Transcript Treatment Related MR Imaging Findings in Patients

eEdE-91
Treatment-Related MR Imaging
Findings in Patients with Glioma after
Radiotherapy and Chemotherapy
Xiao Li, MD ([email protected])
Fanny Morón, MD
Baylor College of Medicine, Houston, Texas
Disclosure
• No potential conflicts of interest to disclose.
Introduction
• Purpose
– To provide a broad review of the various treatmentrelated changes and characteristic MR imaging findings
in patients with glioma after undergoing radiotherapy
and chemotherapy.
• General Categories
– Treatment strategies and treatment response
monitoring
– Chemotherapy-related imaging changes
– Radiotherapy-related imaging changes
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• Treatment and Monitoring
– Treatment Strategies
– RANO Criteria
• Chemotherapeutic effects
– Pseudoprogression
• Anti-angiogenic agent effects
– Pseudoresponse
• Radiotherapy side effects
– Leukoencephalopathy
– Radiation necrosis
– Radiation-induced
• Meningioma
• Cavernous malformation
• Microbleeds
Treatment Strategies
• Glioblastoma is the most common malignant
primary brain tumor
• 30% of patients will have treatment-related
changes on imaging.
• Standard of Care
– Surgical resection
– First line: XRT with concomitant/adjuvant
temozolomide (TMZ) chemotherapy.
– Second line: Anti-angiogenic therapy, Bevacizumab
(BEV) for recurrent glioblastoma.
Response Assessment in Neuro-Oncology
(RANO) Criteria
Enhancing
disease
Complete
Response
Disappearance of
all enhancing
disease sustained
for > 4 weeks
Partial Response Stable Disease
>50% decrease
in measureable
enhancing lesions
sustained > 4
weeks
Progression
Does not qualify 25% of more
for complete
increase in
response, partial enhancing lesions
response or
progression
Non-enhancing
disease T2/Flair
lesions
New lesions
Stable/improved
Stable
Increase
No new lesions
Present
Clinical Features
Stable or reduced corticosteroids (compared to
baseline) clinically stable or improved
Clinical
deterioration
Chemotherapy Imaging-Related Changes
• Traditional chemotherapy primarily induce
DNA damage to dividing cells and/or interfere
with DNA repair.
• Chemotherapy treatments also create
difficulty in post-treatment response
interpretation.
Pseudoprogression
• Non-tumoral increased enhancement +/- size
of lesion after treatment
• Most cases result in spontaneous “remission”
in first 3 months or stability for 6 months
• Can occur in combination with XRT (30%)
• More common in (+) methylated status
• Sign of good response
Mechanism of Pseudoprogression
• Demyelination (hypoxia and endothelial
damage, necrosis)
• Necrosis
• Activation VEGF: Increase permeability of
blood-brain barrier (BBB) leading to
enhancement and vasogenic edema
Concordant Imaging
(Treatment response)
TRIF
Temozolomide
Related Imaging
Findings
Concordant Imaging
(True tumor
progression)
Discordant Imaging
(False tumor
progression)
Pseudoprogression
• Reduction
– Contrast
enhancement
– FLAIR hyperintensity
– DWI hyperintensity
– ADC hypointensity
– rCBV
• Worsen: All of the above
features + high rCBV
• Increase
– Contrast
enhancement
• Decrease
– rCBV
• F/U
– Resolution of
enhancement
Pseudoprogression / TRIF
Initial
Postoperative:
No significant
residue
T1+C
FLAIR
rCBV
DWI
T1+C
3 Months later after XRT-TMZ: New
enhancing lesion along the margins of the
resection cavity without increased perfusion
T1+C
9 Months Later: Spontaneous resolution of
enhancing, non-hyperemic lesion
rCBV
Biological Imaging-related Changes
• Biological therapy
– Treatments that exploit the immune system
to recognize and fight cancer cells
– For example, Bevacizumab (BEV) inhibits
angiogenesis by acting as an antibody that
targets vascular endothelial growth factor
(VEGF).
Bevacizumab (Avastin) Facts
• Antiangiogenic drug used for recurrent GBM
– “Normalize”-stabilize tumor vasculature and BBB.
– Has measurable radiographic response
• Overall Benefit?
– Improves symptoms from mass effect and quality of life,
but does not improve overall survival
– May not be beneficial in unselected populations
– However, no validated biomarkers for patients
stratification
BEV Pseudoresponse
• Post-treatment decrease in contrast
enhancement usually not associated with true
tumor reduction.
