Foote RL, et al. Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients. Neurosurgery. 2001;49:1029-1037 [discussion: 1037-1038].
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49. Mathiesen T, Kihlstrom L, Karlsson B, Lindquist C. Potential complications following radiotherapy for meningiomas. Surg Neurol. 2003; 60:193-198 [discussion: 199-200]. Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 19 September 2018; accepted 13 December 2018 Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2018.12.117 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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SUPPLEMENTAL APPENDIX 1
MAGNETIC RESONANCE IMAGING PROTOCOLS
The protocols of 1.5T (Siemens, MAGNETOM Avanto) magnetic resonance imaging (MRI) were as follows: axial spin-echo T1weighted imaging (T1WI) (repetition time/echo time [TR/TE], 2000 ms/7 ms; field of view [FOV], 16e22 cm; slice thickness/ spacing, 5 mm/6.5 mm; matrix, 320 228), fast spin-echo T2weighted imaging (T2WI) (TR/TE, 3730 ms/108 ms; FOV, 16e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 384 261), fluid-attenuated inversion recovery (FLAIR) (TR/TE, 9000 ms/92 ms; FOV, 16e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 209), and T2-weighted gradient-recalled echo (GRE) (TR/TE, 830 ms/26 ms; FOV, 16e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 168). Contrast-enhanced (CE) images were obtained using axial and coronal T1WI (TR/TE, 1950 ms/8 ms; FOV, 16e23 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 216) after intravenous administration of 0.1 mmol/ kg body weight of gadobutrol (Gadovist [Schering, Berlin, Germany]) or gadoterate meglumine (Dotarem [Guerbet, Villepinte, France]). Diffusion-weighted imaging (DWI) was performed by sequential application in the x, y, and z directions using the following parameters: TR/TE, 3800 ms/105 ms; flip angle, 90 ; slice thickness/spacing, 5 mm/6.5 mm; and b, 0, 500, and 1000 seconds/mm2. The apparent diffusion coefficient (ADC) maps were obtained from these imaging data. The protocols for 1.5T (Signa HDxt [GE Healthcare]) MRI were as follows: axial T1WI (TR/TE, 2000 ms/11 ms; FOV, 20e20 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 192), T2WI (TR/TE, 3600/108 ms; FOV, 20e20 cm; slice thickness/spacing, 5
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mm/6.5 mm; matrix, 320 224), FLAIR (TR/TE, 9002 ms/140 ms; FOV, 20e20 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 160), and T2-weighted GRE (TR/TE, 450/15 ms; FOV, 18e24 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 288 160). CE axial and coronal T1WI (TR/TE, 2131 ms/8 ms; FOV, 18e20 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 288 160) with intravenous administration of 0.1 mmol/kg of gadobutrol or gadoterate meglumine. DWI was performed by sequential application in the x, y, and z directions with the following parameters: TR/TE, 6600 ms/73 ms; flip angle, 90 , slice thickness/spacing, 5 mm/6.5 mm; b, 0 and 1000 seconds/mm2. The ADC maps were obtained from these imaging data. The protocols for 3T (Discovery MR750 [GE Healthcare]) MRI were as follows: axial T1WI (TR/TE, 3400 ms/24 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 352 224), T2WI (TR/TE, 5200 ms/102 ms; FOV, 22e22 cm; slice thickness/ spacing, 5 mm/6.5 mm; matrix, 384 320), FLAIR (TR/TE, 1000 ms/95 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 192), and T2-weighted GRE (TR/TE, 567 ms/20 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 192). CE axial and coronal T1WI (TR/TE, 1800 ms/ 22 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 224) after intravenous administration of 0.1 mmol/ kg of gadobutrol or gadoterate meglumine. The DWI was performed by sequential application in the x, y, and z directions with the following parameters: TR/TE, 8000 ms/64 ms; flip angle, 90 , slice thickness/spacing, 5 mm/6.5 mm; and b, 0, 1000, and 1500 seconds/mm2. The ADC maps were obtained from these imaging data.
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Prediction of Recurrence in Parasagittal and Parafalcine Meningiomas: Added Value of Diffusion-Weighted Magnetic Resonance Imaging Ching-Chung Ko1, Tai-Yuan Chen1,2, Sher-Wei Lim3,4, Yu-Ting Kuo1,5, Te-Chang Wu1,6, Jeon-Hor Chen7,8
BACKGROUND: Parasagittal and parafalcine (PSPF) meningiomas recur more frequently than other intracranial meningiomas owing to the difficulty in achieving gross total resection. The present study investigated the preoperative magnetic resonance imaging (MRI) features for the prediction of progression/recurrence (P/R) in benign PSPF meningiomas with an emphasis on the apparent diffusion coefficient (ADC) values.
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METHODS: We retrospectively investigated the preoperative MRI features for the prediction of P/R in benign (World Health Organization grade I) PSPF meningiomas. Only patients who had undergone preoperative and postoperative MRI follow-up studies for ‡1 year were included. From October 2006 to December 2015, 48 patients with a diagnosis of benign PSPF meningioma were included (median followup period, 42.5 months). Of these 48 patients, 12 (25%) developed P/R (median time to P/R, 23 months).
