Key-words:
Incidence - race - spinal meningioma - survival
Introduction
Spinal meningioma is a slow-growing benign tumor of the spinal cord.[[1]] It generally occurs outside the cord but within its dural covering. It accounts
for 7.5%–12.7% of all meningiomas (cranial and spinal) and 25%–46% of spinal neoplasms.[[2]] Spinal meningioma typically occurs among older individuals (age: 50–70 years),[[3]] but in rare instances, affects children.[[4]] It is more prevalent among females than males (ratio 3–4.2:1).[[5]] Spinal meningioma can be fully surgically resected without causing any neurological
damage, and patients generally have an excellent prognosis.[[2]]
Several factors have been identified with the prognosis of spinal meningioma. The
outcomes studied include postsurgical neurological functional status, recurrence,
and survival.[[3]],[[6]] A recurrent tumor status, higher Ki-67 index, and poor preoperative neurological
functions were associated with poor postsurgical neurological functional status.[[6]] On the other hand, male gender, higher tumor grade, recurrent tumor status, and
a Simpson resection III were significantly associated with meningioma recurrence.[[6]] Although spinal meningioma is more prevalent among females, mortality from it is
higher among males.[[3]]
Race is a significant prognostic factor in various types of cancer.[[7]] In the US, African–Americans have a higher incidence and lesser survival of all
malignancies combined compared to other races.[[8]] Race differences in susceptibility to cancers are partially due to the genomic
diversity among the races. Studies have shown more genetic diversity and fewer levels
of linkage disequilibrium in Africans relative to all other populations.[[9]] Furthermore, there are multiple single-nucleotide polymorphisms and copy number
variations associated with racial diversity. In addition, a difference in DNA methylation
between Europeans and Africans, which is an early step before cancer development,
showed that there was an epigenetic difference by race.[[10]]
All this evidence suggests that race might have a prognostic value in the case of
spinal meningioma, but data are lacking in this regard. A large-scale epidemiological
study indicated that the incidence was higher among the Asian Pacific Islanders, Caucasians,
and Hispanics.[[11]] Other small-scale studies also reported a racial difference in spinal meningioma.[[12]]
The current study used information contained in the surveillance, epidemiology, and
end results (SEER) database and aimed to assess the association between race and survival
in patients with spinal meningioma.
Materials and Methods
We obtained patients' data from the SEER database 18 registries of the US National
Cancer Institute.[[13]] The data were extracted using SEER*Stat software version 8.3.5.
Ethical consideration
This was a secondary analysis of publicly available data from the SEER database. No
additional ethical approval was required.
Data collection
All patients diagnosed with spinal meningioma between 2000 and 2016 were eligible.
The primary tumor sites that were considered included spinal meninges (C70.1), spinal
cord (C72.0), and cauda equina (C72.1). Patients were excluded if: (1) the diagnosis
of spinal meningioma was not microscopically confirmed or was made from an autopsy,
(2) the primary tumor site was unknown, and (3) they did not have an active follow-up.
We also extracted data on the following variables: race (Caucasian, African-American,
American Indian/Alaska Native, and Asian or Pacific islander), gender (male, female),
age at diagnosis into quartiles (<52, 52–63, 64–73, and >73), marital status (divorced/separated,
married or domestic partner, single, and widowed), therapy including radiation and
surgery (received and did not receive), vital status, tumor type (benign, borderline
malignancy, and malignant), and size (<1 cm and ≥1 cm). There were no restrictions
on any of the aforementioned variables except for race; patients with unknown race
were excluded from the study.
Incidence statistics
The age-adjusted incidence rate (per 100,000) of spinal meningioma between 2000 and
2016 was calculated using the SEER*Stat software version 8.3.5. Its frequency, percentage,
and rate of incidence were also determined for each race.
Statistical analyses
Statistical analyses were performed using R Studio version 3.2.5 software. Since variables
related to patients' characteristics were all categorical, they were presented as
frequencies and percentages. Comparison of these variables across the four racial
groups was made using Chi-square or Fisher's exact test, whichever was more appropriate.
A Kaplan–Meier curve was used to demonstrate the overall survival probability of the
different racial groups, and a log-rank test was used to compare between them. Univariable
and multivariable Cox regression models were used to compare the overall survival
between the different races. The Caucasian race was used as a reference in the regression
models, and adjustment was performed for the following covariates: age, gender, marital
status, tumor site, size, behavior, radiation, and surgery. A two-sided P < 0.05 was
considered statistically significant.
Results
Patient population and baseline characteristics
A total of 3502 patients with spinal meningioma were identified between 2000 and 2016
according to eligibility criteria. Of those, 2895 (82.7%) were Caucasian, 272 (7.8%)
were African-American, 310 (8.8%) were Asian or Pacific Islanders, and 25 (0.7%) were
American Indian/Alaska Native. The distribution of patients by age was <52 (23.5%),
52–63 (27.4%), 64–73 (24.3%), and >73 years (24.8%). Females were the majority overall
(81%) as well as in each racial group. Almost all patients (96%) received surgical
resection of their tumors, and a tiny minority (1.7%) received radiation. At last
follow-up, 80.2% of the African-American patients were alive; the corresponding percentages
were 85.5% for Caucasian, 89.0% for Asian or Pacific Islanders, and 96.0% for American
Indian/Alaska Natives. The distribution of age, gender, marital status, surgery, and
vital status were significantly different across the four racial groups [[Table 1]].