• Fast reduction in tumor contrast enhancement
(within days)
• Decreased vascular permeability, improves
edema
BEV Related Imaging Findings (BRIF)
Imaging role?
– Biomarker to better select suitable patients
– Early detection of treatment failure (avoid
complications, minimize neurological
damage, avoid unnecessary procedures and
early therapy modification)
– Currently, follow-up imaging is the most
often used method for treatment
monitoring.
BEV Related Imaging Findings (BRIF)
•
•
•
•
MRP: rCBV values tend to be lower in BRIF
compared to tumor and normal WM
DWI: Restricted diffusion is more prominent
on BRIF than GBM and normal WM
MRS: Cho/Cr and Cho/NAA ratios are
elevated in recurrent tumor
Combination of modalities increases
accuracy.
• Reduction
– Contrast
enhancement
– FLAIR hyperintensity
– DWI hyperintensity
– ADC hypointensity
– rCBV
Concordant Imaging
(Treatment response)
BRIF
Bevacizumab
Related Imaging
Findings
Concordant Imaging
(True tumor
progression)
•
Worsen: All of the
above features + high
rCBV
• Reduction
Discordant Imaging
(Failed treatment)
Pseudoresponse
– Contrast
enhancement
• Increase
– DWI hyperintensity
– ADC hypointensity
Pseudoresponse with Worsening Restricted Diffusion
Baseline recurrent GBM: Bifrontal enhancing tumor with extensive FLAIR hyperintensity, small focal
areas of restricted diffusion (↑), and no significant increased perfusion.
T1+C
FLAIR
DWI
ADC
CBV
2 months after Avastin: Resolution of enhancement with worsening areas of restricted diffusion (↑).
T1+C
FLAIR
DWI
ADC
CBV
Pseudoresponse with Local Improvement but New
Metastasis and Gliomatosis
T1+C
T1+C
T1+C
T1+C
FLAIR
DWI
rCBV
Recurrent L
frontal
enhancing and
hyperfused (↑)
tumor
FLAIR
DWI
rCBV
3 Months
After Avastin:
Improved L
frontal local
recurrent (↑)
tumor
FLAIR
DWI
rCBV
However, new
infiltrating
gliomatosis
(↑) and
hyperperfused
metastasis (↑)
Pseudoresponse with Transient
Restrictive Diffusion (Part 1)
T1+C
At presentation:
Ring-enhancing GBM
T1+C
S/P Near Total
Surgical resection
3 months after SX/XRT/TMZ: Recurrent enhancing tumor was started on BEV
T1+C
FLAIR
DWI
ADC
Pseudoresponse with Transient Restrictive Diffusion,
Possible Pseudoinfarct. (Part 2)
T1+C
FLAIR
DWI
ADC
rCBV
3 months after BEV: Improved enhancement.
New area of restricted diffusion without increased perfusion. (↑)
T1+C
FLAIR
12 m after BEV: Stable resolution of restricted diffusion
DWI
Explanations for BRIF Pseudoresponse
•
•
•
•
•
•
Viable hypercellular tumor
Pseudo-infarct/infarct
Atypical necrosis
Promotes metastasis and gliomatosis phenotype
Mix of tumor and treatment effect
Resistance to therapy (vessel co-option, mimicry,
hypoxia-induced upregulation of other angiogenic
factor, among other mechanisms)
Treatment Effects Related to Radiation
• Leukoencephalopathy
• Radiation necrosis
• Radiation-induced
– Meningioma
– Vascular malformation
• Telangiectasia
• Cavernous Malformation
– Microbleeds
Radiation Injury Mechanism
•
•
•
•
Targeting dividing cells directly/indirectly
Vascular damage
Endocrine disturbance
Neural structural fibrosis
Phases of Irradiation Changes
• Acute phase (during or shortly after radiation): Only
focal damage with reversible glial glycogen depositions
• Subacute phase (up to 12 weeks after radiation): Cell
death of myelin-producing oligodendrocytes occurs
followed remyelinization of the brain tissue.
• Chronic phase (months to years after completing
radiation): Diffuse changes due to wall thickening of
the vascular structures, decreasing number of glialsupporting cells, and diffuse demyelinization.
Leukoencephalopathy
• Leukoencephalopathy develop months to years
after treatment.
• Often seen in post-XRT and exacerbate in
combination with chemotherapy.
• MRI Findings
– Progression of white matter confluent FLAIR
hyperintensity.
– Progressive atrophy
– May have transient areas of white matter
enhancement.