-
RESULTS: PSPF meningiomas in male patients, subtotal resection, large tumor diameter, high diffusion-weighted imaging signal, and lower ADC values or ratios were significantly associated with P/R (P < 0.05). The cutoff points of the ADC value and ADC ratio for the prediction of
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Key words ADC - DWI - Meningioma - Parafalcine - Parasagittal - Recurrence -
Abbreviations and Acronyms ADC: Apparent diffusion coefficient CE: Contrast-enhanced DWI: Diffusion-weighted magnetic resonance imaging FLAIR: Fluid-attenuated inversion recovery FOV: Field of view GRE: Gradient-recalled echo GTR: Gross total resection ICC: Intraclass correlation coefficient NAWM: Normal-appearing cerebral white matter P/R: Progression/recurrence PSPF: Parasagittal and parafalcine ROI: Region of interest RT: Radiotherapy SSS: Superior sagittal sinus STR: Subtotal resection
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P/R were 0.83 3 10e3 mm2/second and 0.99, with an area under the curve of 0.82 and 0.83, respectively (P [ 0.001). On multivariate Cox proportional hazards analysis, male sex and low ADC values (<0.83 3 10e3 mm2/second) were high-risk factors for P/R, with a hazard ratio of 12.37 and 30.2, respectively (P < 0.05). Kaplan-Meier analysis showed that lower ADC values and ratios predicted for significantly shorter progression-free survival (P < 0.05). CONCLUSIONS: The preoperative ADC values and ratios for the prediction of P/R offer additional valuable information for the treatment planning for PSPF meningiomas.
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INTRODUCTION
M
eningiomas are the most commonly diagnosed primary brain tumors.1 Although most meningiomas will be benign tumors (World Health Organization [WHO] grade I) using the 2016 WHO classification system,2 a subset of WHO grade I meningiomas will show early progression/ recurrence (P/R) in the first years after surgical resection.3-5 It has been reported that parasagittal and parafalcine (PSPF) meningiomas recur more frequently than other intracranial
T1WI: T1-weighted imaging T2WI: T2-weighted imaging TR/TE: Repetition time/echo time WHO: World Health Organization From the 1Section of Neuroradiology, Department of Medical Imaging, Chi-Mei Medical Center, Tainan, Taiwan; 2Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan; 3Department of Neurosurgery, Chi-Mei Medical Center, Chiali, Tainan, Taiwan; 4Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan; 5Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; 7Department of Radiology, E-DA Hospital, E-DA Cancer Hospital, I-Shou University, Kaohsiung, Taiwan; and 8 Center for Functional Onco-Imaging of Radiological Sciences, School of Medicine, University of California, Irvine, California, USA To whom correspondence should be addressed: Ching-Chung Ko, M.D., Ph.D. [E-mail: [email protected]] Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2018.12.117 Journal homepage: www.journals.elsevier.com/world-neurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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meningiomas, and investigators have demonstrated that the relatively high recurrence rates are related to incomplete tumor removal.6,7 In addition, the surgical outcome of PSPF meningiomas has remained poor owing to the frequent involvement of the superior sagittal sinus (SSS) and deep draining veins.8,9 Postoperative complications will occur in 34.8% of patients.10 Patients can develop mutism and hemiparesis due to injury of the supplementary motor cortex, cingulated cortex, and corpus callosum.11,12 Although postoperative adjuvant radiotherapy (RT) can be implemented for the prevention of P/R, it has been reported that seizures, focal deficits, and intracranial hypertension caused by symptomatic post-RT edema will occur mostly in PSPF meningiomas.13,14 Therefore, the main challenge in the treatment of PSPF meningiomas is to determine the factors that correlate with P/R. Conventional magnetic resonance imaging (MRI) findings such as tumor size, proximity to major sinuses, and bone osteolysis have been reported as important variables related to P/R in PSPF meningiomas.3,15 Although apparent diffusion coefficient (ADC) values acquired in diffusion-weighted MRI (DWI) have been used to differentiate between benign and atypical/malignant (WHO grade II or III) meningiomas,16-22 the association between the ADC and clinical outcomes in benign meningiomas has rarely be studied. In the present study, we investigated the preoperative MRI features for the prediction of P/R in benign PSPF meningiomas, with an emphasis on the quantitative ADC values. METHODS Ethics Statement Our institutional review board approved the present retrospective study. The requirement for written informed consent was waived because our retrospective study would not affect or alter the healthcare of the included individuals. All patient records were anonymized and de-identified before analysis. Patient Selection The inclusion criteria for the present study preoperative brain MRI studies, including DWI and corresponding ADC imaging, sequential diagnosis of benign PSPF meningioma (WHO grade I) by MRI findings, and pathological confirmation. Only patients with postoperative MRI follow-up studies for >1 year (at least every 6e12 months) were included, in accordance with previous studies.3,23,24 From October 2006 to December 2015, 409 patients had a diagnosis of pathologically confirmed meningioma. Of these 409 patients, 107 had a diagnosis of PSPF meningioma by MRI and were selected for further evaluation. Eleven patients with a diagnosis of high-grade (WHO grade II or III) meningioma pathologically were excluded. In addition, 8 patients were excluded because of incomplete preoperative MRI studies or poor imaging quality of the DWI/ADC due to severe susceptibility artifacts resulting from skull bone or intratumoral calcification. Another 25 patients were excluded owing to a postoperative MRI follow-up duration of <1 year. Also, 14 patients who had received postoperative adjuvant RT before the development of P/R were excluded. Finally, 1 patient with a diagnosis of neurofibromatosis type 2 was also excluded. Thus, 48 patients (16 men and 32 women; age 26e84 years; median age, 56 years) with a diagnosis of PSPF meningiomas (WHO grade I) were included in the present
