Peritumoral Edema Relative to Meningioma Size Predicts Functional Outcomes after Resection in Older Patients

Peritumoral Edema Relative to Meningioma Size Predicts Functional Outcomes after Resection in... Abstract BACKGROUND Resection of meningiomas in older adults is associated with increased complications and postoperative functional deficits. Extent of peritumoral edema (PTE), which has been associated with surgical prognosis, may represent a preoperative risk marker for poorer outcomes in older adults. OBJECTIVE To quantitatively evaluate the relationship between preoperative PTE and postresection outcomes in older meningioma patients. METHODS One hundred twelve older meningioma patients (age ≥ 60) with evidence of PTE on MRI were reviewed. Extent of PTE, measured as a ratio of edema to tumor volume (edema index, EI) using semiautomatic image-processing software, was correlated with postresection outcomes. Other preoperative factors were included as covariates in multivariate analyses. Results were compared to matched nonedema older patients. Receiver operating characteristic (ROC) curve analysis was performed to identify cut-off EI values to predict postoperative outcomes. RESULTS EI was associated with functional decline (as measured by Karnofsky Performance Status, KPS) at 6 mo, 1, 2 yr, and most recent follow-up (Ps < .05), but not among the nonedema matched patients. Seizure or prior stroke additionally trended towards increasing the likelihood of lower KPS at 2 yr (odds ratio = 3.06) and last follow-up (odds ratio = 5.55), respectively. ROC curve analysis found optimal cut-off values for EI ranging from 2.01 to 3.37 to predict lower KPS at each follow-up interval. Sensitivities ranged from 60% to 80%, specificities from 78% to 89%, and positive and negative predictive values from 38% to 58% and 80% to 97%. CONCLUSION Preoperative PTE may represent a significant marker of poor functional outcome risk in older adults and provides a quantitative measurement to incorporate into surgical decision-making. Meningioma, Edema, Elderly, Aging, Outcomes ABBREVIATIONS ABBREVIATIONS ASA American Society of Anesthesiologists CI confidence interval CPF convexity, parasagittal, or falcine EI edema index KPS Karnofsky Performance Status FLAIR fluid-attenuated inversion recovery MRI magnetic resonance imaging NPV negative predictive value OR odds ratio PPV positive predictive value PTE peritumoral edema ROC receiver operating characteristic The incidence of meningioma increases with age such that older adults are 3 or 4 times more likely to be affected.1-3 Resection in older patients is associated with more complicated resections, longer hospital stays, and less improvement in independence level compared to younger adults.3-7 Thus, it is important to recognize preoperative markers to identify appropriate surgical candidates. Researchers have created graded scales (eg, Sex, Karnofsky Performance Scale, American Society of Anesthesiology Class, Location of Tumor, and Peritumoral Edema (SKALE), Geriatric Scoring System (GSS), Clinical-Radiological Grading System (CRGS)) to identify factors that best predict the prognosis and functional outcomes post resection in elderly adults.8-10 These scales have been associated with survival time, tumor recurrence, and functional outcome.2,11-15 An integral component of these scales focuses on the extent of peritumoral edema (PTE) present. PTE is known to be present in the majority (about 60%) of intracranial meningioma.16,17 PTE in meningioma patients, regardless of age, has been linked to a greater rate of complications, prolonged hospital stays, poorer long-term outcomes, and increased risk of tumor recurrence postoperatively in addition to impaired visualization of a safe resection plane intraoperatively.16,18-22 Extent of PTE was classified in most research, however, through subjective assessments of the preoperative imaging (eg, “severe,” “moderate/mild,” or “none”), but did not use an objective measure of the volume of edema, particularly relative to the tumor size. Other studies have made strides to correlate quantitative measure of PTE to clinical outcomes in meningioma patients using an edema index (EI) metric calculated as the ratio of PTE volume to tumor size. In these studies, increased preoperative EI was associated with irregular tumor margins, arterial supply, and high-grade classification.23-25 Yet, preoperative PTE and tumor volumes were calculated by an ellipsoid shape approximation of the tumor and surrounding edema (ie, V = 4/3π × a/2 × b/2 × c/2, where a, b, and c are maximum cross-sectional diameters), which still does not precisely portray the extent of PTE or tumor size as meningiomas often extend along the dural covering of venous sinuses and PTE rarely spreads only concentrically around the tumor.19,20,26,27 Thus, in the present study, semiautomatic segmentation was utilized to accurately obtain quantitative preoperative measurements of PTE and tumor volumes.19,28 Older patients (greater than 60 yr) who presented with an intracranial meningioma and known PTE on preoperative imaging, and subsequently underwent surgical resection, were retrospectively analyzed to evaluate the clinical outcomes of this at-risk group given the degree of PTE present. METHODS Patients The retrospective study was approved by the medical center's Institutional Review Board and written informed consent was waived. Medical records of 248 consecutive patients from 2002 to 2016 who were at least 60 yr of age at time of primary meningioma resection were reviewed. Of these, 123 patients had a known area of PTE on preoperative magnetic resonance imaging (MRI). Eleven patients were excluded due to unavailable preoperative imaging, nonintracranial location (eg, spinal), or insufficient data, resulting in a final sample of 112 older-aged patients. Demographic and preoperative data collected for each patient included body mass index (BMI), comorbidities, American Society of Anesthesiologists (ASA) score, presenting symptoms, preoperative radiation treatment, dexamethasone use, and functional status as measured by Karnofsky Performance Status (KPS) score.29 In addition to the PTE and tumor volume variables of interest, other tumor characteristics prior to resection included location (skull base or in convexity, parasagittal, or falcine [CPF] areas) and T2-weighted signal intensity. Distributions of the older-aged patients by preoperative characteristics and imaging features are depicted in Table 1. Table 1. Preoperative Patient Clinical Characteristics and Imaging Features Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  SRS = stereotactic radiosurgery; CPF = convexity, parasagittal, falcine; PVD = peripheral vascular disease; KPS = Karnofsky Performance Status; ASA = American Society of Anesthesiologists; IQR = interquartile range. Mann–Whitney U-tests or Pearson's r correlations were applied as appropriate on each characteristic for edema index, tumor volume, and edema volume. View Large Table 1. Preoperative Patient Clinical Characteristics and Imaging Features Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  SRS = stereotactic radiosurgery; CPF = convexity, parasagittal, falcine; PVD = peripheral vascular disease; KPS = Karnofsky Performance Status; ASA = American Society of Anesthesiologists; IQR = interquartile range. Mann–Whitney U-tests or Pearson's r correlations were applied as appropriate on each characteristic for edema index, tumor volume, and edema volume. View Large Imaging Analysis Patients received preoperative MRI scans typically within 30 d of resection (median time = 4 d, 103 [92.0%] within 30 d). Tumor and PTE volumes were measured using segmentation processing software (3D Slicer, Version 4.6, http://www.slicer.org)30 by consensus with an experienced neuroradiologist blinded to clinical outcomes or other patient data (intraclass correlation coefficient: 0.91, F = 11.03, P < .001). Tumor volumes were obtained from T1-weighted postcontrast MRI. PTE volumes were obtained from T2-weighted fluid attenuated inversion recovery (FLAIR) images, which included the area of the tumor. Each image slice was segmented for tumor and PTE volumes using the label map effect tools available in the processing software. Each slice was automatically multiplied by the slice thickness and aggregated to compute the total tumor or PTE volume. The preoperative EI for each patient was calculated offline by dividing PTE volume by tumor volume, such that an EI of 1 was defined as no surrounding edema present.24,29,31 Clinical Outcomes Intraoperative features included operative time, tumor consistency (soft or firm), Simpson grade of resection,32 and use of blood transfusions. Postoperative clinical outcomes included complications, length of hospital stay, long-term dexamethasone use, further radiation treatment, tumor recurrence, World Health Organization (WHO) tumor grade,33 1-yr survival, and change in KPS29 score at last known follow-up and at 6 mo, 1, 2, and 5 yr of follow-up when available. Comparison with Nonedema Controls Of the 125 remaining older patients without a known area of PTE on preoperative MRI, 84 with an intracranial meningioma presenting for primary resection only with sufficient preoperative imaging and data were matched against the 112 older patients with present PTE on gender, tumor location, ASA score, grade of resection, and WHO grade utilizing a propensity score matching technique34 and compared on significant clinical outcomes. Statistics Univariate analyses of each preoperative variable with the intra- and postoperative clinical outcomes were evaluated using Pearson's Chi-square, Fisher's exact test, or Mann–Whitney U-tests where appropriate. Preoperative and postoperative KPS scores were compared using Wilcoxon signed-rank tests. Clinical characteristics with a P-value ≤ .10 on univariate analysis were included as covariates in the multivariate regression for each outcome variable.3,35 Patients without sufficient data (eg, lost to follow-up) for an outcome variable were excluded from that specific analysis. Receiver operating characteristic (ROC) curve analysis was performed to identify cut-off EI values predictive of outcomes. