This document provides an overview of the management of gliomas. It discusses the general management and specific management of low grade and high grade gliomas.
For low grade gliomas, the main treatment options are observation, surgery, radiation, and chemotherapy. Surgery aims for maximal safe resection followed by radiation therapy. Chemotherapy with PCV may provide a survival benefit for high risk patients based on one trial, but requires further study.
For high grade gliomas, prognostic factors like age, performance status, extent of resection, and molecular markers are discussed. Treatment involves maximal safe surgery followed by concurrent chemoradiation and adjuvant chemotherapy with temozolomide, which has become the standard of care based on clinical trials
Gliomas are the commonest tumor of brain arising from the supportive cells of the brain with diverse form and presentation the treatment of which is surgical and demands adjuvant therapy for most of circumstances.
Gliomas are the commonest tumor of brain arising from the supportive cells of the brain with diverse form and presentation the treatment of which is surgical and demands adjuvant therapy for most of circumstances.
Medulloblastoma- A primitive neuroectodermal tumors (PNETs) is the most common malignant brain tumor of childhood (WHO IV)
arising from the vermis in the inferior medullary velum.
It comprises up to 18% of all pediatric brain tumors.
WNT and Shh pathway plays major role in its pathogenesis.
c-erbB-2 (HER2/neu) oncogene expression has prognostic value. Norcantharidin, Vismodegib, Sonidegib are the future in medulloblastoma.
Don't miss our upcoming webinars. Subscribe today!
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
Follow CCSN on social media:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurvivorNet
Instagram: https://www.instagram.com/survivornet_ca/
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Radiosurgery is a discipline that utilizes externally generated ionizing radiation in certain cases to inactivate or eradicate a defined target(s) in the head or spine without the need to make an incision. Its uses in Neurosurgery is immense.
Brain metastasis is an advance diseases with poor overall prognosis management of which is full of controversies. This slide aims to make metastasis simplified.
It is an oncologic emergency. This slides contains a brief discussion on mechanism of spinal cord compression , common malignancies presenting with spinal cord compression , approach to a patient with cord compression like features and management this catastrophic situation.
Medulloblastoma- A primitive neuroectodermal tumors (PNETs) is the most common malignant brain tumor of childhood (WHO IV)
arising from the vermis in the inferior medullary velum.
It comprises up to 18% of all pediatric brain tumors.
WNT and Shh pathway plays major role in its pathogenesis.
c-erbB-2 (HER2/neu) oncogene expression has prognostic value. Norcantharidin, Vismodegib, Sonidegib are the future in medulloblastoma.
Don't miss our upcoming webinars. Subscribe today!
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
Follow CCSN on social media:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurvivorNet
Instagram: https://www.instagram.com/survivornet_ca/
Pinterest - https://www.pinterest.com/survivornetwork
Radiosurgery is a discipline that utilizes externally generated ionizing radiation in certain cases to inactivate or eradicate a defined target(s) in the head or spine without the need to make an incision. Its uses in Neurosurgery is immense.
Brain metastasis is an advance diseases with poor overall prognosis management of which is full of controversies. This slide aims to make metastasis simplified.
It is an oncologic emergency. This slides contains a brief discussion on mechanism of spinal cord compression , common malignancies presenting with spinal cord compression , approach to a patient with cord compression like features and management this catastrophic situation.
the role of brachytherapy in oral cavity carcinoma.
physics of brachytherapy
radiobiology of brachytherapy
clinical application in tongue, buccal mucosa cancer
describes relationship between radiation dose and the fraction of cells that “survive” that dose
model of cell killing
target model
linear quadratic model
EBCTCG METAANALYSIS
INDICATION OF POST OP RADIOTHERAPY
Immobilization devices
Conventional planning
Alignment of the Tangential Beam with the Chest Wall Contour
Doses To Heart & Lung By Tangential Fields
Energy Absorption in Radiobiology
Ionization vs. Excitation
Ionizing Versus Non-ionizing Radiation
Absorption Mechanisms
Ionization by alpha particle, Xray & neutron
Edward B. Garon, MD, MS, Jamie E. Chaft, MD, and Matthew D. Hellmann, MD, prepared useful Practice Aids pertaining to lung cancer management for this CME/MOC/CE activity titled "Improving Patient Outcomes With Cancer Immunotherapies Throughout the Lung Cancer Continuum: State of the Science and Implications for Practice." For the full presentation, monograph, complete CME/MOC/CE information, and to apply for credit, please visit us at http://bit.ly/2ATq0qp. CME/MOC/CE credit will be available until November 21, 2019.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
21 marzo 2014: Trattamenti stereo-RT e radiochirurgici come opzioni standard di trattamento: stato dell’arte in base a linee guida internazionali
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
17 marzo 2014: Trattamenti ipofrazionati ed ipofrazionati-accelerati: nuove possibilità di prevenzione e trattamento della tossicità acuta e tardiva
Presentation is highlighting the integration of different modalities in the management of locally advanced and metastatic prostate cancer pointing to the proven values of adding chemotherapy. A special note has been made to oligometastatic disease.