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study. None had undergone previous cranial RT. The median follow-up time was 42.5 months (range, 12e118). In 12 patients with P/R, the median interval to P/R was 23 months (range, 7e92). Clinical Data The clinical data of the study subjects were obtained from the clinical records. The degree of SSS invasion and Simpson grade of surgical resection were determined by a review of the surgical operative notes and preoperative and postoperative MRI findings. For equivocal cases, judgment was made in consensus by the neuroradiologist (C.C.K.) and neurosurgeon (S.W.L.). Using the classification of Sindou et al.,25 the degree of SSS invasion was grouped into 6 types: type 1, meningioma attached to the lateral wall of the sinus; type 2, invasion of 1 lateral recess; type 3, invasion of 1 lateral wall; type 4, invasion of 1 lateral wall and roof; and types 5 and 6, total sinus occlusion, with the contralateral wall free of tumor in type 5. The tumors were also divided into anterior, middle, and posterior types according to their origin in the falx. The anterior third extends from the floor of the frontal fossa to the coronal suture, the middle third from the coronal suture to the lambdoid suture, and the posterior third from the lambdoid suture to the torcula.26 Simpson grade IeIII resections were considered gross total resection (GTR), and Simpson grade IV and V resections were considered subtotal resection (STR).27 Imaging Acquisition The MRI scans were acquired using a 1.5T MRI scanner (MAGNETOM Avanto [Siemens, Munich, Germany]) for 22, 1.5T MRI scanner (Signa HDxt [GE Healthcare, Chicago, Illinois, USA]) for 19, or 3T MRI scanner (Discovery MR750 [GE Healthcare]) for 7. All were equipped with 8-channel head coils. The MRI protocols were as follows: axial and sagittal spin echo T1-weighted imaging (T1WI), axial and coronal fast spin-echo T2-weighted imaging (T2WI), axial fluid-attenuated inversion recovery (FLAIR), and axial T2*-weighted gradient-recalled echo (GRE). DWI was performed by sequential application in the x, y, and z directions, and ADC maps (b ¼ 1000 seconds/mm2) were obtained from these imaging data. Analysis of the diffusion changes was performed by “in-line” calculation of the ADC values using the Stejskal and Tanner equation.28 Contrast-enhanced (CE) images obtained on axial and coronal T1WI were performed after intravenous administration of 0.1 mmol/kg of body weight of gadobutrol or gadoterate meglumine. Details of the imaging parameters for the MRI scanners have been provided in Supplemental Appendix 1. Image Analysis and Interpretation The preoperative MRI features were evaluated by 2 neuroradiologists (C.C.K., with 5 years’ experience; and T.Y.C., with 17 years’ experience). Both were kept unware of the clinical and radiologic outcomes of the studied patients. P/R was defined as tumor recurrence after GTR (Simpson grade IeIII resection) or enlargement of residual tumor after STR (Simpson grade IV and V resection) on CE-T1WI. For the patients who had undergone STR, the threshold for P/R was defined as a 10% increase in the tumor volume compared with the postoperative brain MRI studies. The tumor volume measurements were the sum of the tumor area multiplied by the slice thickness on axial CE-T1WI using the
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Table 1. Continued
Table 1. Clinical Data and Magnetic Resonance Imaging Features Stratified by Progression/Recurrence
P/R
P/R Characteristic
Yes
No
Patients (n)
12
36
8 (66.7)
8 (22.2)
Sex
P Value
0.01*
Male Female
4 (33.3)
28 (77.8)
Age (years)
56 (49e64.3)
56 (49.3e65.8)
Parasagittal or parafalcine 7 (58.3)
27 (75)
Parafalcine
5 (41.7)
9 (25)
Histological subtype 8 (66.7)
24 (66.7)
Transitional (mixed)
1 (8.3)
8 (22.2%)
Fibroblastic (fibrous)
2 (16.7)
2 (5.6%)
Angiomatous
1 (8.3)
2 (5.6%)
Degree of SSS invasion (Sindou classification)
0.19
None
15 (41.7)
3 (25)
Type 1e3
15 (41.7)
4 (33.3)
Type 4e6
6 (16.7)
5 (41.7)
Location
0.48
Anterior third
8 (22.2)
4 (33.3)
Middle third
25 (69.4)
8 (66.7)
3 (8.3)
0 (0)
Posterior third Simpson grade resection Grade IeIII (GTR)
0.03* 7 (58.3)
32 (88.9)
Grade IVeV (STR)
5 (41.7)
4 (11.1)
Maximum diameter (cm)
5.9 (4.1e7.3)
4 (2.9e5.4)
3
Tumor volume (cm ) Peritumoral edema
54.8 (13.7e139.9) 21.8 (10.2e41.7)
0.009* 0.07
8 (66.7)
21 (58.3)
0.74
Edema size (cm)
3.9 (1.9e4.3)
2.9 (1.4e5.4)
0.65
Heterogeneous enhancement
6 (50)
12 (33.3)
0.33
Irregular margin
2 (16.7)
0 (0)
0.06
Calcification
2 (16.7)
12 (33.3)
0.47
Necrosis
1 (8.3)
4 (11.1)
1
Hemorrhage
0 (0)
2 (5.6)
1
Cystic change
2 (16.7)
4 (11.1)
0.63
Adjacent bone invasion
4 (33.3)
3 (8.3)
0.06
0 (0)
4 (11.1)
0.56
Reactive hyperostosis
Continues
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No
P Value
Dural tail sign
4 (33.3)
12 (33.3)
1.00
Multiplicity
2 (16.7)
1 (2.8)
0.15
1 (8.33)
2 (5.6)
0 (0)
15 (41.7)
11 (91.7)
19 (52.8)
DWI
0.03*
Isointensity 0.89
0.5
Meningothelial (syncytial)
Yes
Hypointensity
0.29
Parasagittal
Characteristic
Hyperintensity ADC (10e3 mm2/second)
0.76 (0.67e0.81) 0.88 (0.79e0.96)
0.001*
ADC ratio
0.95 (0.88e1.04) 1.17 (1.04e1.24)
0.001*
Data presented as n (%) or median (interquartile range) for continuous variables. P/R, progression/recurrence; SSS, superior sagittal sinus; GTR, gross total resection; STR, subtotal resection; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient. *Statistically significant (P < 0.05).
