Year wise chronological distribution of total primary malignant brain tumors s reported from January 2008 to January 2018

Distribution of total primary malignant brain tumors by age group and gender from January 2008 to January 2018

Distribution of total primary malignant brain tumors by age group and gender from January 2008 to January 2018 occurring at high altitudes

The most common anatomic sites involved by PMBT were overlapping lesions, i.e., lesion involving two or more contiguous sites of brain (149/416, 35.81%) followed by frontal lobe (116/416, 27.88%). The least common sites were occipital lobe and pineal region with both amounting to 0.8% and cerebellum 1.08% of cases as shown in [Table 4]. As illustrated in [Table 5], most of the PMBTs were found to be of glial origin (94.3%). Further subset analysis for various histopathology of PMBTs show that most often encountered histological subtypes were GBM (165/416, 39.66%) [Figure 1], diffuse astrocytoma (112/416, 26.92%) [Figure 2], anaplastic astrocytoma (39/416, 9.30%), oligodendroglial tumors (22/416, 5.28%), oligoastrocytic tumors (22/416, 5.28%), ependymal tumors (21/416, 5.04%), and embryonal tumors Medulloblastoma (13/416 3.12%) while very rare histological subtypes reported were Gliosarcoma (1/416), gliomatosis cerebri (1/416), central neurocytoma (1/416), hemangiopericytoma (3/416) [Figure 3], and tumors of pineal region (4/416) [Figure 4]. Two patients developed secondary GBM from Grade II astrocytoma over a period of 4–5 years. About 40% were positive for promoter methylation (O-6-methylguanine-DNA-methyltransferase [MGMT]). In 183 patients who had a history of exposure to high altitude areas also glial tumors dominated. 92/183 patients had GBM while 59/183 patients had diffuse astrocytoma as shown in [Table 6]. On subset analysis of patients posted at high altitude, we found that maximum number (48/183) of patients belonged to 30–34 years of age group as shown in [Table 7]. [Table 8] shows the distribution of patients according to altitude and duration of stay. We did not find any difference in the distribution of patients according to altitude. At all altitudes, glial tumors were the most common.

Topographical distribution according to anatomic sites

Distribution of total primary malignant brain tumors as per their histological patterns reported from January 2008 to January 2018

Distribution of primary malignant brain tumors as per their histological patterns occurring in high altitude areas

Distribution of total primary malignant brain tumors s as per their histological patterns by age group from January 2008 to January 2018 at high altitude

Distribution of total primary malignant brain tumors as per their histological patterns by duration from January 2008 to January 2018 at different stages of high altitude

Discussion

Brain tumors although are not frequent can lead to significant morbidity and mortality in view of proximity to vital centers. Review of various articles denotes prevalence of PMBTs to be around 1%–2% of all adult cancers[8],[9] and incidence of brain tumor are reported to be around 3.9/100,000 in males while 2.4/100,000 in females.[5] The prevalence of PMBTs in our study was observed to be around 1.05% (416/39,437) of all cancers reported which is nearly similar with the world literature. An estimated 79,270 new cases of primary malignant and nonmalignant brain tumors are expected to be diagnosed in the United States in the US in 2017.[10] The US incidence rate for primary brain and nervous system tumors in adults aged 20 years or older is estimated to be 4.67–5.73/100,000 persons.[11]

Our analysis suggested a male preponderance in overall incidence rates in all the age groups which is also in agreement with several other studies reported from various parts of the world. In a study by Yole BB in five Indian cancer registries including Mumbai, Delhi, Bengaluru, Chennai, and Bhopal also found a greater incidence of malignant brain tumors in males while benign tumors such as meningiomas were more common in females.[7] Out of 416 cases of PMBTs, 75 cases are on regular follow-up with our institute. We have observed only seven cases had a recurrence in due course of their illness and were offered optimum management according to the standard guidelines followed at our institute. Interesting finding in our study was that maximum patients were young males, belonging to an age group of 30–39 years. In a similar study by Dasgupta et al.,[12] they observed that the median age of glial tumors was seen to be at least a decade earlier than reported in the Western population, which could be partially explained by the lower life expectancy and a higher proportion of the younger population in India. Most common histopathology which we observed in our study was GBM which constituted almost 40% of all tumors which is in accordance with the worldwide literature. While in the similar study by Dasgupta et al.,[12] the most common tumor was astrocytoma (34.7%) followed by medulloblastoma and supratentorial peripheral neuroectodermal tumors (22.4%) and craniopharyngioma. In the USA, the incidence of anaplastic astrocytomas and GBM increase with age, peaking in the 75–84 age groups. There also gliomas are more common in men than women with the exception of pilocytic astrocytomas which occur at similar rates in men and women.[13]

The association between various occupational risk factors such as ionizing radiation, electromagnetic radiation need to be studied further. No comprehensive review of occupational risk factors for brain tumors has been published since 1986 but some issues discussed then are relevant even today. Since the report of Wertheimer and Leeper in 1979[14] of an increased incidence of brain tumors in children living in homes with an expected higher exposure to power-frequency electric and magnetic fields, exposure to electromagnetic fields have become an area of interest in the study of factors affecting brain tumor risk. Only few studies found clear indication of an association between radio frequency (RF) exposure and brain tumors. Out of this one was a cohort study by Kyrylenkos et al.,[15] and two were case–control studies.[16],[17] Although brain tumors are rare and the population attributed to risk is low assuming 13% of adults being occupationally exposed to RF fields assuming a relative risk of 1.3, about 4% of brain tumors can be attributed to RF exposure, i.e., 2200 cases per year in US.[18] Last few decades universal increase in the use of mobile phones emitting continuous RF radiation (non-Ionizing radiation) has created a lot of scientific buzz in area of epidemiological research for the keens to prove or disprove whether there is any association between brain tumors and exposure to RF radiation of which most of the studies quoted no any association between the both.