Physical Models For Time Dose & FractionationIsha Jaiswal
Physical Models For Time Dose & Fractionation
Strandqvist Plot
Cohen’s Formula
Fowler Concepts
NSD Model
TDF model
Target Theory
L Q model
BED calculation of different fractionation regimen
Introduction
Time dose & fractionation
Therapeutic index
Four R’s Of Radiobiology
Radiation response
Survival Curves Of Early & Late Responding Cells
Various fractionation schedules
Clinical trials of altered fractionation
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.
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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.
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.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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
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.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
2. Topics to be covered
General management
Management of low grade gliomas: overview
Pilocytic astrocytoma
non pilocytic/diffuse infiltrating gliomas
Management of high grade gliomas: overview
Anaplastic gliomas
Glioblastoma multiformae
3. Medical management
For Cerebral oedema:
Glucocorticoids used :Dexamethasone preferred because of minimal mineral-corticoid
effects.
Lower doses :shown to be as effective as higher doses-2 to 4 mg bd preferred
should be discontinued or tapered to the lowest dose necessary, as soon as possible.
taper is necessary to prevent rebound in cerebral edema and also to allow the pituitary–
adrenal axis to recover.
4. For seizures
Patients with seizures require anticonvulsants.
Levetiracetam preferred: non–hepatic isozymes inducing
carbamazepine, phenobarbital, and phenytoin (induce hepatic cytochrome P450
isozymes) reduce the efficacy of corticosteroids & chemotherapy.
Prophylactic anticonvulsant use remains controversial
American Academy of Neurology recommended against it because of lack of efficacy and
potential side effects like cognitive impairment, myelosuppression, liver dysfunction, and
dermatologic reactions.
FOR PATIENT WHO HAVE UNDERGONE ANY TREATMENT…ANY FORM OF SURGERY,BIPSY
OR RR: prophylactic anticonvulsant given for shortest period of time
*Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain
tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;54:1886–
1893.
7. Goals:
• Prolong progression-free survival & overall survival
• Improve, maintain, slow the decline in neurological function
• Minimize treatment-related effects
Treatment Options:
• Observation
• Surgery
• Radiation
• Chemotherapy
8. Observation:
• Includes MRI monitoring at regular intervals (e.g., every 6 months) to detect
radiologic progression before new signs and symptoms occur.
PROS:
• Low grade Gliomas: considered relatively favourable natural history compared o high
grade
• lack of proven benefit for surgery or radiation therapy in improving overall survival
• No treatment associated morbidities
CONS:
• Natural history is significantly worse than that of an age- and sex matched control
population
9. Based on this observation is under treatment
Maximal Safe Surgical Resection followed by PORT improve survival , and may cure pts.
Survival curves for pts with various subtypes of low-grade glioma compared age and sex
matched control population.
,Adapted from Shaw EG: The low-grade glioma debate. Evidence defending the position of early radiation therapy. Clin Neurosurg 42:488-494, 1995.
10. Surgery
Pros:
• benefits of surgery on seizures / raised ICT are fairly dramatic
• Early Surgery delays reappearance of symptoms and tumor growth
• Imaging can be misleading in upto 40% cases ,surgery provides
histological confirmation
• Survival advantage to gross resection in retrospective literature
Cons:
• Possibility of complications in a minimally symptomatic person
11. With advancement in technology ,morbidity of surgery has decreased
hence surgery is the mainstay of treatment
Observation with MRI monitoring :can be reserved for very few patients with ≤ 1cm tumor
and minimal symptoms
Extent of resection :No prospective randomized trials to assess the impact of maximal
tumor resection so maximal safe resection preferred
13. Adjuvant radiotherapy
PROS
Improves outcome in unresectable & partially resectable tumors
increased Progression Free Survival
RT does not decrease seizure
CONS
No improvement in overall survival
Increased morbidity especially in young pt :neurocognitive decline , dementia ,
behavioural changes, vasculopathy, development of 2nd malignancy.
