Abstract
Background
Limited data exist on long-term quality of life (QOL) for patients diagnosed with intracranial meningioma.
Methods
The data are on 1722 meningioma cases diagnosed among residents of Connecticut, Massachusetts, California, Texas, and North Carolina from May 1, 2006 through March 14, 2013 and 1622 controls frequency matched to the cases by age, sex and geography. These individuals were participants in a large, population-based case/control study. Telephone interviews were used to collect data on QOL at time of initial diagnosis or contact, using the Medical Outcomes Study (MOS-36). QOL outcomes were compared by case/control status.
Results
Patients diagnosed with meningioma report levels of physical, emotional, and mental health functioning below those reported in a general healthy population. Case participants and controls differed most significantly in the domains of physical and social functioning, role-physical, role-emotional and vitality.
Conclusions
Patients with meningioma experience statistically significant decreases in quality of life compared to a healthy control of similar demographic breakdown, though these differences vary in clinical significance.
Keywords: meningioma, quality of life, case-control studies, SF-36, brain tumors
Precis:
Patients with meningioma experience statistically significant decreases in quality of life compared to a healthy control of similar demographic breakdown, most notably in the domains of physical and social functioning, role-physical, role-emotional and vitality. These differences, however, vary in clinical significance.
Introduction
Within the United States, meningioma is the most frequently diagnosed primary brain tumor in adults1,2. While generally defined histologically as benign, these lesions are frequently associated with neurological complications and decreased quality of life (QOL).3–5 Despite this, few studies, all of which include relatively small numbers of patients, have explicitly examined quality of life among meningioma patients.6–13
As the use of imaging throughout the United States has intensified, so has the number of persons diagnosed with meningioma, with up to 1% of the general adult population estimated to have such a lesion,1 although many of those patients will remain asymptomatic. For those patients who present with symptoms or with brain imaging that is clinically concerning, surgical resection remains the most commonly selected intervention, with a much smaller number receiving radiation therapy as first course of treatment. Thus, both presentation and treatment may affect patient quality of life. Although numerous studies report decreased quality of life for patients with malignant brain tumors,6–13 it is of interest to examine outcomes specifically for meningioma patients to better define whether similar post-treatment counseling strategies are needed relative to patients with malignant brain tumors such as glioma and metastatic lesions, as these patients generally receive both radiation and chemotherapy in addition to surgery as part of treatment. Our analysis represents the largest effort to date to describe the symptoms and quality of life for a population-based series of meningioma patients treated with surgical intervention, examining these variables in a sample that is almost ten-fold larger than any prior work.17
Materials and Methods
Study Population
Case patients eligible for the study included all persons diagnosed between May 1, 2006 and March 14, 2013 with a histologically confirmed intracranial meningioma among residents of the states of Connecticut, Massachusetts, and North Carolina, and several counties in California (Alameda, San Francisco, Contra Costa, Marin, San Mateo, and Santa Clara) and Texas (Brazoria, Fort Bend, Harris, Montgomery, Chambers, Galveston, Liberty, and Waller). Case patients were diagnosed between the ages of 20–79 and were identified through the Rapid Care Ascertainment systems and state tumor registries at their respective study site. Controls were obtained through random-digit dialing performed by an outside consulting firm (Kreider Research and Consulting) and were frequency matched with case patients by 5-year age interval, sex, and state of residence. Patients with a prior history of meningioma and/or a brain lesion of unknown pathology were not eligible for inclusion. The study, consent forms, and questionnaire were approved by the institutional review boards at Yale University School of Medicine, Brigham and Women’s Hospital, University of California at San Francisco, MD Anderson Cancer Center, and Duke University School of Medicine. The study was also approved by the State of Connecticut Department of Public Health Human Investigation Committee, with some data directly obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health as well as the Massachusetts Tumor Registry.
