CHAPTER 4
Tumors of the Brain
SEONG-JIN MOON, MD • DANIEL T. GINAT, MD, MS •
R. SHANE TUBBS, MS, PA-C, PHD • MARC D. MOISI, MD, MS
BACKGROUND
Tumors of the brain present a special challenge for both
patients and physicians. Every year, a new brain tumor
is discovered in 6.4 cases per 100,000 persons with an
overall 5-year survival rate of approximately 33.4%.1
Nearly 700,000 Americans live with a primary brain
tumor. Brain tumors can occur at any age, but the great-
est incidence is with ages 65 years and older, and there
is a slightly higher predominance in men than in
women.2,3 Over a person’s lifetime, there is an approx-
imately 0.6% risk of being diagnosed with a central ner-
vous system cancer. The impact that a diagnosis of brain
tumor has on a patient cannot be overstated: some
brain tumors can cause significant disability and drasti-
cally worsen quality of life, whereas others do not. New
treatments offer opportunities to extend life and mini-
mize disability.
CLASSIFICATION
Intracranial tumors are generally classified into either
malignant or benign tumors. Furthermore, malignant
tumors can be either primary or metastatic. Metastatic
lesions are more common than primary tumors.4
Generally, the proportion of adults with brain
tumors increases with age, given that metastatic lesions
are more prone to develop over time. The most
prevalent brain tumor types in adults are meningi-
omas, which make up nearly 33.8% of all primary
brain tumors5; gliomas (i.e., glioblastomas, ependy-
momas, astrocytomas, oligodendrogliomas) make
up almost 80% of malignant brain tumors.6 Intracra-
nial tumors are often divided into World Health
Organization (WHO) classification scale, which can
provide patients and clinicians with further informa-
tion regarding prognosis and management.7 The
WHO scale divides brain tumors into four different
classes, from 1 through 4. WHO grade 1 tumors
are generally nonmalignant, slower growing, better
prognostic lesions. WHO grade 2 tumors are
generally nonmalignant but can also be malignant
and have a higher propensity for recurrence than grade
1 tumors. WHO grade 3 tumors are aggressive malig-
nant lesions and often recur as higher grade lesions.
WHO grade 4 tumors exhibit the most aggressive of
lesions and generally exhibit a very high recurrence
ratedthey demonstrate the poorest prognosis for
patients.
CLINICAL PRESENTATION
The clinical presentation of intracranial tumors can
vary widely and run the spectrum from a patient who
presents with clinical obtundation to an asymptomatic
presentation. The location of an intracranial tumor
along with its size and mass effect dictates its clinical
presentation. Many patients present with clinical signs
and symptoms of increased intracranial pressure:
headache, nausea/vomiting, ocular palsies, altered
mental status, loss of balance, seizures, or papille-
dema.8 Some patients can present solely with one
clinical symptom, whereas others present with no
symptoms at all. For lesions within the frontal lobe,
memory, reasoning, personality, and thought process-
ing can be affected. For lesions within the temporal
lobe, behavior, memory, hearing, vision, emotion,
and speech can be affected. For lesions within the
parietal lobe, sensory perception and spatial relations
can be affected. For lesions within the occipital lobe,
vision can be affected. For lesions within the brainstem
or cerebellum, balance and coordination can be
affected. A pituitary tumor can compress the optic
nerve and cause a bitemporal hemianopsia. A tumor
within Broca’s area can present with expressive
27
28 Central Nervous System Cancer Rehabilitation

aphasia, whereas a tumor within Wernicke’s area can
present with fluent aphasia. Meningiomas are dural-
based lesions; they are found alongside the dural
meninges, and their clinical effects are often related
to local mass effect on surrounding tissue. Glioblas-
tomas are very aggressive WHO grade 4 neoplasms
with a poor prognosis for recovery. Primary cerebellar
lesions that are not metastatic in origin are often
hemangioblastomas.9 Often, such lesions can cause
considerable mass effect on surrounding tissue and
structures and also have significant surrounding
edema as well.

Meningioma. Axial postcontrast T1 MR images show a dural-based mass along the inferior aspect of the left
tentorium cerebellum, with a dural tail that extends to the left internal auditory canal.

