Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3618_Библиотеки_им_академика_М_И_Перельмана
.pdf
72 Treatment planning part II
()
D
Lung dose is determined using the total
injected activity A
and the LSF by A
total
lung
= A
total
× LSF with an assumed mass of 1 kg [International
Commission on Radiological Protection (ICRP),
1975]. Patient-specic evaluation of lung mass is
not routinely performed for clinical radioembolization procedures owing to the lack of volumetric information provided by planar scintigraphy.
is extension for calculating the absorbed dose
to the lung is given in Equation 4.4 and can be
applied to routine radioembolization treatment
scenarios:
A
GBqLSF 49.98(J s)
×× ⋅
1(kg)
(4.4)
Gy
()
avg
total
=
While convenient for routine clinical care, estimating lung dose from a 2D projection image has
several limitations. Without an anatomical image,
lung and liver contours on planar scintigraphy can
be subjective. Because of the high uptake of activity in the liver, small variations in the denition of
the border between the liver and lung may result
in large variations in the measured activity to the
lung. In addition, planar scintigraphy is not easily corrected for photon attenuation and scatter,
leading to large potential uncertainties in lung and
liver MAA activity. Using the GM of LSFs determined from a conjugate pair of anterior and posterior planar images may mitigate the dierences
in photon attenuation due to depth; however, the
GM technique does not correct for scatter and fails
to compensate for photon attenuation dierences
due to varying tissue densities as exhibited in liver
and lung.
4.3.2 ADVANCED TECHNIQUES
e use of
estimation of lung dose from arteriovenous shunting. ree-dimensional (3D) image reconstruction in conjunction with attenuation and scatter
corrections using tissue densities derived from a
coregistered anatomical CT image improves the
quantication of liver and lung activity uptake for
calculation of the LSF. e anatomical CT image
also provides information about the lung volume
and the ability to perform patient-specic densitovolumetry. However, the time to obtain the
necessary planar projections for 3D SPECT reconstruction is lengthy and free breathing during the
99m
Tc-MAA SPECT can improve the
image acquisition may result in misregistration of
activity around the diaphragm. Liver activity can
be blurred into the lung region dened by the CT
that was acquired within a few seconds during a
specic phase of the respiratory cycle, resulting in
an overestimation of the lung activity.
Yu et al. (2013) proposed a method of calcu-
lating the MLD based on
99m
Tc-MAA SPECT/
CT. MLD is approximated by the mean dose in
a subregion of the lung (Lung
) that excludes
sub
the portion of lung that is within 2 cm of the
diaphragm in order to avoid spillover from liver.
LSFs to Lung
in Lung
sub
were determined from activities
sub
and external body within the scan
region contoured on the CT. MLD was determined retrospectively for 71 patients by Equation
4.3 using a mass calculated from the volume of
Lung
and an assumed lung density of 0.3 g/cm3
sub
(Van Dyk et al., 1982). e lung doses calculated
from SPECT were compared with those from an
LSF estimated from lung and liver regions on planar scintigraphy assuming a total lung mass of
1000 g. In almost all patients, the lung dose from
planar scintigraphy exceeded the dose derived
from SPECT, with a mean planar scintigraphy to
SPECT lung dose ratio of 3.8 ± 4.0. For patients
at highest risk for radiation-induced pneumonitis
from treatment with estimated lung doses greater
than 15 Gy according to planar scintigraphy, the
ratio was 2.7 ± 1.1. e authors further studied
the eect of ignoring the misregistration due to
breathing and failure to make attenuation and
scattering corrections during the reconstruction of the SPECT images, concluding that each
will result in roughly 50% overestimation of
the lung dose. Recognizing the subjectivity and
potential inaccuracy of LSF estimation based on
planar scintigraphy, the authors recommended
using SPECT for more accurate mean lung dose
estimation.
A recent study by Kao et al. (2014) further
demonstrated the uncertainties using planar
images for estimating MLD and the importance
of using SPECT/CT for individualized MLD estimation. Kao et al. (2014) compared lung doses
calculated from
99m
Tc-MAA SPECT/CT to the
conventional planar scintigraphy method for a
cohort of 30 Southeast Asian patients. e technique for estimating lung dose from 3D SPECT/
CT was similar to that used by Yu et al. (2013).
