Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
The combined use of radiation therapy and chemotherapy in cancer treatment is a logical and reasonable approach that has already proven beneficial for several malignancies.
This is a presentation on total body irradiation. This presentation explains about various techniques. positions used for TBI. Advantages and disadvantages of TBI.
It also gives an idea on Dosage and side effects.
Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of time (usually a matter of minutes). The major cause of this syndrome is depletion of immature parenchymal stem cells in specific tissues.Examples of people who suffered from ARS are the survivors of the Hiroshima and Nagasaki atomic bombs, the firefighters that first responded after the Chernobyl Nuclear Power Plant event in 1986, and some unintentional exposures to sterilization irradiators.
The combined use of radiation therapy and chemotherapy in cancer treatment is a logical and reasonable approach that has already proven beneficial for several malignancies.
This is a presentation on total body irradiation. This presentation explains about various techniques. positions used for TBI. Advantages and disadvantages of TBI.
It also gives an idea on Dosage and side effects.
Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of time (usually a matter of minutes). The major cause of this syndrome is depletion of immature parenchymal stem cells in specific tissues.Examples of people who suffered from ARS are the survivors of the Hiroshima and Nagasaki atomic bombs, the firefighters that first responded after the Chernobyl Nuclear Power Plant event in 1986, and some unintentional exposures to sterilization irradiators.
SLE Systemic lupus erythematosus 2022
Basics, updates Prof. Hanan Ali Taha, professor of Internal Medicine and Head of the immunology unit, Faculty of Medicine, Beni-Suef University University
this tells about the overview of glaucoma and the primary open angle glaucoma
valve surgery and cyclodestruction surgery are not listed, however they are important
Hodgkin Lymphoma - Diagnosis to ManagementSubhash Thakur
Presentation is about Hodgkin lymphoma, its incidence and epidemiology, diagnosis, molecular and immunophenotype, work up, staging, treatment and follow up
This presentation is about chronic lymphocytic leukemia (CLL), its epidemiology and incidence, staging, molecular characteristics, clinical features and management.
This presentation is about anemia of chronic disease, nowadays also called as anemia of Inflammation. I have dealt with anemia in CKD and malignancy in detail.
Treating Metastatic NSCLC with Immunotherapy - Update 2019Subhash Thakur
This presentation discusses about important trials like keynote 042 and Checkmate 227, emerging role of immunotherapy in metastatic non small cell lung cancer.
Patient Positioning and Immobilization Devices In Radiotherapy PlanningSubhash Thakur
This is a overview of the devices used in the radiotherapy planning. These are specifically designed for patient proper positioning, reproducibility and immobilization of patient during radiotherapy treatment.
2D, 3D, VMAT and electron planning done for IMN field
considering all aspects, including PTV coverage, dose homogeneity, OAR doses, Electron for IMN was the best
TBI is the radiotherapy technique to irradiate whole body before doing stem cell transplant. The main purpose of doing TBIB is to condition the immune system of body so that there will be maximum chance of transplant acceptance.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
LONG TERM TOXICITIES AND QUALITY OF LIFE AFTER RADIATION TO CENTRAL NERVOUS SYSTEM
1.
2. INTRODUCTION
Radiobiological perspective
Acute toxicity: within days to weeks after radiation
Early delayed toxicity : within 1-6 months postirradiation
Late toxicity : >6 months post irradiation
Clinical Perspective : RTOG defined
Acute toxicity : <90 days post radiation
Late toxicity : >90 days post radiation
Front Oncol. 2012; 2: 73.
