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102 Treatment planning part III
(a) (b)
Figure 5.6 (a) Results of fully automated atlas-based segmentation of the left and right liver lobes
using the MIM 6 (MIM Software Inc., Cleveland, OH) software package. (b) Atlas-based segmentation
followed by manual correction (shaded areas).
Figure 5.7 Three-dimensional liver volume generated with contours on only six axial CT slices using
the free DICOM viewer OsiriX 5.8.2 (Osirix Foundation, Geneva, Switzerland).
5.10 Treatment planning calculations / 5.10.1 Lobar therapy 103
=×
=
V
67mL
15.8%
=×
=
V
122mL
28.7%
q2
986mL 424mL
V
+
5.10 TREATMENT PLANNING
CALCULATIONS
is section functions as a guide that will provide instructive examples of radioembolization
treatment planning in both lobar and segmental
therapies. Dierent treatment planning models are
considered for both resin and glass microspheres.
5.10.1 LOBAR THER APY
As a surgeon aims to resect a margin of normal
parenchyma surrounding a liver tumor, radioembolization is oen purposefully nonselective, so as to
treat microscopic metastatic disease. Patients with
liver metastases are usually noncirrhotic and have a
greater functional hepatic reserve, and are therefore
commonly treated with microsphere infusion to an
entire hepatic lobe. Lobar therapy is also desirable in
the setting of liver metastases due to the propensity
for multifocal disease, making superselective infusion impractical. It should be noted that this methodology applies to HCC patients with multifocal
disease in the absence of clinical and serologic indicators of severe underlying liver disease. However,
in the setting of underlying liver impairment, minimizing nontarget embolization to nontumor hepatic
tissue is preferred, so as to preserve hepatic function
(Salem and urston, 2006).
5.10.1.1 Example case
A 61-year-old female presents with lung cancer
and four metastatic lesions to the le hepatic lobe.
ere is no serologic or radiologic evidenceof cirrhosis or biliary obstruction. Figure 5.8a shows a
hepatic protocol CT of one centrallynecrotic metastatic lesion in the le hepatic lobe, with corresponding hypermetabolic activity by
CT (Figure 5.8b). In all treatment planning scenarios (1–4 below) a le lobar therapy is assumed
using conventional anatomic boundaries. Each
lobe was contoured in three dimensions to determine relative volumes of the le lobe, right lobe,
and total liver (Figure 5.8c).
e volume of the le lobe tumors can be
contoured based on the contrast-enhanced CT or
18
FDG-PET/CT (Figure 5.8a and b). In this par-
ticular case, the tumor is not avidly enhancing
18
FDG-PET/
on the portal venous phase CT and manual
segmentation of the CT image set would be limited to corresponding hypodensity visualized in
18
Figure 5.8a. e
FDG-PET/CT identies the
tumor as centrally necrotic and highly FDGavid along its periphery. Due to these dierences,
manual contouring from contrast-enhanced CT
and semiautomated threshold-based contouring
based on PET/CT yielded le lobe tumor volumes of 67 and 122 mL, respectively. ese volumes include out-of-slice lesions not visualized
in Figure 5.8.
5.10.1.2 Scenario 1: Empiric model
for resin microspheres
Based on these measurements, the percentage tumor inltration in the liver is as follows in
Equations 5.15 and 5.16 for the tumor volumetry
performed on CT and PET/CT, respectively:
tumor,CT
tumor,PET
=
I
I
It is important to note in Equations 5.15 and
5.16 that the percent inltration was calculated
only for the lobe to be treated, that is, using the volume of tumor and volume of normal liver within
the le lobe only. As denoted in Table 5.4, the rec-
ommended whole-liver treatment dosage (A
for this level of inltration is 2.0 and 2.5 GBq, for
15.8% and 28.7% tumor inltration, respectively.
Recall that the empiric model is dened for wholeliver therapy and the dosage must be scaled for the
treated lobe. Equation 5.17 shows this calculation
for the 2.5 GBq prescription:
GBq GB
AA
() ()
GBq
⋅
e nal step illustrated in Equation 5.17 is crit-
ical. is can be appreciated using Equation 5.3 to
tumor
+
VV
tumornormal
=
tumor
+
VV
tumornormal
=⋅
emp
424mL
424mL
V
wholeliver
424mL
treated
=
0.75GBq
100%
100%
.5
=
(5.15
(5.16)
emp
(5.17)
)
)
104 Treatment planning part III
BS
20
50
(c) (d)
(a) (b)
Figure 5.8 (a) Hepatic protocol CT performed on a patient with lung cancer metastases to the liver.
