The document discusses the evolution of treatment strategies for brain gliomas. It begins by providing background on gliomas and their classification. It then discusses advances in surgery, including neuronavigation, fluorescent guided resection, and intraoperative imaging. It also covers the evolution of radiotherapy techniques from early 2D approaches to modern 3D conformal radiotherapy and intensity modulated radiotherapy. Adjuvant therapies like chemotherapy and targeted drugs are also mentioned. Overall the document traces the development of surgical and radiation based approaches for glioma treatment over time.
Aim of this ppt presentation:
To understand the standard of care for both GBM and anaplastic glioma.
To know what is the new advances and modifications to the standard of care?
Contents:
Introduction: 2 slides.
GBM:
Epidemiology: 1 slide.
Molecular biology & New trends: 5 slides
EORTC/NCIC trial: 10 slides.
MGMT: 1 slide.
Evidence-based medicine: 6 slides.
Avastin in GBM: 2 slides.
Novocure (TTF): 2 slides.
Gliadel (BCNU) wafers: 1 slide.
Anaplastic astrocytoma: 7 slides
Take home message.
Aim of this ppt presentation:
To understand the standard of care for both GBM and anaplastic glioma.
To know what is the new advances and modifications to the standard of care?
Contents:
Introduction: 2 slides.
GBM:
Epidemiology: 1 slide.
Molecular biology & New trends: 5 slides
EORTC/NCIC trial: 10 slides.
MGMT: 1 slide.
Evidence-based medicine: 6 slides.
Avastin in GBM: 2 slides.
Novocure (TTF): 2 slides.
Gliadel (BCNU) wafers: 1 slide.
Anaplastic astrocytoma: 7 slides
Take home message.
Brain metastasis is an advance diseases with poor overall prognosis management of which is full of controversies. This slide aims to make metastasis simplified.
This presentation reviews the current neurosurgical management of patients with medulloblastoma, including the data on molecular subtyping; uses “medulloblastoma” as a springboard to discuss other topics / tumor cell biology in general; and formulates research questions to further advance neurosurgical basic science.
Brain metastasis is an advance diseases with poor overall prognosis management of which is full of controversies. This slide aims to make metastasis simplified.
This presentation reviews the current neurosurgical management of patients with medulloblastoma, including the data on molecular subtyping; uses “medulloblastoma” as a springboard to discuss other topics / tumor cell biology in general; and formulates research questions to further advance neurosurgical basic science.
Primary brain tumours are a diverse group of neoplasm arising from different cells of the central nervous system.
It accounts for about 2% of all cancers with an overall annual incidence of 22 per 1,00,000 population.
Most common brain tumour in adults is Brain Metastasis.
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This presentation will highlight the promising new therapeutic strategies in the treatment of gliomas, with a focus on trials or therapies that will soon be available for Canadian patients.
View the YouTube video: https://youtu.be/ibbEuvSF7xY
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Giant Glioblastoma in a Patient with Previous Prostate Adenocarcinoma_Crimson...CrimsonPublishersAICS
Giant Glioblastoma in a Patient with Previous Prostate Adenocarcinoma by Anna Aldea Parés, Adrián Téllez Santoyo, Pedro Castro Rebollo and Ramón Estruch Riba* in Advancements in Case Studies
This is a PDF of a presentation given to the Radiation Oncology department at the University of Minnesota in October 2015. This PDF focuses on evaluation, management, and state-of-the-art approach to gliomas from a medical neuro-oncology perspective.
Understanding Uterine Cancer Treatment Optionsbkling
Join Dr. Bhavana Pothuri, gynecologic oncologist at NYU Langone Medical Center, as she breaks down the different types of uterine cancer treatments available to patients based on their particular diagnosis. Learn about new research and treatment updates, options for when cancer recurs, side effects, and more.