freehand region of interest (ROI) tool on the Picture Archiving and Communication System (INFINITT PACS [INFINITT Healthcare, Seoul, Republic of Korea]) workstations. The degree of SSS invasion (Sindou classification) was determined from the coronal T2WI and CE-T1WI scans.25 The anterior, middle, and posterior third locations of the tumors were determined from the sagittal CE-T1WI scans. The size of peritumoral edema was determined by the maximum diameter between the tumor border and edematous edge on axial T2WI and FLAIR scans. Smooth or irregular tumor margins were determined from the T2WI and CE-T1WI studies. Adjacent bone invasion was determined from the coronal and sagittal CE-T1WI scans. Intratumoral calcifications were identified as the presence of susceptibility artifacts on T2*weighted GRE and hypointensity on T1WI and T2WI studies. Intratumoral calcification, adjacent bone invasion, and reactive hyperostosis were also confirmed on preoperative brain computed tomography scans, which were performed routinely for navigation (stereotactic surgery) in our hospital. DWI Signals and Quantitative ADC Value For the DWI signals, each lesion was evaluated as predominantly hyperintense, isointense, or hypointense relative to the contralateral normal-appearing cerebral white matter (NAWM). For ADC measurement, the ROI was placed to avoid volume averaging with the inclusion of calcified foci, necrosis, and cystic regions that might influence the ADC values in PSPF meningiomas. A circular ROI with area from 38 to 84 mm2 (mean, 72.4 4.6) was placed within the tumor area to obtaining the measurements for all patients. For normalization of individual variance, an equal ROI was placed in the contralateral NAWM for each patient. Next, the ADC ratio was calculated by dividing the ADC value of the tumor by the ADC value of the contralateral NAWM in the same patient in accordance with the recommendations documented in previously reported studies.24,29,30
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PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
Figure 1. Imaging studies of a 58-year-old man with pathologically proven right parietal parasagittal and parafalcine meningioma (World Health Organization grade I). (A) Axial contrast-enhanced T1-weighted magnetic resonance image showing an enhancing tumor (arrow) arising from the right parietal falx and superior sagittal sinus, with poorly enhancing central necrotic components in the tumor observed. (B) Diffusion-weighted image showing hyperintensity in the solid part of the tumor (arrow). (C) Measured apparent diffusion coefficient value (circular region of interest) and
Statistical Analysis Statistical analyses were performed using the statistical package SPSS for Windows, version 24.0 (IBM Corp., Armonk, New York, USA). The c2 test or Fisher exact test and the Mann-Whitney U test were used to evaluate the categorical and continuous data, respectively. Receiver operating characteristic analysis of the ADC value and ratio was performed to discriminate between patients with and without P/ R. Kaplan-Meier analysis was used to assess the progression-free survival. The log-rank test was used to assess the significance in the recurrence rates. Univariate and multivariate Cox proportional hazard regression analyses were performed to determine the hazard ratio of each parameter. P < 0.05 was considered statistically significant. The interobserver reliabilities in the categorical and continuous data were determined using the Cohen k coefficient and intraclass correlation
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apparent diffusion coefficient ratio were 0.62 10e3 mm2/second and 0. 75, respectively. (D) Gross total resection was performed, and World Health Organization grade I meningioma was confirmed pathologically. (E) Recurrent tumor (arrowheads) was observed 12 months after surgical resection. (F) The proliferation rate determined from the immunohistochemical Ki-67 labeling index was 8%. Only the dark brown stained nuclei were considered immunopositive (original magnification 400).
coefficient (ICC), respectively. The Cohen k coefficient and ICC were interpreted using the methods described by Landis and Koch.31 Cohen k coefficient values of 0.8e0.96 were obtained for categorical MRI, indicating almost perfect reproducibility. An ICC of 0.79e0.94 were obtained for the continuous data. Owing to the substantial to almost perfect reproducibility in the ICC, the subsequent statistical evaluation of continuous data was performed using the mean value calculated from both raters. RESULTS Clinical Data and MRI Findings The clinical data and MRI features of the PSPF meningiomas with and without P/R are summarized in Table 1. Of the 48
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PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
Figure 2. Box plot of (A) apparent diffusion coefficient (ADC) values and (B) ADC ratios in parasagittal and parafalcine meningiomas with and without progression/recurrence (P/R). Lower (A) ADC values and (B) ADC ratios in the P/R group (median ADC value, 0.76 10e3 mm2/second; median ADC ratio, 0.95) compared with the non-P/R group (median ADC value,
patients, 12 (25%) had developed P/R. Male sex, STR, and a larger maximum diameter were more frequent in the P/R group than in those without P/R (P < 0.05). Most of the 12 PSPF meningiomas with P/R (n ¼ 11; 91.7%) exhibited hyperintense DWI signals compared with the contralateral NAWM (P ¼ 0.03; Figure 1). The median ADC values and ADC ratios were lower in the P/R group than in those without P/R (P ¼ 0.001; Figure 2). Receiver Operating Characteristic Curve Analysis of ADC The sensitivity, specificity, area under curve (AUC), and optimal cutoff points for the ADC values and ratios for differentiation between the P/R and non-P/R groups are summarized in Table 2. The cutoff points for the ADC value and ADC ratio were 0.83 10e3 mm2/second and 0.99, respectively. An AUC of 0.82 and 0.83 were obtained for the ADC value and ADC ratio, respectively. Recurrence Rate and Cox Proportional Hazards Regression Analysis The median follow-up duration for all patients was 42.5 months. In the 12 patients with P/R, the median time to P/R was 23
0.88 10e3 mm2/second; median ADC ratio, 1.17; P ¼ 0.001, Mann-Whitney U test) were observed. Boxes indicate the interquartile range, and whiskers indicate the range. The horizontal line represents the median in each box. Circles represent outliers, defined as distances >1.5 times the interquartile range less than the first quartile or greater than the third quartile.