3. RISK FACTORS FOR LATE CNS TOXICITIES
Volume of normal brain tissue irradiated
The total irradiation dose
The fractionation schedule
The use of concurrent medications
Host variables :
Age
Use of concurrent or sequential chemotherapy
Genetic factors
4. MECHANISMS OF CNS TOXICITY
POST IRRADIATION
Photons to heavy charged particles produce toxicity in CNS
Ionizing particles have physical ability to generate free radicals
that cause direct or indirect DNA damage
CNS is particularly susceptible to metabolic stress
Most accepted mechanism : double stranded DNA damage
leading to mitotic catastrophe
5. But, this mechanism is more relevant in cells undergoing active
cell division
CNS : limited mitotic potential so there is growing evidence to
suggest other mechanisms of radiation induced damage, which
includes
Oxidation of lipid bilayer
Changes in microvascular permeability
Cell-cell junctional complex rearrangements and
Mitochondrial alterations inducing additional oxidative stress
MECHANISMS OF CNS TOXICITY
POST IRRADIATION
6. OXIDATIVE STRESS
Contribute to both acute and chronic radiation injury
They produce Reactive oxygen species (ROS) which have
unpaired electron in shells, which are highly reactive
RADIATION
Hydrolysis of H2O
Increased ROS
RADIATION
Injury and inflammation (injured
endothelial cells, epithelial and
inflammatory cells)
Generation of reactive nitrogen
species (superoxide and nitric oxide )
7. Brain is highly susceptible to oxidative stress because
1. High rate of aerobic glycolysis
(Continual supply of ROS within mitochondria)
2. Relative to other tissue, glial cells and neurons contain
low levels of antioxidant system such as SOD, catalase,
glutathione peroxidase etc
3. Myelin membranes contain high levels of perodizable
fatty acids, making them exceptionally vulnerable to ROS
OXIDATIVE STRESS
8. CHANGES IN MICROVASCULAR
PERMEABILITY
VEGF is the first growth factors upregulated during the
pathogenesis associated with late delayed effects
It is intimately involved in the development of vascular
pathologies and white matter necrosis
9. Brain radiation
Upregulation of VEGF
Gradual depletion of vascular endothelial cells
Diminishes the integrity of BBB
Vasogenic edema, inflammation and tissue
hypoxia
Induction of HIF-1 alpha and VEGF
Exacerbates disruption of BBB, worsening edema,
inflammation and tissue hypoxia
Further increase in VEGF
Induce endothelial proliferation (angiogenesis)
10. Dramatic increase in endothelial cells – k/a
“conditional renewal”
This angiogenic response persists for
approximately 20 weeks
Ultimately fails to restore BBB integrity
Decline in number of endothelial cells
Eventually leading to white matter necrosis
11. THE PARENCHYMAL HYPOTHESIS OF
RADIATION INDUCED BRAIN INJURY
OLIGODENDROCYTES
Radiation
Loss of oligodendrocyte type 2 astrocyte (O-2A)
reproductive capacity
Demyelination and white matter necrosis
12. ASTROCYTES
(50% of total brain cells)
Radiation
Astrocytes – proliferation, hypertropic nuclei/cell
bodies and increased expression of glial fibrillary
acidic protein (GFAP)
Increased COX-2 and ICAM - 1
Aid the infiltration of leucocytes into brain viz BBB
breakdown
13. MICROGLIA
(12 % of total brain cells)
Radiation
Microglia becomes activated, characterized by rounding of
cell body, retraction of cell process and proliferation and
increased production of ROS, cytokines and chemokines
Neuroinflammation
14. NEURONS
Once considered radioresistant population as they no
longer could divide, neurons have now been shown to
respond negatively to radiation
CHANGES IN NEURONS DUE TO RADIATION
Neuronal receptors expression of immediate early gene
activity regulated cytoskeleton associated protein (Arc)
NMDA receptor subunits
Glutaminergic transmission
Hippocampal long term potentiation
Important for synaptic plasticity and cognition
15. CLINICAL MANIFESTATIONS
Acute : 1-6 weeks
Fatigue
Headache
Seizure and
Coma
Cause :
Secondary to
edema and
Disruption of BBB
Front Oncol. 2012
Early delayed
Reversible symptons
Generalized weakness
Somnolence : transient
demyelination
Late
Irreversible neurological
consequences
Minor to sever cognitive defects
focal diffuse necrosis of brain
parenchyma
17. LATE TOXICITIES
Radiation necrosis
Neurocognitive Dysfunction
Endocrinopathies
Cerebrovascular effects
Migraine like headache Syndrome
Effects on the eyes and optic pathways
Ototoxicity
Secondary Tumor Formations
18. RADIATION NECROSIS
Typically develops 1 to 3 years after radiation
Dose that causes 5% of radiation necrosis using conventional 2
Gy/# is usually estimated to be 72 Gy
Increased risk with high dose/# and the use of concurrent
chemotherapy
Location :Adjacent to the original site of tumor
Symtoms
Depend on the location of lesion
Can include focal neurological deficits or symptoms due to
raised ICP
19. DIAGNOSIS: RADIATION NECROSIS
Very difficult with conventional imaging
