Spectrum of primary intracranial tumors at a tertiary care neurological institute: A hospital-based brain tumor registry
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.181535
Source of Support: None, Conflict of Interest: None
Background: Hospital-based cancer registries (HBCRs) provide information on the magnitude and distribution of cancers in a given hospital. Hospital-based brain tumor registry (HBBTR) data on primary intracranial tumors from a tertiary care neurological center is presented. This is compared with related national and international data.
Keywords: Adult central nervous system tumors; brain tumors; epidemiology; hospital-based cancer registry; pediatric central nervous system tumors
In the sphere of global public health, the increasing burden of cancer in developing (middle- and low-income) countries is a crucial problem. The Globocan 2012 study by the International Agency for Research on Cancer reported that 56.8% of all patients diagnosed with cancer, and 64.9% of cancer-related deaths occurred in “less developed regions of the world.” The same study revealed that, in India, over a million new cases were diagnosed in 2012, comprising more than 7% of the global cancer burden estimated from 184 countries worldwide. These dismal figures, thus, represent both a crisis and a challenge for healthcare systems in India. The lack of infrastructure, low health budget, and limited healthcare services are just a few of the many problems that developing nations struggle with. To cope with these difficulties, the long-term strategy necessitates prediction, preparation and prevention of the escalating cancer epidemic in our rapidly increasing population.
In this respect, cancer registries work as an important resource for the “accurate measurement of cancer burden and are crucial for the assessment of national control programmes and other preventive and treatment efforts.” Population-based cancer registries (PBCRs) form the key to the estimation of incidence and patterns of tumors in a population, allowing policy-makers to make informed decisions and raise the standards for enhanced and equitable cancer care. Although hospital-based cancer registries (HBCRs) are generally oriented toward administration, policy and individual patient needs of a hospital, they also form an integral part of all PBCRs.
Tumors of the central nervous system (CNS) are rare and account for about 1–2% of all malignancies in cancer patients. However, their association with a high morbidity and mortality makes them the most dreaded form of cancer. Generation of hospital-based brain tumor registry (HBBTR) data examining the spectrum of brain tumors within the Indian population would help us to contribute to large-scale studies nationally, similar to the ones done internationally. HBBTRs would provide us with the necessary clinical benchmark for comparison of data of CNS tumors with previous and future studies, as well as world literature. Such data would be invaluable not only in highlighting healthcare and policy needs of the nation, but also in directing academic research into brain tumors.
Few studies on brain tumors are available in India coming from major institutes such as Tata Memorial Hospital (TMH), Mumbai, and All India Institute of Medical Sciences, Delhi., In addition, some epidemiological studies in India have focused solely on the pediatric population., Thus, there is a limited availability of robust statistical data for use in national cancer registries and epidemiology studies in India, which could aid in the calculation of accurate incidence rates for various brain tumors in our country.
The aim of this study is to provide a comprehensive spectrum, both clinical and histopathological, and distribution of various primary intracranial neoplasms diagnosed at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India - a major neurosciences tertiary care hospital in South India. In addition, we compare this data with data from TMH Mumbai as well as an international brain tumor registry - the Central Brain Tumor Registry of the United States (CBTRUS).
The schematic flowchart, as shown in [Figure 1], represents the workflow for the generation of this 5-year HBBTR. Data of all intracranial tumors diagnosed and registered at the Department of Neuropathology, NIMHANS, between January 1, 2010 and December 31, 2014 was collected (n = 5147) from the neuropathology records. Patients' gender, age, and histological diagnosis were entered into our database and any personally identifiable details of patients were delinked from the collected data.
The inclusion criteria were all primary intracranial neoplasms codified under the World Health Organisation (WHO) 2007 classification. In addition, tumors of the pituitary gland (though not codified under WHO 2007) were also included in this registry. Based on exclusion criteria, cases with incomplete clinical data, inconclusive pathology, or differential diagnoses; entities not codified under WHO 2007 or International Classification of Diseases for Oncology, Third Edition (ICD-O-3), all metastatic, residual, and recurrent intracranial tumors, bony tumors, and benign non-tumorous cystic lesions (arachnoid cysts, colloid cysts, epidermoid cysts etc.) were excluded from the analysis.
The raw data obtained after setting these inclusion and exclusion parameters was then cross-checked and validated. Patients within the age range 0–18 years were categorized as pediatric, whereas those 19 years and above were categorized as adults in accordance with the CBTRUS database. Once complete, this data was codified and statistical analysis was carried out using the statistical software - SPSS version 16 (SPSS, Inc., Chicago, IL, USA) and graphs were generated for data visualization.