14. total 362 eligible pts
accrued between 1998 and 2002.
Median follow-up time 4 years.
For 111 favourable pts observed on Arm 1,
OS at 2- and 5-yrs is 99% and 94%.
PFS at 2- and 5-yrs is 82% and 50%
Risk Factors predictive of a poorer PFS
1. Pre-operative tumor diameter of >/=4 cm
2. Astrocytoma histology
3. Residual tumor of >/=1 cm2 on Postop MR
Patients with:
All 3 unfavorable factors- PFS at 5years -13%
None of the three factors- PFS at 5years -70%
RT vs observation
A Phase II Study Of Observation In Favourable Low-grade Glioma And A Phase III Study
Of Radiation With Or Without PCV Chemotherapy In Unfavorable Low-grade Glioma
15. Indications for observation
So, on the basis of above data
Observation after surgery can be a reasonable strategy for the most favorable
subset i.e.
age ≤ 40 years
Preoperative tumor diameter <4 cm
Oligodendroglioma histology
gross total resection (GTR).
<1 cm residual tumor
16. • phase III trial :311 pts (WHO 1–2, 51% astro., 14% oligo., 13% mixed oligo-astro)
• treated with surgery (42% GTR, 19% STR,35% biopsy)
• randomized to observation f/b RT at progression vs. post-op RT to 54 Gy.
• RT improved median PFS (5.3 year vs. 3.4 year hazard ratio 0.59, p<0.0001) but not OS median survival 7.4
years RT arm vs. 7.2 in observation arm p=0.872).
• 65% pts in observation arm received salvage RT.
• Better seizure control rates at 1 year with early RT
• No difference in rate of malignant transformation (66–72%).
• QOL not studied whether time to progression reflects clinical deterioration not known
• CONCLUSION:
early radiotherapy improves symptoms control & PFS but no improvement in OS
delayed radiotherapy does not jeopardize survival
EORTC 22845 (Karim et al. 2002; van den Bent et al. 2005)
17. • prognostic factor analysis done on Phase III adult LGG trials (EORTC 22844 and 22845):
• Risk Factors identified from EORTC 22844 & Validated in EORTC 22845
• Patients with pilocytic astrocytoma were excluded
• Multivariate analysis showed that unfavorable prognostic factors for survival were
age ≥ 40 years,
astrocytoma histology subtype
largest diameter of the tumor > or = 6 cm
tumor crossing the midline
presence of neurologic deficit before surgery
• Low Risk Patient: </= 2 factors (Median Survival- 7.7 years)
High Risk: 3 or more factors (Median Survival- 3.2 years)
• Low risk patients are typically observed postoperatively and given RT at disease progression or recurrence
18. Flaws in pignatti score
• KPS ,Extent of resection not taken into account
• No weightage of individual prognostic factors
19. • HOWEVER NOT VALIDATED IN ANY RANDOMIZED CONTROLLED TRIALS
20. Timing of RT : Early vs. delayed
Immediate,
if significant mass or symptoms
For incompletely resected unresectable or only biopsy tumors
presence of ≥3 “high-risk” features on the basis of Pignatti score
Delayed,
if minimal mass or symptoms
after gross total resection
≤ 2 high-risk” features on the basis of Pignatti score
21. DOSE OF RT:THREE PHASE III TRIALS
RT improved median PFS (5.3 year vs. 3.4
year)(p<.001) but not overall survival.
Consequently, low-dose radiotherapy, 45
-54 Gy in 1.8 Gy-2Gy per fractions, has
become an accepted practice
22. CTV= T2 FLAIR IMAGES +1-2 cm MARGIN may be used.
PTV = CTV +0.5cm
LGG Gliomas Do Not Enhance On Mri
If Enhancing Treated As Hgg
Target Volume For Radiotherapy in LGG
.
