5. Statistics
• Near 10 million new cases are
detected each year
• Near 20 million people living with
cancer in the world today
• Near 7 million people will die from
cancer
• Every day, around 1700 Americans
die of the disease
• 1 in 3 people will be diagnosed with
cancer in the UK and
• 1 in 4 will die from their disease
5
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6. Lung
Breast
Colon/Rectum
Stomach
Liver
Prostate
Cervix uteri
Oesophagus
Bladder
Non-Hodgkin
Lymphoma
Leukaemia
Oral cavity
Pancreas
Kidney
Ovary
1000 800 600 400 200 0 200 400 600 8001000
Men Women
From: D.M. Parkin The Lancet Oncology 2: 533-543 (2001)
(Thousands)
Incidence
Mortality
337
293
105
0
370
241
318
446
234
165
166
471
233
133
111
76
33
121
68
113
86
47
97
101
101
34
71
192
114
810
902
558
405
255
499
398
384
204
543
279
260
227
99
93
167
144
109
81
170
116
112
57
119
5.3 million cases
3.5 million deaths
4.7 million cases
2.7 million deaths
The Global Burden of Cancer 2000
6
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7. Levels of evidence
Level I=large double blind RCTs, or, meta-analysis of sma
RCTs , with clinically relevant outcomes
I a=evidence from meta-analysis of RCT
I b=evidence from at least 1 RCT
Level II=small RCTs, non-blinded RCTs
II a=evidence from one well designed non-RCT
II b=evidence from one well-designed quasi-
experimental study
Level III=observational [cohort ] studies , case-
control studies , non-RCTs
Level IV=opinion of expert committees,
or Rspected authorities
Level V=expert opinion
7
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13. Just a look
13
• Brain tumors account for 85% to 90% of all primary central nervous system (CNS)
tumors
• Anaplastic astrocytoma and glioblastoma account for approximately 38% of
primary brain tumors
• Meningiomas and other mesenchymal tumors account for approximately 27%
• Other less common primary brain tumors include
– PITUITARY TUMORS,
– SCHWANNOMAS,
– CNS LYMPHOMAS,
– OLIGODENDROGLIOMAS,
– EPENDYMOMAS,
– LOW-GRADE ASTROCYTOMAS,
– MEDULLOBLASTOMAS, IN DECREASING ORDER OF FREQUENCY.
• Spinal tumors.
– Schwannomas,
– Meningiomas, and e
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14. WHY
• Exposure to vinyl chloride may predispose to the
development of glioma
• Epstein-Barr virus infection has been implicated in the
etiology of primary CNS lymphoma
• Transplant recipients and patients with the acquired
immunodeficiency syndrome have substantially increased
risks for primary CNS lymphoma.
• The familial tumor syndromes
• Prior radiation
• Mobile phones-?
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15. The familial tumor syndromes
• Neurofibromatosis type i (17q11)
• Neurofibromatosis type ii (22q12)
• Von hippel-lindau disease (3p25-26)
• Tuberous sclerosis (9q34, 16p13)
• Li-fraumeni syndrome (17p13)
• Turcot syndrome type 1 (3p21, 7p22)
• Turcot syndrome type 2 (5q21)
• Nevoid basal cell carcinoma syndrome (9q22.3
• Multiple enchondromatosis (Maffucci/Ollier )
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16. Clinical behavior
• Raised ICT
• Pressure effect
• Deficits
• Other nonspecific symptoms
• Seizures are a presenting symptom in approximately
20% of patients with supra-tentorial brain tumors
• 70% with primary parenchymal tumors and 40% with
metastatic brain tumors develop seizures at some
time during the clinical course
16
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28. Surgery
• Maximal safe resection with the aim of total
excision whenever feasible.
• Open or stereotactic biopsy for very extensive
and diffuse tumours or those in eloquent
areas where near total excision could result in
significant deficit.
• Histological proof may not be required in
diffuse pontine gliomas or Neurofibromatosis
type 1 associated optic pathway gliomas
28
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29. Role of chemotherapy
• Children < 3 years of age: Partially excised or only
biopsied tumours in critical sites such as optic
pathway, hypothalamus or thalamus, or presence
of neurological deficit or mass effect: Initial
chemotherapy (Packer’s regimen or ICE) for 6 – 12
months and to defer radiotherapy till the age of 3
years for minimising the late radiation sequelae.