LSFs were determined using counts from lung
4.4 NTE, RP, and their effects / 4.4.1 Extrahepatic uptake and clinical strategies used to treat 73
and liver volumes segmented on the CT. A distance of 1.5 cm superior to the domes of the diaphragm was selected to exclude lung counts from
misregistration of activity in the liver due to free
breathing during image acquisition. MLD was
determined using Equation 4.3 with a patientspecic lung parenchyma mass determined by
CT densitovolumetry for the lung volume above
the exclusion zone. Lung and liver activities were
also measured from conventional planar scintigraphy and a statistically signicant dierence
between mean LSFs from planar (5.96 ± 4.59%)
and SPECT (7.36 ± 4.96%) was found. However,
the mean lung absorbed doses from both methods
was not statistically signicant. e mean lung
mass for their patient cohort was 830 g, not vastly
dierent from the standard lung mass of 1000 g.
For patients with particularly smaller lung mass,
such as patients postlobectomy, the planar image
method may underestimate the MLD.
RP from arteriovenous shunting is a rare
complication in treatment of liver cancer using
90
Y radioembolization, with an occurrence of less
than 1% (Chan et al., 1995; Salem et al., 2008). A
contraindication of treatment arises only if lung
dose is greater than a single treatment dose of
30 Gy or cumulative dose of 50 Gy (Riaz et al.,
2014). e conventional method of determining
lung and liver activity from planar scintigraphy
99m
of
Tc-MAA may result in an overestimation
of MLD due to the inaccuracy of delineating
regions representing lung and liver volumes and
the inability to apply attenuation and scatter corrections to 2D images. Likewise, the necessity of
using an assumed standard lung mass of 1000 g
for dosimetric calculation from planar scintigraphy may contribute to an over- or underestimation of patient lung dose depending on patient
size and lung physiology. Lung dose estimation
from 3D
99m
Tc-MAA SPECT/CT using patientspecic lung mass oers an improved and more
precise assessment of lung dose from shunting.
However, even if SPECT/CT is used, interpretation of lung dose from 90Y microsphere activity
based on surrogate
99m
Tc-MAA scintig raphic
imaging is still associated with error. Erosion and
fragmentation of the albumin aggregates reduce
the particle size resulting in a larger amount of
99m
Tc-MAA activity traveling to the lungs compared with 90Y microspheres, which have a rigid
structure.
4.4 NONTARGET EMBOLIZATION,
RADIATION PENUMONITIS,
AND THEIR EFFECTS
Planar
determine LSF and to exclude gastrointestinal
shunting. In particular,
imaging provides fused functional and anatomic
data, adds clarity and condence in the identication of extra hepatic ow, and can guide target
embolization of extrahepatic feeders. However,
SPECT/CT should not be solely used to absolutely exclude gastrointestinal shunting. Rather,
it should be considered an adjunctive imaging
modality of the gastrointestinal tract. Exclusion
of gastrointestinal ow should be accomplished
by use of the combined information obtained
from hepatic angiography, 3D CT angiography,
and SPECT imaging.
99m
Tc-MAA imaging is performed to
99m
Tc-MAA SPECT/CT
4.4.1 EXTRAHEPATIC UPTAKE AND
CLINICAL STRATEGIES USED
TO TREAT
As discussed in Chapter 3, planning angiography
is necessary before radioembolization as it provides an overview of normal and variant anatomy.
With advanced technologies in C-arm CT and
new catheter types, the frequency of prerequisite
prophylactic coil embolization to prevent hepaticoeneteric ow has decreased. Nontarget deposition of microspheres can have grave consequences.
e most common sites of undesired particle
deposition are in the gall bladder, gastrointestinal
(GI) system, and pulmonary system.
Radiation cholecystitis results from uptake of
radioactive microspheres in the gall bladder. is
can be prevented by preemptive identication of
the cystic artery and placement of the catheter
tip beyond the origin. If blood ow is signicant
and injection beyond the origin is not possible,
then embolization may be considered (Salem and
urston, 2006b). is is managed by supportive
care and if refractory, cholecystectomy should be
performed (Atassi, 2008).
tion provides a sensitive predictor for radiation
cholecystitis. Figure 4.3 shows uptake in the gallbladder along with the uptake in the liver and the
tumor in the
99m
Tc-MAA SPECT/CT. is example
99m
Tc-MAA simula-
74 Treatment planning part II
illustrates the importance of
99m
Tc-MAA simulation in order to prevent complications such as radiation cholecystitis.
e incidence of GI ulceration is less than
5% if meticulous techniques are used (Mallach
et al., 2008; Szyszko et al., 2007). Although pretreatment hepatic angiography should assist in
reducing these complications, misdirected microspheres can enter hepaticoenteric ow. ese
patients may have intense embolic pain during
or aer the procedure. As shown in Chapter 13,
if GI NTE is suspected, conrmation using 90Y
PET/CT aer the microsphere infusion can aid in
medical management of these patients. Denitive
diagnosis can be made by upper endoscopy. ese
toxicities can be attributed to unrecognized variants, collateral circulation, and changes in ow
(a)
dynamics during infusion (Murthy et al., 2007).
ese patients should be aggressively managed
with proton pump inhibitors to prevent more
serious complications such as ulceration and/or
perforation that may eventually require surgical
management.