Imaging features are entirely overlapping with high grade
glioma
However, PWI : decreased CBV : rad necrosis and increased
CBW : tumor
DWI : restricted diffusion : active tumor
MRS : lipid peak : necrosis
PET : increased FDG/methionine : tumor
Ultimate diagnosis : biopsy
23. TREATMENT: RADIATION NECROSIS
Usually it is self limiting process
If symptomatic, steroid, T. Dexa 8 mg tds and the tapering
No respone to steroid : Bevacizumab
• Bevacizumab @ 7.5 mg/kg 3 weekly for 2 cycle
• MRI done, if favourable response further 2 cycles
• And then MRI every 3 monthly for 24 months
• Concluded : bevacizumab stopped the progression of radiation
necrosis
24. Surgical resection if diagnostic uncertainity
Advantage : decreases mass effect
Decreases post op steroid requirements
25. NEUROCOGNITIVE IMPAIRMENT
High dose radiation : demyelination and vasculopathies
Low dose exposure : cognitive dysfunction without obvious
morphologic changes
Exact pathogenesis of radiation induced cognitive dysfunction
is unknown
Recent studies suggest that impaired neurogenesis within the
subgranular zone (SGZ) of the dentate gyrus of hippocampus
WBRT as low as 2 Gy are sufficient to reduce the rate of
proliferation among neuronal progenitor cells within the sub-
granular zone (SGW)
26. NEUROCOGNITIVE IMPAIRMENT
Radiation induced cognitive impairment including
dementia occurs in 50-60% of adult brain tumor patients,
living > 6 months post irradiation
Cognitive impairment is marked by
Decreased verbal memory
Spatial memory
Attention and
Novel problem solving ability
Front Oncol. 2012; 2: 73.
27. Radiation induced cognitive impairment occasionally progress to
dementia where patient experience
Progressive memory loss
Ataxia and
Urinary incontinence
Radiation induced dementia is a rare occurrence with
fraction size < 3 Gy
However patients surviving more then 2 years after
fractionated whole brain irradiation are at increasing risk of
dementia over time
NEUROCOGNITIVE IMPAIRMENT
28. All these late sequel can be seen in the absence of the radiographic
or clinical evidence of demyelination or white matter necrosis
NEUROCOGNITIVE IMPAIRMENT
Front Oncol. 2012; 2: 73.
29. IMAGING FOR RADIATION INDUCED COGNITIVE
IMPAIRMENT
Radiation induced cognitive impairment occur in the absence
of radiographic e/o gross anatomical changes
CT, T1/T2 and MRI are not likely to provide information
relevant to the occurrence and progression of Radiation
induced cognitive impairment.
MRI and PET have been used to evaluate Neurocognitive
impairment
MRS utilizes MR scanner to identify and quantify metabolites
that reflect altered cellular properties in specific region of
normal brain tissue
31. ENDOCRINOPATHIES
Hypothalamic and pituitary endocrinopathies – 80% of
patients post XRT that includes these structures
Dose <20 Gy : may cause endocrinopathies
Abnormal serum hormonal levels long before clinical
symptoms
Screening
Baseline endocrine evaluation in a year of RT
completion and annual blood to screen for HPA
dysfunction
33. PITUITARY INSUFFICIENCY
Prevalence of pituitary failure
6% @ 1 year
35% @ 2 year
56% @ 3 year and
62 % @ 4 and 5 year
GH deficiency occurred at mean of 2.6 year
Failure of pituitary gonadotropin and hyperprolactinemia after 3.8
years
ACTH insufficiency after 6 years and
Finally TSH insufficiency after a mean of 11 years
J LAB CLIN MED 109 : 364 - 372
34. Included
32 pts with brain tumor, 6 to 65 years
f/u – 2 to 13 years, post crainial RT
Dose of radiation : 40 -70 Gy and 9 pts : 18 to 39.6 Gy to C-S axis
Results
Thyroid deficiency : 9 pts, 28%
Oligomenorrhoea : 7/10 postpubertal, premenopausal ladies, 70%
Low serum testosterone, 3/10, 30%
Hyperprolactinemia : 50%
No endocrine abnormality : 3/32, 9%
NEJM 1993
35. CEREBROVASCULAR EFFECTS
Children are more susceptible
Vulnerable sites : supraclinoid region of ICA and Circle of
Willis
Risk factors :
Conc. Chemotherapy
Young age
Radiation dose
Neurofibromatosis I
Radiation field including Circle of willis (>10 Gy)
Prevention
Use of antiplatelet therapy
Management of other Cardiovascular risk factors
36. MIGRAINE LIKE HEADACHE SYNDROME
Reversible syndrome
Focal neurologic signs and/or seizure lasting days to weeks
SMART (Stroke Like Migraine Attacks After Radiatin Therapy)
37. EFFECTS ON THE EYES AND OPTIC PATHWAYS
Cataract
Presents with painless visual impairment 2 to 8 years
following RT
Retrospective studies, TBI done for BMT, 10 Gy/single #
- 60% developed cataract
12 Gy fractionated dose : 43% cataract
Strongly correlated with chronic use of steroids in these
patients
38. Xeropthalmia
If lacrimal gland > 30 Gy
Retinopathy :
Usually presents with painless loss of vision
Months to years post XRT
Unusual, <45 Gy
Optic Neuropathy
Presents with painless mono-ocular or binocular visual
impairment
Usually begin between 6 to 24 months post irradiation
< 55 Gy with 2 Gy/# : unusual
3-7% with 55-60 Gy
7-20% with >60 Gy
39.