How the role of radiotherapy has evaluated in pancreatic cancer. Now it has become indispensable for treatment in pancreatic cancer. Radiotherapy can be used in the form of EBRT/SBRT/IORT.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Phone Us ❤85270-49040❤ #ℂall #gIRLS In Surat By Surat @ℂall @Girls Hotel With...
Evolution of treatment strategies of brain tumors
1. EVOLUTION OF TREATMENT STRATEGIES
FOR BRAIN GLIOMAS
By Dr Anil Gupta
Moderator Dr Amit Bahl
2. Introduction
Glial cells are supportive cells in
CNS
Makes 90% of brain
Gliomas refers to neoplastic
transformation of normal glial
cells
Astrocytoma refers to tumours
that have histologic features
similar to astrocytes.
3. WHO grade I Astrocytoma
Well
defined
character
Early age of
onset
Lack of
invasiveness
Good
prognosis
Types
- Pilocytic astrocytoma
- Subependymal giant cell astrocytoma
- Pleomorpic xanthoastrocytoma
Pediatric age group
4. Diffuse Gliomas
Have similar growth patterns and behaviours
Share same genetic driver mutations IDH1
and IDH2 genes.
Share similar prognostic markers.
Has similar management (conventional or
targeted)
“Diffuse astrocytoma is more similar to
oligodendroglioma than it is to pilocytic
astrocytoma”
Not curable by surgical resection
Includes grade II and grade III astrocytic and
oligodendroglial tumors, grade IV glioblastomas, as
diffuse gliomas of childhood
5. Epidemiology
Distribution of Primary Brain and CNS Tumors by Histology Distribution of Primary Brain and CNS Gliomas by Histology Subtypes
CBTRUS Statistical Report: NPCR and SEER, 2009-
2013
Brain tumors account for only 2 percent of all cancers
60-62% are metastatic brain tumors
Overall incidence rate for primary brain and CNS tumors is 21.03 per
100,000
6. Trends of incidence on the basis of age
Age-Adjusted Incidence Rates in Children and
Adolescents of Brain and CNS Tumors
Age-Adjusted Incidence Rates of Brain and CNS
Tumors
CBTRUS Statistical Report: NPCR and SEER, 2008-
2012
7. Survival rates
Histology 1 yr OS2 yr OS 3 yr OS 4 yr OS 5 yr OS
10 yr
OS
Pilocytic astrocytoma 98 96.6 95.5 94.6 94.2 92
Diffuse astrocytoma 74.4 63.6 57.3 53 49.7 39.3
Anaplastic astrocytoma 64.4 45.9 37.4 32.8 29.7 20.9
Glioblastoma 39.3 16.9 9.9 7 5.5 2.9
SEER 18 Registries, 2000-2013
8.
9. Incidence in Future?
0
5,000
10,000
15,000
2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
US
France
Germany
Japan
• Number of newly diagnosed cases of glioblastoma is expected to increase in
the US, France, Germany, and Japan
Decision Resources: Glioblastoma Multiforme. September 2013
11. Is a mean of predicting biological behaviour of a neoplasm
Determines prognosis
Directs treatment strategies
The Kernohan system
- Based on the degree of presence of multiple
- features (i.e., anaplasia, cellular and nuclear pleomorphism,
hyperchromasia, vascularity, cellularity, necrosis,
endothelial proliferation, and mitotic rate)
12. St Anne-Mayo grading system
Nuclear Atypia
Mitoses
Epithelial proliferation
Necrosis
Is binary and
1 criterion = grade 2
2 criteria = grade 3
or 3 or 4 criteria = grade 4
WHO grading system
A
M
E
N
Grade I
St Anne Mayo grading
diffuse astrocytoma without atypia (rare)
WHO grading system
More circumbscribed pilocytic astrocytomas
13. • Uses causal probabilistic models, also
known as Bayesian networks to grade
gliomas
• Is a computerized statistical model
Pros
• Prevents interobserver variability
• Easily reproducible
Still in developmental phase
15. Pre WHO classifications
Classification of tumors of Glioma Group (1926)
Tumors of central nervous system (1952)
International union against cancer (1965)
Atlas of the histology of brain tumor (1972)
- the forerunner of the official WHO editions
- adjectives ‘‘benign,’’ ‘‘semibenign,’’ ‘‘semimalignant,’’ and ‘‘malignant’’
were attributed to heterogeneous groups
Atlas of Gross Neurosurgical Pathology (1975)
16. WHO brain tumor classification
“the blue books”
The First
edition
(1979)
• Histological typing of
tumours of the
nervous system
The second edition (1993)
• Reflected the advances brought about by the introduction
of immunohistochemistry into diagnostic pathology
The third edition (2000)
• Incorporated genetic profiles as additional aids
• Concise commentary on clinico-pathological characteristics
of each tumour type
The fourth edition (2007)
genetic profile updated
Diagnosis, classification and grading based solely on morphology
17. Changes in astrocytic tumors
Explosion of molecular data
-Better insight into biology of human disease
(diagnostic, prognostic and/or predictive value)
– How should clinically relevant molecular information be
incorporated into nervous system tumor classification?