Figure 4.4 shows gastric uptake in the pylo-
rus identied on
99m
Tc-MAA SPECT/CT that
could have potentially resulted in ulceration.
Prophylaxis included coiling the culprit gastric
artery. Figure 4.5a shows the planning angiogram following routine occlusion of the gastroduodenal artery. e MAA uptake detailed in
Figure 4.4 prompted additional occlusion of the
right-gastric artery shown in Figure 4.5b. is
prophylactic measure allowed for safe administration of 90Y radioembolization.
Inadvertent delivery of microspheres can also
occur through the vessels supplying the anterior
abdominal wall via the falciform artery (Liu et al.,
2005) resulting in radiation dermatitis (Leong et
al., 2009). ese side eects can be avoided by prophylactic embolization during pretreatment angiography (Meyer et al., 2014). At our institute, we
use an ice pack/saline bag placed over the abdominal wall that is presumed to cause vasospasm and
redirect ow into the intrahepatic circulation
(Wang, 2013). Figure 4.6 shows the
99m
Tc-MAA
SPECT/CT of a patient with HCC. ere is MAA
uptake corresponding to the tumor in the right
lobe of liver. Additionally, there is a linear focus
of activity extending inferiorly into the anterior
(b)
Figure 4.3 Uptake in the gallbladder (arrow) from
shunting into the cystic artery, with the risk of
radiation-induced cholecystitis. (a) Hepatic protocol CT and (b)
infusion of 4.0 mCi of
99m
Tc-MAA SPECT/CT following
99m
Tc- MAA.
Figure 4.4
potential activity in the pylorus. Additional prophylactic steps must be taken prior to treatment
to avoid gastrointestinal (GI) complication.
99m
Tc-MAA SPECT/CT image shows
4.4 NTE, RP, and their effects / 4.4.3 Radiation pneumonitis 75
(a) (b)
Figure 4.5 Angiography before and after
routine occlusion of the gastroduodenal artery. (b) After identication of nontarget embolization
(NTE) to the pylorus on MAA SPECT/CT, coil occlusion of the right-gastric artery was performed.
99m
Tc- MAA SPECT/CT. (a) Planning angiogram following
4.4.2 EXCESSIVE LUNG SHUNTING
AND CLINICAL STRATEGIES
USED TO TREAT
Arteriovenous anastomoses or shunts in the liver
parenchyma or tumor cause the lung shunting
that potentially could result in RP aer radioem-
NTE
bolization (Wright et al., 2012; Leung etal., 1995).
Various strategies for managing excessive LSF are
described in the literature. ese include cancellation of the procedure in any patient with markedly elevated hepatopulmonary shunting (LSF >
20%) (Leung et al., 1995), reduction in the microsphere dose (10% < LSF < 20%) (Elschot etal.,
2011), bland embolization, or chemoemboliza-
Figure 4.6 Abdominal wall shunting.
SPECT/CT in a patient with hepatocellular carcinoma. MAA uptake corresponding to the tumor
is present in the right lobe of liver. A sagittal
reformat shows linear activity extending inferiorly
into the anterior abdominal wall in the region of
the umbilicus, representing extrahepatic shunting via the falciform artery.
99m
Tc- MAA
tion of the shunt (Gaba and Vanmiddlesworth,
2012) and balloon occlusion of the hepatic vein
while delivering the microspheres could allow
safe 90Y delivery (Ward etal., 2015). Additional
techniques are discussed in other chapters of this
book.
4.4.3 RADIATION PNEUMONITIS
abdominal wall in the region of the umbilicus, representing potential extrahepatic NTE via the falciform artery. Due to pretreatment identication
using MAA, the aforementioned ice pack prophylaxis was employed during the treatment of this
patient preventing side eects.
