BRAIN TUMORS

CONTENTS:

• Abstract
• Introduction
• Pathophysiology
• Overview of brain tumor
• Epidemology
• Signs and symptoms
• Diagnosis
• Types of brain tumor
• Treatment method of brain tumor
• Vaccinations
• Conclusion
 1.ABSTRACT

TITLE: BRAIN TUMORS

 Brain tumor refers to an abnormal cell growth of mass of cells in (or) around the brain.
 Brain tumors may be malignant (cancerous) or non-cancerous.
 It is most common malignant primary intracranial tumors of central nervous system.
 Brain tumor can impair brain function if they grow large enough to compress nearbynerves, blood vessels and tissues.
 Only one third of tumors developed in the brain are developed as cancerous cells.
 Brain tumors discharge molecular data to the circulation.
 Liquid biopsies harvest and examine tumor component in body fluid andthere is growing interest in research of liquid
biopsies as alternative fromtumor markers.
 Tumor-derived biomarkers consist of nucleic acids, proteins andtumor-derived extracellular vesicles that concentrate in
blood (or) cerebrospinalfluid.
 Flowing biomarkers such as O-6-methylguanine DNA methyl transferase,epidermal growth factor, isocitrate
dehydrogenase, flowing tumor cells, flowing cell freemicro RNAs, flowing extracellualr vesicles play a significant role in
inducing a cancer.
OBJECTIVE OF THE PROJECT:

The goal of this project is to create a sophisticated deep learning-based system for early and precise detection and
classification of brain tumors, minimize misclassification hazards, and facilitate individualized treatment planning. The
project also aims to facilitate cognition-sparing radiotherapy by examining radiation-induced changes in brain tissue and
forecasting long-term neurocognitive outcomes to enhance patient care and therapy optimization. The aim of this project is
to create a next-generation deep learning-based system for the early and precise detection and classification of brain
tumors, minimize risks of misclassification, and facilitate personalized planning for treatment. Moreover, the project will
help cognition-sparing radiotherapy through studying radiation effects on brain tissue and forecasting long-term
neurocognitive outcomes in order to optimize patient care and therapy.

SUBJECT OF THE PROJECT:

The topic of this project is the brain tumor detection, classification, and treatment planning with the aid of state-of-the-
art deep learning algorithms and medical imaging. The project aims to examine brain tumor types including gliomas,
glioblastomas, oligodendrogliomas, and pituitary tumors based on imaging data (MRI/CT scans) and molecular
biomarkers in order to improve diagnostic efficiency and treatment measures.
 2.INTRODUCTION
• One of the most aggressive and intricate tumors in humans is a brain tumor. It accounts for about 1.35% of all malignant
neoplasms and is a cause of about 29.5% of cancer fatalities world over. Brain and CNS tumors refer to an array of
neoplasms originating from the brain, cranial nerves, spinal nerves, spinal cord, and meninges. These tumors
are typically divided into malignant (cancerous) and non-malignant (benign) types.
• Based on the World Health Organization (WHO) grading, brain tumors are graded according to their histological
characteristics, and Grade I and II are usually low-grade or benign, while Grade III and IV are high-grade or malignant. The
grading system plays an important role in determining therapeutic management and prognosis.
• Brain tumors represent a heterogeneous population of neoplasms that may be primary (arising in the brain) or
secondary/metastatic (arising elsewhere and disseminating to the brain). Glioblastoma multiforme (GBM) is the most
prevalent primary malignant brain tumor, a highly aggressive tumor arising from glial cells and characterized by
unfavorable survival rates in spite of therapy. GBMs are characterized by rapid growth, resistance to traditional treatments,
and diffuse infiltration of surrounding brain tissue.
• Metastatic brain tumors (MBTs), in contrast, happen when cancer elsewhere in the body (e.g., lung, breast, skin, or kidney)
metastasizes to the brain. The secondary tumors are the most common intra-axial brain tumors in adults. Epidemiological
reports indicate that an estimated one-third of patients who have systemic malignancy will also develop brain metastases
throughout their disease.
• The frequency of brain tumors is increasing, partly due to advances in imaging modalities, heightened awareness, and the
aging population. Additionally, genetic mutations, environmental factors, and immune mechanisms have been implicated in
tumorigenesis of many brain neoplasms. Ongoing research in neuro-oncology, molecular diagnostics, and immunotherapy
is necessary to enhance early detection, treatment outcomes, and quality of life in brain tumor patients.
 3.PATHOPHYSIOLOGY