The present registry generated between the years 2010 and 2014, consisted of a total of 4295 cases, comprising 1847 (43%) female and 2448 (57%) male patients. The proportion of primary intracranial tumors to all cases diagnosed at the Department of Neuropathology in NIMHANS remained relatively consistent between 34% and 37% over this 5-year period [Figure 2].
Upon age-wise distribution, it was noted that the maximum proportion of intracranial tumors was diagnosed in the fourth decade, and 58% of all patients were adults between the ages of 30 and 60 years. About 10% of the cohort comprised patients aged 10 years and below, whereas about 2% were aged 70 years and above [Figure 3]. Overall, pediatric and adult patients accounted for 16.2% and 83.8% of the cases, respectively.
Distribution based on age and tumor grade
Overall, 36.3% tumors in the registry were classified as WHO Grade I, 11.4% as Grade II, 20% as Grade III, and 18.9% as Grade IV tumors. About 13.3% of the cases (encompassing pituitary adenoma, non-Hodgkin's lymphoma, etc.) remain unclassified with respect to the WHO grading system. For the 3723 codified tumors, we looked at the age-wise distribution along with percentage of each tumor grade. The results indicated that, barring the pediatric population, there was an increasing proportion of Grade IV tumors with increasing age [Figure 4]. Inversely, with the exception of the pediatric age group, percentage of Grade I tumors were observed to be consistently decreasing with increasing age. The proportion of Grade II and III tumors, however, changed variably in different age groups.
After this, we analyzed the percentage distribution of all primary intracranial neoplasms based on tumor histology in our cohort [Figure 5]. Subsequently, we grouped it into two broad categories, i.e., into pediatric [0–18 years, n = 694 (16.2%)], and adult [19 years and above, n = 3601 (83.8%)] population. The spectrum of all primary intracranial tumors based on their histopathological diagnosis in these two groups is discussed in the following section.
Histological distribution of all pediatric tumors
Nearly a quarter of all tumors within the pediatric population were astrocytomas (25.1%), followed by embryonal (20.6%) and ependymal tumors (14.8%). Together, these 3 tumor types constituted more than 60% of all pediatric tumors [Figure 6]. Within the embryonal tumors, about 80% were medulloblastomas and 12.6% were atypical teratoid/rhabdoid tumors. Craniopharyngiomas, glioblastomas, glioneuronal tumors, meningiomas, and choroid plexus tumors constituted 9.5%, 5.8%, 5.6%, 4.2%, and 2.3% of all tumors, respectively.
Histological distribution of all adult tumors
The largest proportion of tumors in the adult population was noted to be meningiomas (23.2%), glioblastomas (15.5%), nerve sheath tumors (12.7%), oligodendroglial tumors (11.4%), pituitary adenomas (9.9%), and astrocytic tumors (6.4%). The rarest tumors were glioneuronal, embryonal, pineal, choroid plexus, and germ cell tumors with a combined frequency of <4% [Figure 7].
Histological distribution of gliomas in the adult versus pediatric group
We also looked at the distribution of gliomas exclusively within our cohort [Table 1]. In the adult group, glioblastomas were the most common tumor (38%) followed by anaplastic oligodendrogliomas (24.5%). Meanwhile, in the pediatric group, pilocytic astrocytomas were the most common (44%) glial tumors, making up almost half of all gliomas seen in children, followed by ependymomas (31%).
Distribution based on gender
After the spectrum of tumors based on histological profiles, we analyzed the gender distribution of primary intracranial tumors for each histology. Male-to-female (M:F) ratio was noted as 2.6:1, 2.4:1, and 2.1:1 under germ cell tumors, glioblastomas and lymphomas, respectively. Astrocytic, pineal, and nerve sheath tumors showed a relatively balanced ratio of 1.3:1, 1.1:1, and 1.1:1, respectively. The gender ratios for all other histologies indicated a male preponderance. The only exception was seen in meningiomas, with a ratio of 0.5:1, indicating a distinct female predilection of this tumor [Figure 8].
Comparison with Western and Indian literature
Clinical parameters such as median age at diagnosis in our HBBTR data was compared with world literature, as well as Indian data [Table 2]. For almost all histologies, the median age at diagnosis was similar between the TMH and NIMHANS data, marginally varying by just 1–3 years for most lesions. A few differences were also noted, such as for pineal tumors, the median age at diagnosis was seen to be 18.5 years in the TMH data vs. 25.5 years in the NIMHANS data.