months. When comparing the tumor progression trends, patients with lower ADC values (less than cutoff value of 0.83 10e3 mm2/ second) and lower ADC ratios (less than cutoff value of 0.99) exhibited shorter progression-free survival (P < 0.05; Figure 3). The results of the Cox proportional hazards analyses are summarized in Table 3. On univariate analysis, a statistically significance difference (P < 0.05) was found in sex, STR, maximum diameter, tumor size, and low ADC values (less than cutoff value of 0.83 10e3 mm2/second) between these 2 groups. Furthermore, male sex and low ADC values predicted for a high risk of P/R (P < 0.05) on multivariate analysis with a hazard ratio of 12.37 and 30.2, respectively. DISCUSSION The purpose of the present study was to analyze the preoperative clinical and MRI features for the prediction of P/R in benign PSPF meningiomas. Our results have shown that male sex, STR, large maximum diameter, high DWI signal, and lower ADC values and ratios are significantly more likely to be associated with P/R. Although the risk factors for the recurrence of PSPF meningiomas have been previously reported,15,32,33 to the best of our knowledge,
Table 2. Results of Receiver Operating Characteristic Analysis of Apparent Diffusion Coefficient Value and Ratio for Differentiating Parasagittal and Parafalcine Meningiomas Stratified by Progression/Recurrence Variable
Sensitivity
Specificity
AUC
Cutoff Value
P Value
ADC (10e3 mm2/second)
0.67
0.92
0.82
0.83
0.001*
ADC ratio
0.89
0.75
0.83
0.99
0.001*
AUC, area under the curve; ADC, apparent diffusion coefficient. *Statistically significant (P < 0.05).
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PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
Figure 3. Kaplan-Meier curves showing overall trends of progression-free survival using cutoff points of (A)
the present results are the first to offer quantitative cutoff points for ADC for the prediction of P/R in PSPF meningiomas. Although w90% meningiomas will be classified as WHO grade I benign tumors, 21% of these tumors will recur within 5 years.4,5 DWI has been widely used as a imaging biomarker to evaluate
apparent diffusion coefficient (ADC) value and (B) ADC ratio.
various intracranial tumors and predict their grade of differentiation.34,35 DWI provides biomedical information related to the tissues of interest using measurement of thermally induced diffusion of water molecules (Brownian motion) shown by ADC.36,37 Therefore, unusual ADC values could be an early
Table 3. Results of Cox Proportional Hazards Analysis of Progression/Recurrence Univariate Analysis Variable
Multivariate Analysis
HR (95% CI) for P/R
P Value
HR (95% CI) for P/R
P Value
Sex (fraction male)
6.58 (1.95e22.16)
0.002*
12.37 (2e76.4)
0.007*
Age (years)
0.99 (0.95e1.04)
0.81
NS
NA
SSS invasion (Sindou type 4e6)
2.17 (0.68e6.89)
0.19
NS
NA
Location (middle or posterior third)
1.11 (0.32e3.86)
0.87
NS
NA
STR
4.58 (1.44e14.57)
0.01*
0.86 (0.19e3.87)
0.85
1.5 (1.12e2)
0.007*
1.78 (0.57e5.54)
0.32
Maximum diameter (cm) 3
Tumor volume (cm )
1.01 (1e1.02)
0.02*
0.98 (0.94e1.02)
0.37
Peritumoral edema
1.39 (0.42e4.66)
0.59
NS
NA
Heterogeneous enhancement
1.66 (0.53e5.14)
0.38
NS
NA
Calcification
0.49 (0.11e2.24)
0.36
NS
NA
Necrosis
0.48 (0.06e3.79)
0.48
NS
NA
Cystic change
1.06 (0.23e4.88)
0.94
NS
NA
Adjacent bone invasion
3.1 (0.9e10.62)
0.07
NS
NA
Dural tail sign
1.96 (0.53e7.28)
0.32
NS
NA
Multiplicity
2.16 (0.46e10.19)
0.33
NS
NA
DWI (hyperintensity)
5.86 (0.75e45.89)
0.09
NS
NA
15.27 (1.97e118.59)
0.009*
30.2 (2.4e380.69)
0.008*
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ADC <0.83 10
2
mm /second (cutoff value)
HR, hazard ratio; CI, confidence interval; P/R, progression/recurrence; NS, not significant; NA, not applicable; SSS, superior sagittal sinus; STR, subtotal resection; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient. *Statistically significant (P < 0.05).
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ORIGINAL ARTICLE CHING-CHUNG KO ET AL.