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) are reported. P-value ≤ .05 was considered statistically significant (IBM SPSS, Version 22.0, Armonk, New York). RESULTS Patient Characteristics Preoperative patient characteristics and imaging features by relative distributions are shown in Table 1. The sample was mostly female (74.1%), ranged from 60 to 95 yr at resection (mean ± standard deviation = 71.3 ± 8.0 yr), and nearly a quarter (23.6%) were obese. Patient tumors were located largely in CPF areas (69.6%) and demonstrated mostly hyperintense signal (68.2%) on T2 sequences relative to surrounding tissue. Ten patients (8.9%) received prior radiosurgery to treat their meningioma. The most common presenting symptoms included headaches (32.1%), seizure (20.5%), and weakness (17.9%). Concurrent hypertension diagnosis was common in the majority of older patients (62.5%), followed by hyperlipidemia (36.6%) and diabetes mellitus (23.2%). A majority of patients had a preoperative KPS ≥ 80 (61.6%), signifying an ability to carry on normal activity or work, and had an ASA ≥ 3 (83.9%). Median tumor and edema volumes were 27.0 and 60.1 cm3 (interquartile range [IQR] = 10.7-59.1 cm3 and 25.7-90.9 cm3), resulting in a median EI of 1.65 (IQR = 1.34-2.56). None of the preoperative clinical or imaging features differed by EI. Skull base tumor volumes were significantly smaller than CPF tumors (P = .010) and patients presenting with weakness had greater tumor volumes than those without associated weakness (P = .033). Patients with an ASA ≤ 2 had significantly greater tumor and PTE volumes (P = .066 and .003). Patients with weakness, language dysfunction, or with prior dexamethasone use had significantly greater volumes of PTE (P = .030, .013, and .007, respectively). Representative segmentation of a skull base and a CPF tumor are depicted in Figure 1. EI was highly correlated with tumor volume (P < .001), but not edema volume, while tumor and edema volumes also correlated (P < .001). FIGURE 1. View largeDownload slide Representative preoperative MRI depicting the meningioma (T1-weighted postcontrast, left) and surrounding peritumoral edema (PTE, T2 FLAIR, right) of 2 patients with a convexity (top) and skull base (bottom) tumor. The tumor or PTE of each slice is automatically segmented (yellow outline) on imaging processing software and multiplied by the slice-thickness to obtain accurate tumor and PTE volumes. FIGURE 1. View largeDownload slide Representative preoperative MRI depicting the meningioma (T1-weighted postcontrast, left) and surrounding peritumoral edema (PTE, T2 FLAIR, right) of 2 patients with a convexity (top) and skull base (bottom) tumor. The tumor or PTE of each slice is automatically segmented (yellow outline) on imaging processing software and multiplied by the slice-thickness to obtain accurate tumor and PTE volumes. Clinical Outcomes Intra- and postoperative outcomes are detailed in Table 2. Intraoperatively, the majority of tumors were removed in total (81.3%), resected in < 4 h (55.7%), and noted to be either soft (52.6%) or firm (47.4%). Thirty patients (30.9%) required an intraoperative blood transfusion. Most tumors were WHO grade I (75.0%), followed by 23.2% and 1.8% of WHO grade II and III, respectively. The majority stayed in the hospital < 5 d (68.8%) and discharged to a rehabilitation facility (60.4%). The most common complication was an intracranial hematoma (10.7%). Postoperatively, 18.0% received further radiation treatment, 6.0% were placed on long-term steroids, and 10.4% had a tumor recurrence. Functionally, a substantial portion of patients had a decrease in KPS score at interval periods of follow-up (8.9%-33.3%). Patients were found to have significantly decreased KPS scores at 1 yr (P < .001), 5 yr (P = .049), and at last known follow-up (P < .001) compared to preoperative KPS scores (see Table 2). Table 2. Intraoperative and Postoperative Clinical Outcomes of Older Patients (Age ≥ 60 yr) During and After Meningioma Resection Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  SRS = stereotactic radiosurgery; KPS = Karnofsky Performance Status; DVT/PE = deep vein thrombosis/pulmonary embolism; UTI = urinary tract infection; CSF = cerebrospinal fluid. *P < .05 vs preoperative KPS scores on Wilcoxon signed-rank test. View Large Table 2. Intraoperative and Postoperative Clinical Outcomes of Older Patients (Age ≥ 60 yr) During and After Meningioma Resection Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  SRS = stereotactic radiosurgery; KPS = Karnofsky Performance Status; DVT/PE = deep vein thrombosis/pulmonary embolism; UTI = urinary tract infection; CSF = cerebrospinal fluid. *P < .05 vs preoperative KPS scores on Wilcoxon signed-rank test. View Large Clinical Outcomes Associated With EI On univariate analysis, preoperative EI were not associated with any intraoperative measure (Ps > .10). In addition, EI was not associated with most postoperative clinical outcomes including complications, discharge destination, length of hospital stay, long-term steroid use, subsequent radiosurgery, tumor recurrence, WHO tumor grade, or 1-yr survival rate (Ps > .10). EI was associated with a decrease in KPS score at 6 mo (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.12-2.16, P = .009), 1 yr (OR = 1.32, 95% CI = 0.98-1.78, P = .066), 2 yr (OR = 1.75, 95% CI = 1.05-2.94, P = .033), and at last known follow up (OR = 1.86, 95% CI = 1.29-2.70, P = .001, see Table 3), but the difference at 5 yr postresection did not reach significance (P = .152). On multivariate regression analyses at each follow-up interval as shown in Table 3, which included all preoperative measures that had an association of P ≤ .1, EI remained or increased in significance level, except at 5 yr of follow-up (P = .152). In addition to EI, a trend was found such that presenting with a seizure increased the likelihood of a lower KPS score at 1 yr of follow-up (OR = 3.06, 95% CI = 0.92-10.16, P = .068) and a past history of stroke trended towards an increased risk of having a decreased KPS score at last follow-up (OR = 5.55, 95% CI = 0.84-36.17, P = .073). Table 3. Multivariate Regression Analyses of Preoperative Factors on Functional Outcomes as Measured by Karnofsky Performance Scale (KPS) Score Postresection at Last Follow-up, 6 mo, 1, 2, and 5 yr   Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                        Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                      KPS = Karnofsky Performance Scale; OR = odds ratio; SRS = stereotactic radiosurgery; PVD = peripheral vascular disease; American Society of Anesthesiologists *Odds ratio is incalculable due to 0 patients in any group. Preoperative factors that had at least a trend-level correlation with KPS at each follow-up interval (P < .1) on univariate analysis (example shown for last follow-up) were included as covariates in the multivariate regression. OR with 95% confidence intervals are given for each patient characteristic significant in the regression analyses. View Large Table 3. Multivariate Regression Analyses of Preoperative Factors on Functional Outcomes as Measured by Karnofsky Performance Scale (KPS) Score Postresection at Last Follow-up, 6 mo, 1, 2, and 5 yr   Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                        Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                      KPS = Karnofsky Performance Scale; OR = odds ratio; SRS = stereotactic radiosurgery; PVD = peripheral vascular disease; American Society of Anesthesiologists *Odds ratio is incalculable due to 0 patients in any group. Preoperative factors that had at least a trend-level correlation with KPS at each follow-up interval (P < .1) on univariate analysis (example shown for last follow-up) were included as covariates in the multivariate regression. OR with 95% confidence intervals are given for each patient characteristic significant in the regression analyses. View Large ROC curve analysis on decreased KPS score at each follow-up interval, depicted in Figure 2, demonstrated the best cut-off value for preoperative EI was 2.39, 2.01, 3.37, 2.28, and 2.01 for 6 mo, 1, 2, 5 yr, and last follow-up, respectively (area under the curve = 0.80, 0.73, 0.75, 0.71, and 0.76, respectively; P < .001 for 6 mo, 1 yr, and last follow-up, P > .1 for 2 and 5 yr). At these cut-off values sensitivities ranged from 60% to 80%, specificities from 78% to 89%, PPV from 38% to 58%, and NPV from 80% to 97% (Figure 2). Choosing an EI of 2.00 as a simple cut-off point predicts decreased KPS score with a sensitivity/specificity and PPV/NPV of 80%/68% and 29%/96%, 68%/78% and 52%/88%, 75%/74% and 23%/97%, 60%/67% and 50%/75%, and 70%/78% and 58%/86% for 6 mo, 1, 2, 5 yr, and last follow-up after resection, respectively. FIGURE 2. View largeDownload slide ROC curve analysis of decreased KPS score at each follow-up interval. Optimal EI cut-off values obtained from the ROC curve analysis with corresponding sensitivity, specificity, PPV, and NPV are listed for each follow-up interval postresection. FIGURE 2. View largeDownload slide ROC curve analysis of decreased KPS score at each follow-up interval. Optimal EI cut-off values obtained from the ROC curve analysis with corresponding sensitivity, specificity, PPV, and NPV are listed for each follow-up interval postresection. Comparison with Nonedema Controls Matching with nonedema older patients resulted in 2 matched groups of 57 patients each that did not differ in any baseline characteristic (Table 4). While there was no difference in tumor volumes, the edema patients had significantly greater edema volumes and EI on segmentation analysis (P < .0001). In regard to clinical outcomes, matched groups did not differ in proportion of tumor recurrences (P = .71) or postoperative functional status at any of the follow-up intervals (Ps = .132-.692). On multivariate analysis of the nonedema controls, neither EI nor any of the preoperative measures had an association with a decrease in KPS score at 6 mo, 1, 2, 5 yr, and last follow up (OR = 0.29, 0.78, 2.23, 9.98, and 8.08, respectively, Ps > .45 for preoperative EI). Table 4. Patient Characteristics and Clinical Outcome Comparisons Between Matched Edema (n = 57) and Nonedema (n = 57) Older-Aged (age ≥ 60 yr) Meningioma Patients     Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)        Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)    CPF = convexity, parasagittal, or falcine; ASA = American Society of Anesthesiologists; KPS = Karnofsky Performance Status; IQR = interquartile range. View Large Table 4. Patient Characteristics and Clinical Outcome Comparisons Between Matched Edema (n = 57) and Nonedema (n = 57) Older-Aged (age ≥ 60 yr) Meningioma Patients     Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)        Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)    CPF = convexity, parasagittal, or falcine; ASA = American Society of Anesthesiologists; KPS = Karnofsky Performance Status; IQR = interquartile range. View Large DISCUSSION Meningioma resection in elderly patients can be a risky procedure3-7 and determining preoperative risk markers is crucial in selecting an appropriate treatment. While intracranial edema has been associated with poorer clinical outcomes in both younger and older patient groups,16,18-22 the extent of PTE is largely based on subjective assessment. The present study utilized imaging processing software to objectively compute the extent of PTE to determine its relationship with postresection clinical outcomes. EI was found to be associated with decreased KPS scores up to multiple years following meningioma resection. As an important gauge of functional independence and quality of life, patient care teams need to consider the risk of decreased functional outcomes after tumor resection when faced with an older patient with significant PTE. Previous studies of elderly meningioma patients have also noted a decrease in functional outcomes postresection.9,36 In a study of 250 elderly patients, Cohen-Inbar et al9 found that severity of PTE was related to decreased independence in daily activities 5 yr after resection. However, the extent of edema measured in these studies was based on a qualitative inspection (ie, “minor” or “severe”). In studies that used an ellipsoid approximation calculation, the measure was quantitative, but tumors and especially PTE can be irregularly shaped and do not always spread in a concentric manner.19,20,26,27 Latini et al19 found that spheroid calculations can overestimate PTE by 77%. For instance, Gurkanlar et al37 reported an average EI of 3.22 for patients aged 61 to 70 yr using an ellipsoid estimate of tumor and edema volumes, which was likely an overestimation of EI compared to our mean EI of 2.38, supporting the need of a more objective measurement. Although a minority of older-aged patients decreased in KPS score at each follow-up interval (8.9%-33.3%), most had a KPS score that remained stable or improved. However, given that patient functional status at 1, 5 yr, and last follow-up had significantly decreased compared to prior to surgery (see Table 2), it is important to consider the risk of having a greater EI for those that did have poorer functional outcomes. Multivariate analysis suggested that for every 1.0 increase in EI, such as the difference between no edema (EI = 1) and PTE of twice the tumor volume (EI = 2), there is about a 50% greater chance at 6 mo after resection, about a 33% greater chance at 1 yr, a 2.5 times greater chance at 2 yr, and an almost doubled chance at last given follow-up of a decrease in KPS score compared to time of presentation. As a result, patients with even greater degrees of PTE are at substantially higher risks of declining functionally months to years after resection. Comparatively, EI was not found to correlate with postoperative functional decline at any follow-up interval. Tumor volumes between the matched groups did not differ (see Table 4), yet it is not surprising that EI had no association with functional status in the nonedema patients given EI values were concentrated near 1.0. In light of these findings, several ideas have been proposed to explain how extensive PTE could contribute to poorer functional outcomes. First, extensive PTE can cause limited operative exposure and more difficult resections.20,38 Ouyang et al38 additionally noted lower cerebral blood flow in bordering the areas of PTE, which may lead to decreased regional function. Other researchers have suggested that a large amount of edema can augment the degree of mass effect on adjacent neural structures.18,39,40 Thus, challenging resections and potential damage to adjacent tissue from restricted blood flow or pressure may be a contributing factor to long-term functional decline. Through ROC curve analysis (Figure 2), optimal cut-off values for EI to predict decreased KPS at each follow-up interval ranged from 2.01 to 3.37 with a high degree of specificity (78%-89%) and NPV (80%-97%). We propose that utilizing a simple cut-off value of 2.0 (PTE volume twice that of the tumor) could be a quick objective measure from preoperative imaging that can provide additional information regarding risk of long-term loss of function. Using 2.0 as the cut-off level resulted in a high degree of specificity (67%-78%) and NPV (75%-97%). Thus, calculating an EI of greater than 2.0 will have a high risk of functional decline postresection. Similarly, due to a high NPV, a patient with an EI of less than 2.0 will likely have a constant or improved KPS during follow-up. The EI measure could be incorporated into modified scales already established (eg, SKALE, GSS, CRGS) for predicting clinical outcomes of elderly meningioma patients. Of interest, presenting with a seizure and having a prior stroke also trended towards being independent predictors of functional decline at 1-yr and last follow-up, respectively, though the findings did not reach statistical significance. Previous studies have similarly found that meningioma patients presenting with a seizure41-43 or having a prior stroke44-46 tended to be associated with poor outcomes postresection, though studies were not in the elderly specifically. It is less clear why the effect would only be apparent at 1 yr and last known follow-up. A larger cohort of patients in a future study may reveal a significant effect at more consistent follow-up intervals. The present analysis, however, did not consider outcomes of alternative, more conservative treatments for meningioma and tumor-associated edema. Specifically, stereotactic radiosurgery can noninvasively treat small tumors that are in particularly difficult to access or in critical regions, although increases in cerebral edema due to the radiation treatment have been noted.47,48 However, as the natural history of PTE is still not fully understood,49 in the absence of surgical tumor resection in these older patients, substantial PTE may still lead to similar functional decline over time. As such, we do not recommend withholding surgical resection of meningioma with extensive PTE, but rather advise clinicians to consider the risks of functional decline given an elderly patient's extent of PTE. Future work should address the possibility of similar functional decline in elderly adults receiving more aggressive versus conservative treatment management. Additionally, although the study restricted its focus to older patients, previous studies have associated PTE with increased surgical complications, postoperative disability, and tumor recurrence in younger adult samples,16,18,20,22 and, thus, it is possible we may find similar results in younger patients presenting with substantial PTE. Therefore, larger scale studies with long-term outcome measures are necessary to specifically assess the risks and benefits of surgical resection to determine, in particular, the most effective treatment plans for older patients with concurrent PTE. CONCLUSION Surgical resection for intracranial meningiomas is a relatively safe and effective treatment option, but the risk of poor postoperative outcomes increases for the elderly and those with extensive PTE. The authors pose that a simple quantitative measurement of edema and tumor volumes on preoperative imaging can add valuable prognostic information when finalizing treatment plans for at-risk elderly patients. Although the decision to surgically remove a tumor should be determined individually for each older-aged patient based on various factors, the evidence for poorer postoperative functional outcomes should be considered for clinical situations in which extensive PTE is present. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Ostrom QT, Gittleman H, Farah P et al.   CBTRUS Statistical report: Primary brain and central nervous system tumors diagnosed in the united states in 2006-2010. Neuro Oncol . 2013; 15( suppl 2): ii1- ii56. Google Scholar CrossRef Search ADS PubMed  2. Schul DB, Wolf S, Krammer MJ, Landscheidt JF, Tomasino A, Lumenta CB. 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Prognostic value of peritumoral edema and angiogenesis in intracranial meningioma surgery. J BUON . 2013; 18( 2): 430- 436. Google Scholar PubMed  19. Latini F, Larsson EM, Ryttlefors M. Rapid and accurate MRI segmentation of peritumoral brain edema in meningiomas. Clin Neuroradiol . 2017; 27( 2): 145- 152. Google Scholar CrossRef Search ADS PubMed  20. Vignes JR, Sesay M, Rezajooi K, Gimbert E, Liguoro D. Peritumoral edema and prognosis in intracranial meningioma surgery. J Clin Neurosci . 2008; 15( 7): 764- 768. Google Scholar CrossRef Search ADS PubMed  21. Alvernia JE, Sindou MP. Preoperative neuroimaging findings as a predictor of the surgical plane of cleavage: prospective study of 100 consecutive cases of intracranial meningioma. J Neurosurg . 2004; 100( 3): 422- 430. Google Scholar CrossRef Search ADS PubMed  22. Fetouh I, Ibrahim H, Reffat M. Peritumoural brain oedema as a predictor for short-term surgical outcome of supratentorial meningioma patients. Pan Arab J Neurosurg . 2011; 15( 2): 53- 60. 23. Lee KJ, Joo WI, Rha HK et al.   Peritumoral brain edema in meningiomas: correlations between magnetic resonance imaging, angiography, and pathology. Surg Neurol . 