Download Stereotactic Body Radiation Therapy of Liver Tumors

Stereotactic Body Radiation Therapy
(SBRT) of Liver Tumors: Imaging
Appearances and Implications on
Evaluation of Response
Haddad MM, Merrell K*, Johnson GB, Hallemeier CL*,
Olivier KR*, Fidler JF, Venkatesh SK
Radiology and *Radiation Oncology,
Mayo Clinic, Rochester, Minnesota
Disclosures
• None
Learning Objectives
• Describe SBRT induced changes in tumors
and adjacent liver on CT, MRI and PET
• Describe limitations and possible interpretative
errors in the evaluation of therapeutic
response following SBRT
Target audience
• Radiologists, Radiology residents and fellows
• Radiation Oncologists
Stereotactic Body Radiation Therapy
(SBRT)
• SBRT is a noninvasive method of
treatment for primary hepatic tumors and
selected patients with liver- confined
metastatic disease.
• Ablative doses of radiation are delivered
to a target volume in a single or small
number of high dose fractions.
• SBRT is performed with steep dose
gradient and rapid dose fall off outside of
the target so as to minimize dose to
adjacent normal tissues.
• Radiation to liver is minimized such that
at least 50% of liver receives <19.2Gy.
Pathophysiology of SBRT in Liver
SBRT results in
• Coagulation necrosis (ablation) of target volume
consisting of tumor and a safety margin of non tumor
bearing liver (5-10mm)
• Inflammatory response in surrounding liver receiving non
ablative radiation injury is histologically similar to venoocclusive disease
Baseline CT showing tumor (yellow arrow), SBRT planning CT showing target
volume. Follow-up CT showing hypodensity in tumor and reaction in adjacent liver
included in the target.
Imaging changes after SBRT
• Tumors may show response, stay stable or progress
following SBRT.
• Surrounding liver shows inflammatory response known as
focal liver reaction (FLR) that is variable on duration
following SBRT- a reflection of chronic changes that
follow radiation and liver repair.
• Imaging after 3-6 months is most suitable for
assessment.
• Currently there are no guidelines for follow-up and
assessment of response in tumors undergoing SBRT
Response to SBRT on CT
• Responding tumors show
• reduced enhancement
• reduced uptake on PET
• gradual reduction in size over months
Baseline
4 months
9 months
Response to SBRT on MRI
• Responding tumors show
• reduced enhancement
• reduced uptake on PET
• gradual reduction in size over months
Baseline
3 months
10 months
Response to SBRT on PET
• Responding tumors show
• reduced enhancement
• reduced uptake on PET
• gradual reduction in size over months
Baseline
3 months
Response to SBRT on CT
• Responding tumors show
• reduced enhancement
• reduced uptake on PET
• gradual reduction in size over months
4.5cm
5.7cm
Baseline
5 months
3.0cm
9 months
Response to SBRT on MRI
• Responding tumors show
• reduced enhancement
• reduced uptake on PET
• gradual reduction in size over months
5.1cm
Baseline
3.3cm
3 months
2.8cm
6 months
Progression of disease
• Failure of response can be evidenced by increase
in size of tumor or disease spread elsewhere
3.9cm
Baseline
Baseline
7.9cm
3 months
18m
Minimal change following SBRT
• Some tumors may show minimal change in
enhancement and stay stable in size following
SBRT suggestive of partial or no response.
Baseline
8m
Baseline
8m
Post SBRT changes in LiverFocal Liver Reaction
• SBRT also results in focal liver reaction (FLR) in normal
or non-tumor bearing liver parenchyma around the tumor.
• The extent and degree of FLR is dependent on dose
administered, SBRT technique, prior chemoembolization,
concurrent chemotherapy and underlying chronic liver
disease.
• The pathogenesis of FLR is not well understood but is
similar to radiation induced liver disease (RILD) which
manifests histologically as venoocclusive disease (VOD).
Pathophysiology of FLR
Acute (1-3 months)
• atrophy of the central hepatic cells
• severe sinusoidal congestion/hyperemia and hemorrhage
• mild dilatation of the central veins with red blood cells.
Subacute (2-6 months)
• fibrin deposition in central veins/ sinusoids and activation of clotting
mechanism
• Sub lobular veins show significant obstruction by fine collagen fibers.
Chronic (>6 months)
•
•
•
•
Fibrosis of the central veins, collapse of some lobules and fibrous bridging
Accumulation of Kupffer cells and in late stages loaded with hemosiderin.
Liver parenchyma generally recovers and heals over months
Lobular architecture may be distorted without any clinical manifestations.
Imaging appearance of FLR
Acute (1-3 months)
• sinusoids in the irradiated area receive contrast agent later than normal
in the portal venous phase leading to hypoenhacement
• enhancement similar to rest of to liver in the later phases as there is still
clearing of contrast.