Data Collection
Physicians for eligible case patients were contacted to obtain permission to approach the patient about participation in the study. Case patients receiving permission from their physician and potentially eligible patients identified by Krieder Research were sent an introductory letter. Within 1–2 weeks, these letters were followed up with a phone call by a trained interviewer, who described the study and administered the interview by telephone. Interviews took an average of 52 minutes. The questionnaire asked both cases and controls detailed questions regarding their demographics, family history with cancer, pregnancy and menstrual history, exogenous hormone history, medical history, and quality of life.
Physicians of 94% of eligible cases consented to (or did not deny) patient contact (n=2923); an additional 8 cases were self-referred. Of these, 361 did not have a current telephone number or address. There were thus 2,570 eligible cases with current contact information and physician consent or self-referral. Of those, we interviewed 1,722 (12 by proxy) (67%); 271 (10.5%) could not be reached; 544 (21.2%) refused; and 31 participated in other portions of the study, but were not interviewed. Among controls, 151 (5.8%) did not have a current telephone number or address. There were thus 3,254 controls with current contact information and of those, we interviewed 1,622 (50%); 493 (15%) could not be reached; 10 (<1%) withdrew; and 1,129 refused. The majority of cases were interviewed within one year from time of initial surgery, with a median (mean) time between surgery and interview of 0.59 (0.93) years, respectively. The sample used in this analysis includes data from 1722 cases and 1622 controls.
Statistical Analysis
Health-related quality of life (QOL) was measured using the Medical Outcomes Study 36-item short form version (MOS-SF-36).14 This instrument includes eight individual scales for physical functioning, role function-physical, bodily pain, social functioning, mental health, role function-emotional, vitality and general health perceptions. Each scale is scored from 0 to 100, with 100 representing the best score. The SF-36 also has two summary scales-the Physical Component Summary Scale (PCS) and the Mental Component Summary Scale (MCS). The summary scales are standardized to a reference healthy population with a mean score of 50 and a standard deviation of 10.
Statistical analysis included descriptive statistics and were computed using the R version 3.2.3 and Statistical Analysis Software SAS (VERSION 9.4). T-tests, chi-square, and Fisher’s exact tests as well as unadjusted odds ratios (OR) with 95% confidence intervals (CI) were used to examine whether descriptive characteristics of the study population differed between cases and controls while generalized linear models (GLM) were used to provide adjusted estimates of outcome risk. The effect of multiple comparisons was controlled for using a Bonferroni correction to make pairwise comparisons across the two study groups. Estimates of MOS SF-36 means were adjusted for the effects of age (continuous), race (white/nonwhite), comorbid conditions (myocardial infarction, stroke, cancer), education (some college or more/no college), sex, menopausal status (females only), radiation therapy (cases only), and case/control status. The MOS SF-36 variables were coded according to the guidelines presented in Ware et al.14
Results
Summary statistics are given in Table 1. The majority of study subjects were female, White, and had attended some college. Cases and controls did not differ significantly by mean age (57.6 years for cases versus 57.3 for controls), sex, residence or number of comorbid conditions. Control participants were more likely than cases to be white (p = 0.02) and to have completed their education beyond the high school (p < 0.01). Approximately 11% of cases received radiation therapy in addition to surgery. Female cases were more likely than controls to report a surgical menopause, possibly due to the known association between uterine fibroids and meningioma.17 Among cases, tumors were evenly divided between the right and left hemispheres.
