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
501/17/18
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 0 200 400 600 800
1000
Men Women
From: D.M. Parkin The Lancet Oncology 2: 533-543 (2001)
(Thousands)
Incidence
Mortality
337
293
105
0370
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
601/17/18
12. Glioblastoma (WHO grade IV)
• Previously known as glioblastoma multiforme
• Peak age of onset is 50-60yrs.
• Common in deep white matter, basal ganglia,
thalamus, rarely in cerebellum
• Grossly may appear circumscribed
• Microscopic infiltrates widely, often to other
hemisphere via corpus callosum.
• May be Multifocal
• Extracranial metastasis rare.
• Survival 1-1.5 yrs after treatment.
1201/17/18
13. • Central yellow or white zone of necrosis and
hemorrhage surrounded by of endothelial
hyperplasia.
• Surrounded by edematous brain (mixture of
vasogenic edema, tumour infiltrates and gliosis)
• TP53, IDH1 and IDH2 mutation less common in
primary.
• 30-40% have EFGR mutation
• MGMT mutation- favorable prognosis.
Glioblastoma (WHO grade IV)
1301/17/18
19. Chemo-RT schedule
• RT - Five fractions per week
• Prophylactic antiemetics
• PCP prophylaxis
• Low dose steroids with H1 blocker
• Weekly blood counts
• Give Temozolomide for a maximum of 49 days and then STOP2001/17/18
23. Response evaluation
• The most widely used criteria for assessing
treatment response are based on a 2D
measurement of the enhancing area on MR
imaging known as the
• Macdonald Criteria
• RANO criteria
2401/17/18
27. Radiation effect
• Acute
– (during radiation),
• Subacute or early-delayed
– (up to 12 weeks after radiation ends)
• Late
– (months to years post radiation)
2801/17/18
28. Cause-acute and sub-acute
• Both the acute and subacute types of
radiation-induced injury are thought to be
caused by vasodilation, disruption of the BBB,
and edema.
2901/17/18
30. INCREASED ENHANCEMENT
• Increased enhancement can be induced by a
variety of non-tumoral processes, such as
treatment-related inflammation.
–Postsurgical changes,
– Ischemia,
–Subacute radiation effects,
–And radiation necrosis
Micro-ischemic lesions immediately after
surgery and radiotherapy can cause BBB
disruption
3101/17/18
34. MRI FINDINGS
• Edema
• New lesions
• Increased size of contrast-enhancing lesions
within the immediate vicinity of the irradiated
tumor volume.
3501/17/18
35. • Reduced NAA peaks
• Increased choline peak
• Increased choline/creatinine ratio
• Choline/creatinine peak>3:1 predicts high
grade tumour.
MR spectroscopy-recurrance
3601/17/18
42. Radio-necrosis
• Radiation necrosis typically occurs 18–24
months post-treatment and has repeatedly
been shown to be difficult to distinguish from
recurrence.
4301/17/18
47. obtained 10 months after resection and radiation
P.C. Sundgren AJNR Am J Neuroradiol 2009;30:1469-1476
Slightly increased Cho and normal NAA
and Cr signal intensities are indicative of
radiation injury,
4801/17/18
48. PET-CT
• FDG-PET can demonstrate differences in the analysis
of areas of radiation injury and residual/recurrent
brain tumors.
• However the reported sensitivity and specificity are
low.
• LIMITATION-The high glucose use in the brain, which
results in high background activity and by the fact
that inflammatory processes can demonstrate high
glucose metabolism on PET examinations.
4901/17/18
53. PSEUDO-PROGRESSION
• Essentially psPD refers to post-treatment imaging
changes in the tumor.
• Where the tumor appears larger and/or brighter
from greater contrast uptake as compared to the
pre-treatment baseline CT or MRI image.
5401/17/18
54. Patho-physiology
• Effective treatment can involve disruption of the
BBB, which facilitates passage of the drug and, thus,
results in an enhancement of its activity.
• This damage to the BBB can persist for several
months after treatment, showing an enhanced
lesion that appears larger than before initiation of
RT and thus simulates disease progression.
5501/17/18
59. Time to onset
• Pseudo-progression has been reported to
occur predominantly (in almost 60% of cases)
within the first 3 months after completing
treatment, but it may occur from the first few
weeks to 6 months after treatment
6001/17/18
60. O6-Methylguanine DNA MGMT Promoter
• The methylation status of the MGMT promoter has
been shown to be a potent prognostic factor in
patients with GBM.
• Methylated MGMT may be a good indicator of
therapeutic response and a better prognosis, given that
an increased overall survival has been observed in
these patients
• MGMT promoter status may predict pseudo-
progression in 90% of patients with methylated
glioblastoma.
6101/17/18
61. Clinical course of pseudoprogression in a 65-year-old patient with glioblastoma multiforme.
Alba A. Brandes et al. Neuro Oncol 2008;10:361-367
Copyright 2008 by the Society for Neuro-Oncology 62
Psot
sx
Post
RT
01/17/18
64. rCBV
• rCBV values are also useful for differentiating
treatment-related effects from viable tumor
because they can provide evidence of
neoangiogenesis in lesions.
• Recently, rCBV values have been used to
predict pseudoprogression
6501/17/18
66. Mangla R-Radiology 2010;256:575–84
• rCBV values in patients with GBM before and 1
month after RT+TMZ.