harbinger of a biologic abnormality.34 Several studies have reported that high DWI signals and lower ADC values (more restricted diffusion) are related to atypical or malignant meningiomas.16-22 However, the correlation between ADC values and recurrence in benign meningiomas has rarely been studied. According to the 2016 WHO guidelines, benign meningiomas will be characterized by a count of <4 mitotic cells/10 high power fields and <3 of the atypical features. These atypia features include increased cellularity, small cells (high nuclear/cytoplasmic ratio), spontaneous necrosis, sheeting, and prominent nucleoli.2 Hwang et al.23 was the first to report that lower ADC values were found in benign meningiomas with 1e2 histopathologic atypia features compared with those without atypia. Thus, lower ADC values could represent more histopathologic features of atypia in benign meningiomas even if they are all classified as WHO grade I. In addition, Hwang et al.23 reported that the ADC value and extent of surgical resection can predict for P/R of meningioma better than using the WHO histopathologic grade.23 Furthermore, that low ADC values will predict for a high rate of recurrence in skull base meningiomas was first reported in our previous study.24 However, it is known that the genetic mechanisms between PSPF meningiomas and skull base meningiomas are different.38-40 Therefore, specific ADC data for the prediction of P/R in PSPF meningiomas are essential because of the difficulty in achieving GTR and the high rate of P/R in this anatomic location.6,7 Although we were unable to correlate the ADC values with Ki-67 because of the lack of complete Ki-67 data in the present retrospective study, some investigators have reported that the ADC values correlated inversely with the Ki-67 proliferation index in meningiomas and are helpful in differentiating low-grade and aggressive meningiomas.17,22,41 Baskan et al.41 reported an ADC value of 0.81 10e3 mm2/second and Ki-67 of 2.19% in low-grade meningiomas compared with an ADC of 0.66 10e3 mm2/second and Ki-67 of 11.2% in high-grade meningiomas. Surov et al.22 reported a threshold ADC value of 0. 85 10e3 mm2/second for detecting meningiomas with a high proliferation potential (Ki-67 5%). Therefore, ADC values that lead to a high rate of P/R in PSPF meningiomas could be explained by a high Ki-67 proliferation index. It is known that some differences could exist in the DWI and ADC between 1.5T and 3T MRI scanners. However, the association between a low ADC and a high rate of P/R was similar for both 1.5T (n ¼ 41) and 3T (n ¼ 7) MRI scanners in our study. With the 1.5T MRI scanner, the median ADC value was 0.77 10e3 mm2/ second and the ADC ratio was 0.96 for patients with P/R (n ¼ 11). Similarly, a lower ADC value (0.65 10e3 mm2/second) and lower ADC ratio (0.9) were observed for the patient with recurrence who had undergone MRI with the 3T MRI scanner. Although the extent of tumor resection is an important key factor in determining the rate of recurrence in PSPF meningiomas,26,42,43 the surgical outcome of PSPF meningiomas has remained poor.8,9 The postoperative complications have included deterioration of motor function and/or consciousness level and death from intracranial hematoma, brain edema, venous thrombosis or infarction, and air embolism.8,9 It is known that adjuvant
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RT will improve local tumor control and disease-free survival in those with high-grade meningiomas.44 However, the role of postoperative adjuvant RT for benign PSPF meningiomas is still unclear, resulting in inconsistent practice in each institution.45 Whether adjuvant RT will be beneficial for patients without evidence of tumor growth is controversial, because it could increase the risk of complications such as symptomatic peritumoral edema, venous occlusion, cranial nerve deficits, internal carotid artery stenosis, and neurologic deficits.13,46-49 Furthermore, the incidence of post-RT complications has been greater with PSPF meningiomas than with other tumors.13,14 The preoperative prediction of P/R would, thus, offer vital information for determining the extent of surgical resection and the necessity for adjuvant RT. For benign PSPF meningiomas with high-risk factors for P/R, aggressive tumor resection during primary surgery, combined with postoperative adjuvant RT and close imaging follow-up, should be considered. In contrast, for patients with a lower possibility of P/R, the aim of surgery might be the relief of the mass effect and clinical symptoms to avoid postoperative neurological deficits. Adjuvant RT should be used more conservatively because all radiotherapeutic procedures have long-term side effects and might affect future treatment.46-49 Therefore, our results have provided added valuable information for the planning of treatment of benign PSPF meningiomas. In contrast, patients with postoperative adjuvant RT before P/R were excluded from our study because adjuvant RT could have affected the independent predictive value of ADC for P/R. Recently, application of ADC to differentiate low-grade (WHO grade I) and high-grade (WHO grade II/III) PSPF meningiomas has been reported.19-21 Compared with the reported data, we offer the new concept that preoperative ADC could also be used to evaluate the clinical outcomes for WHO grade I PSPF meningiomas. This concept is clinically significant and useful regarding the treatment choices, because most PSPF meningiomas will be classified as WHO grade I. However, the present study still had limitations. The retrospective nature of the present study could have resulted in bias. Just as in other ROI-based studies, the subjective placement of the ROIs could have influenced the accuracy of the ADC measurements. Furthermore, the ADC values could have differed among the different MRI systems, although similar parameters were used with each scanner. The relatively small sample size and short follow-up time could have limited our statistical power to detect potential associations between some of the imaging features and P/R. Finally, our retrospective study lacked complete histopathologic findings, including Ki-67, for correlation with the ADC values. CONCLUSIONS Our results showed that PSPF meningiomas in male patients, STR, a large maximum diameter, a high DWI signal, and lower ADC values and/or ADC ratios were all associated with P/R. The preoperative ADC values and ratios for the prediction of P/R offer clinically vital information for the planning of PSPF meningioma treatment, including the extent of tumor resection, implementation of postoperative adjuvant RT, and the imaging follow-up strategy.
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REFERENCES 1. Wiemels J, Wrensch M, Claus EB. Epidemiology and etiology of meningioma. J Neurooncol. 2010;99: 307-314.
PREDICTING RECURRENCE OF PSPF MENINGIOMAS BY ADC
15. Escribano Mesa JA, Alonso Morillejo E, Parron Carreno T, et al. Risk of recurrence in operated parasagittal meningiomas: a logistic binary regression model. World Neurosurg. 2018;110: e112-e118.
2. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131:803-820.
16. Nagar VA, Ye JR, Ng WH, et al. Diffusionweighted MR imaging: diagnosing atypical or malignant meningiomas and detecting tumor dedifferentiation. AJNR Am J Neuroradiol. 2008;29: 1147-1152.
3. Ildan F, Erman T, Gocer AI, et al. Predicting the probability of meningioma recurrence in the preoperative and early postoperative period: a multivariate analysis in the midterm follow-up. Skull Base. 2007;17:157-171.
17. Tang Y, Dundamadappa SK, Thangasamy S, et al. Correlation of apparent diffusion coefficient with Ki-67 proliferation index in grading meningioma. AJR Am J Roentgenol. 2014;202:1303-1308.
