The higher tumor volume (4.2–268 cm3) calculated for occult primary tumors as compared with that of multiple brain tumors with diverse origin (0.70–164. 59 cm3) shows that occult tumor is deadlier and more proliferative. Brain tumor cell of less than 2cm can be treated using chemotherapy [19]. Medulloblastoma can affect children of greater than 3-years. Pediatric tumors, global and neuronal are more sensitive to chemotherapy [20]. Lomustine is not effective in the treatment of brain tumors hence may not be effective in human. Therefore there is need for standardized design and treatment outcomes for brain tumors [21]. Elderly patients with malignant astrocytoma’s received limited treatments which are correlated with survival variation, suggesting that in clinical neurooncology, patient age is associated with lack of effective therapy and worse prognosis [22]. Diagnostic and treatment modalities of brain tumors have been advanced by neuroimaging [23] despite the increased incidence in all the age groups especially the older adults [24]. Strict adherence to treatment protocol of brain tumors in pregnant allow term delivery via vagina [25]. The most frequent brain tumors are gliomas, therefore optimal treatments should be standardized and individualized [26]. Although, chemotherapy plays a significant role in childhood in edulloblastoma, low-grade gliomas, and high-grade gliomas, others such as a typical teratoid tumors, brainstem gliomas, malignant gliomas and malignant infantile tumors remain therapeutic dilemmas [27]. Early detection of gliobhlastoma multiform has little effect on survival of elderly patients [28]. Patients with tumor volume less than 20 cm3 have lower risk of death than the patients with tumor volume higher or equal to 20 cm3 [29]. ZIC1 and ZIC2 are markers of meningiomas while ZIC4 is for medulloblastoma and may reflect properties of tumor tissue [30] invariably determining the mechanisms of action of their anticancer drugs. However, intracranial hemorrhage is common with patients of brain tumors [31]. Tetrahydroxycannabinol has antitumor activity against recurrent glioblastoma multiform in phase 2 trial in human [32]. Combination of surgery, chemotherapy and radiotherapy is the cornerstone of pediatric tumor management [33]. Dexamethasone is recommended for symptom relief in primary high-grade glioma at a maximum dose of 16mg in 4equal doses and should be tapered rapidly where necessary. But patients with high-grade brain tumors can take maintenance dose (0.5–1.0 mg) daily. But when one of the followings endocrine, muscular, skeletal, gastrointestinal, psychiatric and haemalotogic complication is observed, the drug should be withdrawn immediately [34]. Mobile cell phone can cause glioma meningioma and acoustic neuroma [35]. Lack of specialized multidisciplinary team may make surgical intervention difficult [36]. There was more incidence of benign CNS tumors (61%) than malignant CNS tumors (39%) suggesting the need for specialized care [37]. A blunt age-related decline in basal metabolic rate (BMR) was associated with high mortality reflecting poor health status [38] indicating that young cancer patients may respond better to the cancer chemotherapy than the very elderly ones. Metabolic reporgramming in brain tumors influenced by tumor microenvironment contribute to drug resistance and tumor recurrence. However, altered metabolism may provide effective therapy for brain tumors [39]. The calculated radius (4 cm) of glioblastoma, planum sphenoidale meningioma (1.85 cm), multimeningioma (0.55 cm) secondary to pituitary adenoma ( Table 2) shows that pituitary adenoma could cause secondary brain tumors in both man and woman] of 50–63 year. Pancreatic cancer of 4.5cm could lead to brain metastasis of 4cm in woman [40]. Primary brain tumors occurred in the adults within age range of 37–82 years. Females are more affected and surgical removal remains the major intervention and the prognosis is poor [41]. Side of head of interventional cardiologists/radiologists is more vulnerable to brain tumours [42]. Prognosis of congenital brain tumours is poor with the longest median survival seen in choroid plexus papilloma and astrocytoma, but teratomas are rapidly fatal [43]. However, Kernel statistical method for evaluation of continuous risk variables could be combined with Cox model that determines threshold of continuous variables for determination of survivability of patients with primary brain tumours [29]. Mathematical model of glioblastomas that incorporates tumor growth, cancer cell diffusion and cell proliferation rate is clinically useful and predictive [9]. Regardless of treatment protocol, the life expectancy of gliomas is 9–12 months [44]. The maximum tolerated dose of single