2008; 69( 4): 350- 355. Google Scholar CrossRef Search ADS PubMed  24. Kim B-W, Min-Su K, Kim S-W, Chang C-H, Kim O-L. Peritumoral brain edema in meningiomas : correlation of radiologic and pathologic features. J Korean Neurosurg Soc . 2011; 49( 1): 26- 30. Google Scholar CrossRef Search ADS PubMed  25. Osawa T, Tosaka M, Nagaishi M, Yoshimoto Y. Factors affecting peritumoral brain edema in meningioma: special histological subtypes with prominently extensive edema. J Neurooncol . 2013; 111( 1): 49- 57. Google Scholar CrossRef Search ADS PubMed  26. Sindou MP, Alvernia JE. Results of attempted radical tumor removal and venous repair in 100 consecutive meningiomas involving the major dural sinuses. J Neurosurg . 2006; 105( 4): 514- 525. Google Scholar CrossRef Search ADS PubMed  27. Lobato RD, Alday R, Gomez PA et al.   Brain Oedema in Patients with Intracranial Meningioma. Acta Neurochir  1996; 138( 5): 485- 494 Google Scholar CrossRef Search ADS PubMed  28. Xie K, Yang J, Zhang ZG, Zhu YM. Semi-automated brain tumor and edema segmentation using MRI. Eur J Radiol . 2005; 56( 1): 12- 19. Google Scholar CrossRef Search ADS PubMed  29. Sheehan JP, Cohen-Inbar O, Ruangkanchanasetr R et al.   Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study. J Neurooncol . 2015; 125( 2): 317- 324. Google Scholar CrossRef Search ADS PubMed  30. Fedorov A, Beichel R, Kalpathy-Cramer J et al.   3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging . 2012; 30( 9): 1323- 1341. Google Scholar CrossRef Search ADS PubMed  31. Hoe Y, Choi YJ, Kim JH, Kwon DH, Kim CJ, Cho YH. Peritumoral brain edema after stereotactic radiosurgery for asymptomatic intracranial meningiomas: risks and pattern of evolution. J Korean Neurosurg Soc . 2015; 58( 4): 379- 384. Google Scholar CrossRef Search ADS PubMed  32. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry . 1957; 20( 1): 22- 39. Google Scholar CrossRef Search ADS PubMed  33. Kleihues P, Louis DN, Scheithauer BW et al.   The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol . 2002; 61( 3): 215- 225. Google Scholar CrossRef Search ADS PubMed  34. Burden A, Roche N, Miglio C et al.   An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma. Pragmat Obs Res . 2017; 8: 15- 30. Google Scholar CrossRef Search ADS PubMed  35. Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code Biol Med . 2008; 3( 1): 17. Google Scholar CrossRef Search ADS PubMed  36. D’Andrea G, Roperto R, Caroli E, Crispo F, Ferrante L. Thirty-seven cases of intracranial meningiomas in the ninth decade of life: our experience and review of the literature. Neurosurgery . 2005; 56( 5): 956- 961. Google Scholar PubMed  37. Gurkanlar D, Er U, Sanli M, Ozkan M, Sekerci Z. Peritumoral brain edema in intracranial meningiomas. J Clin Neurosci . 2005; 12( 7): 750- 753. Google Scholar CrossRef Search ADS PubMed  38. Ouyang T, Zhang N, Wang L, Li Z, Chen J. Sphenoid wing meningiomas: surgical strategies and evaluation of prognostic factors influencing clinical outcomes. Clin Neurol Neurosurg . 2015; 134: 85- 90. Google Scholar CrossRef Search ADS PubMed  39. Djindjian M, Caron JP, Athayde AA, Fevrier MJ. Intracranial meningiomas in the elderly (over 70 years old). Acta Neurochir . 1988; 90( 3-4): 121- 123. Google Scholar CrossRef Search ADS PubMed  40. Regelsberger J, Hagel C, Emami P, Ries T, Heese O, Westphal M. Secretory meningiomas: a benign subgroup causing life-threatening complications. Neuro Oncol . 2009; 11( 6): 819- 824. Google Scholar CrossRef Search ADS PubMed  41. Kleinpeter G, Böck F. Invasion of the cavernous sinus by medial sphenoid meningioma—“radical” surgery and recurrence. Acta Neurochir . 1990; 103( 3-4): 87- 91. Google Scholar CrossRef Search ADS PubMed  42. Chen WC, Magill ST, Englot DJ et al.   Factors associated with pre- and postoperative seizures in 1033 patients undergoing supratentorial meningioma resection. Neurosurgery . 2017; 81( 2): 297- 306. Google Scholar CrossRef Search ADS PubMed  43. Chaichana KL, Pendleton C, Zaidi H et al.   Seizure control for patients undergoing meningioma surgery. World Neurosurg . 2013; 79( 3-4): 515- 524. Google Scholar CrossRef Search ADS PubMed  44. DeMonte F, Smith HK, Al-Mefty O. Outcome of aggressive removal of cavernous sinus meningiomas. J Neurosurg . 1994; 81( 2): 245- 251. Google Scholar CrossRef Search ADS PubMed  45. van Alkemade H, de Leau M, Dieleman EM et al.   Impaired survival and long-term neurological problems in benign meningioma. Neuro Oncol . 2012; 14( 5): 658- 666. Google Scholar CrossRef Search ADS PubMed  46. Kreisl TN, Toothaker T, Karimi S, DeAngelis LM. Ischemic stroke in patients with primary brain tumors. Neurology . 2008; 70( 24): 2314- 2320. Google Scholar CrossRef Search ADS PubMed  47. Patil CG, Hoang S, Borchers DJ 3rd et al.   Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas. Neurosurgery . 2008; 63( 3): 435- 442. Google Scholar CrossRef Search ADS PubMed  48. Cai R, Barnett GH, Novak E, Chao ST, Suh JH. Principal risk of peritumoral edema after stereotactic radiosurgery for intracranial meningioma is tumor-brain contact interface area. Neurosurgery . 2010; 66( 3): 513- 522. Google Scholar CrossRef Search ADS PubMed  49. Sughrue ME, Rutkowski MJ, Aranda D, Barani IJ, McDermott MW, Parsa AT. Treatment decision making based on the published natural history and growth rate of small meningiomas. J Neurosurg . 2010; 113( 5): 1036- 1042. Google Scholar CrossRef Search ADS PubMed  Acknowledgments The authors would like to thank the American Federation of Aging Research (AFAR) for providing a Medical Student Training in Aging Research scholarship (to J.L.) to make the completion of this work possible. COMMENTS The authors report on a well conducted, albeit retrospective study on the effect of peritumoral edema (PTE) on outcomes following surgical resection of meningiomas in older patients. They find a strong correlation between PTE and KPS both immediately postoperatively, at 6 months, and even down to several years from surgery. Although edema has been implicated with a number of different intra-op and post-op outcomes in meningioma surgery, prior studies have not used the type of semi-automatic quantification process that the authors use. I think that is important as it makes the process less operator-dependent and more robust. The strength of the association both on univariate and multivariate analyses is impressive and is a good addition to the existing literature. Unfortunately, the patients with the extensive peritumoral edema end up being the patients for whom surgical intervention is usually more necessary in an acute way, as it does not often allow for radiation therapy safely. As a result, although the findings in this paper are important and should be considered in the counseling of patients, it may be that PTE predicts a difficult to avoid suboptimal outcome prescribed more by the disease rather than the treatment. I would caution any readers from utilizing the data herein to make an argument for withholding surgical treatment in the elderly with a tumor presenting with significant PTE as those patients, if left untreated and specifically if no surgery is performed, will likely not do well. Unfortunately, as the authors state, this study was not designed to address the comparison in outcome in such patients between surgery and other forms of treatment including observation. Therefore, although the risks of poorer outcome increase with larger PTE indexes, I would caution all readers from changing patterns of practice based on the limited data presented. A prospective trial in older patients, and even in all patients may help elucidate the exact relationship between PTE and outcome. Philip Theodosopoulos San Francisco, California We enjoyed reading this article which confirms, in a very systematic way, that more extensive peritumoral edema (PTE) predicts worse functional outcome following meningioma resection in older patients. The authors evaluated 112 patients > 60 years old with evidence of PTE on MRI FLAIR sequences. They calculated the edema index (EI), a ratio obtained by dividing the PTE volume by the tumor volume, based on semi-automatic image-processing software. It should be noted that the PTE volume includes the tumor volume such that an EI of 1.0 would be no edema and a ratio of 2.0 would indicate PTE twice that of the tumor volume. They found a larger EI correlated with worse Karnofsky Performance Status (KPS) at 6 months, 1 years, 2 years, and most recent follow-up. PTE more than twice to 3 times the tumor volume was particularly associated with a decline in KPS. Of course, the conclusion is not surprising as it has been well recognized that extensive edema surrounding a meningioma usually portends a poor dissection plane with the brain, possible pial invasion, and more postoperative deficits. Once again, while it is not surprising that greater PTE results in a more difficult recovery after surgery it is not clear what to do when a patient over the age of 60 years presents with a meningioma and an EI > 2.0? Often surgery is the only viable option as radiation runs the risk of exacerbating the edema and presumably observation is rarely recommended for tumors causing symptoms or a large amount of edema? This manuscript strongly supports that patients with extensive PTE should be counseled they face a higher risk of a poorer functional recovery. Perhaps if auto-segmentation software becomes more widely available, additional studies will further define an EI that is critical and patients with mild PTE adjacent to a meningioma could be counseled to undergo surgical resection before the PTE progresses and threatens a worse postoperative result? Michael J. Link Joshua D. Hughes Rochester, Minnesota Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Operative Neurosurgery Oxford University Press

Peritumoral Edema Relative to Meningioma Size Predicts Functional Outcomes after Resection in Older Patients

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Congress of Neurological Surgeons
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Copyright © 2018 by the Congress of Neurological Surgeons
ISSN
2332-4252
eISSN
2332-4260
D.O.I.