Table 1:
Population Summary Table
| Meningioma Group | Control Group | ||||
|---|---|---|---|---|---|
| (n = 1722) | (n = 1622) | ||||
| Characteristic | No. | % | No. | % | P-Value |
| Age at initial onset/interview, years | |||||
| 20–39 | 137 | 8.0 | 131 | 8.1 | 0.3907 |
| 40–49 | 323 | 18.8 | 310 | 19.2 | |
| 50–59 | 480 | 28.0 | 482 | 29.8 | |
| 60–69 | 515 | 30.0 | 435 | 26.9 | |
| 70+ | 261 | 15.2 | 257 | 15.9 | |
| Average Age | 57.6 | 57.3 | |||
| SD | 11.8 | 12 | |||
| Sex | |||||
| Male | 476 | 27.6 | 454 | 28.0 | 0.8225 |
| Female | 1246 | 72.4 | 1168 | 72.0 | |
| Race | |||||
| White | 1433 | 83.3 | 1396 | 86.1 | 0.0245 |
| Non-White | 287 | 16.7 | 225 | 13.9 | |
| Education | |||||
| Grade School/Some High School | 91 | 5.3 | 47 | 2.9 | <0.0001 |
| High School Graduate | 467 | 27.2 | 304 | 18.8 | |
| Some College | 406 | 23.7 | 347 | 21.4 | |
| College Graduate/Higher | 750 | 43.8 | 921 | 56.9 | |
| Menipausal Status * | |||||
| Premenopausal | 288 | 23.2 | 281 | 24.0 | 0.0089 |
| Perimenopausal | 163 | 13.1 | 144 | 12.3 | |
| Postmenopausal (nonsurgical) | 643 | 51.8 | 650 | 55.7 | |
| Postmenopausal (surgical) | 148 | 11.9 | 93 | 8.0 | |
| Marital Status | |||||
| Single/Never Married | 160 | 10.1 | 170 | 11.7 | 0.5930 |
| Married | 1068 | 67.3 | 941 | 64.7 | |
| Separated | 23 | 1.5 | 21 | 1.4 | |
| Divorced | 210 | 13.2 | 189 | 13.0 | |
| Widowed | 107 | 6.7 | 113 | 7.8 | |
| Living with Partner | 18 | 1.1 | 20 | 1.4 | |
| Comorbidity** | 0.2521 | ||||
| One or More | 378 | 21.9 | 383 | 23.6 | |
| Radiation*** | |||||
| No Radiation | 1517 | 89.1 | -- | -- | |
| Radiation | 185 | 10.9 | -- | -- | |
| Tumor Laterality*** | |||||
| Right Hemisphere | 748 | 49.6 | -- | -- | 0.7574 |
| Left Hemisphere | 761 | 50.4 | -- | -- | |
Women Only
Other Cancers, Myocardial Infarction, and Stroke
Cases only
Sample Sizes Vary due to Missing Values
Symptoms reported by case participants at time of diagnosis are presented in Table 2. The most common presenting symptoms were: headache (35.4%), visual disturbance (20.2%), seizures (16.3%), numbness/tingling (13.0%) and weakness/motor deficit (11.1%). In general, patients with right-sided tumors reported higher rates of symptoms than did those with left-sided tumors. This difference was most noticeable for visual disturbance (p = 0.04), headache (p < 0.01), nausea/vomiting (p = 0.01), and weakness or motor deficit (p < 0.01). As expected, patients with left-sided tumors had higher rates of difficulty with speech (p < 0.01).