FLAIR
T1+C
rCBV
CBV
2 years after whole
brain radiation and
boost to the L
thalamus+TMZ
FLAIR
At presentation: Non-enhancing
non-hyperemic infiltrating glioma
FLAIR
Atrophy &
Leukoencephalopathy in
3 years interval
FLAIR
3 years with progression of
atrophy and confluent
FLAIR hyperintensity
FLAIR
Radiation Necrosis
• Incidence: 5-25%
• Often occurs 3-12 months after treatment, but
can occur up to years/decades later
• Potentiates in combination with chemo
Radiation Necrosis vs Reoccurrence
• Similarities
– Contrast enhancement
– Mass effect
– Vasogenic edema
• Differences
– Tumor, not radiation necrosis, has increased rCBV
– Radiation necrosis tends to be stable or improved
over time
Radiation Necrosis Imaging
Patterns of
Enhancement
• New enhancement on initially non-enhancing
tumor
• Distant enhancing foci
• Periventricular and callosal enhancing foci
• Soap bubble or Swiss cheese
Evolution
• Stable or improved (70%)
• Variable (30%):
- Re-appear
- Progress (re-radiation)
- New distant lesions
Advanced
Imaging
• Low rCVB.
• No restricted diffusion
• MRS low choline peak
FLAIR
T1+C
Preoperative MRI shows
infiltrative glioma.
Radiation-Induced
Necrosis (Part 1)
FLAIR
T1+C
T1+C
2 years after Sx and
completion XRT/TMZ:
No significant residue.
ASL
3 years: New enhancing lesion without
increased perfusion (radiation necrosis
on pathology).
Radiation-Induced Necrosis (Part 2)
T1+C
FLAIR
4.5 years: New enhancing “soap bubble” distant foci (↑) , not
hyper-perfused on DSC (↑), still on surveillance thought to be
new distant foci of radiation necrosis
CBV
Radiation-Induced Meningioma
• Most common CNS neoplasm known to be
caused by ionizing radiation
• Risk increases with increased doses. Even low
doses significantly increase risk
• Often present with multiple meningiomas and
higher proportion of atypical or anaplastic
compared to spontaneous meningioma
• Lower mean age of presentation in those
exposed to radiation. 29 to 38 years for those
exposed to high dose radiation versus 45-58 years
in spontaneous
Radiation-Induced Meningioma
Recurrence 18 months after total resection/XRT (60Gy)/TMZ, (no extra-axial lesions/clean surgical flap),
underwent redo GBM resection.
T1+C
T1+C
T1+C
CBV
T1+C
Follow up 11 months later,
after GBM Resection x 2 +
XRT boost (20 Gy) +TMZ, a
collision meningioma in
the resection-radiation
site (at bone flap) is
present.
Vascular Malformation
•
Radiation can cause early vascular changes such as increased capillary
permeability and vasodilation as well as delayed injury leading to
occlusion/infarction and proliferative changes such as capillary telangiectasia and
cavernous malformation.
•
Capillary telangiectasias are thin walled capillaries with intervening normal brain
parenchyma and occurs 3-9 months after irradiation. Cavernous malformation do
not contain the intervening brain parenchyma and tend to develop years later.
•
Cavernous malformation on imaging
– Distinctive “popcorn “ appearance with minimal surrounding edema
– CT show ring-like calcification with core reticulation of variable attenuation
– MRI show core heterogeneous intensity with dark peripheral hemosiderin rim
Radiation-Induced Cavernous
Malformation
Initial: Brainstem pilocytic astrocytoma at
presentation. Received wide-field
radiation.
(↑): Popcorn appearance with
surrounding hemosiderin rim
(↑): minimal/no enhancement.
10 years later: New
lesion in the left
temporal
lobe consistent
with cavernous
malformation
CO: Jeremy Jones MD
Cerebral Microbleeds
• Radiation can cause cerebral hemorrhage that results
in the formation of cerebral microbleeds (CMBs).
Contain focal perivascular collections of hemosiderin
and persists for years.
• Imaging
– Hemosiderin contains iron and has associated
susceptibility effects.
– Small, round, hypointense lesions on T2*-weighted images
obtained using gradient echo sequences.
– Increase in number over time since irradiation and
correlate with dose and target volume
– May be a useful measurement of radiation injury
Radiation-Induced Vascular Lesions
History: 15 yo s/p infratentorial medulloblastoma resection with radiation 6 years ago
New tiny left temporal parietal hypointense foci in otherwise unremarkable supratentorial brain. (↑)
CO: Jeremy Jones MD
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