29
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30. WHO grading-Gliomas
• Grade I –
– Pilocytic Astrocytoma
– SEGA
• Grade II-
– Fibrillary
– Protoplasmic
• Anaplastic astrocytoma (AA) grade III
• Glioblastoma multiforme (GBM) grade IV
• Gemistocytic astrocytoma equivalent to AA
30
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36. Surgery
Maximal safe resection with the aim of total
excision whenever feasible.
Open or stereotactic biopsy for very extensive
and diffuse tumours or those in eloquent areas
where near total excision could result in
significant deficit.
Histological proof may not be required in
diffuse pontine gliomas or Neurofibromatosis
type 1 associated optic pathway gliomas
36
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39. Surgery/MEDULLOBLASTOMA
• Goal
– Total or near total excision
– Normalization of ICP
– Ext ventricular drainage
– VP shunt→ resection (not recommended)?
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40. Surgical resection
Albright et al Neurosurgery. 1996 Feb;38(2):265-71.
• T 3b, T4,residual > 1.5 cm, M+
– PFS was 20% better at 5yr in pts with < 1.5cm residual disease
– PFS was 20% better at 5yr in pts with M0 disease
– Extent of residual tumor does correlate with prognosis in certain children
especially those who are > 3 years old, with no tumor dissemination
Jenkin et al IJROBP 1990 Aug;19(2):265-74
• Post-operative meningitis, a residual disease on PO scan, disseminated disease
were unfavorable factors
• Five-year DFS
– Stage I (total resection, no adverse factor) 100%
– Stage II (total resection with one or more adverse factor or less than total
resection with no other adverse factor) 78%
– Stage III (less than total resection with one or more adverse factor) 18%.
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41. Extent of Surgery
• Total – No visible tumour in operative bed and
on post op scan
• Near Total– post op scan reveals a nodular
enhancement in the surgical bed
• Sub total– 51%-90% resection done
• Partial-11%-50% resection done
• Biopsy-<10%
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42. CHEMOTHERAPY
• COMPARING TO SX/RT ,CHEMO HAS MINIMAL
ROLE
• TEMOZOLAMIDE SHOWED THE SURVIVAL 2YR
AND 5YR BENEFIT IN GLIOBLASTOMA
• NOW SOME NEW DRUGS LIKE AVASTIN
APPROVED
• PCV[PROCARBAZINE+CCNU+VINCA] IN OLIGOS AS
ADJUVANT AND RECURRENT TUMORS
• IN CHILDREN BELOW 3 YEAR OLD
• METHOTREXATE IN CNS LYMPHOMAs
42
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43. ROLE OF RADIOTHERAPY
• IN HIGH GRADE GLIOMAs AS ADJUVANT
• IN GRADE II GLIOMAs AS PER PIGNATTIS CRITERIA
• UNRESECTABLE/RESIDUAL LOW GRADE GLIOMAS
• ALL BRAIN STEM GLIOMAs
• ALMOST PAEDIATRIC BRAIN TUMORS
• SPINAL CORD TUMORS
• METASTATIC BRAIN TUMORS
• GERM CELL TUMORS
43
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46. History - radiation
1896 – Becquerel - Radioactivity
1898 – Madam Curie / Pierre Curie - Radium
1903 – Nobel Prize for Curie’s & Becquerel
1903 – First successful case of malignancy basal
cell carcinoma of face
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47. GOALS
High dose to tumor tissue-Tumor control
Normal tissue sparing
Minimize long and short term toxicities
Better Quality of life
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48. Treatment
• Delivered 5 days per week over 6-8 weeks
• Typical treatment takes around 5 minutes
• Treatment is painless--like having an X-ray taken
• No radioactive substances involved; beam goes
on/off
• Side effects usually temporary; controlled with
medication/diet
• Covered by Medicare and many other insurance
companies
•
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49. Role of radiation
S- Size >6cm
A- ASTRO component
D- Deficit
A- Age >40
M- midline shift
49
S-MRS activity
W-Wish
MIB index>6%
P- perfusion
E-Enhancement
•Pignatti’s criteria are used to assist in
decision making for observation:
•If more than 2 criteria are present
then patients to be offered immediate
radiotherapy
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50. Evolution of Treatment Techniques
CONVENTIONAL RT
Collimator shapes Beam
Rectangular Treatment Field
Shaped Treatment Field
1970s and earlier
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59. WHO grading-Gliomas
Grade I –
Pilocytic Astrocytoma
SEGA
Grade II-
Fibrillary
Protoplasmic
Anaplastic astrocytoma (AA) grade III
Glioblastoma multiforme (GBM) grade IV
Gemistocytic astrocytoma equivalent to AA
59
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60. MENINGIOMA
• Grade -1
– Surgery
– Surgery plus radiation therapy
is used in selected cases, such
as for patients with known or
suspected residual disease or
with recurrence after
previous surgery.