• In the 19th century, Stephen Paget postulated the "seed and soil" hypothesis, which focused on the fact that growth of
metastatic tumors is not a matter of chance but rather is contingent upon the relationship between cancer cells (the seed)
and the target organ environment (the soil). This theory suggests that some organs create an optimal environment for
metastatic growth so that cancer cells can colonize and establish themselves better. This idea has been built upon
through the finding that metastasis is driven by tumor heterogeneity, such that various cancer cells in one tumor are
able to invade, disseminate, and proliferate in different organs at varying levels. Consequently, only a subpopulation of
cancer cells has the required properties to finish the entire metastatic process, which consists of evading the immune
response, surviving the new microenvironment, and developing secondary tumors.

• In addition, the continuous crosstalk between the primary tumor and its environment, referred to as the tumor
microenvironment (TME), is also key to cancer survival and progression. The TME is composed of several elements,
such as immune cells, fibroblasts, blood vessels, and extracellular matrix proteins, all of which communicate with
cancer cells to facilitate tumor development and metastasis. In tumors of the brain, this communication is especially
crucial, as not only does it affect tumor behavior but also promotes angiogenesis—growth of new blood vessels to
supply the tumor—and helps bring about resistance to therapies like chemotherapy and radiation. Unraveling these
intricate interactions is vital to creating more effective treatments that target the tumor and its microenvironment to
suppress or treat metastasis.
 4.AN OVERVIEW OF BRAIN TUMOR

The markers involved in the brain tumor are as follows:

A. Circulating tumor cells
B. O-6 methylguanine-DNA methyltransferase mutations (MGMT):
C. Epidermal growth factor receptor
D. Isocitrate dehydrogenase
E. Circulating free DNA
F. Circulating proteins
G. Tumor protein39.
H. Tumor protein 53.
A.Circulating tumor cells :Circulating tumor cells (CTCs) are shed from primary ormetastatic tumors in the body fluids, such as blond,
cerebrospinal fluid, andurine. CTCs decide the potential of epithelial tumor cells to metastasize.These various forms of potential
biomarkers in the blood can exist incell-free forms, bound to lipid or protein structure or delivery by circulatingextracellular vesicles or
platelets.

B. O-6 methylguanine-DNA methyltransferase mutations (MGMT):The O-6-methylguanine DNA methyltransferase (MGMT) gene
is located on chromosome 10q26. Alkylating chemotherapeutic agents like temozolomide, which methylate DNA base pairs, inhibit
DNA replication.Alive MGMT reverses the action of temozolomide, allowing normal DNAreplication to take place in a tumor. O-6-
methyl transferase DNAmethyltransferase leads to DNA repair by reversing alkylation of DNA andremoving the guanine-alkyl group,
thus avoiding apoptosis. MGMThas recently been proved to be a tumor diagnostic biomarker.

C. Epidermal growth factor receptor:The majority of signaling pathways and physiological responses such as migration,
proliferation, survival, and tumor formation are initiated by the epidermal growth factor receptor (EGFR). EGF, TGF-, heparin-
bindingepidermal growth factor-like factor (HB-EGF), amphiregulin (AR),betacellulin (BTC), neuregulins (NRGs), or neuregulin;
neudifferentiation factors; glial growth factors; acetylcholine receptor inducingactivity; and epiregulin are all part of the EGF
superfamily (EPR).