Meningioma. Axial T2 and postcontrast T1 MR images show an enhancing mass centered in the left sphenoid
triangle with associated vasogenic edema in the left temporal lobe and extension into the left orbit.
 CHAPTER 4 Tumors of the Brain 29

Glioblastoma. FLAIR and postcontrast T1 MR images show a heterogeneously enhancing mass that spans
posterior corpus callosum.

Lung cancer metastases. Axial postcontrast T1 MRI shows Breast cancer metastasis. Sagittal postcontrast T1 MRI
multiple enhancing nodules in the bilateral cerebral shows a heterogeneously enhancing dural-based mass
hemispheres. along the frontal convexity.
30 Central Nervous System Cancer Rehabilitation

Hemangioblastoma. Axial postcontrast T1 MR images show cystic tumors in the cerebellum with enhancing
nodules.

Primitive Neuroectodermal Tumor (PNET). Axial FLAIR and postcontrast T1 MR images show a mass in the
right frontal lobe with irregular peripheral enhancement and surrounding edema with midline shift.
 CHAPTER 4 Tumors of the Brain 31

PHYSICAL EXAMINATION MANAGEMENT

A thorough physical and neurologic examination Adult intracranial tumors are best managed by a multi-
should be performed on all patients with intracranial disciplinary team of clinicians. Management options
tumors. Neurologic examination consists of a mental include observation surveillance, surgical resection,
status examination with a complete cranial nerve assess- chemotherapy, radiation therapy, or a combination
ment, along with motor/sensory testing, reflex testing, thereof. No two intracranial tumors are the same, which
and cerebellar testing. Elements of complex motor sys- means that no two intracranial tumors are managed the
tem testing and speech and memory testing should same.
also be assessed. As stated previously, the location of A variety of scales may aid the patient and clinician
an intracranial tumor dictates its presentation. For in determining the baseline functional status of a
example, a patient with a tumor present within the mo- patient, which aids in the patient’s decision-making.
tor strip may present with profound contralateral motor In neuro-oncology, some notable examples include
weakness, whereas a patient with a pituitary tumor may the Karnofsky performance status scale12 (outlined in
complain of visual blurriness or generalized hormone the following section) and the Eastern Cooperative
discrepancy. A cerebellar tumor may present in a patient Oncology Group (ECOG )13 performance status. Such
with primary gait imbalance, or a patient with hearing scales assist the patient and clinician in making the
difficulty may present with a vestibular schwannoma. most informed decision regarding further therapies
A thorough cranial nerve assessment can also provide and different treatment modalities.
further clues for the astute clinician in localizing the
location and most likely differential diagnoses of intra-
cranial tumors. Karnofsky Performance Status Scale Definitions Rating (%)
Criteria
Able to carry on normal 100 Normal no complaints; no
DIAGNOSIS
activity and to work; no evidence of disease.
Diagnosis of adult intracranial lesions is generally special care needed. 90 Able to carry on normal
through a combination of history and physical examina- activity; minor signs or
tion findings, corroborated by imaging support. A symptoms of disease.
clinician approaching a patient with either known or 80 Normal activity with
suspected concern for intracranial tumors should collect effort; some signs or
a thorough history, which often provides clues to the symptoms of disease.
location, duration, and classification of intracranial Unable to work; able to 70 Cares for self; unable to
tumors. In general, a physician will order a computed to- live at home and care for carry on normal activity or
most personal needs; to do active work.
mography (CT) scan of the head or a magnetic resonance
varying amount of 60 Requires occasional
imaging scan of the brain to better evaluate intracranial
assistance needed. assistance, but is able to
tumors. The aforementioned imaging sequences provide care for most of his/her
structural and anatomic characteristics of the intracranial personal needs.
tumors in question, which aids clinicians in generating a 50 Requires considerable
differential diagnosis as well as in further management. assistance and frequent
MR spectroscopy and PET scans offer further clues into medical care.
the nature of such intracranial tumors, which in turn Unable to care for self; 40 Disabled; requires special
can aid in making an accurate diagnosis.10 requires equivalent of care and assistance.
For some intracranial tumors, identification of institutional or hospital 30 Severely disabled; hospital
care; disease may be admission is indicated
the vascular supply is critical to the subsequent man-
progressing rapidly. although death not
agement. These intracranial tumors warrant further
imminent.
vascular imaging, in the form of CT angiography/ 20 Very sick; hospital
magnetic resonance angiography (CTA/MRA), as well admission necessary;
as venous modalities as well i.e., CT venography/ active supportive
magnetic resonance venography (CTV/MRV). For treatment necessary.