A centrally necrotic metastatic lesion is present in the lateral left hepatic lobe (a) and corresponding hypermetabolic activity by 18FDG-PET/CT is shown in (b). Automatic contouring of the lesion was
performed in (b) based on a threshold of 40% of SUV
used to contour both the left and right lobe volume (white line) as well as the tumor based (blue line)
on anatomical boundaries. (d) Pretreatment
normal left lobe tissue region (white line).
99m
Tc-MAA SPECT with tumor boundary (blue line) and
calculate the average absorbed dose to the le liver
lobe if the step in Equation 5.17 is not performed.
Applying a density of 1.05 kg/L to this patients’
424 mL le lobe, we obtain a mass of 0.445 kg.
A dosage of 2.5 GBq, according to Equation 5.3,
would yield an average absorbed dose of 280 Gy to
the lobe. is level of absorbed dose would likely
result in severe toxicity in the uninvolved tissues of
that lobe.
(blue line). (c) The hepatic protocol CT was
max
1.62 m (5 feet, 4 inches). erefore, her body surface
area can be calculated according to Equation 5.6:
0.72
.725
.425
A(m )0.2025 height (m)
=× ⋅
0.425
weight (kg)
=× ⋅
0.2025 1.62 (m)64(kg)
=
1.68m
2
One must keep in mind that the units of height
(m) and weight (kg) are critical as shown in
5.10.1.3 Scenario 2: Resin
microspheres using the
BSAmodel
Now let us change gears and consider the BSA treatment planning model for this scenario. is female
patient has a weight of 64 kg (141 lb.) and a height of
Equation 5.18:
A
bsa
=−+
GBq BSA 0.2
()
=+
1.68–0.2
=
1.767GBq
V
tumor
+
VV
tumornormal
122 mL
424 mL
(5.19)
(5.18)
5.10 Treatment planning calculations / 5.10.1 Lobar therapy 105
()
gl
DM
0.45
=
FU
T
0.50
=
In Equation 5.19, the BSA dosage (A
) has been
BSA
calculated based on the tumor volumes identied
18
using
FDG-PET/CT. A
would be slightly lower
BSA
had the tumor volumes from contrast-enhanced
CT been used.
Once again, the BSA model is dened for
whole-liver therapy and the dosage (A
) must be
BSA
scaled for the treated lobe. is process is shown
in Equation 5.20. Note that the nal recommended
treatment activity using the BSA method (0.53
GBq) is less than when the empiric method is used
(0.75 GBq):
V
GBq GBq
AA
=⋅
() ()
BSA
1.767GBq
=⋅
=
0.53GBq
V
986 mL424 mL
treated
wholeliver
424 mL
+
(5.20)
5.10.1.4 Scenario 3: Glass
microspheres using the
recommended treatment
planning method
Treatment planning for the le lobe therapy of the
same patient using glass microspheres is considerably more straightforward. e percent tumor
burden is not necessary and the solution is dependent only on the total mass of tissue in the le lobe:
0.445 kg. In fact, the most dicult part is select-
ing an absorbed dose endpoint within the recommended 80–150 Gy range.
For the purposes of this example, selecting a
conservative 100 Gy absorbed dose treatment endpoint, we obtain
⋅
0
=
=
49.98(J s)
100Gy0.445 kg
49.98
0.89GBq
Gy (kg)
av
=
GBq
A
()
Note that the absorbed dose endpoint shall
be selected based on the many clinical and serologic factors discussed in the case introduction.
However, in this patient without chronic liver
iver
⋅
⋅
(5.21)
disease or biliary obstruction, any endpoint in
100–120 Gy would likely be appropriate.
5.10.1.5 Scenario 4: Resin
microspheres using the
partition model
Lobar therapies will result in microsphere deposition in normal liver parenchyma and microsphere
deposition in the tumor according to the T:N
ratio. e partition model accounts for measured
T:N aswell as normal liver and tumor volumes to
design a patient-specic treatment plan. Figure
5.8d describes the measurement process of T:N
following
lobar infusion of 150 MBq of
formed 2 weeks before treatment with the catheter
tip positioned carefully at the expected treatment
location. Tumor contours from the metabolically
active region on
been copied onto the
(Figure 5.8d). Areas of uninvolved liver are also
shown. T:N was calculated in this case according
to Equation 5.4 to be 2.8:1. Based on the pretherapy MAA mapping procedure, a lung SF for this
patient was measured to be 5%. With this information, we can calculate the FU in tumor and
uninvolved liver.