• Clinical applications lagging behind
– Few translated into tangible medical advances
– Most remain unused
Since 2007
18. 1. Diagnostic entities should be defined as narrowly as possible
2. Diagnoses should be “layered
3. Determinations should be made for each tumor entity as to whether
molecular information is required
4. Some pediatric entities should be separated from their adult
counterparts
5. Input for guiding decisions regarding tumor classification should be
solicited from experts in complementary disciplines of neuro-oncology
6. Entity-specific molecular testing and reporting formats should be
followed in diagnostic reports
ISN-Haarlem consensus 2014
19. Multi layered reporting format
Layer 1: Integrated diagnosis (incorporating all tissue-based information)
Layer 2: Histological classification
Layer 3: WHO grade (reflecting natural history)
Layer 4: Molecular information
Layer 1 : diffuse astrocytoma, IDH
mutant type, grade II
Layer 2: gemistocytic astrocytoma
Layer 3 : II
Layer 4 :IDH mutant, ATRX loss
20. WHO 4th edition
revised 2016
WHO 4th edition
(2007)
Strongly
discouraged,
only in rare
cases where
both 1p19q
codeletion
and ATRX
positive
NOS- when
IHC
inconclusiv
e or not
available
21. Molecular testing
IDH1 and IDH2 (isocitrate dehydrogensase) mutations
Good prognostic marker
Can be done by IHC, PCR or pyrosequencing
1p19q co-deletion
Mainly seen in ODG
Good prognostic factor
Can be done by PCR, FISH
ATRX gene mutation (alpha thalassemia-mental retardation, X linked)
Seen in 45% of anaplastic astrocytoma
Considered as hallmark of astrocytoma
ATRX loss is a good prognostic factor
Can be done by IHC,FISH, PCR
NOA-04 trial
22. MGMT (O-6 methylguanine methyltransferase)
promotor status
Is crucial for genome stability
It repairs methylation of DNA
It also reverses the cytotoxic effects of
alkylating agent
Inactivation of MGMT makes it sensitive
to alkylating agent
Is a prognostic and predictive marker
Done by PCR, pyrosequencing
In PGI, panel of IDH1, ATRX, Ki67, p53,
GFAP is done routinely
1p19q codeletion is done by FISH
MGMT promotor status is not done
M Hegi et al NEJM
2005
HGGs
23.