23. Chemotherapy for Low Grade Gliomas
• Previously no role for chemotherapy in adult patients with low-grade
gliomas
24. INT/RTOG 9802 trial
From 1998 to 2002,
251 patients
median follow up 6 years
RESULTS
5-year OS rates for RT versus RT/PCV were 7.5 years
versus not reached respectively (hazard ratio [HR] =
0.72, p = 0.33)
trend toward improved 5 year PFS 63 vs. 46%(p =
0.06)
acute grade 3/4 toxicity occurred in 67% in RT plus
PCV, vs. 9% in RT alone.
Phase III Study Of Radiation With Or Without PCV
Chemotherapy In Unfavorable Low-grade Glioma
Initial results 2006
Conclusion: PCV do not provide a survival advantage over RT alone
25. median follow-up time is 11.9 years.
RT followed by PCV yielded significantly longer median survival (MST) compared to RT alone
(13.3 vs. 7.8 years, p = 0.03; HR = 0.59)
improvement in PFS (10.4 vs. 4.0 years, p = 0.002; HR = 0.50).
Treatment arm was identified as a prognostic variable in favour of RT + PCV for both OS (p =
0.003; HR = 0.59) and PFS (p < 0.001; HR = 0.49).
Molecular markers were not pre-specified; post-hoc analysis of these is ongoing.
International Journal of Radiation Oncology • Biology • Physics , Volume 90 , Issue 1 , S37 - S38
Conclusion: PCV provided significant survival advantage over RT alone
27. Role of temozolomide
• more preferable option compared to PCV chemotherapy
• oral administration
• better toxicity profile
• Retrospective series and small phase II studies showed objective response in disease
progression 1-3
• First-line treatment with TMZ compared to RT did not improve PFS in high-risk LGG patients
(EORTC 22033)
• Further phase III trials needed
1. Hoang-Xuan K, Capelle L, Kujas M, et al. Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or
oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004;22:3133–3138
2. Brada M, Viviers L, Abson C, et al. Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann
Oncol 2003;14:1715–1721.
3. Quinn JA, Reardon DA, Friedman AH, et al. Phase II trial of temozolomide in patients with progressive low-grade glioma. J Clin Oncol
2003;21:646–651.
28. Conclusion for chemotherapy in high risk LGG*
• RTOG 9802 (1998-2002) shows significant survival advantage with PCV chemotherapy
• However, in the intervening decade novel molecular markers as well as newer
chemotherapy agents such as temozolomide have been developed.
• So optimal parameter for selecting patients for adjuvant PCV has yet to be decided
• And It is still unclear if temozolomide can replace PCV
• Hence further trials needed
*Van den Bent MJ. Practice changing mature results of RTOG study 9802: another positive PCV trial makes adjuvant
chemotherapy part of standard of care in low-grade glioma. Neuro-Oncology. 2014;16(12):1570-1574.
*Radiation Therapy Oncology Group 9802: Controversy or Consensus in the Treatment of Newly Diagnosed Low-Grade
Glioma? Seminars in Radiation Oncology Volume 25, Issue 3, July 2015, Pages 197–202
29. SUMMARY
Grade I Gliomas
• Complete resection: offers excellent survival, :majority (>90%) cured of the tumor; no
adjuvant therapy is necessary.
• Incomplete resection: associated with long-term survival rates of 70% to 80% at 10 years
hence usual recommendation is for close follow-up,
• PORT: indicated in very few cases depending on the location of the tumor, the extent of
residual disease, the feasibility of repeated surgical excision, and availability for follow-up
30. Grade II Gliomas
• Maximal surgical resection
• Postoperative radiotherapy improves progression-free survival and seizure
control were superior. The typical radiotherapy dose is 45 to 54 Gy
• Chemotherapy: investigational
32. HIGH GRADE GLIOMAS
• WHO grade III
• Anaplastic astrocytoma
• Anaplastic oligodendroglioma
• Anaplastic oligoastrocytoma
• WHO grade IV
• Glioblastoma multiforme (GBM)
34. Recursive Partitioning Analysis
Curran et al1 developed a statistical tool based on RTOG trials including 1578 pts. with malignant
gliomas from 1974 to 1989 treated with RT without TMZ
identification of significant prognostic factors & classification of patients into groups with similar
outcomes
six treatment-related variables were analysed.
Age & KPS are most important prognostic factor
Other prognostic factors:
• Histology
• Duration of mental symptoms before any treatment
• Extent of resection
• Mental status
1. Curran WJ Jr, Scott CB, Horton J, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J
Natl Cancer Inst 1993;85:704–710.
35.