40.
41. PREVENTION OF RADIATION INDUCED BRAIN
INJURY
Reducing Oxidative Stress
Reducing Chronic inflammation
Use of Neuronal stem cells
Advanced Radiation Techniques
Pharmacological agents
42. PREVENTION OF RADIATION INDUCED BRAIN
INJURY
Oxidative stress :
Reactive Oxygen Species scavengers
Anti-inflammatory agents
ROS scavengers are given little attention as they are likely to
protect brain tumors to the same extent as they protect
normal brain
43. Anti-inflammatory agents
Anti-inflammatory peroxisome proliferative activated agonists
(PPAR). Eg. Pioglitazone
Preclinical study
Pioglitazone was give 3 days prior to, during and for 4 to 54
weeks after radiation to brain
Assessed cognitve function at 52 weeks : reduced the
radiation-induced cognitive impairment
PREVENTION OF RADIATION INDUCED BRAIN
INJURY
Br.J.Radiol. 2007
44. Chronic inflammation
Brain Renin angiotensin system (RAS) is involved in
modulation of BBB, stress, memory and cognition
Both Angiotensin Converting Enzyme inhibitors (ramipril)
and Angiotensin receptor blocker have been proved
effective in treating experimental radiation neuropathy
(Moulder et al 2003)
45. Neurogenesis
Use of various stem cell therapies to restore neurogenic
niche and improve cognition
Rational :
Radiation
Decreased
hippocampal
neurogenesis
Cognitive impairment
PREVENTION OF RADIATION INDUCED BRAIN
INJURY
46. Direct injection of NSCs into rodent brains after WBI partially
restores neurogenesis and hippocampal dependant cognitive
function
Then NSCs not only diffrentiate into neurons, but also
oligodendrocytes, astrocytes and endothelial cells
Study in human : lacking
PREVENTION OF RADIATION INDUCED BRAIN
INJURY
PROC NATL ACAD SCI USA
2009
47. •Hippocampal avoidance volume : 3.3 cm3
•Helical Tomotherapy spared the hippocampus with median dose
of 5.5 Gy and maximum dose of 12.8 Gy
•Linac based IMRT spared hippocampus with median dose of 7.8
Gy and maximum dose of 15.2 Gy
•Conclusion Modern IMRT techniques allow for sparing of the
hippocampus with acceptable target coverage and homogeneity.
49. USE OF PHARMACOLOGICALAGENTS FOR
RADIATION INDUCED COGNITIVE
IMPAIRMENT
For symptomatic treatment several drugs have been evaluated
Psychostimulants (METHYLPHENIDATE)
Reversible Choline esterase inhibitors (DONEPEZIL)
NMDA receptor antagonist (MEMENTINE)
50. PSYCHOSTIMULANTS
Mechanism of Action : Dopamine reuptake inhibitor
Dose : 10 mg twice a day
Result
Significant improvement in cognitive functions
Functional improvements :
Improved gait
Increased stamina
1 case : increased bladder control
AE were minimal
No increase in seizure frequency and
Majority of patients required lower dose of steroids
51. REVERSIBLE CHOLINE ESTERASE
INHIBITORS
Donepezil
Trial by wake forest community clinical oncology
programme research base
200 brain tumor patients
Surviving > 6 months
Placebo Donepezil 10mg/day for 6
months
Significant improvement in energy
level, mood and cognitive functions
53. TRIAL BY RTOG
Dose : 20 mg/d, within 3 days of initiating
radiotherapy for 24 weeks
Primary end point : memory deficits
No preliminary results
Trial closed after accrual of 554 patients
54. QUALITY OF LIFE (QOL) AFTER CNS
IRRADIATION
Quality of life is a concept that encompasses the
multidimensional well being of a person and reflects an
individual’s overall satisfaction with life.