fraction of radiation surgery is 15–24 y for tumor diameter (≤ 20mm – 40mm) [45]. The brain synchronizes billions of neuronal cells for physiological and psychological function. But malignancy changes the function of brain as observed in glioblastoma patients with 5% chance of 5years survival in adult and 20% chance of 5 years survival for glioma in children [46]. The patients treated of glioma could have neurological impairment leading to low intelligent quotient (IQ). The concentration of the tumor mutant alleles varied from < 5–3000 copies /ml of cerebiospinal fluid (CSF) and of somatic mutations have been identified [47]. Mobile phone radiation could cause glioma, acoustic neuroma, meningioma and brain cancer when phones are used < 1–5 years [48]. However, methyl cholanthrene could cause brain tumors [49]. However fish intake was associated with lower risk of brain cancer risk [50], despite the increased risk of glioblastoma multiforme being associated with environmental or life style factor [51]. Brain metastases are commonly associated with cancers of lung, breast and colon. The symptoms are headache, nausea and vomiting, seizures, dizziness, weakness in hands, arms, feet and legs, blurred vision, slurred speech and decreased memory or concentration [52]. Genetic disposition of brain tumor with the increased incidence from the age 30 years and low incidence of 75 years and male: female ratio of 1.5:1 show that women are more likely to develop meningiomas than men [53], suggesting that gene therapy may be a potentially beneficial to human brain tumors as opposed to aggressive surgical resection, radiation and chemotherapy. The WHO grading of CNS tumors is as follows: grade I (slow-growing tumor, postoperative healing after resection, long term survial), grade II (comparatively slow growing, progresses to malignancy, often recurs), grade III (High proliferative potential, malignant, requires adjuvant radiation/chemotherapy) and grade IV (rapidly proliferative, malignant, highly aggressive) respectively [54]. However, radiotherapy of parkinsomsm patient with brain tumor is relatively safe [55].Assessment of potential risk should be based on tissue or organ radiation dose and understanding of the corresponding dose-response relationships [56].Tissue weight is relative to radiosensitivity and assumed total risk of radiation. Hence hypothetical tissue factor is assumed to be 1.0 [57] but weighting factor for brain is 0.01 [58].
Table 2
Mathematical parameters of multiple primary brain tumors with diverse origin in human
S/N | Tumour Type | Sex | Age | Location | Dimension (cm) | TV (cm3) | TW (g) | Density | TP | RM (cm2/yr) | Radius (cm) | Comments |
1. | Meningioma/diffuse astrocytoma | F | 68 | LFL | 4.5x4.5 | 47.7 | 45.56 | 0.96 | 7.9 x 1010 | 20.25 | 2.25 | Dead |
2. | Glioblastoma multiform/pituitary adenoma | M | 63 | RFPL | 5.2x6.8x5.4 | 164.59 | 99.14 | 0.60 | 1.7 x 1011 | 36.72 | 3.40 | Dead |
3. | Glioblastoma multiform/pituitary adenoma | M | 63 | SF | 2.0x2.1x2.9 | 12.77 | 6.39 | 0.50 | 1.1 x 1010 | 6.09 | 1.45 | High survival |
4. | Planum sphenoidale meningioma pituitary adenoma | F | 62 | PS | 3.7x3.0x1.8 | 26.52 | 16.65 | 0.63 | 2.9 x 1010 | 11.1 | 1.85 | Dead |
5. | Pituitary adenoma/multi meningiomas | F | 50 | SR | 1.1. x 1.0 | 0.70 | 0.55 | 0.79 | 9.5 x 108 | 1.10 | 0.55 | High survival |
Keys: LFL = Left frontal lobe; RFPL = Right frontoparietal lobe; SR = Sellar region; PS = Planum sphenoidale; TV = Tumor volume; TW = Tumor weight; TP = Total proliferation; RM = Rate of migration |
Hypoxia PET tracers could be used to identify tumors at preclinical stage [59]and manual radiotherapy may yield better result than automated radiotherapy [60]. Histological primary brain tumors are pilomyxoid astrocytoma, pleomorphic xantho-astrocytoma, subependymal giant cell astrocytoma, fibrillary astrocytoma, anaplastic astrocytoma, glioblastoma, giant cell glioblastoma, gliosarcoma, glioblastoma with oligodendroglial component, small cell glioblastoma, glioblastoma with primitive neuroectodermal tumor-like component, adenoid glioblastoma, granular cell glioblastoma, gliomatosis cerebri, oligodendroglioma, mixed oligo-astrocytoma, myxo-papillary ependymoma, sub-ependymoma, cellular ependymoma, clear cell ependymoma and tranycytic ependymoma. Others are demoplastic medulloblastoma, classic medulloblastoma, anaplastic medulloblastoma, CNS- primitive neuroectodermal tumor, atypical teratoid tumor, ganglioma, gangliocytoma, astrocytoma, dys-embryoplastic neuroectodermal tumor, central neurocytoma, extra-ventricular neurocytoma, cerebellar liponeurocytoma, papillary glio-neuronal tumor, Rossatte forming tumor of the 4th ventricle, choroid plexus papilloma, atypical choroid plexus papilloma, choroid