24. The RTOG RPA model for prognosis of
glioblastoma
Age <50 or >50
KPS score (< vs. ≥ 90
for patients < 50
y or < vs. ≥ 70
for patients ≥ 50
y
Extent of
resection
Resection vs
biopsy
Neurologic
function
Able to work or
not
Original (1998 ) Modified
(2010)Age <50 or >50
KPS score (< vs. ≥ 90 for
patients < 50 y or <
vs. ≥ 70 for patients
≥ 50 y
Extent of resection Resection vs biopsy
Neurologic function Able to work or not
Mental status Normal or abnormal
RT dose <54.4 Gy or >54.4
Gy
Excluded
AA
RTOG trials
74-01, 79-
18, and 83-
02, 90-06
and 94-11
30. • Treatment-induced changes in brain permeability introduce challenges in detecting response
to therapy and disease recurrence by MRI[1]
Challenges in Response Assessment:
Pseudoprogression and Pseudoresponse
Pseudoprogression
Apparent increase of tumor lesion
on imaging that is not due to
actual tumor growth
Pseudoresponse
Apparent decrease of tumor lesion
on imaging that does not reflect
true tumor reduction
Often occurs with antiangiogenic
agents such as bevacizumab
Observed in 5%–31% patients* after
RT/chemotherapy
• -Also been observed after treatment
with immunotherapies, but is often
followed by tumor regression
• -Apparent increases in tumor lesions
in these cases may be a result of
immune-cell infiltration of the tumor
33. Surgical resection of brain tumor
Goals of surgical resection:
(1) Establishing histological diagnosis
(2) Tumor cytoreduction for:
- improving neurological status
- Possible change in tumor kinetics
Advent of brain surgery
1873: Gupta Longati first discovered Brain Cancer
In 1879, first successful brain tumor surgery was done to remove blood clots
Early 1990s brain tumor surgery was frequently done
With betterment in anaesthesia and imaging, perioperative mortality reduced
34. Gross total tumor resection is
associated with longer survival
8-yr PFS after STR without adjuvant therapy
is 56% if residual tumour is 1.5 cm3 and 45% if the volume
is >1.5 cm3
Neurosurgery 68:1548–1555, 2011
Complete resection (>90% cure
rate)
Incomplete resection (70% to
80% 10 yr- OS)
35. Treatment of WHO grade I astrocytoma
Complete surgical resection whenever
feasible is curative and mainstay therapy
Near total excision results in delayed
recurrence and malignant transformation
Resection difficult in optic pathway,
hypothalamus ,deep midline structures
In these instances if asymptomatic , can be
kept on observation
Potentially curable by surgical
resection
36. Diffuse gliomas
Generally not considered surgically curable, due
to diffuse brain infiltration
Not curable by surgical resection
J Neurooncol 2015
35 retrospective studies attempted to correlate EOR with OS in
LGGs
• 6 of these studies showed no correlation
• 3 studies showed a correlation but was not significant
• 23 showed it increases OS
lack of class I evidence and limited examples of class II
evidence,
37. Advances in surgery
Neuronavigation
5- ALA fluorescent porphyrins
Use of intraoperative MR
Helps in complete resection of tumor
Intra-operative cortical stimulation mapping
Identifies functionally critical areas (eloquent brain)
by placing electrodes on functional areas
In PGI, awake craniotomy is performed, in tumor
such as insular gliomas
glioma cells
38. More patients in the iMRI group had complete tumour resection (23 [96%] of 24 patients)
than in the control group (17 [68%] of 25, p=0·023
Postoperative rates of new neurological deficits did not differ between patients in the
intraoperative MRI group (three [13%] of 24) and controls (two [8%] of 25, p=1·0
Contrast-enhancing tumour was resected completely in 90
(65%) of 139 patients assigned ALA compared with 47
(36%) of 131 assigned white light p<0·0001
39. Recurrence
Diffuse gliomas tend to reccur
Patients with glioblastoma invariably recur despite optimal upfront treatment with
the majority of recurrences occurring within the first year
Publication Location in relation to original site
Wallner et al (1989) <1 cm
Gasper et al (1992) <4 cm
Choucar et al (1986) 90% occur at site of tumor
42. Early era of radiotherapy in glioma
1940s, kilovoltage X-rays
whole brain RT
1960s , megavoltage X-
rays or 60Cobalt
teletherapy whole brain
RT
1970s there was a move
away from whole brain
radiotherapy for the entire
course of treatment.