A probable hypothesis for increase in the incidence of PMBTs in the young persons in our study could be excessive exposure to cosmic radiation at high altitudes as they are regularly been deployed at various hilly regions of Jammu-Kashmir and North East India due to service exigencies, with the maximum altitude deployment at around 6400 meters (≈21,000 feet). Average background radiation in an Individual at ground level is approximately 370 mRem/year which increases to 1 mRem/year with every 200 feet ascent in altitude. Although the cumulative exposure does not cross the average safety limit, a continuous low-dose exposure could be one of the reasons for the de novo changes.[19],[20]

Various studies have found an association between low-dose radiation exposure and malignancies are going on at present world over. Except for therapeutic X-rays, no environmental or lifestyle factor has unequivocally been established as risk factor or brain tumors. During the last decades of the 20th century, some types of brain tumors show a steady increase of a few percentage per year, which might be some extent related to the introduction of computed tomography and other high-resolution neuroimaging methods. In a study by Bondy et al.,[21] found that even the comparatively low doses (averaging 1.5 Gy) used to treat tinea capitis have been associated with relative risks of 18.10 and 3 for nerve sheath tumors, meningiomas, and gliomas, respectively. There was increased mortality among airline pilots was reported due to brain tumors possibly implicating exposure to cosmic radiation at high altitude in the same study.[21] Occupational risk findings from atomic energy and airline employees were equivocal. A small but statistically significant elevated risk of 1.2 for the occurrence of brain tumors in nuclear facility employees and nuclear materials production workers has been reported by Hodges et al. [22] While the similar study by Gundestrup and Storm,[23] noticed that although malignant melanoma and skin cancer were in excess in cockpit crew members, there was no increased risk of brain cancers in pilots.

A latest research by the National Aeronautics and Space Administration has revealed the results of a major new study into the effect of radiation at high altitude. Cosmic rays from the sun and space crash into molecules in the atmosphere, causing particle decay, and radiation which can be harmful to our health. The new study, using weather balloons, took some of the first radiation measurements of their kind at altitudes from 26,000 feet to over 120,000 feet above earth. While we are mostly safe from this radiation on the ground, pilots, and aircrew are exposed to the dangerous radiation as are astronauts. Earth's magnetosphere acts as a magnetic shield and blocks most of the radiation from reaching the planet. However, particles with enough energy can penetrate the magnetosphere and the atmosphere and can harm the people getting exposed.[24]

Apart from other factors, the concept of different genetic pathways leading to cancer has gained considerable acceptance as far as GBMs are concerned. Two main types have been described primary GBMs which mainly occur in elderly patients and are characterized by mutation in the phosphate and tensin homolog gene and epidermal growth factor receptor while secondary GBMs are a feature of the younger population and have P53 and platelet-derived growth factor mutations.[12] We had two cases of secondary GBMs, and both our cases were P53 positive. Promoter methylation (MGMT) was positive in 40% of our patients. The frequency of methylation status reported in the literature varies probably because each laboratory uses a slightly different technique. Various methods for quantitative measurement of MGMT methylation are being formulated to remove this discrepancy.

Conclusions

A major task which is still not accomplished over the years in descriptive brain tumor epidemiology is the explanation of gender and ethnic differences for gliomas and meningiomas. Further analytic studies of various factors such as diet, occupational factors, and potentially relevant polymorphism are likely to improve our understanding of this devastating disease. Since currently established or suggested risk factors do not account for most cases, novel concepts of neurocarcinogenesis are required before a comprehensive picture of the natural history and pathogenesis of brain tumors can be formed. Given these formidable challenge, future epidemiologic research on brain tumors is likely to be exciting. Although brain tumors are rare and nothing concrete has been found about its etiological factors, several predisposing risk factors postulated by various studies are white race, family history of brain cancer, certain chemical exposures, and exposure to ionizing radiation. In our study, we have postulated a hypothesis of increased incidence of PBMT in younger population due to exposure to cosmic radiation at high altitude which needs to be explored further.

Conflict of Interest

There are no conflicts of interest.

Acknowledgments

Ethical approval: Written informed consent to publication was obtained from the patients. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. We also like to extend our gratitude to departments of Pathology and Molecular Science, Surgical Oncology, Medical Oncology, Nuclear Medicine and Radiology, Army Hospital (Research and Referral), New Delhi and Command Hospital (Southern Command), Pune, India.

References