36. RTOG RPA OF MALIGNANT GLIOMA
RPA classification retains prognostic significance in patients treated with RT+temozolomide2
as evaluated in EORTC 26981 they used age, WHO performance status, extent of surgery, and
the Mini-Mental Status Examination as prognostic variable
2. Mirimanoff RO, Gorlia T, Mason W, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive
partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol 2006;24:2563–2569.
37. • More recently nomograms 3 have developed integrating variables such as MGMT
promoter methylation status, age, performance status, extent of resection, and
MMSE
3. Gorlia T, van den Bent MJ, Hegi ME, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma:
prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 2008;9:29–38.
38. TREATMENT OF GBM
Surgery
Concurrent Chemo-RT
Adjuvant Chemotherapy
39. SURGERY
• Extent: Maximum safe surgical resection preferred.
• depend on
• performance status
• tumor location
• patient choice
• surgical procedures
• Other options:
• surgical debulking for mass effect
• Biopsy only
• CSF diversion procedures for inoperable site
• Extent of surgery has prognostic significance
Hardesty DA, Sanai N. The Value of Glioma Extent of Resection in the Modern Neurosurgical Era. Frontiers in Neurology. 2012;3:140.
40. Radiotherapy
• RCT by BTCG demonstrated a clear survival benefit to the use of RT with without
nitrosoureas after surgery for malignant gliomas
41. DOSE
• Standard dose:60 Gy in 30 fractions.
• Walker et al. reported a dose–response analysis in BTSG Trial.
• WBRT 45 vs. 50 vs. 55 vs. 60 Gy.
• significant improvement in MS from 28 to 42 weeks with doses of 50 to 60 Gy
• MRC study also showed a significant survival advantage with 60 Gy/30 fx.
• randomized 474 patients to 45 Gy/20 fx vs. 60 Gy/30 fx.
• No adjuvant chemo.
• MS 12 month (60 Gy) vs. 9 month (45 Gy, p = 0.007)
Walker MD, Strike TA, Sheline GE. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J
Radiat Oncol Biol Phys 1979;5:1725–1731
Bleehen NM, Stenning SP. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4
astrocytoma. The Medical Research Council Brain Tumour Working Party. British J Cancer 1991;64:769–774.
42. DOSE ESCALATION TECHNIQUES
Rationale:
• majority of tumor recurrences occurring within the irradiation field
• poor outcomes associated with standard therapy
• Various techniques used to deliver a larger dose to improve local control and
enhance survival.
3DCRT
IMRT,
SRT boost,
brachytherapy
hyperfractionation accelerated treatment
Proton therapy & Boron neutron capture therapy
• Studies have shown no benefit in median survival from dose escalation beyond
60Gy
43. Hypofrctionated radiotherapy
• For patients with poor pretreatment prognostic factors
• Older patients (>65 years) KPS≤50
• limited expected survival ,not able to tolerate conventional treatment of 6week
• a shorter course of treatment provides good palliation
• 40 Gy/15 fx Roa et al. (2004)
• phase III: 100 patients with GBM age ≥60 and KPS ≤50
• randomized to 60 Gy/30 fx vs. 40 Gy/15 fx. Enhancing tumour and oedema plus 2.5 cm margin
• No difference in MS (5.1 vs. 5.6 month).
• Fewer patients in short course RT arm required increased steroids (23 vs. 49%).
• 30 Gy/10 fx Bauman et al. (1994):
• single arm prospective study. 29 pts with GBM age ≥65 and KPS ≤50
• treated with WBRT 30 Gy/10 fx
• RT increased MS vs. best supportive care (10 vs.1 month).
OTHER OPTION 25Gy/5# in INDIAN studies
45. • Phase III trial 573 patients, age 18 -70 years WHO PS 0–2
• newly diagnosed glioblastoma (16% biopsy only, 40% GTR, 44% STR)
• For 485 (85%) of 573 patients, slides or tumour tissue was available for central pathology
review, glioblastoma was confirmed in 450 (93%) of these.
• Randomized to RT alone 60 Gy/30 fx. vs. RT + concurrent and adjuvant TMZ
• Concurrent daily (75 mg/m2/day) 7 days/week & adjuvant (150–200 mg/m2/day × 5days)
q4 weeks × 6 month.
• primary endpoint was overall survival
EORTC/NCIC
(Stupp et al. 2005, 2009)
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.
Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma
in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459–466
46. RESULT
Initial results: 2005
• median follow-up of 28 months
• Concurrent and adjuvant TMZ significantly improved MS (14.6 vs. 12.1 month) P<0.001
by the log-rank test)
• 2-year survival rates of 26% and 6%,
• Toxicity :7% grade 3/4 hematologic toxicities in Combined arm vs. none in RT alone
Updated results:2009
• median follow-up of 61 months (range 11 days to 79 months).
• 278 /286 (97%) pts. in RT alone & 254/287 (89%) in combined- group died during 5
years of follow-up
• 5-year OS (9.8 vs. 1.9%)
47. Updated results:
• benefit in all subgroup
• including patients aged 60–70 years.
• MGMT methylation was strongest predictor for benefit from TMZ
48. Kaplan-Meier estimates of overall survival by treatment
RPA class III (A). RPA class IV (B). RPA class V (C).
Benefit In class III-V
Maximum in Class III
49. DOSE INTENSE TMZ
• 833 pts Eligibility criteria included age > 18 yrs, KPS ≥ 60,
• randomized to receive standard therapy TMZ plus RT followed by
• Arm 1: standard TMZ (150-200 mg/m2 x 5 d) or Arm 2: dd TMZ (75-100 mg/m2 x 21 d) q 4 wks
for 6-12 cycles.
• Primary Endpoint was OS. Secondary analyses evaluated impact of MGMT status.
• No statistical difference was observed between Arms 1 and 2 for median OS (16.6, 14.9 mo, p =
0.63), or median PFS (5.5, 6.7 mo, p = 0.06), or by methylation status.
• MGMT methylation was associated with improved OS (21.2, 14 mo, p < 0.0001), PFS (8.7, 5.7
mo, p < 0.0001) and response (p = 0.012).
• There was increased grade ≥ 3 toxicity in Arm 2 (19%, 27%, p = 0.008); mostly lymphopenia and
fatigue.
Gilbert MR, Wang M, Aldape KD, et al. RTOG 0525: A randomized phase III trial comparing standard adjuvant
temozolomide with a dose-dense schedule in newly diagnosed glioblastoma. J Clin Oncol 2011;29:abstr 2006.
50. Management of GBM : summary
• Maximal surgical resection
• Postoperative radiotherapy 60 Gy in 6 weeks along with standard
dose TMZ , given during and after radiotherapy
51. Anaplastic astrocytoma ( WHO GRADE 3)
Anaplastic gliomas constitute approximately 25% of high-grade gliomas in adults
anaplastic astrocytomas
anaplastic oligodendrogliomas
anaplastic mixed oligoastrocytomas
Tteatemnt options
Surgery
Radiotherapy
Chemotherapy
1p-19q co deletion is prognostic in anaplastic oligodendroglioma
52. • Maximal surgical resection is generally associated with more favorable
outcome and is recommended whenever feasible.
• Postoperative radiotherapy has been shown to provide a survival advantage in
several clinical trials (included WHO grade III and IV tumors; no trial for only
grade III tumors has been conducted)
• Dose:60Gy/30# @ 2 Gy/#
53. Chemotherapy in grade III gliomas
• The role and which chemotherapy to be used remains undefined.
• Patients with co deletions of 1p and 19q have a more favorable
prognosis and respond better to both chemotherapy and
radiotherapy
54. Between August 13, 1995, and March 3, 2002
368 patients newly diagnosed anaplastic oligodendroglioma
Central pathology review confirmed presence of an oligodendroglial tumor in 257
patients (AOD, 175; mixed AOA, 82)
randomly assigned to either 59.4 Gy of RT or same RT f/b 6 cycles of adjuvant PCV.
primary end points :overall survival (OS) and PFS.
Patients tested for 1p/19q status, IDH status, and MGMT promoter methylation status
exploratory analysis of the correlation between 1p/19q status and survival was part of
study.
55. median follow-up of 140 months
OS in the RT/PCV arm was significantly longer (42.3 v
30.6 months in the RT arm, hazard ratio [HR], 0.75; 95%
CI, 0.60 to 0.95).
PFS was significantly better after RT/PCV (median PFS,
24.3 months after RT/PCV v 13.2 months with RT only;
HR, 0.66; 95% CI, 0.52 to 0.83;
Results
56. Subgroup Analysis by 1p/19q Status: OVDERALL SURVIVAL
In 80/316 cases (25%) with tissue available for 1p/19q
assessment,codeletion of 1p/19q was found.