D. Isocitrate dehydrogenase:Isocitrate dehydrogenase (IDH) is an enzyme protein that codes genes onchromosome 2, the primary role
of IDH in the Krebs cycle is catalyzingoxidative decarboxylation. IDH has been classified into two classes (IDH 1and IDH 2). Mutation
of isocitrate dehydrogenase 1 (IDH-1) in glioblastomawas first observed by following an integrated genomic analysis of
humanglioblastomasamples. The IDH-1 protein guards the cytoplasm againstoxidative damage. In 12% of glioblastoma samples, a
heterozygous point-mutation at R132 was found. Glioblastomas known to have arisen from lower-grade tumors had a significantly
higher frequency ofIDH-1 mutation (83%). Grade II/III astrocytomas, oligoastrocytomas,and oligodendrogliomas all contain isocitrate
dehydrogenase, which can beused to differentiate primary from secondary glioblastomas.
E. Circulating free DNA: Cell-free DNA (cfDNA) as a double-stranded, DNA pieces that areshed from the breakdown of cancer
tissue by blood of size about 150 to200base pairs and matching nucleosome-related DNA may be shed from cellsunder both
physiological and pathologic conditions also. It is indicated thatcfDNA may come from apoptotic or necrotic cells, cycling cells, or
CTCs. Blood cfDNA is primarily of genomic DNA origin released with inflammation or cell death in individuals without cancer.
Because of phagocyte clearance, the content of cfDNA in the blood is low in physiological conditions. Circulating protein markers
can be employed to monitor the effectiveness of therapy in brain tumor patients.

F. Circulating proteinsSeveral:Tumor-derived circulating nucleic acids (e.g., ctDNA, cmtDNA,mRNA, non-coding RNAs such as
miRNAs, long non-coding RNAs) thatcan be detected from bloodor other forms of body fluids such as urine,cerebrospinal fluid
(CSF), saliva, pleural fluid, andascites. In brain tumorpatients, the secretion of the proteins may result in an increase in thelevel of
circulating proteins (CPs) in the blood and urine and/or CSF [4].Angiogenesis-related protein markers were found in malignancies.
The level of vascularendothelial growth factor was found to be significantly higher in brain tumor patientscompared with healthy
individuals.

G.Tumor protein 39 (TP39): Tumor protein 39A (TP39A) is a member of the Transmembrane protein 39families (TMEM39), which
include TMEM39A and TMEM39B. The twoTMEM39 isoforms are generated through alternative splicing. The encoding gene of
TMEM39A is asusceptibility causes the brain tumor. Transmembrane proteins across the plasma membrane from one side to the
other. Movement of materials across biological membranes is controlled by a number oftransmembrane proteins. Susceptibility to
multiple sclerosis can be attributed to the gene encoding TMEM39A.MTEM39A has also been associated withsystemic lupus
erythematosus

H.Tumor protein 53 (TP53): TP53 is a classic tumor suppressor gene at 17p13.1. This codes for the nuclease protein p53. In order to
control the expression of its target genes the p53protein responds to various cellular stresses and thus induces cell cycle arrest,
apoptosis, senescence, DNA repair, or metabolic changes. A few human malignancies, such as Li-Fraumeni syndrome and many
hereditary gliomas, are associated with mutated TP53 genes and overexpressed aberrant p53protein with a longer half-life than wild
type p53.
5.EPIDEMOLOGY

Population-based studies are more accurate

and less biased than the more restricted
clinical (or) autopsy-based series. The true
incidence ofbrain metastases is not known.
The epidemiological study is conducted by
utilizing the hospital records, tumor registers,
and death certificates. Lastly from this study,
the incidence of brain metastases appears to
be equal to the incidence of gliomas.
Thesurvival rate by histology is tabulated in
the figure 1

Figure 1:CNS tumor epidemiology -the incidence of brain tumor in

different regions of brain.
A.Meningiomas:

Meningiomas are the most frequent brain tumors

in adults represent approximately36% of all brain
tumors in united states central brain tumor registry
(CBTRUS). In 2015, CBTRUS projected that
there will be an estimated24,000 new
meningiomas diagnosed within the united states.
Incidence of meningioma increases steadily with
age being twicemore common in women than in
men and 20% more prevalent in blacks thanin
whites. While benign meningiomas are a trivial
cause of death, skull-basedtumors may produce
significant morbidity. Atypical and malignant
meningiomas,however, are associated with high
recurrence rates and significantmorbidity and
mortality. Meningioma is illustrated in Figure 2.
Because telomeraseactivity is found in all
anaplastic/malignant. and most atypical (WHO
grade II) meningiomas, there is an association
Figure 2.Brain meningioma.
between telomerase activity and meningioma
grading
B. Glioma
Gliomas may occur in almost any part of the
brain, with varying frequency at different
locations. The most common location is the
frontal lobe, accounting for approximately
23.6%, followed by temporal lobe in 17.4%,
parietal lobe in 10.6%, and occipital lobe in
2.8%. Besides cerebral hemispheres, gliomas
may also present, though with lesser frequency,
in the cerebellum, brainstem, and spinal cord.
These variations in location often impact the
clinical symptoms, prognosis and the treatment
strategies. For example, gliomas in the frontal
lobe might affect cognitive functions and
behavior, whereas those occurring in temporal
lobe might have an impact on speech and
memory. Figure 3 displays the anatomical sites
of glioma, which gives a visual perception of Figure 3.Glioma.
its distribution across various regions of the
brain. This broad potential for occurrence, in
addition to its virulent character, especially
with glioblastoma, highlights the utmost
importance of early diagnosis and specific
treatment modalities.
C. Pituitary tumor
Pituitary tumors are the third most frequent
brain tumor in adults, representing about 15%
of all primary brain tumors. Pituitary tumors
arise in the pituitary gland, a small but vital
endocrine gland at the base of the brain,
which controls many of the body's hormonal
functions. The majority of pituitary tumors
are benign adenomas, i.e., non-cancerous and
usually slow-growing. Still, though they are
benign, they may present important health
problems owing to their size and location.
Figure 4 shows the position and appearance
of a pituitary tumor, usually located in the
sella turcica at the base of the skull.
Improved imaging and endocrinology have
made detection and treatment of pituitary
tumors much more effective, and treatment is
usually a combination of medication, surgery, Figure 4.Pituitary tumor.
and occasionally radiation therapy based on
the type of tumor and its impact on hormone
levels and adjacent tissues.
 6.SIGNS AND SYMPTOMS
• A. Headache : Headache occurs commonly in all brain tumor patients. The headache is saidto develop in the temporal and
the spatial, relation to the neoplasm andresolves 7 days of surgical removal or treatment with corticosteroidsHeadache in
pituitary brain tumorThe presence of headache has been shown to be more highly associated withfamily history than the
tumor sizeHeadache appears to be the most common presenting symptom (41% ofpatients in some studies). It tends to
occur with other symptoms such asvomiting, unsteadiness, behavioral problems, and cranial nerve palsies, andThe
mechanism of headache in brain tumors may include the traction onvascular structure, cranial or central sensitization
through neurogenicinflammation as well as the component of central sensitization throughtrigeminovascular afferents on
the meninges and the cranial nerves
• B. Nausea and vomiting: Nausea and vomiting occur when the chemo trigger zone in the area postrema,located on the
floor of the fourth ventricle is stimulated. Raised intracranialpressure leads to vomiting. It can also occur in the absence of
elevatedintracranial pressure in brain stem tumors involving the nucleus solitarius.Mechanism of vomitingNausea and
vomiting are highly conserved responses and the survivaladvantages in survival vertebrates. Vomiting is primitive, low-
threshold,brain stem response that allows the human to purge the gastrointestinal tractof orally consumed noxious
substances.
• C. Altered mental status: Mental and cognitive abnormalities may be specific, or nonspecific. Specificfindings include
aphasia, agnosia, abulia, alexia, or apraxia. In about 16–34%ofpatients, the symptoms for brain tumor patients include
irritability, changein personality, emotional liability, forgetfulness, lack of enthusiasm orspontaneity, and slowed response
progressing apathy and lathery
 7.DIAGNOSIS
• Diagnostic progress in brain tumor detection has increasingly emphasized the application of biomarkers, which hold much
potential for early tumor identification prior to the development of major clinical symptoms. Such biomarkers, which can
be genetic, proteomic, or molecular markers present in blood, cerebrospinal fluid, or tumor tissue, assist in characterizing
the types of tumors and their possible behavior. Early identification with such biomarkers can enhance treatment outcomes
and facilitate less aggressive intervention methods.
• Clinically, the evolution of neurologic deficits—such as weakness of a motor area or region, difficulty speaking, or visual
alterations—and acute seizure onset will usually trigger an extensive neurological workup. MRI is the initial imaging tool
employed, with the ability to obtain excellent quality images and great sensitivity to picking up on the complicated features
of brain tumors, including glioblastomas. MRI can also emphasize tumor margins, edema, necrosis, and patterns of contrast
enhancement that are important for treatment planning and diagnosis. Computed tomography (CT) with or without contrast
enhancement is less sensitive than MRI in general, particularly for identifying the fine and heterogeneous characteristics of
aggressive tumors such as glioblastoma.