4. Maillo A, Orfao A, Espinosa AB, et al. Early recurrences in histologically benign/grade I meningiomas are associated with large tumors and coexistence of monosomy 14 and del(1p36) in the ancestral tumor cell clone. Neuro Oncol. 2007;9: 438-446. 5. Perry A, Stafford SL, Scheithauer BW, Suman VJ, Lohse CM. Meningioma grading: an analysis of histologic parameters. Am J Surg Pathol. 1997;21: 1455-1465. 6. Melamed S, Sahar A, Beller A. The recurrence of intracranial meningiomas. Neurochirurgia. 1979;22: 47-51. 7. Huo WY, Li L, Zhang YF. Resection of recurrent parasagittal meningiomas with complete obstructed superior sagittal sinus. Int Congr Ser. 2004;1259:53-57. 8. Oyama H, Kito A, Maki H, Hattori K, Noda T, Wada K. Surgical results of parasagittal and falx meningioma. Nagoya J Med Sci. 2012;74:211-216. 9. Raza SM, Gallia GL, Brem H, Weingart JD, Long DM, Olivi A. Perioperative and long-term outcomes from the management of parasagittal meningiomas invading the superior sagittal sinus. Neurosurgery. 2010;67:885-893. 10. Skudas G, Tamasauskas A. [Prognosis of the surgical treatment of parasagittal meningioma]. Medicina (Kaunas). 2002;38:1089-1096. 11. Crutchfield JS, Sawaya R, Meyers CA, Moore BD III. Postoperative mutism in neurosurgery: report of two cases. J Neurosurg. 1994;81: 115-121. 12. Tahta K, Cirak B, Pakdemirli E, Suzer T, Tahta F. Postoperative mutism after removal of an anterior falcine meningioma. J Clin Neurosci. 2007;14: 793-796. 13. Conti A, Pontoriero A, Siddi F, et al. Post-treatment edema after meningioma radiosurgery is a predictable complication. Cureus. 2016;8:e605. 14. Kalapurakal JA, Silverman CL, Akhtar N, et al. Intracranial meningiomas: factors that influence the development of cerebral edema after stereotactic radiosurgery and radiation therapy. Radiology. 1997;204:461-465.
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www.SCIENCEDIRECT.com
18. Lin L, Bhawana R, Xue Y, et al. Comparative analysis of diffusional kurtosis imaging, diffusion tensor imaging, and diffusion-weighted imaging in grading and assessing cellular proliferation of meningiomas. AJNR Am J Neuroradiol. 2018;39: 1032-1038. 19. Aslan K, Gunbey HP, Tomak L, Incesu L. The diagnostic value of using combined MR diffusion tensor imaging parameters to differentiate between low- and high-grade meningioma. Br J Radiol. 2018;91:20180088. 20. Gihr GA, Horvath-Rizea D, Garnov N, et al. Diffusion profiling via a histogram approach distinguishes low-grade from high-grade meningiomas, can reflect the respective proliferative potential and progesterone receptor status. Mol Imaging Biol. 2018;20:632-640. 21. Surov A, Gottschling S, Mawrin C, et al. Diffusionweighted imaging in meningioma: prediction of tumor grade and association with histopathological parameters. Transl Oncol. 2015;8:517-523. 22. Surov A, Ginat DT, Sanverdi E, et al. Use of diffusion weighted imaging in differentiating between maligant and benign meningiomas: a multicenter analysis. World Neurosurg. 2016;88: 598-602. 23. Hwang WL, Marciscano AE, Niemierko A, et al. Imaging and extent of surgical resection predict risk of meningioma recurrence better than WHO histopathological grade. Neuro Oncol. 2016;18: 863-872. 24. Ko CC, Lim SW, Chen TY, Chen JH, Li CF, Shiue YL. Prediction of progression in skull base meningiomas: additional benefits of apparent diffusion coefficient value. J Neurooncol. 2018;138: 63-71. 25. Sindou MP, Auque J, Jouanneau E. Neurosurgery and the intracranial venous system. Acta Neurochir Suppl. 2005;94:167-175. 26. Chung S-B, Kim C-Y, Park C-K, Kim DG, Jung HW. Falx meningiomas: surgical results and lessons learned from 68 cases. J Korean Neurosurg Soc. 2007;42:276-280. 27. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry. 1957;20:22-39.
28. Stejskal EO, Tanner JE. Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient. J Chem Phys. 1965; 42:288-292. 29. Server A, Kulle B, Maehlen J, et al. Quantitative apparent diffusion coefficients in the characterization of brain tumors and associated peritumoral edema. Acta Radiol. 2009;50:682-689. 30. Toh CH, Castillo M, Wong AM, et al. Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging. AJNR Am J Neuroradiol. 2008;29:471-475. 31. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159-174. 32. Colli BO, Carlotti CG Jr, Assirati JA Jr, Dos Santos MB, Neder L, Dos Santos AC. Parasagittal meningiomas: follow-up review. Surg Neurol. 2006; 66(suppl 3):S20-S27 [discussion: S27-S28]. 33. Nowak A, Marchel A. Surgical treatment of parasagittal and falx meningiomas. Neurol Neurochir Pol. 2007;41:306-314. 34. Padhani AR, Liu G, Mu-Koh D, et al. Diffusionweighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia. 2009;11:102-125. 35. Higano S, Yun X, Kumabe T, et al. Malignant astrocytic tumors: clinical importance of apparent diffusion coefficient in prediction of grade and prognosis. Radiology. 2006;241:839-846. 36. Le Bihan D, Poupon C, Amadon A, Lethimonnier F. Artifacts and pitfalls in diffusion MRI. J Magn Reson Imaging. 2006;24:478-488. 37. Gass A, Niendorf T, Hirsch JG. Acute and chronic changes of the apparent diffusion coefficient in neurological disorders—biophysical mechanisms and possible underlying histopathology. J Neurol Sci. 2001;186(suppl 1):S15-S23. 38. Clark VE, Erson-Omay EZ, Serin A, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science. 2013;339:1077-1080. 39. McGovern SL, Aldape KD, Munsell MF, Mahajan A, DeMonte F, Woo SY. A comparison of World Health Organization tumor grades at recurrence in patients with non-skull base and skull base meningiomas. J Neurosurg. 2010;112: 925-933. 40. Sade B, Chahlavi A, Krishnaney A, Nagel S, Choi E, Lee JH. World Health Organization grades II and III meningiomas are rare in the cranial base and spine. Neurosurgery. 2007;61:1194-1198 [discussion: 1198]. 41. Baskan O, Silav G, Bolukbasi FH, Canoz O, Geyik S, Elmaci I. Relation of apparent diffusion coefficient with Ki-67 proliferation index in meningiomas. Br J Radiol. 2016;89:20140842.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.117
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42. Mansouri A, Klironomos G, Taslimi S, et al. Surgically resected skull base meningiomas demonstrate a divergent postoperative recurrence pattern compared with non-skull base meningiomas. J Neurosurg. 2016;125:431-440. 43. Nanda A, Bir SC, Maiti TK, Konar SK, Missios S, Guthikonda B. Relevance of Simpson grading system and recurrence-free survival after surgery for World Health Organization grade I meningioma. J Neurosurg. 2017;126:201-211. 44. Kaur G, Sayegh ET, Larson A, et al. Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review. Neuro Oncol. 2014;16: 628-636. 45. Maclean J, Fersht N, Short S. Controversies in radiotherapy for meningioma. Clin Oncol (R Coll Radiol). 2014;26:51-64.