43. Manual marking for Whole Brain RT
Upper, lateral border- 1cm flash in air
Lower border- inferior orbital ridge to tragus
dose:20 – 40 Gy in 5 to 20 fractions
44. Flouroscopy simulation
Left and right opposed lateral fields
with 6-10mv photons
Anterior temporal lobe, cribiform
plate, posterior aspect of eyes
included
Inferior field edge in lower border of
C2 vertebrae and base of skull
German Helmet
technique
Limitations
-Most recurrences were in
close proximity to the
original tumour
-Survival differences
between WBRT and coned
down RT were not
significant (Shapiro et
al;BTCGTrial 8001. J Neurosurg
1989)
-Neurotoxictiy
47. Conventional planning
Limitations
Irradiation of large volumes of brain with
normal tissue also
Higher toxicity and side effects
Lack of 3D visualization of tumor
2D planning of 3D tumor
50. Intensity Modulated Radiotherapy (IMRT)
First launched in 1996
It uses multiple small photon beams of varying intensities to precisely
irradiate a tumor
The radiation intensity of each beam is controlled, and the beam shape
changes throughout each treatment
51.
52. IMRT did not significantly improve target coverage compared with 3D-CRT
However, it resulted in a decreased Dmax to the spinal cord, optic nerves,
and eye by 16%, 7%, and 15%
It is unlikely that IMRT will improve local recurrence without dose escalation However,
it might result in decreased late toxicities associated with radiotherapy
53. Volumetric modulated arc therapy
(VMAT)
Is a novel extension of IMRT wherein the dose is
delivered in a single gantry rotation while the
multileaf collimator leaves are in motion
Launched in 2007
57. Low grade gliomas- younger age, better survival
High grade glioma-more recurrences, dose escalation can be tried
Int. J. Radiation Oncology Biol. Phys., Vol. 45, No. 5, pp. 1117–1126, 1999
hr. J. Radiation Oncology Bid Phys. Vol. 22, pp. 287-294
Less integral dose, dose escalation
can be tried
With 90 CGE by
PBT
safe and efficacious, OS similar to photon
58. Contouring guidelines
RTOG
Phase I-CTV- postoperative peritumoral edema plus a 2 cm margin( low grade 1 cm)
Phase II- CTV- residual tumor plus 2 cm margin
peritumoral
oedema as these
areas are believed
to contain high
concentrations of
tumour cells
EORTC- 2–3 cm
dosimetric margins
around the tumor
(as evaluated by
MRI)
59.
60. Radiation doses
Low grade gliomas
J Clin Oncol 20:2267-2276
(EORTC) STUDY 22844: 1996
2 Randomized trials
2-year actuarial incidence
grade 3 to 5 radiation necrosis
low-dose RT - 2.5%
high-dose RT- 5%
High grade gliomas
Short course RT for elderly
6.8 months --25 Gy/5#
6.2 months --40 Gy/15#
De Castro et al 2017
RTOG 7401,BTSG 8001
no additional prolongation in
survival with doses >60Gy
61. Brachytherapy
First used in 1953
Placing radioactive material directly into or near the brain tumor
Potential radiobiological advantages over EBRT :-
Reduced damage to normal tissue
More concentrated delivery of radiation to the tumor bed >80% of recurrences
are within 2 cm of the site of origin
Low dose rate irradiation ( 1cGy/min)- better therapeutic ratio
Application of Brachytherapy :-
Treatment option for recurrent tumors
Primary RT
Boost RT
Can be used as radical or palliative treatment
62. Median survival 58.8 weeks vs 68.1 weeks for interstitial brachytherapy arm (p- 0.1)
Conclusion: no long-term survival advantage of increased radiation dose with 125I seeds in
newly diagnosed glioma patients
Another single institute prospective trial showed no survival advantage
Acute
Hemorrhagic complications (1-5%)
Infections
Poor wound healing
Raised ICT
Delayed
Radiation necrosis in 50% of patients Gutin et al
Atrophy
Gliosis
Progressive neurologic decline— occlusion of small and
great arteries
63. Stereotactic radiosurgery (SRS)
“a single high-dose fraction of radiation, stereotactically directed to an intracranial
region of interest”
A high ablative dose is applied to the lesion of interest
Three widely used systems are
1. the Leksell Gamma Knife (Elekta, Stockholm, Sweden)
2. the Cyberknife (Accuray, Sunnyvale, CA, USA)
3. the Novalis (BrainLAB, Feldkirchen, Germany)
Stereotactic radiotherapy (SRT) uses more than 1 fraction
64. Gamma Knife
Launched by Lars Leksell in 1972
Mechanical focusing of 192 radiation sources of
cobalt allows shaping of an extremely defined
irradiated volume in the brain
The stereotactic head frame guarantees the precision
needed to protect healthy brain tissue and directs
the radiation focus into the target.