Table 2:
Symptom Frequency Table
| Meningioma Group | Tumor in Left Hemisphere | Tumor in Right Hemisphere | Difference Between Right and Left Hemispheres | ||||
|---|---|---|---|---|---|---|---|
| (n = 1722) | (n = 761) | (n = 748) | |||||
| Symptom | No. | % | No. | % | No. | % | P-Value |
| Headache | 603 | 35.4 | 244 | 32.1 | 287 | 38.6 | p = 0.0087 |
| Visual Disturbance | 343 | 20.2 | 130 | 17.1 | 158 | 21.2 | p = 0.0432 |
| Seizures | 276 | 16.3 | 119 | 15.7 | 128 | 17.2 | p = 0.4248 |
| Numbness/Tingling | 201 | 13.0 | 99 | 13.0 | 99 | 13.3 | p = 0.8963 |
| Weakness or Motor Deficit | 190 | 11.1 | 65 | 8.6 | 105 | 14.1 | p = 0.0007 |
| Difficulty Remembering New Facts | 168 | 9.9 | 81 | 10.7 | 64 | 8.6 | p = 0.1740 |
| Difficulty Getting Words Out | 137 | 8.0 | 89 | 11.7 | 39 | 5.2 | p < 0.0001 |
| Personality Change | 133 | 7.8 | 46 | 6.1 | 65 | 8.7 | p = 0.0494 |
| Nausea/Vomiting | 122 | 7.2 | 42 | 5.5 | 66 | 8.9 | p = 0.0129 |
| Difficulty Remembering Old Facts | 109 | 6.4 | 61 | 8 | 35 | 4.7 | p = 0.0079 |
| Excess Sleepiness | 95 | 5.6 | 42 | 5.5 | 44 | 5.9 | p = 0.7512 |
Sample Sizes Vary due to Missing Values
The adjusted mean levels of the MOS SF-36 health domains are presented in Table 3. Statistically lower scores were reported for cases versus controls in all health domains except bodily pain. In fact, all domains had p-values less than 0.001 with the exception of bodily pain (p = 0.132). The greatest differences between the controls and cases occurred in Role-Physical (17.96 points), Role-Emotional (9.32 points), and Social Functioning (7.88 Points) domains. Patients who received radiation therapy reported significantly lower scores for vitality, role-physical, and social functioning relative to patients who only received surgery. Despite these differences, the majority of both cases (82.7%) and controls (90.6%) reported having good/very good/excellent health.
Table 3:
MOS SF-36 Adjusted Group Means
| Adjusted* | Adjusted* | ||
|---|---|---|---|
| MOS SF-36 Health Domain | Control Mean (n = 1449) | Case Mean (n = 1544) | P-Value |
| Physical Functioning | 77.02 | 70.50 | <0.001 |
| Role-Physical | 64.48 | 46.52 | <0.001 |
| Bodily Pain | 67.96 | 66.56 | 0.132 |
| General Health | 69.90 | 67.06 | <0.001 |
| Vitality | 58.85 | 51.74 | <0.001 |
| Social Functioning | 78.58 | 70.7 | <0.001 |
| Role-Emotional | 75.71 | 66.39 | <0.001 |
| Mental Health | 76.77 | 72.79 | <0.001 |
Means adjusted for age (continuous), race (white vs. non-white), sex, menopausal status (for females), case/control status, use of radiation, education (college grad/no college), and other comorbid conditions (stroke, myocardial infarction, and other cancers)
Discussion
This is the largest study to examine health related quality of life for patients with meningioma, being tenfold larger than prior reports. 6–13 Our study benefits from a large, population-based sample of patients and controls.17 The instruments used in this study (MOS SF-36) have been previously validated and have population norms.14
Our study identified statistically lower scores for cases than for controls in seven of the eight SF-36 domains. Prior studies (Table 4) 6–13, (using both the SF-36 as well as other QOL instruments) have reported a variety of case/control differences; One study found no significant quality of life differences between cases and controls9 while, later studies found significant differences in General Health and Vitality13, and Physical Role10. Of note, the 2013 case-control study performed by Waagemans et al.13 found case scores to be lower than control scores in all eight SF-36 scales, but most differences were not statistically significant due to the small sample size (n=21). One study that did find impaired executive functioning correlated with significant differences in seven of the eight scales6, but drew no conclusions between case and control group means. Our ability to consistently detect such variation between cases and controls is likely due to the large sample size.