To compute the FU, we must determine the
volume of uninvolved parenchyma in the le lobe
(V
normal
Table 5.5. If we assume tumor volumes based on
18
FDG-PET/CT, then V
mL. e corresponding mass of uninvolved le
lobe parenchyma is 0.317 kg:
FU 1SF
99m
Tc-MAA SPECT/CT imaging. A le
18
FDG-PET/CT (Figure 5.8b) have
99m
99m
Tc-MAA was per-
Tc-MAA SPECT image set
), which was not previously included in
= 424–122 mL = 302
normal
V
=−
()
normal
=−
10.05
()
1SF
=−
()
tumor
1 0.05
=−
()
T:N
T:N
normal
VV
⋅+
tumornormal
302 mL
⋅+
2.8 122 mL 302 mL
⋅
V
tumor
N
⋅+
VV
tumornormal
2.8 122mL
⋅
2.8 122mL 302mL
⋅+
(5.22)
(5. 2 3)
106 Treatment planning part III
()
yk
0.77GBq
rt
DM
0n
()
Table 5.5 Volumetric measurements of the patient presented in Figure 5.8
Structure Volume (mL) Mass (kg)
Total liver 1,410 1.480
Total right lobe
Total left lobe
Left lobe tumor, manually contoured
from CT
Left lobe tumor, automatically measured
Right lobe tumor 0 mL 0 kg
Note: The patient has a weight of 64 kg (141 lb.) and a height of 1.62 m (5 feet, 4 inches).
a
b
18
from
0.4 · SUVmax
Mass calculated by multiplying volume (L) by the density of liver tissue, 1.05 (kg/L) (ICRU, Photon, Electron,
Proton and Neutron Interaction Data for Body Tissues, International Commission on Radiation Units and
Measurements, 1992).
Includes contributions from uninvolved tissue and tumor tissue.
b
b
FDG-PET/CT with threshold =
986 1.035
424 0.445
67 0.070
122 0.128
a
We can now determine the activity required to
reach a tumor-absorbed dose endpoint as shown
in Equation 5.24. Given that this patient has metastatic liver cancer with no underlying chronic
liver disease, a tumor-absorbed dose of 150 Gy
for radioembolization using resin microspheres is
appropriate:
G
tumo
=
GBq
A
()
0
150Gy0.128(kg)
()
=
=
⋅
()
⋅
49.98 FU
⋅
⋅
49.98 0.50
umor
tumor
g
(5.24)
Assuming accuracy of T:N measurement, a
dosage of 0.77 GBq will result in a 150 Gy average tumor dose. However, this dosage must still
be back substituted into Equation 5.12 to ensure
that normal liver toxicity thresholds are not
exceeded. is is illustrated in
D
normal
A
Gy
=
()
0.77GBq 49.98 0.45
=
=
55Gy
⋅⋅
M(kg)
normal
⋅⋅
()
0.317(kg)
ormal
(5.25)
GBq 49.98 FU
As previously discussed, the maximum tolerable dose to normal, noncirrhotic, liver tissue
from radioembolization is approximately 80 Gy. A
treatment dosage of 0.77 GBq in this case is likely
to be safe, particularly in the setting of a le-lobe
therapy due to the small fraction of liver tissue irradiated. is particular point is carefully detailed in
Chapter 8.
5.10.1.6 Other considerations
Each case above represented an example of treatment planning for a single-session therapy.
Fractionation of radioembolization treatments is a
recommended practice, which may decrease toxicity to normal liver (Salem and urston, 2006;
Cremonesi et al., 2008). Multicycle therapy will be
discussed in more detail in Chapter 8.
5.10.2 SELECTIVE THERAPY
Segmental and selective therapies will result in
microsphere deposition in tumor and normal tissues within the segment according to T:N and
should yield little or no deposition outside of that
segment except in cases of reux. While outside
the scope of this chapter, vascular planning for
segmental therapy has been discussed elsewhere
(Salem and urston, 2006; Riaz et al., 2011) and
in Chapter 3. Instead, this section will focus primarily on dosimetric aspects of selective therapy.
In all cases of lobar therapy reviewed in the previous section, treatment planning was always dependent on the volume of the treated lobe. In selective
and segmental therapy, one must instead identify
the volume of tissue perfused by the treatment that
may consist of only tumor or tumor and normal
liver tissue within one or more segments.
5.10 Treatment planning calculations / 5.10.2 Selective therapy 107
As shown in Figure 5.9, the patient has a 22
cm solitary liver metastasis from parotid adenoid
Figure 5.9 Contrast-enhanced CT of a patient
with a 22 cm solitary liver metastasis from parotid
ACC. Contrast-enhanced CT and pretreatment
angiography suggest that the tumor is well
perfused and solid, with no substantial areas of
necrosis.
cystic carcinoma (ACC). e patient’s total liver
volume is 3500 mL, with 2200 mL attributable to tumor. Contrast-enhanced CT and pretreatment angiography suggest that the tumor
is well perfused and solid, with no substantial
areas of necrosis. is patient was referred for
radioembolization using resin microspheres.