– Radiation therapy for patients
with unresectable tumors
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61. ATYPICAL MENINGIOMA
• WHO grade II meningiomas (i.e.,
atypical, clear cell, and chordoid)
• WHO grade III meningiomas (i.e.,
anaplastic/malignant, rhabdoid,
and papillary), and
hemangiopericytomas are
• worse than for patients with low-
grade meningiomas because
complete resections are less
common and the proliferative
capacity is greater
• Surgery plus radiation therapy.
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62. GLIOBLASTOMA MULTIFORMAE
• WHO grade 4
• Commonest glial tumor & most
malignant form of diffuse
astrocytic glioma
• De-novo or tumor progression
from diffuse / anaplastic
astrocytoma (secondary)
• Male predominance
• Sixth decade
• Cerebral hemispheres (temporal,
parietal & frontal)
• Radiology :-large irregular mass
with a peripheral ring area of
contrast enhancement & a dark
hypodense centre representing
necrosis
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63. Sub categories
1. Giant cell glioblastoma- giant cells predominate
2. Epithelioid glioblastoma-
- large sheet like collections of cells with large nuclei & prominent nucleoli,
- mimic metastatic carcinoma,
- IHC is necessary
3. Small cell glioblastoma:-
- Predominantly small poorly differentiated cells
- Diagnostic difficulty with anaplastic oligodendroglioma & metastatic small
cell carcinoma
Gliosarcoma :-
- Evidence of mesenchymal differentiation in addition to typical features of
glioblastoma
- Generally sarcomatous
- Often has features of malignant fibrous histiocytoma or angisarcom or
fibrosarcoma
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64. Oligodendroglioma
• 4 - 5%, who grade 2.
• Fourth and fifth decades of life, with a
male predominance.
• Cerebral hemispheres, cerebellum,
brainstem and spinal cord.
• Focal neurological signs and seizures
accompanied by headaches.
• MRI scans show poorly defined
hypodense tumours in the subcortical
white matter with calcification.
• Older than those with
oligodendroglioma grade 2 tumours,
• There is no clear distinction between
grade 2 and grade 3 tumours, because
the criteria for differentiation are
controversial and ill defined.
• Similar clinical features
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65. Ependymomas
• Slow-growing tumours
• Walls of the cerebral ventricles, or
occasionally from the spinal canal.
• Children and young adults,
• Children-posterior fossa
• Adults-lateral ventricles and the
third ventricle
• Present with signs and symptoms
of raised intracranial pressure and
hydrocephalus
• MRI shows a well-circumscribed
lesion protruding into the ventricle,
often with areas of cyst formation
and haemorrhage
• Gross-soft grey-pink tissue with
areas of cyst formation and
occasional focal haemorrhage.
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66. CRANIOPHARYNGIOMA
• Surgery alone if the tumor is
totally resectable.
• Debulking surgery plus
radiation therapy if the
tumor is unresectable
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67. PITUITARY ADENOMA
• Surveillance after surgery
– Completely excised non
secretory adenoma--
• Radiation after surgery
– Incompletely excised non
secretry adenoma,
– Hormone secretory tumours
(Acromegaly, Cushings,
Prolactinoma, Nelsons
syndrome) not controlled
with surgery and /or medical
therapy
– Suprasellar extension
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69. BRAIN METASTASIS
• Single lesion- Sx
RADIATION
• Multiple lesion- RADIATION
• Role of chemotherapy–
• Temozolamide is
questionable
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70. Gliomatosis Cerebri
• Diffuse glial tumour infiltrating the
brain and extensively involving at
least two cerebral lobes
• Bilateral
• Adults - fifth decade
• GFAP-positive astrocytic cells with
an elongated morphology that
typically infiltrate the white matter in
parallel bundles
• Prognosis - poor
• Dead within 1 year of diagnosis.