intracranial tumors that warrant critical vascular find- 10 Moribund; fatal processes
ings and close affinity with vascular structures, a diag- progressing rapidly.
nostic cerebral angiogram may be necessary.11 0 Dead
32 Central Nervous System Cancer Rehabilitation
Eastern Cooperative Oncology Group (ECOG) Performance
Status*
Grade ECOG
0 Fully active, able to carry on all predisease
performance without restriction
1 Restricted in physically strenuous activity but
ambulatory and able to carry out work of a light
or sedentary nature, e.g., light house work, office
work
2 Ambulatory and capable of all self-care but
unable to carry out any work activities. Up and
about more than 50% of waking hours
3 Capable of only limited self-care, confined to bed
or chair more than 50% of waking hours
4 Completely disabled. Cannot carry on any self-
care. Totally confined to bed or chair
5 Dead
*Published in Oken MM, Creech RH, Tormey DC, Horton J, Davis TE,
McFadden ET, Carbone PP. Toxicity And response criteria of the
Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5:
649e655.
Management of the patient with an intracranial tu-
mor requires addressing the tumor itself as well as its
neurologic sequelae. For example, a patient who is
acutely obtunded from a large brain tumor should
have his/her airway evaluated and stabilized first. Sei-
zures should be controlled either with medication or,
if sometimes required, deep sedation. Hydrocephalus
due to obstruction caused by an intracranial tumor can
be managed in the acute setting with an external ventric-
ular drain versus emergent decompressive surgery for
resection of said lesion. If hydrocephalus persists, the pa-
tient may require cerebrospinal fluid diversion, likely in
the form of a ventriculoperitoneal shunt.14
If surgical resection is a possibility, a consultation
with a neurosurgeon should be made so that the details
and feasibility of such a surgery, as well as risks and
benefits, could be explained to the patient and his/her
family. Some intracranial lesions are more amenable
to gross total resection, whereas other tumors will
require a surgical biopsy first, which in turn will
dictate further management. The neurosurgeon may
discuss with the patient which surgical approach and
operative management would be best to treat the pa-
tient’s intracranial tumor. For example, a neurosurgeon
may discuss with the patient the possibility of
approaching a pituitary tumor via a transsphenoidal
approach or by a pterional craniotomy. How the neuro-
surgeon delivers such medical information is often as
important as the medical information itself.15 Different
surgical approaches that are specific to the individual
characteristics and location of the tumor may be
utilized; however, the basic operative principle is to pro-
vide the neurosurgeon the maximal exposure through
the operative corridor, without any or minimal damage
to the surrounding normal tissue. Supratentorial tu-
mors are often approached with a standard pterional
craniotomy, whereas infratentorial tumors are often
approached with a retrosigmoid craniotomy.16
Some intracranial tumors are not amenable to
surgical resection, or the characteristics of such a lesion
make it more appropriate to be managed with radia-
tion therapy instead. For example, if a lesion is small,
or present in several parts of the brain, or within
an area of the brain where surgical resection may
potentially cause more harm than benefit, radiation
therapy is a consideration. A consultation with a radi-
ation oncologist can provide the patient with a variety
of radiotherapy treatment options to target the tu-
mor(s). For example, a patient with diffuse multiple
metastases that are too many for surgical resection
may benefit from whole brain radiation therapy,
whereas a patient with a single small lesion that is
radiosensitive may benefit from stereotactic radiosur-
gery. Patients who also undergo surgical resection of
their intracranial tumors often receive radiation ther-
apy to the surgical resection bed.17
Chemotherapy is also utilized as an adjunct for some
tumors. A consultation with a neuro-oncologist should
be made, and the variety of chemotherapeutic regimens
should be discussed. Traditionally, the utilization of
chemotherapy within the brain was limited, as the
unique nature of the blood-brain barrier limited the ef-
ficacy of the medication traveling across the barrier.18
Recent studies and research have paved the way for
new chemotherapeutic drugs, however, and some
patients receive a combination of surgery, radiation
therapy, and chemotherapy as a result. Taxol is a well-
known example.19
While chemotherapy and radiation regimens have
evolved, some guidelines have proven successful in
changing the standard of care. One prominent example
is the advent of the Stupp protocol in 2005. The Stupp
regimen tackled the most aggressive of primary intracra-
nial neoplasms, glioblastoma multiforme (GBM). For
newly diagnosed GBM, the Stupp regimen called for
maximal surgical resection, followed by radiation
therapy, in conjunction with either simultaneous or
adjuvant chemotherapy, specifically temozolomide.20
Temozolomide is an alkylating/methylating drug,
where its mechanism is to alkylate usually the N-7 or

