Epidemiology of primary brain tumors in dr. Kariadi Hospital Semarang in 2015-2018

Background: Primary brain tumors are neoplasm originated from brain parenchyma and its surrounding structures. Although primary brain tumors is only 1,4% of all cancers, they causes significant morbidity and mortality. Objective: To study the epidemiology of primary brain tumors in Dr. Kariadi General Hospital Semarang between 2015 and 2018. Methods: a descriptive epidemiological study taken from medical records of hospitalized patients with primary brain tumors during 2015 - 2018. The data includes demographic characteristics and clinical characteristics. Results: There were 175 suspected cases of primary brain tumor, 38.3% occurred in males and 61.7% in females. The peak incidence is in 41-50 years (34.3%). 61.1% live in coastal areas. The frequent symptoms is headache (44.9%), with the most common location was in the frontal lobe (17.7%). The most common type was meningioma (24.5%). Meningioma were more common in females (90.7%), whereas glioma were more common in males (60%). 46.3% patients experienced clinical improvement at the time of discharge. Conclusions: The incidence of primary brain tumors are more common in females, the peak incidence are age 41-50 years, and most of them live in coastal areas.


Introduction
Primary brain tumors are a group of neoplasm arising from brain parenchyma and its surrounding structures. These tumors divided into degrees of malignancy from the benign to aggressive. Although primary brain tumors only 1,4% of all cancers, they are including the most aggressive tumors which result in mortality rate of about 60%. Despite these tumors, incidence are a relatively low, brain tumors cause significant health problems in worldwide by their high mortality and morbidity 1, 2. Benign tumor can be lethal due to their site in the brain, their ability to infiltrate locally and to transform into malignancy 3.
WHO classified central nervous system tumors based on the histological and molecular profile. By the year 2007, WHO classified based on the histopathological characteristic. And by the year of 2016, WHO renewed the diagnosis criteria by adding the molecular parameter 4, 5. Primary brain tumors etiology is still unsure, but some studies investigated the risk factors such as genetic, ion radiation, viral infection, head trauma, tobacco, and alcohol. Patients with brain tumors' clinical features are based on the volume and location of the tumor, either general from the increased intracranial pressure or focal neurological symptoms 2.
The workup diagnostic for brain tumors including imaging diagnostic by CT-scan, MRI, PET scan of the brain, and cerebrospinal fluid (CSF) analysis. Contrast head MRI is the first imaging modality choice because it produces detail image of the soft tissues, but still, histopathology is the gold standard diagnosis in brain tumors. Treatments for brain tumors are conservative management to reduce intracranial pressure, surgery, radiation, and chemotherapy as indicated 6.
The importance of the brain tumors epidemiology is to know the prevalence and characteristics of brain tumors either the histological or the sociodemography of the patients. There are still limited data about brain tumors epidemiology in Indonesia so that authors study the epidemiology of primary brain tumors in RSUP dr. Kariadi Semarang. It is expected that the presence of epidemiological data can help increase knowledge and early detection of brain tumors patients can be approached.

Methods
The research was descriptive epidemiological research with retrospective approach to describe the profile of primary brain tumor patients in RSUP dr. Kariadi Semarang. Data were taken from inpatients' medical records since year 2015 to 2018. The subjects were all inpatients who diagnosed as primary brain tumors. Data that were collected were patient's demographic characteristics including gender, age, geographic region, clinical manifestation, tumors location, histopathologic features, and patient's condition at the time of discharge. Data that have been collected then analyzed descriptively to perceive the primary brain tumors' profiles.

Subjects characteristics
There were 175 brain tumor cases suspected as primary brain tumors at RSUP dr. Kariadi Semarang between 2015-2018. All cases that suspected as primary brain tumors included in the research, including cases of unknown imaging results, no surgery, and unknown histopathological results.

Clinical characteristics
The most clinical feature which was gotten from thorough history taking and physical examination was headache which was found in 142 subjects (44,.9%).
Based on the imaging of the brain, frontal lobe was the most location. As the result of the biopsy, the most common tumor according to histopathological feature   Embryonal tumors, ependymoma, and craniopharyngioma more common in less than 20 years old.

Discussion
This research was descriptive epidemiological research with primary brain tumors patients who were treated in RSUP dr. Kariadi Semarang year 2015 -2018 as the subjects by retrospective approach from patients' medical records. In this research, female incidence was more common than male, i.e. 38.3% male and 61.7% female, concordant to the older references from the study in Spain and Korea which the frequency of women was higher than men, i.e. 57.25% and 61.4%, while the database from CBTRUS and meta-analysis study in America claimed that the incidence of female was more than men which were 24.77 vs 20.34 per 100.000 populations and 15.8 vs 14.33 per 100.000 populations. However, Pineros et al. claimed from the recent study that the incidence of male was equal to female 1, 7, 10, 13, 14. Primary brain tumor patients were mostly at the age of 41-50 years old, which was different from other recent studies that primary brain tumor's incidence increased by the age, especially high-grade glioma which often found at the age of more than 60 years old 7-9.
The most common symptoms were headache concordant to the recent studies in which headache was the most common symptom of either primary or metastatic brain tumors as the result of increased intracranial pressure. Adams et al. claimed that the incidence of headache was 48-56% 11, 12.
In this research, brain tumors most were in frontal lobe, while some recent studies claimed meninges as the most location of brain tumors wherefor in this research, the incidence of axial tumors e.g. astrocytoma was more than the tumors of meninges 7.
The most histopathological feature in this research was meningioma (24.5%). There were various results of the recent studies, the studies from RSCM, Pineros et al. from America, and Fuentes-Raspall et al. from Spain claimed that the most histopathological feature was glioma, while CBTRUS claimed that the most common primary brain tumor was meningioma. Some studies showed that the incidence of meningioma was higher in western than in Asia 7,10,15,16.
Most patients got better at the time of discharged, but because of the data limitations, factors affecting the outcomes were not analyzed.
Most common primary brain tumors in this study are meningioma (24.5%), similar to the literature that showed the ratio of male: female were 1:1.4-2.6 16.
Glioma was found more in men than women (55.8% vs 44.2%) which concordant to the recent references and studies. Sun et al. claimed that there was oncogenic and genetic mutation mechanism which is higher in men so that the prevalence of glioma is higher in men than women 7, 17, 18.
Data on environmental exposure to primary brain tumors remain unknown and controversial. In this research, the geographic region was categorized based on Samodra et al. Most patients with primary brain tumors lived in the coastal areas (< 100 m a.s.l). There were no studies that analyzed the altitude of residence to primary brain tumors. In this research, 61.14% patients lived in the coastal areas, but there was no data about the environmental and occupational exposures. In Indonesia which is an agrarian country, almost all residents work as a farmer. According to Badan Pusat Statistik (BPS), populations aged >15 years old who work in agricultural is about 38.35%. This fact proves that there is high exposure to agricultural chemicals such as pesticides that are believed to be neurotoxic and carcinogenic. A metaanalysis study in 1998 by Kuder et al showed a moderately increased risk that was statistically significant for primary brain tumors among farmworkers. Otherwise, coastal area also has more pollution from industry and vehicles than the highland 2, 19-21 .

Conclusion
There were 175 cases of brain tumors suspected as primary brain tumors in RSUP dr. Kariadi Semarang between 2015-2018. The incidence more common in females than males, which most in the age of 41-50 years old, and almost all lived in the coastal areas. The most common clinical feature is headache caused by space-occupying effect and increased intracranial pressure. The most type of tumor according to histopathological feature is meningioma, which found more common in female. Patients mostly live on the coast where there is agricultural chemicals exposure as one of the brain tumor risk factors.