RP represents an acute manifestation of radiationinduced lung disease caused by increased hepatopulmonary shunting with an associated increased
estimated radiation dose to the lungs. Most of the
cases in the literature are a result of external beam
76 Treatment planning part II
irradiation aer treatment for lung and breast cancers (Leung et a l., 1995), lymphoma, and whole-body
irradiation for stem cell transplantation (Camus,
2004). MLD, lung volume receiving a specied dose,
and normal tissue complication probability (NTCP)
are the three widely studied parameters used to
assess the risk for RP (Graves etal., 2010). Rodrigues
et al. (2004) highlighted that direct comparisons
between studies could not be achieved given the
heterogeneity of outcome variables. However, most
studies did show an association between dose–volume histogram parameters and RP. It is noted that
dosimetric parameters play a lesser role than patient
characteristics for the prediction of lung toxicity
(Dehing-Oberije et al., 2009). Ramella et al. (2010)
determined addition of ipsilateral constraints (i.e.,
volume of lung receiving 30 Gy) to standard lung
dosimetric factors in patients with RP in non–smallcell lung cancer treated with 3D conformal RT and
concurrent chemotherapy resulted in a reduction in
the incidence of pneumonitis from 14.4% to 6.8%.
According to Riaz et al. (2009), RP is a complication that has not been studied optimally. In their
report involving 58 patients, none developed RP
with cumulative lung doses exceeding 50 Gy (Salem
et al., 2008). However, there is a case report (Wright
et al., 2012) with RP in a patient with a lung dose
of 31.0 ± 13.0 Gy. It is presumed in this case that
RP was not predicted using the currently used 90Y
dosimetry models that assume uniform distribution
in the lungs (Salem et al., 2008), which may explain
the ndings of Wright et al. (2012).
RP patients generally present with gradual onset
of dyspnea, fever, bronchoalveolar lymphocytosis
and eosinophilia. is initially presents as a mild
restrictive process on pulmonary testing, with illdened patchy opacities and ground-glass nodularity in a symmetric (i.e., “bat-wing”) pattern with
relative peripheral/hilar sparing 1–2 months aer
therapy. e features can also resemble an organizing or chronic eosinophilic pneumonia. ese may
resolve or progress toward localized brosis, traction bronchiectasis, and focal honeycombing. Late
complications include pneumothorax and superinfections (Leung et al., 1995; Camus, 2004; Riaz
et al., 2009).
e rst line of management of RP is corticosteroids, which may reduce the degree of inammation (Leung et al., 1995). Rubin and Casarett (1968)
demonstrated that when corticosteroids were
given aer clinical pneumonitis had developed,
an objective response was seen. However, when
given prophylactically they failed to prevent RP.
Pentoxifylline (a platelet inhibitor with immunomodulating/anti-inammatory properties mediated through interleukin-1/tumor necrosis factor)
is thought to be helpful in preventing radiotoxicity by inhibiting platelet aggregation and tumor
necrosis factor (Ozturk et al., 2004).
In summary, it should be emphasized that the
incidence of RP is low. A cautious approach should
be of paramount importance when the hepatopulmonary shunt fraction would result in a lung dose
exceeding 30 Gy (Murthy et al., 2005).
4.5 CORRELATION BETWEEN
99m
TC-MAA AND 90Y
RADIOEMBOLIZATION:
GENERAL DISCUSSION AND
OTHER CONSIDERATIONS
In the current practice of radioembolization, estimating the LSF plays a key role in preventing inadvertent RP. As previously discussed, determination
of LSF involves the use of
99m
Tc-MAA as a surrogate
for radioembolization in a separate planning procedure. e distribution of these particles within
the liver, however, is in large part currently ignored
in routine clinical practice. Although
99m
Tc-MAA
is trusted as a surrogate for 90Y microspheres in the
measurement of the LSF, its utility in the accurate
modeling of hepatic distribution of radioembolization has not been unequivocally demonstrated. In
this section, literature reviewing the accuracy of
99m
Tc-MAA as a surrogate for radioembolization
is reviewed, beginning rst with evaluation of LSF
with the use of MAA.
4.5.1 LSF EVALUATED USING
99m
TC-MAA
It is routine practice to inject
hepatic arterial branch 2–4 weeks before the injection of 90Y microspheres. Aer injection of
MAA, planar scintigraphy is routinely performed
and ROIs over the lungs and the liver are used
to measure LSF as previously described. In addition, SPECT/CT imaging of the upper abdomen is
employed at many sites to visually assess the distribution of particles in the liver and extrahepatic
99m
Tc-MAA into the
99m
Tc-
4.5 Correlation between
99m
Tc-MAA and 90Y radioembolization/ 4.5.2 Effect of ow dynamics 77
territory to ensure future safe delivery of 90Y radioactive microspheres.