15Gy (3.1 – 4cm), 18Gy (2.1 to 3cm) or 24Gy (2cm or less)
65. Cyberknife
Is a robot-controlled 6-MV linear accelerator (LINAC) with non-isocentric
cone beams
Launched in 2007
Non invasive
66. Now generally accepted, that radiosurgery has no additive effect when given as
boost or in connection to initial standard treatment with surgical resection and
fractionated radiotherapy
Reserved for recurrences
Fractionated RT cannot be repeated and the surgery not always possible in
recurrence. Survival in recurrences after -
SRS 6.5 to 30 months
Resurgery 3.5-9 months
Temozolamide 4.5 months
bevacizumab 4.5 months
SRS has proven to be an
effective alternative treatment
option
67. Radiotherapy in Grade I astrocytoma
Defintive
In children, with cerebellar and optic pathway
pilocytic astrocytoma
In adults used for hypothalamic pilocytic
astrocytoma
Post Operative Radiotherapy
Residual – progression
Recurrent
Timing of adjuvant radiotherapy
Immediate
post-
operative
Delayed
In young children with
unresectable, non-progressive
low grade gliomas
In adults and older
children with
impractibility of repeated
surgical excision, extent
of residual disease,
location of tumor
proton beam therapy is often considered for these
patients
68. Who undergo a gross total resection have a 52% risk of tumor progression 5-years
after surgery, warranting close follow-up and consideration for adjuvant treatment.
Diffuse low grade astrocytoma
Shaw et al;J Neurosurg 109:000–000, 2008
EORTC 22845 randomised trial
Lancet 2005; 366: 985–90
69. Radiotherapy in high grade gliomas
The irradiated cases had a 6-month survival
rate of 64 per cent and a one-year survival
rate of 19 per cent;
The non-irradiated cases a 6-month survival
rate of 28 per cent and a one-year survival
rate of 0 per cent
A. P. Andersen (1978) Postoperative Irradiation of
Glioblastomas: Results in a Randomized Series, Acta
Radiologica
70. Chemotherapy
Drug therapies are effective for only few types of CNS tumors
(eg primary CNS lymphoma)
But are useful for adjunctive therapy for many CNS tumors
Poor efficacy due to :-
difficulty in crossing blood brain barrier
active transport mechanism of drug efflux
high plasma binding of agents
intrinsic and acquired resistance
High intratumoral interstitial pressure
Only low molecular weight lipophilic drugs
freely cross the BBB
71. Chemotherapy in WHO grade I
astrocytoma
Chemotherapy is often utilised as the initial therapeutic option in young
children to avoid long term sequelae of RT
Multi centric trial suggestive of 50% of reduction in volume of tumor vs
none in placebo group
72. Chemotherapy in low grade diffuse gliomas
18 to 39 years of age with STR or biopsy
EBRT 54 Gy/ 30#/6 wks
PCV- 6 cycles
N Engl J Med. 2016;374(14):1344.