Table 4:
Literature Review Table
| Case/Control Studies | |||
|---|---|---|---|
| Authors & Year | No. Cases | QOL Method(s) | Statistically Significant MOS SF-36 Health Domains |
| Staplers et al (2007) | 95 | SF-36 | Not Reported (Abstract Only) |
| van Nieuwenhuizen (2007) | 18 | SF-36, EORTC-BCM20, KPS, BADLI | None |
| Waagemens et al (2011) | 89 | SF-36 | Role Physical |
| van Nieuwenhuizen (2013) | 21 | SF-36 | General Health, Vitality |
| Case Series | |||
| Authors & Year | No. Cases | QOL Method(s) | Statistically Significant Health Domains |
| Chan et al (1984) | 257 | KPS | N/A |
| Mohsenipour et al (2001) | 82 | IHD(NS), NHP | N/A |
| Santos et al (2011) | 29 | IHD(NS), NHP | NHP: Pain, Emotional Reactions, Sleepiness, Physical Abilities* |
| IHD(NS): Physical Condition, Independence, Physcological Condition* | |||
| Drewes et al (2016) | 248 | EQ-5D-3L | None |
Significance between patients before and after surgery
Quality of Life Method Glossarry
BADLI Barthel Activities of Daily Living Index
EORTC-BCM20 European Organization for Research and Treatment of Cancer–Brain Cancer Module-20 Questionnaire
EQ-5D-3L EuroQol Five Dimension Questionnaire
IHD(NS) Innsbruck Health Dimensions Questionnaire for Neurosurgical Patients
KPS Karnofsky Performance Scale
NHP Nottingham Health Profile
SF-36 Medical Outcomes Study Short Form 36 Questionnaire
Cases who reported undergoing radiation treatment (generally used to treat lesions that are not entirely removed by surgery or lesions that are viewed as being more aggressive histologically) reported statistically lower scores in vitality, role physical, and social functioning than did cases who did not receive radiation therapy. Although radiation therapy for meningioma is more focused than for treatment of other brain tumors such as glioma, our results highlight the presence of the radiation-related side effect of fatigue at least in the time period close to treatment.
The extent to which the observed differences between the cases and controls are regarded as clinically significant varies across domains. Within the literature, the magnitude of difference regarded to be clinically significant are those in which groups are separated by greater than one half of a standard deviation.15,16 The most clinically significantly differences among the eight SF-36 domains are in Vitality, Physical Functioning, Social Functioning, Role-Emotional, and Role-Physical. While the difference between the patient and control groups in the Mental Health scale begins to border on clinical significance, the differences in the General Health scales were each less than one-half the theoretical standard deviation of 5 points. Our results seem to indicate that meningioma patients compared to controls report lower physical and emotional health, and were more likely to report that their physical and social roles were reduced, at least within a year from time of surgery.
In examining tumor laterality, our results seem to indicate, with the exception of speech disturbance, that cases with right-sided lesions reported more symptoms than patients with left-sided lesions. Our symptom frequency results differ from the one prior study that examined laterally, in which patients with left-brain tumors reported a higher symptomology;8 it is difficult to compare the two results given the prior study included only 29 cases. More recent study found no association between tumor laterality and QOL12 and suggested that clinicians underestimate the importance of the right brain.
Caveats to our study include variation in response rate by demographic characteristics. Patients and controls did not differ by sex, age, or geographical site but did differ with respect to race and education, with controls more likely to report being white and college-educated than cases, suggesting a greater willingness among persons of higher socioeconomic status to participate in epidemiology research. Although these variables were adjusted for in all analyses, such differences in socioeconomic status, a factor likely related to quality of life, may lead to bias in estimating the clinical significance of differences between case and control group means. Given the racial/ethnic background of our study population, our results are applicable primarily to a white population. Histological confirmation was obtained for all patients, suggesting that these results may only be applicable to lesions that are deemed in need of surgery rather than conservative management. As QOL data were collected at only one point in time, the analyses are not able to control for baseline psychosocial status nor for status at a time distant from surgery.
Patients with meningioma experience significant decreases in quality of life compared to a healthy control of similar demographic breakdown. The lower QOL for meningioma patients compared to controls is most clinically significant within the domains of physical and emotional role, physical and social functioning, and vitality. The findings suggest that at least within the time period close to treatment, patients may benefit from additional support for these domains.
Acknowledgments
Funding: This work was supported by the Brain Science Foundation, the Meningioma Mommas and by NIH R01 grants CA109468, CA109461, CA109745, CA108473, CA109475, and CA151933.
Footnotes
Disclosures: The authors report no conflict of interest.