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46. Girvigian MR, Chen JC, Rahimian J, Miller MJ, Tome M. Comparison of early complications for patients with convexity and parasagittal meningiomas treated with either stereotactic radiosurgery or fractionated stereotactic radiotherapy. Neurosurgery. 2008;62:A19-A27 [discussion: A27-A28]. 47. Conti A, Pontoriero A, Salamone I, et al. Protecting venous structures during radiosurgery for parasagittal meningiomas. Neurosurg Focus. 2009;27:E11. 48. Stafford SL, Pollock BE, Foote RL, et al. Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients. Neurosurgery. 2001;49:1029-1037 [discussion: 1037-1038].
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49. Mathiesen T, Kihlstrom L, Karlsson B, Lindquist C. Potential complications following radiotherapy for meningiomas. Surg Neurol. 2003; 60:193-198 [discussion: 199-200]. Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 19 September 2018; accepted 13 December 2018 Citation: World Neurosurg. (2019). https://doi.org/10.1016/j.wneu.2018.12.117 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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SUPPLEMENTAL APPENDIX 1
MAGNETIC RESONANCE IMAGING PROTOCOLS
The protocols of 1.5T (Siemens, MAGNETOM Avanto) magnetic resonance imaging (MRI) were as follows: axial spin-echo T1weighted imaging (T1WI) (repetition time/echo time [TR/TE], 2000 ms/7 ms; field of view [FOV], 16e22 cm; slice thickness/ spacing, 5 mm/6.5 mm; matrix, 320 228), fast spin-echo T2weighted imaging (T2WI) (TR/TE, 3730 ms/108 ms; FOV, 16e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 384 261), fluid-attenuated inversion recovery (FLAIR) (TR/TE, 9000 ms/92 ms; FOV, 16e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 209), and T2-weighted gradient-recalled echo (GRE) (TR/TE, 830 ms/26 ms; FOV, 16e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 168). Contrast-enhanced (CE) images were obtained using axial and coronal T1WI (TR/TE, 1950 ms/8 ms; FOV, 16e23 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 216) after intravenous administration of 0.1 mmol/ kg body weight of gadobutrol (Gadovist [Schering, Berlin, Germany]) or gadoterate meglumine (Dotarem [Guerbet, Villepinte, France]). Diffusion-weighted imaging (DWI) was performed by sequential application in the x, y, and z directions using the following parameters: TR/TE, 3800 ms/105 ms; flip angle, 90 ; slice thickness/spacing, 5 mm/6.5 mm; and b, 0, 500, and 1000 seconds/mm2. The apparent diffusion coefficient (ADC) maps were obtained from these imaging data. The protocols for 1.5T (Signa HDxt [GE Healthcare]) MRI were as follows: axial T1WI (TR/TE, 2000 ms/11 ms; FOV, 20e20 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 192), T2WI (TR/TE, 3600/108 ms; FOV, 20e20 cm; slice thickness/spacing, 5
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mm/6.5 mm; matrix, 320 224), FLAIR (TR/TE, 9002 ms/140 ms; FOV, 20e20 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 160), and T2-weighted GRE (TR/TE, 450/15 ms; FOV, 18e24 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 288 160). CE axial and coronal T1WI (TR/TE, 2131 ms/8 ms; FOV, 18e20 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 288 160) with intravenous administration of 0.1 mmol/kg of gadobutrol or gadoterate meglumine. DWI was performed by sequential application in the x, y, and z directions with the following parameters: TR/TE, 6600 ms/73 ms; flip angle, 90 , slice thickness/spacing, 5 mm/6.5 mm; b, 0 and 1000 seconds/mm2. The ADC maps were obtained from these imaging data. The protocols for 3T (Discovery MR750 [GE Healthcare]) MRI were as follows: axial T1WI (TR/TE, 3400 ms/24 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 352 224), T2WI (TR/TE, 5200 ms/102 ms; FOV, 22e22 cm; slice thickness/ spacing, 5 mm/6.5 mm; matrix, 384 320), FLAIR (TR/TE, 1000 ms/95 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 192), and T2-weighted GRE (TR/TE, 567 ms/20 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 256 192). CE axial and coronal T1WI (TR/TE, 1800 ms/ 22 ms; FOV, 22e22 cm; slice thickness/spacing, 5 mm/6.5 mm; matrix, 320 224) after intravenous administration of 0.1 mmol/ kg of gadobutrol or gadoterate meglumine. The DWI was performed by sequential application in the x, y, and z directions with the following parameters: TR/TE, 8000 ms/64 ms; flip angle, 90 , slice thickness/spacing, 5 mm/6.5 mm; and b, 0, 1000, and 1500 seconds/mm2. The ADC maps were obtained from these imaging data.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.12.117