LSF is know n to be higher for HCC than for other
tumors (8.0% vs. 6.3%; p = .048) (Olorunsola et al.,
2015). In one study, high LSF (>20%) occurred in
14% of HCC cases but in only 3% of other tumors
(p = .004) (Gaba et al., 2014). Colorectal cancer
(CRC) metastases (median LSF, 10.6%) and HCC
(11.7%) are known to have a signicantly larger
LSF than metastases from breast cancer (7.4%;
p < .005) (Powerski et al., 2015). Similar results
are reported through the literature, and we have
noticed consistency at our institution as well in
a retrospective review of 39 patients who underwent right lobe
99m
Tc-MAA injections (37 lobar, 2
segmental) before radioembolization for HCC at
the Cleveland Clinic. Among these patients, the
99m
mean
Tc-MAA LSF was 5.9% (SD, 0.03%; range,
0.5–12.1%), with no signicant dierence in LSF
among patients with (n = 7) or without (n = 32)
extrahepatic distribution of
99m
Tc-MAA.
In a study by Lambert et al. (2010), low-quality
whole-body scintigraphy images (dened as visualization of the kidneys when adequate scaling of
the whole-body scintigraphy image had to be performed to assess the liver) were correlated with a
higher LSF. e authors found that 14% of the 90
studies assessed were considered to be of low quality and suggested that LSF was overestimated in
this group.
In the vast majority of patients with primary or
secondary hepatic tumors, LSF measured by
99m
TcMAA is less than 20%. A small fraction of HCC
tumors is known to be associated with higher LSF
(Refaat and Hassan, 2014). In addition, quality of
the scintigraphy images has a signicant impact on
the measurement of LSF and a low-quality study
may result in overestimation of LSF.
4.5.2 EFFECT OF FLOW DYNAMICS
AND PARTICLE SIZE
Arterioles feeding liver metastases in humans
average 30–40 m in diameter. When owing
through arteries, particles concentrate in a periarteriolar fashion. Hence, the concentration of
particles entering a side branch will be lower than
the concentration in the main channel. In addition, smaller particles tend to reach the periphery
of the liver, whereas larger ones do not. In a study
on rats, the mean tumor to liver arterial perfusion
ratio (T:N) was 3:1 for 15- and 32.5-m spheres but
1:1 for 50-m microspheres (Van de Wiele et al.,
2012). Clearly, the size of the particles plays a key
role in their distribution within the liver and subsequent shunting away from the liver.
Two types of microspheres are currently available to perform radioembolization for the treatment of liver cancer: glass-based and resin-based
microspheres. Resin 90Y microspheres measure
approximately 32.5 ± 2.5 m in size, whereas the
glass-based 90Y microspheres measure approximately 25 ± 5 m. In addition, the total number
of spheres per GBq is approximately 20 million
for 90Y resin microspheres and only approximately
400,000 for 90Y glass microspheres (Cremonesi
et al., 2014). us, glass microspheres have a significantly higher amount of radioactivity per microsphere. As a result, for a similar radiation dose
90
Y resin microspheres are expected to be more
embolic than 90Y glass microspheres; however, this
depends on the prescribed radiation dose and the
size of the vascular bed in the liver that is to be
treated.
Compared with 90Y microspheres,
99m
Tc-MAA
particles infused in the planning stage have a
wider range of sizes (5–100 m), with 80%–90%
of the particles falling within the range of 10–70
m (Table 4.1, Zophel et al., 2009). e
99m
TcMAA particles undergo enzymatic hydrolysis
and are phagocytized by reticuloendothelial cells.