10.1093/ons/opy107
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Abstract

Abstract BACKGROUND Resection of meningiomas in older adults is associated with increased complications and postoperative functional deficits. Extent of peritumoral edema (PTE), which has been associated with surgical prognosis, may represent a preoperative risk marker for poorer outcomes in older adults. OBJECTIVE To quantitatively evaluate the relationship between preoperative PTE and postresection outcomes in older meningioma patients. METHODS One hundred twelve older meningioma patients (age ≥ 60) with evidence of PTE on MRI were reviewed. Extent of PTE, measured as a ratio of edema to tumor volume (edema index, EI) using semiautomatic image-processing software, was correlated with postresection outcomes. Other preoperative factors were included as covariates in multivariate analyses. Results were compared to matched nonedema older patients. Receiver operating characteristic (ROC) curve analysis was performed to identify cut-off EI values to predict postoperative outcomes. RESULTS EI was associated with functional decline (as measured by Karnofsky Performance Status, KPS) at 6 mo, 1, 2 yr, and most recent follow-up (Ps < .05), but not among the nonedema matched patients. Seizure or prior stroke additionally trended towards increasing the likelihood of lower KPS at 2 yr (odds ratio = 3.06) and last follow-up (odds ratio = 5.55), respectively. ROC curve analysis found optimal cut-off values for EI ranging from 2.01 to 3.37 to predict lower KPS at each follow-up interval. Sensitivities ranged from 60% to 80%, specificities from 78% to 89%, and positive and negative predictive values from 38% to 58% and 80% to 97%. CONCLUSION Preoperative PTE may represent a significant marker of poor functional outcome risk in older adults and provides a quantitative measurement to incorporate into surgical decision-making. Meningioma, Edema, Elderly, Aging, Outcomes ABBREVIATIONS ABBREVIATIONS ASA American Society of Anesthesiologists CI confidence interval CPF convexity, parasagittal, or falcine EI edema index KPS Karnofsky Performance Status FLAIR fluid-attenuated inversion recovery MRI magnetic resonance imaging NPV negative predictive value OR odds ratio PPV positive predictive value PTE peritumoral edema ROC receiver operating characteristic The incidence of meningioma increases with age such that older adults are 3 or 4 times more likely to be affected.1-3 Resection in older patients is associated with more complicated resections, longer hospital stays, and less improvement in independence level compared to younger adults.3-7 Thus, it is important to recognize preoperative markers to identify appropriate surgical candidates. Researchers have created graded scales (eg, Sex, Karnofsky Performance Scale, American Society of Anesthesiology Class, Location of Tumor, and Peritumoral Edema (SKALE), Geriatric Scoring System (GSS), Clinical-Radiological Grading System (CRGS)) to identify factors that best predict the prognosis and functional outcomes post resection in elderly adults.8-10 These scales have been associated with survival time, tumor recurrence, and functional outcome.2,11-15 An integral component of these scales focuses on the extent of peritumoral edema (PTE) present. PTE is known to be present in the majority (about 60%) of intracranial meningioma.16,17 PTE in meningioma patients, regardless of age, has been linked to a greater rate of complications, prolonged hospital stays, poorer long-term outcomes, and increased risk of tumor recurrence postoperatively in addition to impaired visualization of a safe resection plane intraoperatively.16,18-22 Extent of PTE was classified in most research, however, through subjective assessments of the preoperative imaging (eg, “severe,” “moderate/mild,” or “none”), but did not use an objective measure of the volume of edema, particularly relative to the tumor size. Other studies have made strides to correlate quantitative measure of PTE to clinical outcomes in meningioma patients using an edema index (EI) metric calculated as the ratio of PTE volume to tumor size. In these studies, increased preoperative EI was associated with irregular tumor margins, arterial supply, and high-grade classification.23-25 Yet, preoperative PTE and tumor volumes were calculated by an ellipsoid shape approximation of the tumor and surrounding edema (ie, V = 4/3π × a/2 × b/2 × c/2, where a, b, and c are maximum cross-sectional diameters), which still does not precisely portray the extent of PTE or tumor size as meningiomas often extend along the dural covering of venous sinuses and PTE rarely spreads only concentrically around the tumor.19,20,26,27 Thus, in the present study, semiautomatic segmentation was utilized to accurately obtain quantitative preoperative measurements of PTE and tumor volumes.19,28 Older patients (greater than 60 yr) who presented with an intracranial meningioma and known PTE on preoperative imaging, and subsequently underwent surgical resection, were retrospectively analyzed to evaluate the clinical outcomes of this at-risk group given the degree of PTE present. METHODS Patients The retrospective study was approved by the medical center's Institutional Review Board and written informed consent was waived. Medical records of 248 consecutive patients from 2002 to 2016 who were at least 60 yr of age at time of primary meningioma resection were reviewed. Of these, 123 patients had a known area of PTE on preoperative magnetic resonance imaging (MRI). Eleven patients were excluded due to unavailable preoperative imaging, nonintracranial location (eg, spinal), or insufficient data, resulting in a final sample of 112 older-aged patients. Demographic and preoperative data collected for each patient included body mass index (BMI), comorbidities, American Society of Anesthesiologists (ASA) score, presenting symptoms, preoperative radiation treatment, dexamethasone use, and functional status as measured by Karnofsky Performance Status (KPS) score.29 In addition to the PTE and tumor volume variables of interest, other tumor characteristics prior to resection included location (skull base or in convexity, parasagittal, or falcine [CPF] areas) and T2-weighted signal intensity. Distributions of the older-aged patients by preoperative characteristics and imaging features are depicted in Table 1. Table 1. Preoperative Patient Clinical Characteristics and Imaging Features Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  SRS = stereotactic radiosurgery; CPF = convexity, parasagittal, falcine; PVD = peripheral vascular disease; KPS = Karnofsky Performance Status; ASA = American Society of Anesthesiologists; IQR = interquartile range. Mann–Whitney U-tests or Pearson's r correlations were applied as appropriate on each characteristic for edema index, tumor volume, and edema volume. View Large Table 1. Preoperative Patient Clinical Characteristics and Imaging Features Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  Patient Characteristic  N (%)  Edema Index P-value  Tumor Volume P-value  Edema Volume P-value  Gender  Female  83 (74.1)  .227  .093  .514    Male  29 (25.9)        Age  60-74  72 (64.3)  .570  .183  .539    75+  40 (35.7)        BMI  Non-obese  84 (76.4)  .997  .960  .866    Obese  26 (23.6)        Tumor Location  CPF  78 (69.6)  .302  .010  .188    Skull base  34 (30.4)        T2 Signal Intensity  Iso/Hypointense  35 (31.8)  .954  .432  .300    Hyperintense  75 (68.2)        Preoperative SRS  No  102 (91.1)  .967  .917  .618    Yes  10 (8.9)        Prior dexamethasone use  No  94 (85.5)  .476  .08  .007    Yes  16 (14.5)        Presenting Symptom  Headache  36 (32.1)  .635  .474  .205    Seizure  23 (20.5)  .846  .880  .991    Weakness  20 (17.9)  .569  .033  .030    Dizziness  18 (16.1)  .619  .608  .324    Forgetfulness  17 (15.2)  .435  .080  .070    Vision changes  14 (12.5)  .242  .774  .315    Confusion  12 (10.7)  .649  .216  .132    Language dysfunction  12 (10.7)  .401  .056  .013    Gait dysfunction  11 (9.8)  .654  .086  .105    Loss of consciousness  6 (5.4)  .130  .722  .269    Mental status change  4 (3.6)  .678  .118  .101    None  7 (6.3)  .497  .073  .248  Comorbidities  Hypertension  70 (62.5)  .793  .781  .686    Hyperlipidemia  41 (36.6)  .366  .534  .626    Diabetes Mellitus  26 (23.2)  .256  .545  .225    Heart disease  16 (14.3)  .283  .953  .283    Hypothyroidism  12 (10.7)  .300  .530  .818    Stroke  6 (5.4)  .693  .532  .792    Lung disease  5 (4.5)  .194  .994  .362    PVD  4 (3.6)  .384  .829  .737    Current smoker  4 (3.6)  .842  .593  .482    None  19 (17.0)  .152  .396  .734  Preoperative KPS Score  ≥80  69 (61.6)  .618  .186  .354    ≤70  43 (38.4)        ASA Score  ≤2  18 (16.1)  .954  .006  .003    ≥3  94 (83.9)        Edema Index  Median (IQR)  1.65 (1.34-2.56)  –  .0003  .891   Tumor Volume (in cm3)  Median (IQR)  27.0 (10.7-59.1)  .0003  –  <.0001   Edema Volume (in cm3)  Median (IQR)  60.1 (25.7-90.9)  .891  <.0001  –  SRS = stereotactic radiosurgery; CPF = convexity, parasagittal, falcine; PVD = peripheral vascular disease; KPS = Karnofsky Performance Status; ASA = American Society of Anesthesiologists; IQR = interquartile range. Mann–Whitney U-tests or Pearson's r correlations were applied as appropriate on each characteristic for edema index, tumor volume, and edema volume. View Large Imaging Analysis Patients received preoperative MRI scans typically within 30 d of resection (median time = 4 d, 103 [92.0%] within 30 d). Tumor and PTE volumes were measured using segmentation processing software (3D Slicer, Version 4.6, http://www.slicer.org)30 by consensus with an experienced neuroradiologist blinded to clinical outcomes or other patient data (intraclass correlation coefficient: 0.91, F = 11.03, P < .001). Tumor volumes were obtained from T1-weighted postcontrast MRI. PTE volumes were obtained from T2-weighted fluid attenuated inversion recovery (FLAIR) images, which included the area of the tumor. Each image slice was segmented for tumor and PTE volumes using the label map effect tools available in the processing software. Each slice was automatically multiplied by the slice thickness and aggregated to compute the total tumor or PTE volume. The preoperative EI for each patient was calculated offline by dividing PTE volume by tumor volume, such that an EI of 1 was