Dimensions of QOL
1. Physical or functional status
2. Emotional well being
3. Social well being
55. INSTRUMENTS TO MEASURE QOL
Karnofsky performance status (KPS)
Mini Mental Status Examination (MMSE)
Brain tumor specific QoL : commonly measured using the
Funtional Assessment of Cancer Therapy – Brain (FACT-
Br)
EORTC-QLQ-C30
EORTC-QLQ-B20
56. Generally correlates
with overall QoL
Appears to have
prognostic value
KARNOFSKY PERFORMANCE STATUS (KPS)
57. However Using KPS to measure QOL is problematic because
1. it is only a measurement of functional ability and
2. its reliability and validity depend on observer
KARNOFSKY PERFORMANCE STATUS (KPS)
58. To overcome these problems other evlauation scales used
MMSE
Hopkins Visual Learning Test (HVLT)
The COWA test
Trail Making Test (TMT)
RANO criteria
Brain tumor specific QoL : commonly measured using
the Funtional Assessment of Cancer Therapy – Brain
(FACT-Br)
EORTC-QLQ-C30
EORTC-QLQ-B20
QOLASSESSMENT INSTRUMENTS
59. MMSE
Originally designed to assess the stroke patients, has also been
used to assess Neurocognitive Function (NCF) in patients with
brain tumor.
It tests broad range of cognitive function including :
Oreintation
Recall
Attention
Calculation
Language manipulation and
praxis
60.
61. LIMITATIONS OF MMSE
MMSE (Mini mental Status Examination) : validated for
other cognitive disorders and is relatively insensitive for
assessing Radiation induced cognitive impairment.
Limitations of MMSE
a. Does not avoid memorized learning from repeat testing
b. Is biased against patients with lower educational
background
c. Relatively insensitive to the subtle changes in brain
caused by brain radiotherapy
62. Quick, repeatable measure of verbal learning and memory
12 words are spoken aloud to patient from different
category
12 already spoken words and 12 distractor words are
added, requiring yes/no question
(25 minutes later)
HOPKINS VERBAL LEARNING TEST
63. 5-10 minutes test
Measures verbal fluency
It places high demand on executive control process
Patients are given 1 minute to spontaneously name
as many words as possible, beginning with
predetermined letter or same category
THE CONTROLLED ORAL WORD ASSOCIATION
(COWA) TEST
64. THE TRAIL MAKING TEST (TMT) :
Test of executive function, visual attention and task
switching
The time taken to complete each task reveals the extent
of cognitive impairment
GROOVED PEGBOARD TEST (GP) :
Motor speed and dexterity
Meyers et al Proposed a panel involving the HVLT, COWA
and TMT as a brief and highly sensitive test of global NCF
65. RESPONSE ASSESSMENT IN NEUROONCOLOGY
CRITERIA (RANO)
RANO Criteria working group recommended a battery of
cognitive tests that included at least the HVLT, TMT and
multilingual aphasia examination and COWA
66. BRAIN TUMOR SPECIFIC - QOL
Is commonly measured using the functional assessment of
cancer therapy – Brain (FACT – Br) questionnaire
FACT – Br covers four primary QoL domains :-
Physical well being
Social/family well being
Emotional well being
Functional well being
67. ALTERNATIVES MEASURE OF QOL BY EORTC
EORTC – QLQ – C30
30 item questionnaire
Multi item scales incorporating :-
Five functional scales: physical, cognitive, emotional and
social
3 symptoms scales fatigue, pain, nausea and vomiting
A global health and QoL scale
68. Remaining single items : assess for additional symptoms
commonly reported by cancer patients
Dyspnoea
Appetite loss
Sleep disturbance
Constipation and diarrhoea
Perceived financial impact of disease and treatment
69. EORTC – QLQ – B20
20 item questionnaire that is specific to brain related
symptoms
Requires 10 minutes to complete
The EORTC-QLQ-C30 and FACT-Br are the most widely
used cancer specific questionnaires in clinical trials
FACT-Br Vs EORTC-QLQ-C30 :
Social support and
relationship
More weight on social
activities and family life
70. CONCLUSION
Late term toxicities are increasing as survival of brain tumor
patients post radiation is increasing
Once neurons, considered radioresistant, they have been shown
to respond negatively to radiation
With advances in RT techniques and use of pharmacological
geents, there is hope for prevention of neurocognitive
impairment
FACT Br and EORTC QLQ C30 are most widely used QoL
instruments all over the world