As opposed to 90Y microspheres, the radioactivity associated with a
99m
Tc-MAA dosage does not
necessary vary linearly with particle number. For
example, doubling the particle size will increase
the average radioactivity per particle by a factor of
4. erefore, a particle with a diameter of 40 m
will contain 16 times more radioactivity than a
particle with a diameter of 10 m (Van de Wiele
et al., 2012).
e heterogeneous composition of small
(<20m) and large (>60 m) particles with sig-
nicantly dierent radiation doses per particle
within a dose of
99m
Tc-MAA is likely to aect
imaged intrahepatic and extrahepatic distribution
and have an eect on shunt quantication imaging, since small particles are more likely to pass
through the hepatic capillary bed. is eect may
combine with the propensity of planar scintigraphy to overestimate LSF due to scatter and attenuation, previously discussed. In a study involving 23
78 Treatment planning part II
patients with primary and secondary liver malignancies,
99m
Tc-MAA scans were found to signicantly overestimate LSF when compared with gold
standard postradioembolization 90Y PET/CT scans
(6% vs. 1.8%; p < .01) (Song et al., 2015). In spite
of the more heterogeneous composition in a vial,
99m
Tc-MAA is still used universally as a simulation
surrogate for 90Y radioembolization.
4.5.3 CORRELATION BETWEEN
99m
DISTRIBUTION OF
TC-MAA
AND ABSORBED DOSE
In clinical practice, the distribution of
particles is expected to be similar to the distribution of 90Y microspheres, allowing the particles to
serve as a surrogate for the microspheres. However,
in several studies, the reliability of
a surrogate has been questioned. When prescribing the radiation dosage, one should understand
the signicant dierences in the characteristics of
99m
Tc-MAA and 90Y resin or glass microspheres,
including the size range of the particles/microspheres and the total number of particles/microspheres delivered. Presuming that
90
Y microspheres are delivered at the same site of
infusion in the liver, one can still expect a dierence in their distribution due to dierences in ow
kinetics. e physical properties of the injected
agent and blood ow pattern from the tip of the
catheter at the moment of infusion will dictate the
distribution kinetics of infused particles. is may
explain why procedures are rarely cancelled following suboptimal hepatic distribution of
MAA obtained in simulation.
A study cohort of 66 patients with a total of 435
colorectal liver metastases showed that response to
90
Y resin microspheres was independent of qualitative grading on the degree of pretreatment
MAA uptake in the tumor. Hence, patients could
not be excluded from radioembolization based on
99m
Tc-MAA distribution (Ulrich et al., 2013). In
response to subsequent questions raised about the
possibility of catheter position being an important
factor in these results, the authors later reported
additional results of a subgroup analysis in which
the catheter tip was placed in an identical position
for both
99m
Tc-MAA and 90Y microspheres (41 of
the original 66 patients); there was a similar lack of
correlation (p > .05) (Amthauer et al., 2014).
99m
Tc-MAA
99m
Tc-MAA as
99m
Tc-MAA and
99m
99m
Tc-
Tc-
However, in a study of 17 patients (14 with
HCC, 3 with CRC), Ho et al. (1996) found good
correlation between the doses estimated using the
partition model based on T:N and intraoperative
dosimetry in tumors (r = 0.862) and background
liver (r = 0.804). Ho et al. determined the T:N using
99m
Tc-MAA by dividing the average count rates of
the tumor by the average count rates of the normal
liver. is ratio can be used to estimate the activity of 90Y microspheres that would be partitioned
between the tumor and the normal liver compartment. If the activity delivered to the tumor can
be estimated, Equation 4.3 can then be employed
to determine the amount of 90Y microspheres
required to achieve a certain tumoricidal dose
or to keep below a tolerance limit of normal liver
tissue. Additional details on the utilization of the
partition model for hepatic dosimetry are provided
in Chapter 5. Unfortunately, this technique is not
commonly utilized in routine clinical practice.
As additional conicting evidence regarding
the validity of
99m
Tc-MAA as a radioembolization
surrogate is discussed below, one should keep in
mind that clinical measurement of T:N is likely
to vary substantially from patient to patient. is
variation is not necessarily indicative of inaccuracy
or error and has been shown in large patient studies (Ilhan et al., 2015a). In general, higher values
of T:N occur in cases of neuroendocrine tumors,
HCC, and cholangiocellular carcinoma, while
lower T:N commonly occurs in cases of mammary
cancer, CRC, and sarcoma.