plexus carcinoma, pineocytoma, pineal parenchymal tumor of intermediate differentiation, pineoblastoma, papillary tumor of the pineal region, angiocentric glioma, choroid glioma of the 3rd ventricle, astroblastoma, and cribriform neuroepithetial tumor [61]. Response to analgesics against pain from any of these tumors may be hermetic yohimbine, clopamine, promethazine, levodopa, prostaglandin, cannabinoids, nocistatin, histogranin, calcitomin, hyprenorphine, morphine, and antiemetics may be used [62]. But congenital brain tumors that may manifest few days after birth account for 0.5–1.9% of all paediatric brain tumors, teratoma being the most common type. Diagnosis is usually difficult, though based on clinical characteristics, radiological findings, magnetic resonance imaging and ultrasonography. The prognosis depends on histopathological features and the tumor location, hence the treatment is difficult [63]. Brain tumors are the 2nd most common cancers after haematological malignancies accounting for 21% of all childhood cancers affecting children of ≤ 14 years, males are more affected [64]. Cerebrospinal fluid, flow cytometry, proteomic, micro RNAs analyses could be used for discovery of brain cancers [65]. Pilocytic astrocytoma is associated with high fetal growth [66]. But prostate cancer could cause solitary brain metastasis [67] as trauma could also cause glioma [68], suggesting that benign brain tumors could significantly increase annually with part of temporal attributable to improved diagnostic imaging techniques [69].
A 2-day old male baby weighing 2.6 kg of height 0.43m and cranial circumference 0.34m was diagnosed of brain tumor [70]. Gliosarcoma is a high-grade glioma and a variant of glioblastoma multiforme. It accounts for < 2% of all glioma and 5% of all astrocytomas [71]. Early brain tumor could manifest first sign as bradycardia [72]. Meningiosarcoma (cerebral sarcoma) was treated in a 3-year-old boy by surgery and radiation and 55 years later, rebonced, suggesting that comprehensive medical history could reveal early diagnosed pediatric brain tumors [73]. Large cystic astrocytoma could be removed successfully without recurrence. The affected babies had large heads [74]. Therefore, histology, conventional molecular tests and methylation arrays could be used as diagnostic markers for adult brain tumours [75]. Gliomagenesis by traumatic brain injury could be proven by radiography [76]. Environmental risk factors for brain tumors are ionizing radiation, mobile phone, extremely low frequency electromagnetic fields, specific infections, allergies diet, tobacco, alcohol, chemical agents, occupations and head trauma or injury [53]. But metastatic brain tumors may respond to paclitaxel [77]. Metronomic (low-dose) chemotherapy is effective in children [78]. Hence, there is need to explore formulas that can be used for calculation of safer low doses of chemotherapeutics for brain cancers. Cancer chemotherapy can be classified as primary, an adjuvant and palliative [79]. The three most common brain tumors are medulloblastoma, glioma and ependymoma, but targeting specific brain tumor pathways and mutations to improve efficacy with a reduced toxicity are very important [80]. One drug fits all therapy paradigms should be replaced by individualized therapy for specific brain tumors [81]. High doses of bleomycin are effective and can be used in the treatment of craniopharyngiomas (5- 17.5 mg/kg), glioblastoma 7 mg/kg and astrocytomas 3 mg/kg with few patients exhibiting transient fever, headache, vomiting, lethargy and peritumoral edema [3]. Small molecule kinase inhibitors could be of great benefit for the treatment of glioblastoma multiform and other brain metastases [68]. Born neutron capture therapy (BNCT) is a form of radiotherapy which combines neutron irradiation with a boron. The high linear energy transfer (LFT) is deposited in a range of 10µm, an equivalent of cell diameter [82]. Radiotherapy of glioblastoma multiform (GBM) could lead to more aggressive form of the cancer. But targeting protein (MDA − 9 or Syntenin encoded by melanoma differentiation-associated gene with a small molecule inhibitor may prevent this side effect. Also the drug against brain cancer targets a protein interaction domain in MDA-9, blocking signaling pathways that promote invasiveness and proliferation in glioblastoma cells. Tumor sensitivity to radiation and improved survival is also boosted [83]. Computed tomography-related radiation could increase the risk of brain tumors [84]. The risk factors of child brain tumors are ionizing radiation exposure, cancer syndromes, age, birth defects, and fetal growth among others [85]. Subtle symptoms such as headache are associated with aging and brain tumor [86].