Comparison with the CBTRUS data revealed that while the median age at diagnosis was early in our cohort for all histologies, it was almost a decade early for nerve sheath tumors, lymphomas, and diffuse astrocytomas, revealing a distinct discrepancy. The median age at diagnosis for glioblastoma was noted at 50 years within both TMH and NIMHANS cohorts, which differed significantly from the CBTRUS data at 64 years.
The CBTRUS report is one of the most comprehensive reports providing epidemiological data of all primary CNS tumors seen in the US Population. It has allowed clinicians and researchers to understand the incidence and patterns of CNS tumors in the United States and use them as a point of reference for comparison with data from their own population. Such high-quality and large-scale statistical reports are a crucial resource to the long-term goal of cancer-control, planning, and evaluation.
The Indian Council of Medical Research (ICMR) had first set up the National Cancer Registry Programme in December 1981, allowing data collection to start from January 1, 1982. The 3-year report of PBCR in India published by the ICMR in 2013, states the presence of 27 PBCRs and 7 HBCRs in the country dedicated to the collection of reliable cancer-based data from various regions across India. The generation of HBBTRs, thus, permits the analysis and comparison of occurrence with other countries, laying ground for evidence-based brain tumor research and eventual control measures which need to be taken to reduce the burden of such tumors within our population. The differences and similarities noted between our as well as the TMH and CBTRUS data are discussed in detail below.
CNS tumors in the pediatric population (0–19 years) comprised about 6.6% of overall CNS tumors in the CBTRUS database when compared to 16.2% (0–18 years) in our Indian cohort. This could largely be attributed to the sizeable percentage of young people in our country as compared to the US population. Interestingly, the percentage of male and female patients in the CBTRUS data is recorded as 42% and 58%, respectively, whereas in our HBBTR it was observed inversely at 57% and 43%, respectively. The reason for such variation is unexplained though one cannot rule out any possible bias in seeking medical care. We also had 253 cases of metastatic tumors which constituted about 5% of all the brain tumors collected initially [n = 5147, [Figure 1] and were seen more commonly in male rather than female subjects. However, the data on metastatic tumors is not added to the results since our data reflects only primary intracranial brain tumors.
The percentage of all astrocytomas (including glioblastomas) in our pediatric cohort equals 30.9% [Figure 6]. This figure correlates with the national average of 34.7% quoted in an earlier multi-institutional study carried out across seven tertiary care hospitals in India. Embryonal tumors constituted 20.6% of all pediatric tumors, which was also comparable with the national average.
Similarly, majority of our data corroborates with similar data within India with minor differences. Only for pineal tumors, the median age at diagnosis was seen to be later in our cohort when compared to the TMH data. One likely explanation could be that while the TMH data was collected in 2006, our HBBTR data has been collected from 2010 to 2014, allowing for more data to be collected over a longer duration. Based on the same precept, when looking at the median age in histologies such as oligodendroglial tumors, pineal tumors, and pilocytic astrocytomas, our data lies about midway between the TMH data and the CBTRUS data generated from 2006 to 2010. However, for histologies such as craniopharyngiomas, meningiomas, glioblastomas, anaplastic astrocytomas, and pituitary adenomas, data generated from the Indian cohorts corroborate each other but are seen to occur a decade or two early when compared to the CBTRUS data. A study on another Asian cohort of Chinese glioblastoma patients noted that the age at onset in their population tended to be younger when compared to the Caucasian populations. Another study examining racial differences in primary malignant brain tumors indicated statistically significant difference in the average age at diagnosis among Caucasians and African Americans (54.8 years vs. 50.6 years), within the same cohort. An epidemiological review of gliomas by Ostrom et al., notes that the incidence rates of gliomas significantly differ by “histological subtype, age at diagnosis, gender, race, and country.”
However, apart from the ethnic differences, such trends of early onset of disease are not exclusively limited to brain cancers. The tendency for an earlier age of presentation of the disease in Indians, as compared to international populations, has also been noted for colorectal cancer. Renal cell carcinoma and breast cancer have also been shown to present about a decade early in our population as compared to our Western counterparts.,
One of the factors that can be considered as a plausible explanation for this discrepancy is the average life expectancy of the population in India when compared to the US population. The WHO's global health observatory data repository lists the average life expectancy (both sexes combined) in India at 66 years, compared to 79 years in the United States. The contribution of allele frequencies to the disease risk in people with different ethnic origins has also been hypothesized in some studies on gliomas  and breast cancer.