4.5.3.1 Data suggesting the
99m
validity of
Tc-MAA as a
radioembolization surrogate
Ilhan et al. (2015b) compared the pattern of uptake
in dierent liver tu mors obtai ned using
SPECT with that of 90Y bremsstrahlung SPECT following radioembolization using 90Y resin microspheres. Among a cohort of 502 patients, 20% had
primary hepatic tumors (HCC, 12%; cholangiocellular carcinoma, 8%) and the remaining patients
had metastases from several dierent primary
tumors. e
99m
Tc-MAA and 90Y bremsstrahlung
images were coregistered with contrast-enhanced
CT or MR images. Analysis demonstrated that
lesions with high uptake on
99m
also had high uptake of 90Y microspheres. e
99m
Tc-MAA
Tc-MAA SPECT
4.5 Correlation between
99m
Tc-MAA and 90Y radioembolization/ 4.5.3 Correlation between distribution 79
correlation between
99m
Tc-MAA SPECT and 90Y
microsphere uptake was signicant but weak (r
=0.26; p <.001) (Ilhan et al., 2015b). Other authors
have performed similar analyses comparing
99m
TcMAA SPECT to posttreatment 90Y bremsstrahlung
SPECTwith ndings suggesting reasonable agreement (Knesaurek et al., 2010).
In Section 4.5.3.2, several reports suggesting
poor agreement between
99m
Tc-MAA and radioembolization will be reviewed. However, it is
important to note that agreement of spatial distribution may not be necessary for
99m
Tc-MAA to
serve as a valid tool for predictive hepatic dosimetry using the partition model. For example, Kao
et al. (2013) compared established 90Y PET/CT
to pretreatment
99m
Tc-MAA SPECT/CT in 23
patients treated using resin microspheres. Using
posttreatment 90Y PET/CT as the gold standard,
dosimetry based on MAA SPECT showed good
agreement with a median relative error of just
3.8% (max = 13.2%).
4.5.3.2 Data suggesting
99m
Tc-MAA
is a poor radioembolization
surrogate
Several examples from the literature have
reported a lack of correlation in the distribution
99m
of
Tc-MAA and 90Y radiomicrospheres within
the liver. In a study to assess the ability of
MAA to predict 90Y distribution in 39 patients
treated using 90Y resin microspheres, the predicted amount of 90Y activity in Couinaud liver
segments based on
99m
Tc-MAA SPECT was com-
pared with the actual amount of 90Y based on
90
Y bremsstrahlung SPECT. e absolute mean
dierence between the estimated and actual 90Y
absorbed dose was around 30 Gy, and a dierence
of more than 30% of the mean activity per milliliter was found in 32% of the 225 segments analyzed (Wondergem et al., 2013).
While data presented by Kao et al. (2013) supported the accuracy of MAA-based tumor predictive dosimetr y using 90Y PET/CT as a gold standard,
Song et al. (2015) have reported some discordance
in a 30 patient cohort. Tumor-absorbed dose estimated using
99m
Tc-MAA SPECT/CT was found to
be signicantly lower than that estimated using
90
Y PET/CT (135.4 ± 64.2 Gy vs. 185.0 ± 87.8 Gy;
p < .01). However, dierences in absorbed dose
99m
Tc-
determined to non-target liver were not statistically dierent.
For some of the discrepancies reported in
the distribution of
99m
Tc-MAA particles and 90Y
microspheres, dierences in the exact location
of the catheter tip at the time of delivery of these
materials may have played a role. is hypothesis
was examined by Jiang et al. (2012) by reviewing the perfusion dierences between 81 paired
99m
Tc-MAA hepatic SPECT and posttherapy 90Y
bremsstrahlung SPECT studies; corresponding
angiograms were also reviewed. When the catheter
tip was placed in proximity to an arterial bifurcation or a small branch, this seemed to alter microsphere perfusion or trajectory and was found to be
associated with mismatch (Jiang et al., 2012).
4.5.3.3 Other limitations of
99m
Tc-MAA simulation
Although the anatomical distribution of
MAA particles is considered a surrogate for the
distribution of 90Y microspheres, this technique
fails to quantify the functional aspect of the liver.
Lam et al. (2015) studied the role of intra- arterial
injection of
which was injected aer
99m
Tc-labeled sulfur colloid (SC),
99m
Tc-MAA-SPECT
in the same procedure as a biomarker for functional liver. e authors used the combined
information to study voxel-based partitioning
and dosimetry for subsequent 90Y radioembolization using resin microspheres in 98 patients
and glass microspheres in 24 patients. rough
a fusion of
99m
Tc-MAA SPECT and
images, the liver was divided into four compartments based on uptake (+) and lack of uptake
(–) of each tracer: tumor (
irradiated functional liver (
nonirradiated functional liver (
99m
Tc-MAA+, SC–);
99m
Tc-MAA+, SC+);
99m
SC+); and tumor necrosis, cysts, and major ves-
99m
sels (
Tc-MAA–, SC–). Independent of the
type of microspheres used, HCC had a higher
median tumor/median functional liver absorbed
dose ratio than other tumor types (median 1.8;
p = .02). e median tumor absorbed dose was
correlated with response in both univariate and
multivariate analyses, and the maximum change
in toxicity grade from baseline aer radioembolization was associated with the absorbed
dose in functional liver tissue (p < .0 5). W ith
99m
Tc-
99m
Tc-SC
Tc-MAA–,
80 Treatment planning part II
these results, Lam et al. (2015) demonstrated the
99m
potential use of
Tc-SC as a tracer that could
individualize the tolerance of background liver
in each patient, thereby allowing clinicians to
adjust the radioembolization dose to maximize
tumor response while minimizing the risk of
radioembolization-induced liver disease.