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80. L 1
L 2
L 3
L 4
MR PLAIN SAGITTAL T 1 W
Well defined hyperintense
mass from L4 to S1 vertebrae
engulfing cauda equina
measuring
8 X1.8 cm.
Ependymoma CASE -2….
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83. PILOCYTIC ASTROCYTOMA
• Common in paedriatic
group/posterior fossa
• Surgery alone if the tumor is
totally Resectable.
• Surgery followed by
radiation therapy to known
or suspected residual tumor
• Curative
• WHO grade 1
• Well defined, slow growing
cystic tumor
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84. Brain stem glioma
• 20% of childhood and 5% of adult CNS
tumours.
• Most frequently in children between 3 and
10 years
• Tissue confirmation is frequently not
feasible with infiltrating, except in
expansile tumors
• 60-80%of patients do not have a
histological diagnosis
• Universally associated with dismal
prognosis
• Historically, regarded as a single
entity
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88. •Haemorrhage, calcification
•Cellular, with rosettes/pseudorosettes
•Anaplastic: 10-30%
•Spinal mets: 10-15%
•Ependymoblastoma (PNET)
•Spinal MRI/CSF for post
fossa/anaplastic tumours
Surgery treatment of choice and the most
important prognostic factor
Gross tumour resection (GTR) - 50-75%
long term control
Subtotal resection (STR) - 0-30% GTR
possible in only 50% cases, aggressive
debulking/2nd look
Ependymoma
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89. ATYPICAL TERATOID RHABDOID TUMOR
• Posterior fossa
• Below 2 year age
• High grade
• Highly malignant
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90. High-grade hemispheric gliomas
Relatively rare
Somewhat better outcome
than adults but long-term cure
still rare
Overexp of p53 strong
prognostic factor (NEJM 2002)
Surgery, conv RT std of care
as in adults
Role of chemo not fully
evolved
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91. High-grade hemispheric gliomas
• Randomised trial of RT + adj pCV Vs RT alone
(n=58): 5yr DFS of 46% Vs 18% (CCG 943)
• Results never duplicated (38 % slides reviewed were
not high-grade, Boyett 1998)
• Intensive/pre irradiation chemo: no major impact
• Currently several regimens being tested (TMZ,
thalidomide, carboplatin, topetecan, etc)
Sposto J NeuroOncol
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100. Follow-up policies
Low grade Gliomas and other benign tumours: Post
Treatment baseline imaging at 3 months, then 6
monthly follow up for 5 years and then annually.
Subsequent imaging not routinely recommended
unless there is a neurological worsening or a specific
clinical concern
For children and those with tumours in and around
the sella or this region in the radiation field
(including cranio-spinal) monitor growth (height and
weight) and regular endocrine evaluation
100
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101. Follow-up policies-contd.
High grade gliomas and brain metastasies: First
follow up and Post Treatment baseline imaging at 6
weeks and subsequent follow ups at 2 - 4 months
for2 years and then 6 monthly. Subsequent imaging
not routinely recommended unless there is a
neurological worsening or a specific clinical concern.
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102. CONCLUSION
• Team Work
• Sx Is The Main Stay Treatment
• Maximal Safe Resection Should Be Attempted First
• Pathological review/IHC should be done
• Radiation Has Radical, adjuvant In All Most All Tumors
• Role Of Chemotherapy Is Minimal
• Timely Reference
• Even In Low grade tumors, when to observe team discussion
is helpful to prevent untoward effect
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122. CAUTION
C - Change in bowel or bladder habits
A - A sore that does not heal
U - Unusual bleeding or discharge
T - Thickening or lump in the breast or any part of the body
I - Indigestion or difficulty swallowing
O - Obvious change in a wart or mole
N - Nagging cough or hoarseness
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![DR KANHU CHARAN PATRO
RADIATION ONCOLOGIST
M.D,D.N.B[RT],FAROI[USA],MBA[ICFAI],PDCR,CEPC
6/24/2018 2](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)