COGNITIVE PRESERVATION IN WHOLE BRAIN RADIOTHERAPY

THE CHARIOT OF SEA GOD
TO
THE CHARIOT OF MENTAL HEALTH
11/17/2019 1

STRATEGIES TO NEURO-COGNITIVE PRESERVATION
IN PATIENTS WITH WHOLE BRAIN RADIOTHERAPY
Dr Kanhu Charan Patro
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Defining the cognition
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The cognitive process
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WHICH PART OF BRAIN IS
RESPONSIBLE?
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MAMILLARY BODY
ANTERIOR-
THALAMIC NUCLEUS
CINGULATE GYRUS
HIPPOCAMPUS
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1. The Papez circuit medial limbic circuit, is
a neural circuit for the control of emotional
expression.
2. In 1937, James Papez proposed that the
circuit connecting the hypothalamus to
the limbic lobe was the basis for emotional
experiences.
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What is hippocampus?
• The hippocampus consists of two “horns” that
curve back from the amygdala.
• The hippocampus is important in storing
information in long-term memory.
• If the hippocampus is damaged, a person cannot
build new memories, living instead in a strange
world where everything he or she experiences
just fades away, even while older memories from
the time before the damage are untouched
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1. Seahorse Is the name given to 45 species of small
marine fish in the genus Hippocampus.
2. "Hippocampus" comes from the Ancient
Greek hippokampos (ἱππόκαμπος hippókampos), itself
from hippos (ἵππος híppos) meaning "horse"
and kampos (κάμπος kámpos) meaning "sea monster“.
3. Humans and other mammals have two hippocampi, one in
each side of the brain.
4. The hippocampus is part of the limbic system, and plays
important roles in the consolidation of information
from short-term memory to long-term memory, and
in spatial memory that enables navigation.
SEA HORSE
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1. In Alzheimer's disease (and other forms
of dementia ), the hippocampus is one of the first
regions of the brain to suffer damage; short-term
memory loss and disorientation are included
among the early symptoms.
2. Damage to the hippocampus can also result
from oxygen starvation (hypoxia), encephalitis,
or medial temporal lobe epilepsy. People with
extensive, bilateral hippocampal damage may
experience anterograde amnesia: the inability to
form and retain new memories
WHAT HAPPENS IN ALZHEIMER'S ?
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DR. JALALI SIR’S ANALYSIS
• 28 patients (median age, 13 years) with
residual/progressive brain tumors (10
craniopharyngioma, 8 cerebellar astrocytoma, 6 optic
pathway glioma and 4 cerebral low-grade glioma) were
treated with SCRT to a dose of 54 Gy in 30 fractions
over 6 weeks
• Prospectively collected dosimetric data show younger
age and radiotherapy doses to left temporal lobe to be
predictors of neurocognitive decline, and may well be
used as possible dose constraints for high-
precision radiotherapy planning
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SECONDARY BRAIN TUMORS
• A brain metastasis is a cancer that has
metastasized (spread) to the brain from
another location in the body and is therefore
considered a secondary brain tumour.
The metastasis typically shares a cancer cell
type with the original site of the cancer.
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WHOLE BRAIN RADIOTHERAPY
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1. Early neurocognitive decline, within the first 1-4 months,
which primarily reflects memory.
2. Long-term serious and permanent adverse effects, including
cognitive deterioration in other domains and cerebellar
dysfunction
3. As many as11% of long-term brain metastases survivors (>12
months) treated with WBRT develop severe dementia,
especially with the use of larger dose-per- fraction schedules
Neuro-cognitive toxicity in WBRT
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Pathogenesis of Irradiation-Induced
Cognitive Dysfunction
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NSC – NEUROGENIC STEM CELL
• Mitotically active neural stem cells (NSCs) are located in different
parts of brain, namely in the subependymal zone and in the
subgranular zone of the dentate gyrus, wherefrom they migrate
into the granular cell layer of hippocampus .
• The hippocampal subgranular zone is a critical neurologic center
for learning and memory.
• NSCs have typical features of the stem cells. They are capable of
both self-renewal and generating new differentiated cells.
• Neurogenesis is a complicated process with integration of many
regulatory cells as astrocytes or endothelial cells with coordinate
evolution of neural precursor cells together with each other in a
specific neurogenic microenvironment called “niche”
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When Henry Molaison (now widely known as H.M.)
cracked his skull in an accident, he began blacking out and
having seizures. In an attempt to cure him, daredevil
surgeon Dr. William Skoville removed H.M.'s hippocampus.
Luckily, the seizures did go away — but so did his long-
term memory! Sam Kean walks us through this astonishing
medical case, detailing everything H.M. taught us about
the brain and memory
Henry Gustav Molaison
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VARIOUS COGNITIVE FUNCTION TESTS
• MMSE-Mini‐mental state examination
• VFT-Verbal fluency test
• DST-Digit span test
• EBPM-Event‐based prospective memory
• TBPM-Time‐based prospective memory
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INCIDENCE OF HIPPOCAMPUS MET
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WHY WE SHOULD BE WORRY
WHEN SURVIVAL IS LESS?
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SURVIVAL IS NOT LESS IN TARGETED
MUTATION ERA.
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SURVIVAL IN BRAIN METSTASIS
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EGFR+VE NSCLC - BRAINMET –TKI+WBRT
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WBRT INCREASES THE PERMEABILITY BBB
WHOLE BRAIN RADIOTHERAPY
COULD IMPROVE THE
PERMEABILITY OF THE BLOOD
BRAIN–BARRIER (BBB) AND
HELP TKI CROSS THE BBB
A total of 148 patients
with brain metastases
from EGFR mutation-
positive NSCLC were
analyzed retrospectively
The patients were
orally given gefitinib
(250 mg) or erlotinib
(150 mg) once a day
until intracranial
disease progression,
death, or intolerable
side effects.
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BREAST CANCER WITH BRAIN
METASTASIS
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DOSE CONSTARINTS FOR RTOG 0933
HA-WBRT IMRT
Planning
PTV D2% ≤ 37.5 Gy
D98% ≥ 25 Gy
Hippocampus D100% ≤ 9 Gy
Maximum dose ≤ 16 Gy
Optic Nerves
and Chiasm
Maximum dose ≤ 37.5 Gy
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GRADED PROGNOSTIC INDEX
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Summary
• Follow the graded index to see the outcome
• Whatever may be plan with hippocampus
sparing and add memantine.
• Survival has increased in targeted era.
• Do a minimental test before whole brain
radiotherapy.
• Try to add memantine with whole brain
radiotherapy.
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WHAT MORE TO SPARE?
• Scalp
• Cochlea
• Parotid
• Hippocampus
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HOLISTIC APPROACH IN WBRT
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Do Females have larger hippocampus?
A metaanalysis.
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If you have the answer
PLEASE FORWARD
• DR KANHU CHARAN PATRO
• drkcpatro@gmail.com
• M-9160470564
11/17/2019 99

COGNITIVE PRESERVATION IN WHOLE BRAIN RADIOTHERAPY

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