• No displacement of vessels through FLR differentiates from tumor
Baseline
3 months
Baseline
3 months
Two examples of acute FLR. Hypodensity (black arrows) near target volume. Note
the patent vessels through the FLR
Imaging appearance of FLR
Subacute (2-6 months)
• Delayed or hypoenhancement on portal venous phase persists
• Hyperenhancement in the delayed phases due to reduced
contrast clearing secondary to obstruction of central veins.
Baseline
Portal phase
6 months
Delayed phase
FLR- Arterial phase hyperenhancement
Arterial phase
hyperenhancement
is due to preserved
arterial inflow into
the FLR. This may
be seen at any
stage of follow up.
Also illustrated in
this example is the
delayed
hyperenhancement
that occurs in
subacute phase
Imaging appearance of FLR
Chronic (>6 months)
• FLR gradually returns to normal enhancement pattern but may
remain hypoenhanced in portal venous phase and hyperenhanced in
the late contrast phase.
• Some parenchymal atrophy especially if tumor is near the surface
• Decreased uptake of hepatocyte specific contrast reflects nonfunctioning hepatocytes or down regulation of transporter proteins
Baseline
Post SBRT
Uncommon findings in FLR
• Ring or rim like enhancement around treated tumor may be
seen during early follow up likely representing a ring of FLR.
Baseline
Baseline
1month
3 month
4months
Ring or rim enhancement
(black arrows is seen on
arterial phase or early
portal venous phase
images and resolves during
follow up
9months
Uncommon findings in FLR
• Ring or rim like enhancement around treated tumor may be
seen during early follow up representing a ring of FLR. Seen
especially on arterial phase or early portal venous phase.
Baseline
4 months
10 months
Ring or rim enhancement (black arrows) is seen during early follow up MRI
and resolves on further follow up. Note reduction in size.
Uncommon findings in FLR
6 months
Baseline
In-phase
Opposed phase
In-phase
Opposed phase
• Signal loss ( black arrows) in opposed phase may be rarely
seen.
• Probably due to chronic hemorrhage and hemosiderin in
Kupffer cells following venous congestion and extravasation
of erythrocytes that are phagocytized by activated Kupffer
cells
Factors to Consider During
Evaluation of Response
Baseline
4 months
15 months
46 months
Hypodense FLR (black arrows) around tumor
should not be interpreted as increase in size of
treated lesion as reduction in size usually occurs
after 3-6 months post SBRT
Factors to Consider During
Evaluation of Response
• Fiducial markers adjacent to tumors may result
in streak artifacts that limits assessment
Baseline
7 months
1 year
On the CT performed after 7 months following SBRT, the target tumor was
thought to be treated. However at 1 year, enlarging hypodensity seen
suggesting progression of tumor. Note the fiducial marker (black arrow) next
to tumor causing streak artifacts limiting assessment of size of the tumor.
Factors to Consider During
Evaluation of Response
• MRI can be useful in assessing response if fiducial
markers limit assessment on CT
Baseline
6 months
Assessment of size of lesion difficult on CT performed after 6 months
following SBRT. Reduction in size of tumor is well demonstrated on MRI
consistent with response.
Factors to Consider During
Evaluation of Response
• PET may also be useful in assessing response
if fiducial markers limit assessment on CT
Baseline
4 months
Another example showing limitation of CT in assessing tumor size due to
fiducial markers. Residual tumor seen on follow up PET scan.
Factors to Consider During
Evaluation of Response
• Continuous thin rim enhancement should not be
interpreted as residual tumor
Baseline
4 months
8 months
14 months
Thin continuous rim of enhancement (black arrow) probably representing
FLR/inflammatory response may be seen in late arterial or portal venous
phase and should not be interpreted as residual tumor. The rim disappears
on follow up confirming its benign nature.
Nodular rim or rim showing washout and/or similar to tumor before treatment
should raise the suspicion of residual/recurrent tumor
Summary
• SBRT produces ablative changes in tumor that
typically results in reduced enhancement and gradual
decrease in size over months.
• Focal liver reaction has variable appearance and
may be dependent on dose administered and time
interval since SBRT.
• Imaging features should be interpreted with
consideration of changes induced by radiation in
surrounding liver to avoid errors in response
evaluation
• MRI and/or PET may provide more information
when CT features are difficult to interpret.
Take home points
• Earliest response in liver tumors to SBRT is
reduction in enhancement.
• Reduction in size typically occur after 6-9 months
• Thin continuous enhancing rim around tumor is
benign.
• Unusual appearances in surrounding liver should
be interpreted with caution.
• MRI and/or PET may be useful for assessment of
response when CT is uninterpretable.
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•
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