defined as no surrounding edema present.24,29,31 Clinical Outcomes Intraoperative features included operative time, tumor consistency (soft or firm), Simpson grade of resection,32 and use of blood transfusions. Postoperative clinical outcomes included complications, length of hospital stay, long-term dexamethasone use, further radiation treatment, tumor recurrence, World Health Organization (WHO) tumor grade,33 1-yr survival, and change in KPS29 score at last known follow-up and at 6 mo, 1, 2, and 5 yr of follow-up when available. Comparison with Nonedema Controls Of the 125 remaining older patients without a known area of PTE on preoperative MRI, 84 with an intracranial meningioma presenting for primary resection only with sufficient preoperative imaging and data were matched against the 112 older patients with present PTE on gender, tumor location, ASA score, grade of resection, and WHO grade utilizing a propensity score matching technique34 and compared on significant clinical outcomes. Statistics Univariate analyses of each preoperative variable with the intra- and postoperative clinical outcomes were evaluated using Pearson's Chi-square, Fisher's exact test, or Mann–Whitney U-tests where appropriate. Preoperative and postoperative KPS scores were compared using Wilcoxon signed-rank tests. Clinical characteristics with a P-value ≤ .10 on univariate analysis were included as covariates in the multivariate regression for each outcome variable.3,35 Patients without sufficient data (eg, lost to follow-up) for an outcome variable were excluded from that specific analysis. Receiver operating characteristic (ROC) curve analysis was performed to identify cut-off EI values predictive of outcomes. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) are reported. P-value ≤ .05 was considered statistically significant (IBM SPSS, Version 22.0, Armonk, New York). RESULTS Patient Characteristics Preoperative patient characteristics and imaging features by relative distributions are shown in Table 1. The sample was mostly female (74.1%), ranged from 60 to 95 yr at resection (mean ± standard deviation = 71.3 ± 8.0 yr), and nearly a quarter (23.6%) were obese. Patient tumors were located largely in CPF areas (69.6%) and demonstrated mostly hyperintense signal (68.2%) on T2 sequences relative to surrounding tissue. Ten patients (8.9%) received prior radiosurgery to treat their meningioma. The most common presenting symptoms included headaches (32.1%), seizure (20.5%), and weakness (17.9%). Concurrent hypertension diagnosis was common in the majority of older patients (62.5%), followed by hyperlipidemia (36.6%) and diabetes mellitus (23.2%). A majority of patients had a preoperative KPS ≥ 80 (61.6%), signifying an ability to carry on normal activity or work, and had an ASA ≥ 3 (83.9%). Median tumor and edema volumes were 27.0 and 60.1 cm3 (interquartile range [IQR] = 10.7-59.1 cm3 and 25.7-90.9 cm3), resulting in a median EI of 1.65 (IQR = 1.34-2.56). None of the preoperative clinical or imaging features differed by EI. Skull base tumor volumes were significantly smaller than CPF tumors (P = .010) and patients presenting with weakness had greater tumor volumes than those without associated weakness (P = .033). Patients with an ASA ≤ 2 had significantly greater tumor and PTE volumes (P = .066 and .003). Patients with weakness, language dysfunction, or with prior dexamethasone use had significantly greater volumes of PTE (P = .030, .013, and .007, respectively). Representative segmentation of a skull base and a CPF tumor are depicted in Figure 1. EI was highly correlated with tumor volume (P < .001), but not edema volume, while tumor and edema volumes also correlated (P < .001). FIGURE 1. View largeDownload slide Representative preoperative MRI depicting the meningioma (T1-weighted postcontrast, left) and surrounding peritumoral edema (PTE, T2 FLAIR, right) of 2 patients with a convexity (top) and skull base (bottom) tumor. The tumor or PTE of each slice is automatically segmented (yellow outline) on imaging processing software and multiplied by the slice-thickness to obtain accurate tumor and PTE volumes. FIGURE 1. View largeDownload slide Representative preoperative MRI depicting the meningioma (T1-weighted postcontrast, left) and surrounding peritumoral edema (PTE, T2 FLAIR, right) of 2 patients with a convexity (top) and skull base (bottom) tumor. The tumor or PTE of each slice is automatically segmented (yellow outline) on imaging processing software and multiplied by the slice-thickness to obtain accurate tumor and PTE volumes. Clinical Outcomes Intra- and postoperative outcomes are detailed in Table 2. Intraoperatively, the majority of tumors were removed in total (81.3%), resected in < 4 h (55.7%), and noted to be either soft (52.6%) or firm (47.4%). Thirty patients (30.9%) required an intraoperative blood transfusion. Most tumors were WHO grade I (75.0%), followed by 23.2% and 1.8% of WHO grade II and III, respectively. The majority stayed in the hospital < 5 d (68.8%) and discharged to a rehabilitation facility (60.4%). The most common complication was an intracranial hematoma (10.7%). Postoperatively, 18.0% received further radiation treatment, 6.0% were placed on long-term steroids, and 10.4% had a tumor recurrence. Functionally, a substantial portion of patients had a decrease in KPS score at interval periods of follow-up (8.9%-33.3%). Patients were found to have significantly decreased KPS scores at 1 yr (P < .001), 5 yr (P = .049), and at last known follow-up (P < .001) compared to preoperative KPS scores (see Table 2). Table 2. Intraoperative and Postoperative Clinical Outcomes of Older Patients (Age ≥ 60 yr) During and After Meningioma Resection Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  SRS = stereotactic radiosurgery; KPS = Karnofsky Performance Status; DVT/PE = deep vein thrombosis/pulmonary embolism; UTI = urinary tract infection; CSF = cerebrospinal fluid. *P < .05 vs preoperative KPS scores on Wilcoxon signed-rank test. View Large Table 2. Intraoperative and Postoperative Clinical Outcomes of Older Patients (Age ≥ 60 yr) During and After Meningioma Resection Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  Clinical outcome    n (%)  Simpson grade of resection  I-III (Complete Resection)  91 (81.3)    IV-V (Partial Resection)  21 (18.8)  Operative time  <4 h  54 (55.7)    ≥4 h  43 (44.3)  Tumor consistency  Soft  51 (52.6)    Firm  46 (47.4)  Intraoperative blood transfusion  No  67 (69.1)    Yes  30 (30.9)  WHO tumor grade  I  84 (75.0)    II  26 (23.2)    III  2 (1.8)  Length of hospital stay  <5 d  77 (68.8)    ≥5 d  35 (31.2)  Complications  Intracranial hematoma  12 (10.7)    Wound infection  6 (5.4)    Seizure  5 (4.5)    DVT/PE  5 (4.5)    Infarction  3 (2.7)    Extradural hematoma  2 (1.8)    Dysphagia  2 (1.8)    Motor deficit  2 (1.8)    Hydrocephalus  2 (1.8)    UTI  2 (1.8)    CSF leakage  1 (0.9)    Death < 30 d  1 (0.9)    Death < 1 yr  5 (4.5)    None  72 (64.3)  Discharge destination  Home  44 (39.6)    Rehab Facility  67 (60.4)  Postoperative SRS  No  82 (82.0)    Yes  18 (18.0)  Postoperative long-term steroids  No  94 (94.0)    Yes  6 (6.0)  Tumor recurrence  No  69 (89.6)    Yes  8 (10.4)  Postoperative KPS at 6 mo  ≥80  52 (57.1)    ≤70  39 (42.9)   Decreased KPS  No  81 (89.0)    Yes  10 (11.0)  *Postoperative KPS at 1 yr  ≥80  38 (49.4)    ≤70  39 (50.6)   Decreased KPS  No  58 (75.3)    Yes  19 (24.7)  Postoperative KPS at 2 yr  ≥80  31 (68.9)    ≤70  14 (31.1)   Decreased KPS  No  41 (91.1)    Yes  4 (8.9)  *Postoperative KPS at 5 yr  ≥80  9 (60.0)    ≤70  6 (40.0)   Decreased KPS  No  10 (66.7)    Yes  5 (33.3)  *Postoperative KPS at last follow-up  ≥80  51 (51.0)    ≤70  49 (49.0)   Decreased KPS  No  70 (70.0)    Yes  30 (30.0)  SRS = stereotactic radiosurgery; KPS = Karnofsky Performance Status; DVT/PE = deep vein thrombosis/pulmonary embolism; UTI = urinary tract infection; CSF = cerebrospinal fluid. *P < .05 vs preoperative KPS scores on Wilcoxon signed-rank test. View Large Clinical Outcomes Associated With EI On univariate analysis, preoperative EI were not associated with any intraoperative measure (Ps > .10). In addition, EI was not associated with most postoperative clinical outcomes including complications, discharge destination, length of hospital stay, long-term steroid use, subsequent radiosurgery, tumor recurrence, WHO tumor grade, or 1-yr survival rate (Ps > .10). EI was associated with a decrease in KPS score at 6 mo (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.12-2.16, P = .009), 1 yr (OR = 1.32, 95% CI = 0.98-1.78, P = .066), 2 yr (OR = 1.75, 95% CI = 1.05-2.94, P = .033), and at last known follow up (OR = 1.86, 95% CI = 1.29-2.70, P = .001, see Table 3), but the difference at 5 yr postresection did not reach significance (P = .152). On multivariate regression analyses at each follow-up interval as shown in Table 3, which included all preoperative measures that had an association of P ≤ .1, EI remained or increased in significance level, except at 5 yr of follow-up (P = .152). In addition to EI, a trend was found such that presenting with a seizure increased the likelihood of a lower KPS score at 1 yr of follow-up (OR = 3.06, 95% CI = 0.92-10.16, P = .068) and a past history of stroke trended towards an increased risk of having a decreased KPS score at last follow-up (OR = 5.55, 95% CI = 0.84-36.17, P = .073). Table 3. Multivariate Regression Analyses of Preoperative Factors on Functional Outcomes as Measured by Karnofsky Performance Scale (KPS) Score Postresection at Last Follow-up, 6 mo, 1, 2, and 5 yr   Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                        Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                      KPS = Karnofsky Performance Scale; OR = odds ratio; SRS = stereotactic radiosurgery; PVD = peripheral vascular disease; American Society of Anesthesiologists *Odds ratio is incalculable due to 0 patients in any group. Preoperative factors that had at least a trend-level correlation with KPS at each follow-up interval (P < .1) on univariate analysis (example shown for last follow-up) were included as covariates in the multivariate regression. OR with 95% confidence intervals are given for each patient characteristic significant in the regression analyses. View Large Table 3. Multivariate Regression