In order to overcome these constraints, the Weighted Correlation Feature Selection Based Iterative Bayesian Multivariate
Deep Neural Learning (WCFS-IBMDNT) model has been introduced as a strong diagnostic tool. It improves brain tumor
diagnosis by initially using Weighted Correlation Feature Selection (WCFS) to select the most informative and non-redundant
features from the data, thus decreasing dimensionality and concentrating only on the most useful features. After feature
selection, the Iterative Bayesian Multivariate Deep Neural Network (IBMDNN) classifier is employed to classify and
diagnose tumors accurately with low computational complexity. This two-step approach not only maximizes classification
accuracy but also decreases diagnosis time considerably, which makes it extremely suitable for real-time clinical use. The
WCFS-IBMDNT model is a breakthrough in AI-assisted medical diagnostics, providing stable performance even with
intricate and imbalanced datasets.
 8.TYPES OF BRAIN TUMOR

The brain plays an important role in the body by controlling voluntary andinvoluntary processes. It is highly necessary to maintain a
healthy brain to live longer.But some factors like environmental and genetic factors tumors in the brain can bedeveloped . These tumor
causes the damage in healthy tissues and increases thepressure in the brain. Thus, some tissues may get pushed against the skull.
The tumors are classified according to the place they occur and the type of cell asfollows:
1. The type and grade
2. Primary or secondary tumor
3. Malignant or benign tumor
4. Tumor location .
According to WHO (World Health Organization) brain tumors are classified as:
1. Astrocytoma
2. Glioblastoma
3. Oligodendroglioma .
1.Astrocytoma

Astrocytoma tumors develop from the

supportive glial cells of the brain.
Approximately7% of the primary brain tumor
is astrocytoma. A star-shaped tumor that
starts in the brain is referred to as
astrocytoma. In adults, the astrocytoma most
commonly develops in the cerebrum, where
in children it develops in the brain stem
Astrocytoma is depicted in Figure.The basal
ganglia and thalamus are thetwo most
common sites for which the long-term
prognosis is worse than thatforhemisphere
injuries. Post-operative radiation is a form of
low-grade gliomatreatment. Yet one
drawback of radiation is that it results
inneurocognitive injury and fails to lead to
significant improvement.
Consequently,radiation tends to be reserved
for those with tumors that are at high risk
formalignant change. Figure 5: Astrocytoma
2.Glioblastoma
Glioblastomas (GBMs) is the most frequent
and primary aggressive braintumor.
Glioblastoma is illustrated in the Figure 6.
Glioblastoma constitutes 45.6%of primary
malignant brain tumors. Characteristic
molecular alterations in glioblastomainclude
mutation of gene-regulating receptor tyrosine
kinase (RTK) /phosphoinositide 3-kinase
(PI3K), p53, and retinoblastoma protein
(RB)signaling. Secondary glioblastoma is a
type of glioblastoma that developsin younger
individuals when an earlier malignancy, e.g.,
grade II astrocytomaor anaplastic
astrocytoma, somatically mutates into a
glioblastoma