In these patients with codeleted
tumors, OS was not reached in the RT/PCV group versus 112
months in the RT group (HR, 0.56; 95% CI, 0.31 to 1.03;
( Fig 3A).
In the patients with noncodeleted tumors, the risk reduction was
less:
OS of 25 versus 21 months (HR, 0.83; 95% CI, 0.62 to 1.10;
(Fig 3B).
57. In codeleted group, PFS was 157 months after RT/PCV and 50
months after RT only (HR, 0.42; 95%CI, 0.24 to 0.74;
(Fig 4A).
In the patients with noncodeleted tumors,
PFS was 15 months in RT/PCVgroup and 9 months in RTonly
group (HR, 0.73; 95% CI, 0.56 to 0.97;
Fig 4B
Subgroup Analysis by 1p/19q Status: PROGRESSION FREE SURVIVAL
58. In anaplastic oligodendroglioma pt only
1994 to 2002 :291 eligible pts randomly assigned: 148 to PCV plus RT and 143 to RT.
primary end point: overall survival (OS).
At first analysis, PCV did not appear to improve survival for any subgroup.
In a recent updated analysis :survival benefit from PCV in 1p19q codeleted subset.
At median follow-up of >11 years. (range, 0.5 to 16.8 years)
median overall survival for patients receiving RT alone or RT plus PCV was similar.
Unplanned analysis showed, 126 pts with 1p19q codeleted had much longer MS than 135 pts non
1p19q codeletion: (8.7 vs 2.7 years.
1p19q codeletion predicted the benefit from adding PCV to RT.
59. 1p-19q co del in RT arm1p-19q co del in RT+CT arm
OS by treatment grp OS 1p-19q non co del arm OS in 1p-19q co del arm
60. Role of Temozolomide
• temozolomide has shown activity in patients with recurrent
anaplastic astrocytoma. (Yung et al pahse II trial )
• this trial suggest that temozolomide has antitumor activity with an
acceptable safety profile for anaplastic astrocytoma.
• Role is being tested in ongoing phase III clinical trial of non–1p19q-
codeleted anaplastic glioma patients
• CATNON Intergroup trial: To assess whether concurrent and adjuvant
temozolomide improves overall survival as compared to RT alone in
patients with non-1p/19q deleted anaplastic glioma.
61. Management of Grade III glioma: summary
• Maximal safe resection.
• Postoperative radiotherapy 60 Gy in 6 weeks.
• The role of chemotherapy remains undefined for the non-codeleted
anaplastic gliomas.
• Temozolomide is active in recurrent anaplastic astrocytoma and is
currently being tested in the up-front setting.
• PCV chemotherapy has a proven survival advantage over
radiotherapy alone in 1p and 19q codeleted patients.
63. Simulation
Position: supine
immobilization : individualized headrest &
Aquaplast mask
RTP scans using i.v contrast are taken with 1–3 mm
slices from the vault to the base of the skull
CECT-RTP data fused with MRI data
target volumes were defined using CT-MR fusion
data set
64. Target volumes
Low-grade gliomas.
Single phase treatment
EBRT dose: 1.8 Gy/fx to 50.4–54 Gy.
GTV =T2/FLAIR IMAGES
CTV = GTV + 1–2 cm margin.
PTV = CTV + 0.3–0.5 cm.
65. Whole brain RT (WBRT) vs. Partial Brain RT (PBRT) in HGG and margins
WBRT Vs PBRT
• RCT (n=303) of WBRT-60Gy vs WBRT -43Gy + PBRT boost-17Gy
• No difference in outcome (Shapiro, J Neurosurg, 1989).
Margins
• Autopsy studies reveal that microscopic tumour within 2cm of enhancing margins on scan in
90% and only 3% multicentric (Hochberg FH, Pruitt A. Assumptions in the radiotherapy of
glioblastoma. Neurology 1980;30:907–911)
• 78% (25 of 32) of tumors recurred within 2 cm & 56% (18 of 32) in 1 cm of the initial tumor
margin.( Wallner KE, Gallcich JH, Krol G, et al. Patterns of failure following treatment for
glioblastoma multiforme and anaplastic astrocytoma. IJROBP1989;16:1405–1409.)