No trials comparing
temozolamide with PCV for
grade II
High risk diffuse LGGS
73. Chemotherapy in high grade glioma
Nitrosoureas
Historically were standard choice of chemotherapy
Lipid-soluble agents and can cross the BBB
BCNU has mainly been evaluated as single-agent
therapy
Dose 150 to 200 mg/m2 i.v6 to 8 weekly
Toxicities myelosuppression, drug-induced
pulmonary fibrosis increases with cumulative
dosages
80. Carmustine wafers (GLIADEL® Wafer)
Are biodegradable copolymers
impregnated with the alkylating
agent carmustine BCNU (3.5%)
Developed in order to overcome the
limitations of blood-brain barrier
impermeability to antineoplastic
agent
Is implanted in the brain along the
walls and floor of the cavity created
after a malignant glioma has been
surgically removed
• Median survival was 13.1 months in the
Gliadel arm and 11.4 months in the placebo
arm for glioblastoma
Westphal et al (2003)
• Median survival was 53.3 weeks in the
treatment arm and 39.9 weeks in the placebo
arm (p < 0.05) for high grade glioma
Valtonen et al (1997)
81. Targeted therapy
Challenges limiting the efficacy :-
difficulty in crossing blood brain barrier
heterogeneity of tumors
lack of accurate and reproducible biomarker
difficulty in assessing target modulation
82. Bevacizumab received approval by the US Food and Drug Adminstration (FDA) in
2009 for use in recurrent GBM:
Trial Study Arms Ph Study Setting N ORR, % mPFS, mo mOS, mo
BRAIN
BEV
II
Recurrent
glioblastoma
167
28 4.2 9.2
BEV + irinotecan 38 5.6 8.7
NCI BEV II
Recurrent
glioblastoma
48 35 16 wks 31 wks
JO22506 BEV II
Recurrent
glioblastoma
(Japan)
31 28 3.3 10.5
AVAglio[ BEV + RT + TMZ vs
Placebo + RT + TMZ
III
Newly diagnosed
glioblastoma
921 NA 10.6 vs 6.2* 16.8 vs 16.7†
Only transitory clinical and radiographic benefit for a few month
Main benefit is secondary to reduction in cerebral edema
Sanchez et alOncol Lett. 2012 Nov; 4(5): 1114–1118.
Control group – TMZ
BVZ group- BVZ/CPT-11
BVZ/CPT-11
High dose bevacizumab 15 mg/kg 3 weekly
irinotecan 125mg/m2on D1, 8, 22, and 29
83.
84. TT fields (tumor treating fields) Optune ™
Creates alternating, “wave-like” electric fields that travel across the upper part of
the brain in different directions
Side effects -scalp irritation from device use and headache.
FDA approval
2011- recurrent GBM
2015- newly
diagnosed GBM
Cost- $21,000 per month
85. Gene therapy
Trials in humans have entailed the stereotaxic injection of viral vectors directly into brain tumors
to transfect the cells to synthesize genes leading to tumor cell destruction (Ram and Oldfeld,
1977).
Patients receiving VB-111 survived 15 months on average,
compared with 8 months on average for patients receiving
bevacizumab in recurrent glioblastoma
was safe and well-tolerated
Phase III trial going on
Phase II
86. Immunotherapy
Based on concept of harnessing the
patient's own immune system to
stimulate an antitumor response
Immunosuppression is inherently
associated with glioblastoma and is
mediated by a variety of
mechanisms
Rindopepimut
Study mPFS mOS
Sampson et al
(2010)
14.2 m 23.6 m
Sampson et al
(2011)
15.2 m 26 m
88. Levin criteria
WHO oncology
response criteria
Macdonald
criteria
AVAglio
the Response
Assessment in
Neuro-Oncology
(RANO)
Prior to 1990s Since 1990 In 2009 In 2010
edema and
mass effect
measured tumor
area by
multiplying the
maximal cross-
sectional
enhancing
tumor diameters
Complete
response,
partial
response,
stable
disease,
progressive
disease
the effectiveness of
RT and TMZ with or
w/o bevacizumab in
newly diagnosed
glioblastoma