The difference in lifestyle, dietary habits, and environmental exposure are among the many factors yet to be thoroughly evaluated in understanding brain tumor risk in people with different ethnicities. The etiology of cancer is complex and has multifactorial risk factors. Gene-environment and gene–gene interactions are the underlying factors which may also contribute to the observed differences when looking at data generated from geographically diverse populations such as ours, when compared with US populations. Consequently, such interactions warrant well-designed, large-scale, and statistically accurate studies to elucidate the different risk factors.
Furthermore, we looked at the patterns of gender distribution of the commonly noted tumors which stood out from the rest. The most frequently reported histology overall in both CBTRUS and NIMHANS data is meningioma (36% in CBTRUS vs. 20% in NIMHANS). This was followed by glioblastoma, which showed a similar percentage of overall tumors in both CBTRUS (16%) and our HBBTR data (14%) [Figure 5]. The M:F ratio of 0.5:1, better represented as F:M ratio of 2:1, was noted in meningiomas and matches the CBTRUS data on meningiomas. Other review articles have also noted the same results., Due to the female preponderance, the association of disease risk with the presence of sex hormone receptors in meningiomas had been hypothesized , but remained controversial. However, a study in 2008 documented a positive association between the use of hormone replacement therapy and the diagnosis of meningioma in women. Further studies are needed to confirm a definitive underlying cause for the relatively higher incidence of meningioma in female patients. Similarly, gliomas have been implicated as tumors with a distinct male predilection in several studies. Glioblastoma, which accounts for the large majority of gliomas, shows a M:F ratio of 2.4:1, higher than that reported in the WHO 2007 data (1.26: 1 in the United States and 1.28:1 in Switzerland). Sustaining this, the CBTRUS report states that the incidence rate of glioblastoma in men is 1.57 times than that in women. A recent study by Sun et al., found that inactivation of the tumor suppressor retinoblastoma in glioblastoma is noted to be twice the incidence in males than in females, perhaps explaining the predominance of glioblastomas in males. In addition, as our study includes slightly higher number of males than females (57% vs. 43%), the possibility of a cohort specific gender bias cannot be ruled out to explain the distinctly high M:F ratio noted in glioblastoma. A comparable malignant tumor in children is medulloblastoma which accounts for 80% of all embryonal tumors (M: F ratio of 1.9:1). Bolstering this, the WHO 2007 classification describes that “approximately 65% of patients are male,” which can be simplified to a M:F ratio of 1.86:1, similar to that seen in our study.
While our study has generated some corroborating patterns and interesting insights into the prevalence of primary intracranial tumors, it also had certain limitations that need to be considered. Only details of patients who underwent surgery and had confirmed histopathological diagnosis were included in the registry. Along the same lines, this data has been generated from a single tertiary care neuroscience institute in South India and is not representative of the entire Indian/South-Indian population. The varied demographical origin of incoming patients in our HBBTR makes it challenging to calculate even the state-wise incidence rates for comparison purposes with the Western data, since a number of patients from across the country come to our institute for treatment. Furthermore, as our institute is a government hospital, it is likely that the socioeconomic status of our patients is biased towards the low-income populations.
This HBBTR from a single hospital, while giving a glimpse of the varied incidence of brain tumors, is limited in usage. In-depth studies from across various hospitals in the country are important to have a nationally representative data on the incidence of brain tumors in developing countries like India. It is imperative that a concerted effort be made to create such pan-hospital brain tumor databases. In this respect, such registries would be the key drivers for obtaining better and more robust data which could eventually be stored in HBCRs and PBCRs. These could then be used to provide the baseline data to better understand the epidemiological profile and etiology of primary brain tumors and guide research toward those with highest mortality and/or incidence. This would be a step forward toward translational research in the field of neuro-oncology, which would impact future treatment outcomes for brain tumor patients.
We would like to thank and acknowledge the efforts of Apoorva Anil, Shivayogi D. Shwetha, Nagabhishek Natesh, Harsha S. Sugur, and Kruthika B. S. for their contribution to the process of data collection, and M. R. Chandrashekar, A. R. Ananthalakshmi and Tilak D. for their help in retrieving the older records. Also, we would like to thank the Department of Neuropathology, NIMHANS, for allowing us to access their database.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2]