Unfortunately, this case represents a clinical and
technical challenge owing to the large tumor size.
Targeting of this patient’s entire tumor would
result in a subtumoricidal response, even if the
entire 3 GBq resin microsphere dosage was delivered. erefore, the tumor was treated in multiple stages. Figure 5.10a shows the pretreatment
angiography with the catheter positioned in the
right hepatic artery and two dominant branches
supplying the tumor. Figure 5.10b shows a selec-
tive segmental right hepatic arteriogram prior to
99m
Tc-MAA injection. e
99m
Tc-MAA SPECT/
CT in Figure 5.11 shows the volume of tumor
perfused to be 48% of the total tumor volume.
Since MAA deposited almost exclusively in the
tumor, Equation 5.3 could be used directly to
determine the dosage necessary to reach a 120 Gy
endpoint in 48% of the tumor volume:
(a) (b)
Figure 5.10 (a) Pretreatment angiography with the catheter positioned in the right hepatic artery and
two dominant branches supplying the tumor. (b) Selective segmental right hepatic arteriogram prior
99m
to
Tc-MAA injection.
108 Treatment planning part III
() ()
⋅
Gykg
A
DM
Figure 5.11
volume of tumor perfused at the catheter location shown in Figure 5.10b. Perfused volume of
MAA was measured to be 48% of the total tumor
volume.
99m
Tc-MAA SPECT/CT showing the
GBq
()
0
tumortumor
=
120Gy0.482.2L 1.05(kg/L)
=
2.66GBq
=
49.98
⋅⋅ ⋅
()
()
49.98
(5.26)
Large tumor size is certainly not the only reason to treat in stages. A segmental approach to the
treatment of multifocal disease is also an excellent
option, which can reduce toxicity in normal liver
(Riaz et al., 2011). Figures 5.12a and 5.12b show a
hepatic protocol MRI and
111
In Octreotide SPECT
of a patient with NET metastases. Multiple metastatic lesions are present throughout the right lobe.
Given the absence of underlying chronic liver disease and the typically high ecacy of radioembolization in treating NET, a selective multistep
approach was employed. A lateral right hepatic
artery branch was selected (Figure 5.12c and d)
(a) (b)
(c) (d)
Figure 5.12 (a) Hepatic protocol MRI and (b)
neuroendocrine metastases to the liver. Multiple metastatic lesions are present throughout the right
lobe. (c) Angiogram showing right hepatic arterial vasculature. (d) Selective microcatheter positioning
in lateral right hepatic arterial branch that, based on pretreatment
posterior half of the right lobe volume.
111
In octreotide SPECT performed on a patient with
99m
Tc-MAA SPECT, perfused the
Figure 5.13 Posttreatment 90Y PET/CT verifying
that the radioembolization dosage was delivered
to the posterior half of the right hepatic lobe.
that, based on pretreatment
99m
Tc-MAA SPECT,
perfused approximately 50% of the right lobe volume. Treatment planning was performed according to the BSA model for radioembolization using
resin microspheres. e dosage recommended by
the BSA model was reduced by 50% due to the estimated perfused volume of the treatment territory.
Following delivery of 0.81 GBq of 90Y, a 90Y PET/
CT scan was performed verifying limited microsphere deposition outside of the treatment zone
(Figure5.13). One month later, this patient under-
went selective radioembolization of the remaining
untreated lesions in the anterior right lobe.
5.11 CONCLUSIONS
Treatment planning for radioembolization is not
only a multidisciplinary process requiring input
from dierent medical specialists but also a process
that requires signicant experience. Dierences
between patients, even among those with the same
disease type, can vastly eect the treatment decision
and planning process. ese dierences necessitate
a patient-specic approach to treatment planning.
is chapter is but a brief overview of the factors that must be considered by the interventional
radiologists, medical physicists, nuclear medicine
physicians, and/or radiation oncologists involved in
the therapy. In addition to the instruction provided
in this chapter, the most important suggestion that
the authors wish to convey is the importance of
References 109
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periodic meeting to discuss upcoming cases consisting of the treating interventional radiologist,
medical physicist, nuclear medicine physician,
and/or radiation oncologist will help to elucidate
optimal treatment plans through multidisciplinary
discussion. While such meetings can be dicult to
schedule in a busy clinical setting, their importance
cannot be overemphasized and will undoubtedly
lead to improved patient outcomes.
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