Analyses of Preoperative Factors on Functional Outcomes as Measured by Karnofsky Performance Scale (KPS) Score Postresection at Last Follow-up, 6 mo, 1, 2, and 5 yr   Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                        Lower KPS at last  Lower KPS at 6 mo  Lower KPS at 1 yr  Lower KPS at 2 yr  Lower KPS at 5 yr    follow-up (n = 100)  (n = 91)  (n = 77)  (n = 45)  (n = 15)    Univariate  Multivariate  Multivariate  Multivariate  Multivariate  Multivariate  Patient Characteristic  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  OR (95% CI)  P-value  Edema Index  1.86 (1.29-2.70)  .001  1.89 (1.27-2.77)  .001  1.55 (1.12-2.16)  .009  1.34 (1.01-1.85)  .049  2.53 (1.11-5.77)  .028  3.27 (0.65-16.62)  .152   Tumor Volume  0.99 (0.98-1.01)  .601                       Edema Volume  1.01 (0.99-1.02)  .074  –  .087                  Gender  1.34 (0.52-3.47)  .551                      Age > 75 yr  1.56 (0.64-3.79)  .330      –  .081              BMI  1.57 (0.60-4.13)  .358                      Tumor Location  0.93 (0.37-2.38)  .885              –  .09      T2 Signal Intensity  1.27 (0.50-3.21)  .609                      Preoperative SRS  1.44 (0.32-6.47)  .629                      Prior dexamethasone use  1.64 (0.53-5.11)  .381                      Presenting Symptom                           Headache  0.62 (0.24-1.58)  .311                       Seizure  2.07 (0.76-5.62)  .148          3.06 (0.92-10.16)  .068           Weakness  2.18 (0.76-6.24)  .140          –  .097           Dizziness  1.07 (0.34-3.41)  .905                       Forgetfulness  0.97 (0.31-3.03)  .954                       Vision changes  0.75 (0.19-3.00)  .687                       Confusion  3.25 (0.91-11.64)  .060  –  0.106                   Language dysfunction  2.13 (0.60-7.62)  .236                       Gait dysfunction  0.64 (0.13-3.29)  .594                       Loss of consciousness  7.67 (0.76-76.97)  .079  –  .759                   Mental status change  1.17 (0.10-13.44)  .898                       None  Uncalculable*  .174                      Comorbidities                           Hypertension  0.90 (0.37-2.20)  .819                       Hyperlipidemia  0.63 (0.26-1.54)  .308                       Diabetes Mellitus  1.88 (0.70-5.04)  .206          –  .22           Heart disease  0.67 (0.17-2.62)  .559                       Hypothyroidism  0.55 (0.11-2.78)  .467                       Stroke  5.23 (0.90-30.30)  .043  5.55 (0.85-36.17)  .073                   Lung disease  Uncalculable*  .133                       PVD  0.77 (0.08-7.72)  .824                       Current smoker  Uncalculable*  .511                       None  0.68 (0.20-2.27)  .772                      Preoperative KPS Score  0.99 (0.95-1.03)  .466                      ASA Score  1.29 (0.57-2.90)  .546                      KPS = Karnofsky Performance Scale; OR = odds ratio; SRS = stereotactic radiosurgery; PVD = peripheral vascular disease; American Society of Anesthesiologists *Odds ratio is incalculable due to 0 patients in any group. Preoperative factors that had at least a trend-level correlation with KPS at each follow-up interval (P < .1) on univariate analysis (example shown for last follow-up) were included as covariates in the multivariate regression. OR with 95% confidence intervals are given for each patient characteristic significant in the regression analyses. View Large ROC curve analysis on decreased KPS score at each follow-up interval, depicted in Figure 2, demonstrated the best cut-off value for preoperative EI was 2.39, 2.01, 3.37, 2.28, and 2.01 for 6 mo, 1, 2, 5 yr, and last follow-up, respectively (area under the curve = 0.80, 0.73, 0.75, 0.71, and 0.76, respectively; P < .001 for 6 mo, 1 yr, and last follow-up, P > .1 for 2 and 5 yr). At these cut-off values sensitivities ranged from 60% to 80%, specificities from 78% to 89%, PPV from 38% to 58%, and NPV from 80% to 97% (Figure 2). Choosing an EI of 2.00 as a simple cut-off point predicts decreased KPS score with a sensitivity/specificity and PPV/NPV of 80%/68% and 29%/96%, 68%/78% and 52%/88%, 75%/74% and 23%/97%, 60%/67% and 50%/75%, and 70%/78% and 58%/86% for 6 mo, 1, 2, 5 yr, and last follow-up after resection, respectively. FIGURE 2. View largeDownload slide ROC curve analysis of decreased KPS score at each follow-up interval. Optimal EI cut-off values obtained from the ROC curve analysis with corresponding sensitivity, specificity, PPV, and NPV are listed for each follow-up interval postresection. FIGURE 2. View largeDownload slide ROC curve analysis of decreased KPS score at each follow-up interval. Optimal EI cut-off values obtained from the ROC curve analysis with corresponding sensitivity, specificity, PPV, and NPV are listed for each follow-up interval postresection. Comparison with Nonedema Controls Matching with nonedema older patients resulted in 2 matched groups of 57 patients each that did not differ in any baseline characteristic (Table 4). While there was no difference in tumor volumes, the edema patients had significantly greater edema volumes and EI on segmentation analysis (P < .0001). In regard to clinical outcomes, matched groups did not differ in proportion of tumor recurrences (P = .71) or postoperative functional status at any of the follow-up intervals (Ps = .132-.692). On multivariate analysis of the nonedema controls, neither EI nor any of the preoperative measures had an association with a decrease in KPS score at 6 mo, 1, 2, 5 yr, and last follow up (OR = 0.29, 0.78, 2.23, 9.98, and 8.08, respectively, Ps > .45 for preoperative EI). Table 4. Patient Characteristics and Clinical Outcome Comparisons Between Matched Edema (n = 57) and Nonedema (n = 57) Older-Aged (age ≥ 60 yr) Meningioma Patients     Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)        Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)    CPF = convexity, parasagittal, or falcine; ASA = American Society of Anesthesiologists; KPS = Karnofsky Performance Status; IQR = interquartile range. View Large Table 4. Patient Characteristics and Clinical Outcome Comparisons Between Matched Edema (n = 57) and Nonedema (n = 57) Older-Aged (age ≥ 60 yr) Meningioma Patients     Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)        Edema (n = 57) N (%)  Nonedema controls (n = 57) N (%)  P  Patient Characteristic     Gender  Female  40 (70.2)  42 (73.7)  .677    Male  17 (29.8)  15 (26.3)     Age  60-74  42 (73.7)  49 (86.0)  .161    75+  15 (26.3)  8 (14.0)     Tumor Location  CPF  34 (59.6)  30 (52.6)  .450    Skull base  23 (40.4)  27 (47.4)     ASA Score  ≤2  15 (26.3)  12 (21.1)  .509    ≥3  42 (73.7)  45 (78.9)     Preoperative KPS Score  ≥80  37 (64.9)  43 (75.4)  .219    ≤70  20 (35.1)  14 (24.6)     Simpson grade of resection  I-III (Complete)  47 (82.5)  45 (78.9)  .635    IV-V (Partial)  10 (17.5)  12 (21.1)     WHO tumor grade  I  48 (84.2)  48 (84.2)  >.99    II/III  9 (15.8)  9 (15.8)     Edema Index  Median (IQR)  1.73 (1.46-2.81)  1.03 (1.01-1.05)  <.0001    Tumor Volume (in cm3)  Median (IQR)  19.3 (8.1-41.0)  15.7 (8.3-35.9)  .543    Edema Volume (in cm3)  Median (IQR)  45.1 (16.8-77.3)  16.1 (8.9-36.4)  <.0001  Clinical Outcome     Tumor Recurrence  No  37 (90.2)  25 (86.2)  .710    Yes  4 (9.8)  4 (13.8)     Postoperative KPS at 6 mo  ≥80  28 (59.6)  26 (74.3)  .165    ≤70  19 (40.4)  9 (25.7)     Postoperative KPS at 1 yr  ≥80  24 (58.5)  22 (75.9)  .132    ≤70  17 (41.5)  7 (24.1)     Postoperative KPS at 2 yr  ≥80  20 (74.1)  15 (65.2)  .496    ≤70  7 (25.9)  8 (34.8)     Postoperative KPS at 5 yr  ≥80  7 (70.0)  10 (58.8)  .692    ≤ 70  3 (30.0)  7 (41.2)     Postoperative KPS at last follow-up  ≥80  28 (54.9)  26 (66.7)  .259    ≤70  23 (45.1)  13 (33.3)    CPF = convexity, parasagittal, or falcine; ASA = American Society of Anesthesiologists; KPS = Karnofsky Performance Status; IQR = interquartile range. View Large DISCUSSION Meningioma resection in elderly patients can be a risky procedure3-7 and determining preoperative risk markers is crucial in selecting an appropriate treatment. While intracranial edema has been associated with poorer clinical outcomes in both younger and older patient groups,16,18-22 the extent of PTE is largely based on subjective assessment. The present study utilized imaging processing software to objectively compute the extent of PTE to determine its relationship with postresection clinical outcomes. EI was found to be associated with decreased KPS scores up to multiple years following meningioma resection. As an important gauge of functional independence and quality of life, patient care teams need to consider the risk of decreased functional outcomes after tumor resection when faced with an older patient with significant PTE. Previous studies of elderly meningioma patients have also noted a decrease in functional outcomes postresection.9,36 In a study of 250 elderly patients, Cohen-Inbar et al9 found that severity of PTE was related to decreased independence in daily activities 5 yr after resection. However, the extent of edema measured in these studies was based on a qualitative inspection (ie, “minor” or “severe”). In studies that used an ellipsoid approximation calculation, the measure was quantitative, but tumors and especially PTE can be irregularly shaped and do not always spread in a concentric manner.19,20,26,27 Latini et al19 found that spheroid calculations can overestimate PTE by 77%. For instance, Gurkanlar et al37 reported an average EI of 3.22 for patients aged 61 to 70 yr using an ellipsoid estimate of tumor and edema volumes, which was likely an overestimation of EI compared to our mean EI of 2.38, supporting the need of a more objective measurement. Although a minority of older-aged patients decreased in KPS score at each follow-up interval (8.9%-33.3%), most had a KPS score that remained stable or improved. However, given that patient functional status at 1, 5 yr, and last follow-up had significantly decreased compared to prior to surgery (see Table 2), it is important to consider the risk of having a greater EI for those that did have poorer functional outcomes. Multivariate analysis suggested that for every 1.0 increase in EI, such as the difference between no edema (EI = 1) and PTE of twice the tumor volume (EI = 2), there is about a 50% greater chance at 6 mo after resection, about a 33% greater chance at 1 