• In patients with pseudoprogression, There was a
41% mean decrease in rCBV,
• While cases of true tumor progression showed a
12% increase in rCBV from pretreatment to post
treatment.
– Tsien et al
• Demonstrated a reduction in rCBV in patients
with pseud-oprogression
6701/17/18
67. DWI -diffusion-weighted imaging
• DWI has been assessed to differentiate tumor
progression and/or residual tumor from necrosis.
• ADC values were noted to be higher in necrotic
tissue than in recurrent tumor tissue
6801/17/18
70. ANGIOGENESIS
• Angiogenesis is the physiological process
through which new blood vessels form
from pre-existing vessels.
• Tumors induce blood vessel growth
(angiogenesis) by secreting various growth
factors (e.g. VEGF). Growth factors such as
bFGF and VEGF can induce capillary growth
into the tumor, which some researchers
suspect supply required nutrients, allowing
for tumor expansion
7101/17/18
75. MECHANISM
• The early decrease in contrast enhancement suggests a
change in vascular permeability, with a
“normalization” of the BBB, rather than a true tumor
reduction, as being the underlying cause of the
improvement.
• DRUG HOLIDAY
• Normalization of the BBB and subsequent reduction in
the vasogenic edema can result in an
• Improvement of symptoms,
– A reduction of steroid dependence, and
– An improvement of brain function and quality of life,
– Bringing clinical benefits to patients
7601/17/18
94. TAKE HOME MESSAGE
Progression
– New enhancing lesion
– Increase choline peak
– Decrease NAA level
– Increase perfusion
Necrosis
– Enhancing lesion
– Slight Increase choline peak
– Near normal NAA level
– Increase lipid lactate peak
– Decrease perfusion
9501/17/18
95. TAKE HOME MESSAGE
Pseudo-Progression
– Larger enhancing lesion
than before
– Disruption of the BBB
– Seen with in 3months
after RT
– Seen in more than 50% of
cases
– RT+TMZ>RT
– Decrease perfusion
Pseudo-Response
– Seen in treatment with VEGF
inhibitors
– Due to early normalization of
BBB/vessels
– T2 usually shows no response
9601/17/18
A, Postcontrast T1-weighted MR image obtained 12 months after resection and radiation of an ependymoma shows new contrast-enhancing lesions within the irradiated volume suspicious for tumor recurrence (arrow). B, 2D CSI MR spectroscopy (point-resolved spectroscopy sequence; TE, 144 ms, TR, 1500 ms) with manually placed voxels in the contrast-enhancing lesion and in the corresponding region in the contralateral hemisphere. C, (lower row).
A, Postcontrast T1-weighted image obtained 12 months after resection, radiation, and chemotherapy of an astrocytoma in the left frontal lobe shows diffuse feathery contrast-enhancing areas in the vicinity of the resection cavity within the irradiated volume, suspicious for tumor recurrence. B, Multivoxel 2D CSI MR spectroscopy (point-resolved spectroscopy sequence; TE, 144 ms; TR, 1500 ms) with manually placed voxels in contrast-enhancing areas, in the cystic cavity, and in normal-appearing brain parenchyma in both left and right hemispheres. C, verified at histopathology.
A, Axial noncontrast T1-weighted MR image obtained 18 months after resection and radiation of an anaplastic astrocytoma presenting with a hemorrhagic lesion in left parietal region. B, Postcontrast T1-weighted MR image demonstrates feathery. C, Axial T2-weighted MR image shows the extensive edema surrounding the lesion in the left hemisphere.
A and B, Fluid-attenuated inversion recovery (FLAIR) (A) and postcontrast T1-weighted MR (B) images obtained 8 months after resection, radiation, and chemotherapy of an anaplastic oligodendroglioma in the left frontal lobe show a new area of hyperintensity on FLAIR (arrow, A) and a contrast-enhancing nodule (arrow, B) in the right frontal lobe within the irradiated volume, suspicious for radiation injury. C, Multivoxel 2D CSI MR spectroscopy (point-resolved spectroscopy sequence; TE, 144 ms; TR, 1500 ms) with manually placed voxels in the contrast-enhancing lesion and in the corresponding area in the left hemisphere. D,.
A, Postcontrast T1-weighted image obtained 10 months after resection and radiation of an astrocytoma in the left frontal lobe shows an irregular peripherally contrast-enhancing mass lesion with central necrosis surrounded by edema suspicious for tumor recurrence. The patient had the lesion resected, and histopathology revealed a high-grade astrocytoma. B, At follow-up MR imaging 6 months later and after additional radiation, a new diffuse contrast-enhancing lesion was present within the irradiated volume. 1H-MR spectroscopy by using SVS (point-resolved spectroscopy sequence; TE, 144 ms; TR, 2000 ms) was performed with the volume placed in over the contrast-enhancing lesion. C,, which was histopathologically confirmed after additional resection.
Clinical course of pseudoprogression in a 65-year-old patient with glioblastoma multiforme. (A) Presurgical MRI scan. (B) Postsurgical MRI scan. (C) MRI scan performed 1 month after combined temozolomide (TMZ)/radiotherapy; adjuvant TMZ was continued. (D) Four months later, during administration of maintenance TMZ. (E) Eight months later, during administration of maintenance TMZ.
![DR KANHU CHARAN PATRO
RADIATION ONCOLOGIST
MD, DNB[RT],FAROI[USA],MBA[HA],PDCR, CEPC
201/17/18](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)