O-6 positions of guanine residues in DNA. The Stupp
regimen compared those patients undergoing surgery
with chemotherapy and radiation to those patients
undergoing external beam radiation alone: the study
demonstrated a median survival of 14.6 months in
the former group compared with 12.1 months in the
latter group. Other agents such as PCV (procarbazine,
lomustine, vincristine) have found success in the
treatment of recurrent low-grade oligodendrogliomas/
astrocytomas, whereas other patients have benefitted
from carmustine (Gliadel) wafers which are implanted
in the surgical resection cavity after craniotomy.21
Preoperative embolization to reduce the vascular
supply to a tumor and potentially aid in surgical resec-
tion is also a consideration.22
POSTMANAGEMENT COURSE
Postoperative management is equally as important as
the surgical resection of the tumor itself. For intracra-
nial tumors that undergo surgical resection, postoper-
ative management is critical, with close neurologic
monitoring and strict blood pressure control, generally
provided in the ICU. One of the most common issues
that patients with resection of their intracranial tumors
experience is an acute hypertensive episode, which can
generally be managed with careful neurologic checks
in the ICU.23 Patients can sometimes have a weaning
steroid protocol as well, and there are a variety of tools
that the neurosurgeon or neurointensivist can utilize
in the immediate perioperative setting to enable a
smooth transition to recovery. Postoperative seizures
remain a major concern as well.24, Some studies have
suggested that the prevalence of seizures can be as
much as 30%e40% of patients with supratentorial
brain tumors.24e26 One study compared the efficacy
of levetiracetam versus phenytoin and found that the
levetiracetam group experienced a lower frequency of
postoperative seizures.27 Many patients who undergo
surgical resection then undergo a phase of radiation
therapy to the surgical resection bed.
For patients who have undergone their initial treat-
ment phase, it is often the case that patients will have
to follow through generally every 2e4 months to
make sure there are no recurrent signs. This is generally
managed with serial imaging and close follow-up with
their neuro-oncologist, neurosurgeon, and radiation
oncologist. The primary purpose of such follow-up is
to ensure that the patient does not have any further
recurrence of the intracranial tumor and to have the
patient and patient’s family involved in all aspects of re-
covery, as well.
CHAPTER 4 Tumors of the Brain 33
Family support and social needs is also an important
factor in the general recovery and the total care of
the patient with an intracranial tumor. For many
patients and their families, a revelation that their
loved one has an intracranial tumor is often met with
much consternation and sometimes outright fear. It
is therefore critical to guide the patient and their
family through this trying time and to not only address
the patient’s medical concerns but also social needs, as
well.28
CONCLUSION
Intracranial tumors in the adult patient present a
challenging clinical problem for physicians and often
require a general management combination of surgical
resection, radiation therapy, and chemotherapy.
Patients who undergo such a combination require strict
follow-up and close postoperative care, including over-
arching rehabilitation needs and social support. Such
attention to a multifaceted approach for patients with
intracranial tumors allows the clinician to provide the
best overall care for the patient, in some of their most
trying moments.
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FURTHER READING
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Surg Neurol Int. 2013;4(suppl 4):S245eS255. https://
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brain tumor patients. J Exp Clin Cancer Res. 2007;26(3):
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patients with brain tumors and acute stroke: comparative
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