Table 1: Characteristics of the included patients stratified by race
Surveillance, epidemiology, and end results population-based incidence statistics
The age-adjusted rate of spinal meningioma was 0.239/100,000. The rate was highest
in Caucasian patients (0.249), followed by Asian or Pacific Islander (0.23), African-American
(0.173), and American Indian/Alaska Native (0.137) [[Table 2]].
Table 2: Population-based incidence statistics for spinal meningioma stratified by race
Race-specific survival analysis for spinal meningioma patients
The Kaplan–Meier curve showed that Caucasian patients had the worst survival rate,
American Indian/Alaska Native patients had the best survival rate, and Asian or Pacific
Islanders and African-American patients had the intermediate survival rate; the log-rank
test showed that this difference was statistically significant (P = 0.03) [[Figure 1]]. Compared to Caucasians, the overall mortality was 33% lower for African-Americans
(hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.46, 0.98), 31% lower for
Asian or Pacific Islanders (HR = 0.69, 95% CI = 0.48, 0.99), and 80% lower for American
Indian/Alaska Natives (HR = 0.20, 95% CI = 0.03, 1.46); the results were significant
for all the races except American Indian/Alaska Native [unadjusted model; [[Table 3]]]. The mortality, however, was not statistically different among the racial groups
after adjustment with covariates [[Table 3]].
Figure 1: Kaplan-Meier survival curve showing the overall survival for spinal meningioma patients
based on race
Table 3: Uni- and multi-variable Cox proportional hazard model for the effect of race on overall
survival of spinal meningioma
Discussion
In various types of cancer, for example, breast, colon, and leukemia, survival varies
by race.[[14]],[[15]],[[16]] The racial effect in survival among spinal meningioma patients has been unclear.
A number of factors may have contributed to this lack of clarity, such as (1) small-sized
studies, (2) single-center studies, and (3) studies that included patients who received
a specific type of treatment.[[17]],[[18]],[[19]],[[20]] This study contributes to the knowledge by assessing the race effect on survival
by drawing from a large spectrum of spinal meningioma patients in a population-based
database (SEER).
In this study, Caucasian patients had the worst survival rate, American Indian/Alaska
Native patients had the best survival rate, and Asian/Pacific Islanders and African-American
patients had an intermediate survival rate. Nevertheless, there was no race effect
when the model was adjusted for covariates. There are two potential explanations behind
a null finding. The mortality from spinal meningioma is very low; therefore, there
were not enough outcome events to find a difference by race. This study used all-cause
mortality and not cancer-specific mortality (spinal meningioma) as outcome. Due to
competing causes of death, it is difficult to find an effect when all-cause mortality
is used as outcome unless the disease in question is a leading cause of death,[[21]] which spinal meningioma may not be.
Most available studies on spinal meningioma, except one, were descriptive in nature
and pertained to the incidence rates in different racial groups.[[11]],[[22]] The sole study that reported prognostic estimates by race was by Maiti et al.[[12]] It enrolled 38 patients who underwent surgical resection and found no significant
difference between Caucasians and African–Americans in terms of recurrence (P = 0.745)
or functional improvement (P = 0.606) at 1-year follow-up. Although it was a small-sized
study, had a short follow-up, and did not include a broad spectrum of patients, its
findings were supportive of this current study.
This study's findings on spinal meningioma incidence by race were consistent with
earlier published studies. The study by Kshettry et al. showed that Caucasian patients
and Asian Pacific Islanders had the highest incidence of spinal meningioma, and African–American
and American Indian/Alaskan Native individuals had a significantly lower incidence.[[11]] A second study found that nonHispanic Caucasians had a significantly higher incidence
rate than nonHispanic African-Americans.[[22]] The observed racial difference in incidence might be attributed to the disparities
in genetic determinants (for example, polymorphisms, mutations), lifestyle, socioeconomic
status, and health care access.[[23]]
This study had several strengths and limitations. It was a population-based study
with robust sample size. The diagnosis of spinal meningioma and the outcome (survival)
were ascertained by validated means. Although SEER is an important database for clinical
research, the information contained in it might be subject to error (underreporting,
misclassification, etc.,).[[24]] In addition, patients might have migrated in and out of the registry areas, and
the database might not have all the necessary variables. For example, the multivariate
model of this study was not adjusted for several critical variables, such as surgical
complications, treatment compliance, and other medical comorbidities as they were
not available in the SEER database. Meningiomas have a long asymptomatic phase and
are frequently underreported tumors, and therefore, potential variations in reporting
are to be expected. This might have affected the incidence estimates of spinal meningioma.
Conclusions
The incidence of spinal meningioma was highest in Caucasians, who experienced the
worst survival rate, as compared to other racial groups. This racial difference in
survival lost its statistical significance when the model was adjusted for covariates.
Future studies should use spinal-meningioma-specific mortality as outcome to see whether
there is a racial difference in survival.