yr, a 2.5 times greater chance at 2 yr, and an almost doubled chance at last given follow-up of a decrease in KPS score compared to time of presentation. As a result, patients with even greater degrees of PTE are at substantially higher risks of declining functionally months to years after resection. Comparatively, EI was not found to correlate with postoperative functional decline at any follow-up interval. Tumor volumes between the matched groups did not differ (see Table 4), yet it is not surprising that EI had no association with functional status in the nonedema patients given EI values were concentrated near 1.0. In light of these findings, several ideas have been proposed to explain how extensive PTE could contribute to poorer functional outcomes. First, extensive PTE can cause limited operative exposure and more difficult resections.20,38 Ouyang et al38 additionally noted lower cerebral blood flow in bordering the areas of PTE, which may lead to decreased regional function. Other researchers have suggested that a large amount of edema can augment the degree of mass effect on adjacent neural structures.18,39,40 Thus, challenging resections and potential damage to adjacent tissue from restricted blood flow or pressure may be a contributing factor to long-term functional decline. Through ROC curve analysis (Figure 2), optimal cut-off values for EI to predict decreased KPS at each follow-up interval ranged from 2.01 to 3.37 with a high degree of specificity (78%-89%) and NPV (80%-97%). We propose that utilizing a simple cut-off value of 2.0 (PTE volume twice that of the tumor) could be a quick objective measure from preoperative imaging that can provide additional information regarding risk of long-term loss of function. Using 2.0 as the cut-off level resulted in a high degree of specificity (67%-78%) and NPV (75%-97%). Thus, calculating an EI of greater than 2.0 will have a high risk of functional decline postresection. Similarly, due to a high NPV, a patient with an EI of less than 2.0 will likely have a constant or improved KPS during follow-up. The EI measure could be incorporated into modified scales already established (eg, SKALE, GSS, CRGS) for predicting clinical outcomes of elderly meningioma patients. Of interest, presenting with a seizure and having a prior stroke also trended towards being independent predictors of functional decline at 1-yr and last follow-up, respectively, though the findings did not reach statistical significance. Previous studies have similarly found that meningioma patients presenting with a seizure41-43 or having a prior stroke44-46 tended to be associated with poor outcomes postresection, though studies were not in the elderly specifically. It is less clear why the effect would only be apparent at 1 yr and last known follow-up. A larger cohort of patients in a future study may reveal a significant effect at more consistent follow-up intervals. The present analysis, however, did not consider outcomes of alternative, more conservative treatments for meningioma and tumor-associated edema. Specifically, stereotactic radiosurgery can noninvasively treat small tumors that are in particularly difficult to access or in critical regions, although increases in cerebral edema due to the radiation treatment have been noted.47,48 However, as the natural history of PTE is still not fully understood,49 in the absence of surgical tumor resection in these older patients, substantial PTE may still lead to similar functional decline over time. As such, we do not recommend withholding surgical resection of meningioma with extensive PTE, but rather advise clinicians to consider the risks of functional decline given an elderly patient's extent of PTE. Future work should address the possibility of similar functional decline in elderly adults receiving more aggressive versus conservative treatment management. Additionally, although the study restricted its focus to older patients, previous studies have associated PTE with increased surgical complications, postoperative disability, and tumor recurrence in younger adult samples,16,18,20,22 and, thus, it is possible we may find similar results in younger patients presenting with substantial PTE. Therefore, larger scale studies with long-term outcome measures are necessary to specifically assess the risks and benefits of surgical resection to determine, in particular, the most effective treatment plans for older patients with concurrent PTE. CONCLUSION Surgical resection for intracranial meningiomas is a relatively safe and effective treatment option, but the risk of poor postoperative outcomes increases for the elderly and those with extensive PTE. The authors pose that a simple quantitative measurement of edema and tumor volumes on preoperative imaging can add valuable prognostic information when finalizing treatment plans for at-risk elderly patients. Although the decision to surgically remove a tumor should be determined individually for each older-aged patient based on various factors, the evidence for poorer postoperative functional outcomes should be considered for clinical situations in which extensive PTE is present. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Ostrom QT, Gittleman H, Farah P et al.   CBTRUS Statistical report: Primary brain and central nervous system tumors diagnosed in the united states in 2006-2010. Neuro Oncol . 2013; 15( suppl 2): ii1- ii56. Google Scholar CrossRef Search ADS PubMed  2. Schul DB, Wolf S, Krammer MJ, Landscheidt JF, Tomasino A, Lumenta CB. 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Sughrue ME, Rutkowski MJ, Aranda D, Barani IJ, McDermott MW, Parsa AT. Treatment decision making based on the published natural history and growth rate of small meningiomas. J Neurosurg . 2010; 113( 5): 1036- 1042. Google Scholar CrossRef Search ADS PubMed  Acknowledgments The authors would like to thank the American Federation of Aging Research (AFAR) for providing a Medical Student Training in Aging Research scholarship (to J.L.) to make the completion of this work possible. COMMENTS The authors report on a well conducted, albeit retrospective study on the effect of peritumoral edema (PTE) on outcomes following surgical resection of meningiomas in older patients. They find a strong correlation between PTE and KPS both immediately postoperatively, at 6 months, and even down to several years from surgery. Although edema has been implicated with a number of different intra-op and post-op outcomes in meningioma surgery, prior studies have not used the type of semi-automatic quantification process that the authors use. I think that is important as it makes the process less operator-dependent and more robust. The strength of the association both on univariate and multivariate analyses is impressive and is a good addition to the existing literature. Unfortunately, the patients with the extensive peritumoral edema end up being the patients for whom surgical intervention is usually more necessary in an acute way, as it does not often allow for radiation therapy safely. As a result, although the findings in this paper are important and should be considered in the counseling of patients, it may be that PTE predicts a difficult to avoid suboptimal outcome prescribed more by the disease rather than the treatment. I would caution any readers from utilizing the data herein to make an argument for withholding surgical treatment in the elderly with a tumor presenting with significant PTE as those patients, if left untreated and specifically if no surgery is performed, will likely not do well. Unfortunately, as the authors state, this study was not designed to address the comparison in outcome in such patients between surgery and other forms of treatment including observation. Therefore, although the risks of poorer outcome increase with larger PTE indexes, I would caution all readers from changing patterns of practice based on the limited data presented. A prospective trial in older patients, and even in all patients may help elucidate the exact relationship between PTE and outcome. Philip Theodosopoulos San Francisco, California We enjoyed reading this article which confirms, in a very systematic way, that more extensive peritumoral edema (PTE) predicts worse functional outcome following meningioma resection in older patients. The authors evaluated 112 patients > 60 years old with evidence of PTE on MRI FLAIR sequences. They calculated the edema index (EI), a ratio obtained by dividing the PTE volume by the tumor volume, based on semi-automatic image-processing software. It should be noted that the PTE volume includes the tumor volume such that an EI of 1.0 would be no edema and a ratio of 2.0 would indicate PTE twice that of the tumor volume. They found a larger EI correlated with worse Karnofsky Performance Status (KPS) at 6 months, 1 years, 2 years, and most recent follow-up. PTE more than twice to 3 times the tumor volume was particularly associated with a decline in KPS. Of course, the conclusion is not surprising as it has been well recognized that extensive edema surrounding a meningioma usually portends a poor dissection plane with the brain, possible pial invasion, and more postoperative deficits. Once again, while it is not surprising that greater PTE results in a more difficult recovery after surgery it is not clear what to do when a patient over the age of 60 years presents with a meningioma and an EI > 2.0? Often surgery is the only viable option as radiation runs the risk of exacerbating the edema and presumably observation is rarely recommended for tumors causing symptoms or a large amount of edema? This manuscript strongly supports that patients with extensive PTE should be counseled they face a higher risk of a poorer functional recovery. Perhaps if auto-segmentation software becomes more widely available, additional studies will further define an EI that is critical and patients with mild PTE adjacent to a meningioma could be counseled to undergo surgical resection before the PTE progresses and threatens a worse postoperative result? Michael J. Link Joshua D. Hughes Rochester, Minnesota Copyright © 2018 by the Congress of Neurological Surgeons This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Operative NeurosurgeryOxford University Press

Published: May 22, 2018

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