References:
- 1.Vernooij M, Ikram M, Tanghe H, et al. Incidental Findings on Brain MRI in the General Population. N Eng J Med. 2007;357(18):1821–1828 [DOI] [PubMed] [Google Scholar]
- 2.Central Brain Tumor Registry of the United States (CBTRUS) Hinsdale, IL: 2010. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004–2006. www.cbtrus.org [Google Scholar]
- 3.Wiemels J, Wrensch M, Claus EB. Epidemiology and etiology of meningioma. J Neurooncol. 2010;99(3):307–314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Meskal I, Gehring K, Rutten GM Sitskorn. Cognitive functioning in meningioma patients: a systematic review. J Neurooncol. 2016;128(2):195–205. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Pavlatou N, Marvaki C, Kotanidou A et al. Quality of life in patients after brain meningioma resection. Health and Research. 2015;1(1):3–20. [Google Scholar]
- 6.Staplers L, Waagemans M, van Nieuwenhuizen D, et al. Long Term Cognitive Outcome and Quality of Life in Meningioma After Neurosurgery With or Without Radiation.INT J RADIAT ONCOL BIOL PHYS. 2007;69(3):S169 [Google Scholar]
- 7.Mohsenipour I, Deusch E, Gabl M, Hofer M, Twerdy K. Quality of life in patients after meningioma resection. Acta Neurochir (Wien). 2001;143(6):547–53. [DOI] [PubMed] [Google Scholar]
- 8.Santos CB, Silva MF, Aguiar PH. Meningiomas: Quality of life before and after surgery. Journal of Neuroscience and Behavioral Health. 2011;3(1):8–15. [Google Scholar]
- 9.van Nieuwenhuizen D, Klein M, Staplers L et al. Differential effect of surgery and radiotherapy on neurocognitive functioning and health-related quality of life in WHO grade I meningioma patients. Journal of Neurosurgery. 2007;84(3):271–278. [DOI] [PubMed] [Google Scholar]
- 10.Waagemans M,van Nieuwenhuizen D, Dijkstra M et al. Long-term impact of cognitive deficits and epilepsy on patients with low grade meningiomas. Neurosurgery. 2011;69(1):72–79. [DOI] [PubMed] [Google Scholar]
- 11.Chan R, Thompson G. Morbidity, mortality, and quality of life following surgery for intracranial meningiomas. J Neurosurg. 1984;60(1):52–60 [DOI] [PubMed] [Google Scholar]
- 12.Drewes C, Sagberg MS, Jokola AS, Solheim O. Quality of life in patients with intercranial tumors: does laterality matter? J Neurosurg. 2016;125(6):1400–1407. [DOI] [PubMed] [Google Scholar]
- 13.van Nieuwenhuizen D, Ambachtsheer N, Heimans J,Reijneveld JC, Peerdeman SM, Klein M. Neurocognitive functioning and health-related quality of life in patients with radiologically suspected meningiomas. J Neurooncol. 2013;113(3):433–440. [DOI] [PubMed] [Google Scholar]
- 14.Ware JE Jr, Kosinski M, Gandek B: SF-36 Health Survey: Manual and Intepretation Guide. Lincoln, RI, Quality Metric Incorporated, 2005 [Google Scholar]
- 15.Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life. The remarkable universality of half a standard deviation. Med Care 2003;41:582–592 [DOI] [PubMed] [Google Scholar]
- 16.Wyrwich KW, Bullinger M, Aaronson N, Hays RD, Patrick DL, Symonds T and the Clinical Significance Consensus Meeting Group. Estimating clinically significant differences in quality of life outcomes. Qual Life Res 2005;14:285–295 [DOI] [PubMed] [Google Scholar]
- 17.Claus EB, Calvocoressi L, Bondy M, Schildkraut J, Wiemels J, Wrensch M. Family and Personal Medical History and Risk of Meningioma. J Neurosurg 2011;115:1072–77 [DOI] [PMC free article] [PubMed] [Google Scholar]