Figure 6: Giloblastoma
3.Oligodendroglioma

Oligodendroglioma is an infrequent, indolent

brain tumor arising from oligodendrocytes, a
given variety of glial cells involved in myelin
production—the insulation that encloses
nerve fibers of the central nervous system.
Oligodendrogliomas are members of the
more inclusive group of gliomas, the tumors
derived from glial cells, which perform
structural and functional support roles within
neurons in the brain and spinal cord. Even
though they are not as prevalent as
astrocytomas or glioblastomas, these
oligodendrogliomas possess unique
biological and genetic characteristics that
distinguish them.
One of the most important distinguishing
features of oligodendrogliomas is their
molecular genetic profile, specifically the
common presence of loss of heterozygosity
(LOH) on chromosomes 1p and 19q. This co-
deletion is present in a high percentage of
oligodendrogliomas in all tumor grades and is Figure 7: Oligodendroglioma
regarded as a key diagnostic and prognostic
biomarker.
 9.TREATMENT METHOD OF BRAIN TUMOR

When it comes to treating brain tumors, immunotherapy is a potentialtreatment option. Chemotherapy, radiation treatment,
and surgery have allbeen used to treat it in the past. An immune-based cancer therapy uses thebody’s immune system to
destroy cancer cells. If the cells are no longerrequired or pose a hazard, apoptosis, or programmed cell death, will occur tohalt
cell growth.
Cancer progresses and develops through eightprocesses,vaccineswhich are as follows:
1. Stained proliferation.
2. Evasion of growthsuppressor.
3. Cell death resistance.
4. Replicative immortality.
5. Angiogenesis.
6. Metastasis.
7. Reprogrammed metabolism.
8. Evasion of immune destruction.
 10.VACCINATIONS
VACCINES:
• Conventional vaccinations against viral diseases
(e.g., influenza) utilize attenuated or live viruses
along with a danger signal (as an adjuvant) to
stimulate DCs. DCS subsequently engulf the viral
antigen, break it down, migrate to lymph nodes via
lymphatic channels, and stimulate T-cells through
the presentation of different peptide
antigens/antigenic epitopes on MHC moleculesa.
• Peptide vaccines:Peptide vaccine immunization
when presented at thetumor site, peptide
vaccinations induce T-cell immunity by
releasingantigen-specific peptides. APCs ingest
peptides, which are usuallyconjugated with carrier
proteins and adjuvants, and present them on thecell
surface by means of MHC. The treatment approach
by peptide vaccine is discussed in
Figure 8: APCs take up peptides, which are often associated
with carrierproteins and adjuvants, and display them on the
cell surface byway of MHC. Molecules of human leukocyte
antigens (HLA)MHC I (HLA)
 11.CONCLUSION

• In summary, The quantitative, domain-specific information obtained by these studies willenhance our knowledge of brain
toxicity and cognitive impairment related toradiation dose to non-targeted tissue and can serve as the basis for evidence-
basedcognition-sparing brain radiotherapy. Surprisingly, this research presents anasso_x0002_ciation between some of the
WM diffusion changes and radiation-induced memorydecline, which could suggest that other ROIs not examined in this
paper are ones that ought to be looked into as possibly vulnerable areas leading to post-RTcog_x0002_nitive decline.
Additional investigation is required to explore the dynamic pathways oftissue response to radiation in order to better
comprehend how MRI alterations may beutilized to predict significant neurocognitive pathways following
treatment.Treatment and improved outcomes for primary brain tumors have historically laggedbehind those of other
tumors. But a new neuro-oncology era has dawned, with significant breakthroughs both in cancer and CNS immunology
and developments in geneno_x0002_mics.Significantly, neuro-oncology is transitioning into a transformative era,
characterized by accelerated advances in genomics, CNS immunology, and precision medicine.
Advances like immune-based treatments and individualized treatment plans designed for a tumor's molecular makeup are
starting to bring brain tumors to parity with other cancers when it comes to cure rates and survival. With study after study
growing our knowledge, these innovations all together hold out the potential for not only enhancing patient survival, but for
safeguarding neurological function and quality of life in brain tumor survivors.
THANK YOU