Standard Of Care - PBRT encompassing the enhancing tumour + 2-3 Cm
Margins
66. High-grade gliomas:
EBRT: 1.8–2 Gy/fx to 45–46 Gy followed
by boost to 59.4–60 Gy
Phase 1:
• GTV1 = T1 enhancement + T2/FLAIR.
• CTV1 = GTV1 + 2 cm margin.
• PTV = CTV + 0.3–0.5 cm
Phase 2 :
• GTV2 = T1 enhancement.
• CTV2 = GTV2 + 2 cm
• PTV = CTV + 0.3–0.5 cm
RT does not improve symptoms: seizure may increase seizure due to increased edema compressing elooes not decreasquent areas
total of 362 eligible/analyzable pts were accrued between 1998 and 2002. Median follow-up time is 4 years. For the 111 favorable pts observed on Arm 1, OS at 2- and 5-yrs is 99% and 94%. PFS at 2- and 5-yrs is 82% and 50%
on the basis of risk factors for progression(astrocytoma histology ,Ki67 index).
which usually show abnormality beyond any enhancing or nonenhancing tumor
N F Definition 0 No neurologic symptoms; fully active at home/work without assistance. 1 Minor neurologic symptoms; fully active at home/work without assistance. 2 Moderate neurologic symptoms; fully active at home/work but requires assistance. 3. Moderate neurologic symptoms; less than fully active at home/work and requires assistance. 4 Sever neurologic symptoms; totally inactive requiring complete assistance at home or in institution-unable to work.
Walker et al. (1979) BTSG:
pooled three randomized trials.
Compared observation vs. WBRT 45 vs. 50 vs. 55 vs. 60 Gy.
MS increased with higher doses, 4,7,9,10 month.
Walker et al. (1978) BTSG 6901 –
phase III: 222 patients (90% GBM, 10% AA)
surgery : randomized to observation vs. BCNU alone vs. WBRT 50–60 Gy alone vs. WBRT + BCNU.
RT was WB to 50 Gy, then boost to 60 Gy.
RT ± BCNU improved MS by 3–6 month vs. observation or BCNU alone
Roa et al. (2004) –
Bauman et al. (1994):
In a risk-adjusted analysis entering age ( ≤40 vs> 40 years),surgery (biopsy v resection),WHO status (0, 1 v 2), and previous surgery for low-grade glioma (yes v no), the assigned treatment remained an independent factor for OS (HR, 0.76; 95% CI, 0.60 to 0.97).
CHECK
Patients tested for 1p/19q status, IDH status, and MGMT promoter methylation status had similar clinical characteristics and outcome compared with the patients who were not tested, except for a slight increase in resection in the patients tested for IDH and 1p/19q (91% v 81%, and 87% v 77%, respectively, other data not shown). Appendix Table A2 (online only) summarizes themedian OS and PFS according to 1p/19q, IDH, and MGMT status. Both PFS and OS were significantly better in the patients with codeleted tumors compared with the patients with noncodeleted tumors (PFS, 76 v 11 months; HR, 0.39; 95% CI, 0.28 to 0.53; OS, 123 v 23 months; HR, 0.36; 95% CI, 0.26 to 0.50). Similarly, OS and PFS were better in patients with MGMT promoter methylated and in IDH-mutated tumors. Table 1 summarizes the median and 5-year OS in the various subgroups in relation to assigned treatment. Patients with MGMT promoter methylation, IDH-mutated tumors, or confirmed anaplastic oligodendroglial histology seemed to derive more benefit from the addition of PCV. Tests for interaction of these characteristics with assigned treatment remained insignificant. Both MGMT promoter methylation and IDH mutational status could be determined in 158 patients and were correlated (correlation coefficient, 0.51; only two patients with a mutated IDH-1 showed an unmethylated MGMT; all other IDH-mutated patients [n 69] showed MGMT promoter methylation). The OS was similar in patients without MGMT promoter methylation compared with patients with MGMT promoter methylation but no IDH mutation (HR, 0.88; 95% CI, 0.57 to 1.36). In 150 cases, data on both 1p/19q, MGMT, and IDH results were available. In a multivariate prognostic model with these three factors, IDH and 1p/19q were independently significant but not MGMT, with a similar OS HR reduction for IDH-mutated (0.356) and 1p/19q-codeleted (0.424) tumors.
Patients with codeletions of have a more favorable prognosis and respond better to both chemotherapy and radiotherapy, and in this subset,