4.5.4 SUMMARY OF VALIDITY
99m
OF
Tc-MAA AS A
RADIOEMBOLIZATION
SURROGATE
Dierences between tracer distributions are likely
due to the dierences between
90
ticles and
Y microspheres. e number of 90Y
microspheres usually delivered is several orders
of magnitude higher than the number of
MAA particles delivered, which likely results in
an embolization eect and increases redistribution
into background liver, reducing the correlation in
measured T:N. Such a dierence might be higher
with resin microspheres than with glass microspheres due to the vast dierences in the number
of microspheres within a comparable prescribed
radiation dose (Table 4.1). In addition, catheter tip
position and changes in tumor vascularity (due to
tumor growth or histological changes) between the
planning and treatment angiograms might also
play a key role in the dierences between
90
MAA particle and
Y microsphere distribution.
Based on the results of several studies, we can
safely conclude that the distribution and tumor
99m
uptake of
Tc-MAA particles, which are currently
used as a surrogate agent, does not consistently
demonstrate equivalence with the distribution and
uptake of the therapeutic agent (
99m
e LSF measured by
Tc-MAA might be overestimated in some patients and it is therefore possible
that some patients may be unnecessarily excluded
from radioembolization. Hence,
its current form is not an ideal surrogate for
radioembolization.
To minimize this discordance, a tighter l-
99m
tration of
Tc-MAA particles to sizes that
more closely match the size range of
spheres might be considered. In addition, eorts
to increase the embolic burden of
to more closely approximate
99m
Tc-MAA par-
99m
99m
90
Y microspheres).
99m
Tc-MAA in
90
Y micro-
99m
90
Y microspheres
Tc-MAA
Tc-
Tc-
90
Y
may also be considered as a potential method to
improve concordance with radioembolization.
However, such a practice might result in decreased
T:N during treatment due to the pre-embolic eect
of MAA if treatment is performed before MAA
has been completely cleared. Unfortunately, the
time for complete clearance to occur, particularly
in the setting of highly variable neoplasm absent
of Kuper cells, is not known. MAA retention is
known to be prolonged when there is a reduction
in the number of Kuper cells (Tanaka et al., 1996;
Rimola et al., 1984 ; Bilzer et al., 2006).
4.6 ALTERNATIVES TO MAA IN
PROCEDURE SIMULATION
AND/OR PROGNOSTICATION
4.6.1 USEFULNESS OF
PREPROCEDURAL CT/MRI IN
PREDICTING LSF
Previous studies have suggested that pretreatment
hepatic protocol CT may have a role in prognostication of response to radioembolization in patients
with HCC. Tumor hypervascularity compared
with background liver and the amount of intratumoral blood ow estimated on CT has been
reported to correlate with disease response. In an
analysis of CT scans performed before and aer
glass microsphere radioembolization in 23 patients
with unresectable HCC, prolonged progressionfree survival was associated with lower LSF, higher
central tumor hypervascularity, and well-dened
tumor margins, whereas shorter progression-free
survival was associated with abutment of the portal vein by the tumor (Salem et al., 2013).
Morsbach et al. (2013) prospectively evaluated
the ability of CT perfusion to predict morphologic response and survival in 38 patients with
liver metastases who subsequently underwent
resin microsphere radioembolization; dose was
calculated using the BSA method. Five seconds
aer contrast material injection (50 mL of iopromide), 12 spiral acquisitions covering the liver were
obtained in the 4D spiral mode. Arterial perfusion
(AP) in target liver lesions was signicantly higher
in the responders than in the nonresponders (37.5
vs. 11.8 mL/min; p < .001). A cuto AP of 16 mL
90
Y
90
Y
4.6 Alternatives to MAA in procedure / 4.6.3 Is radioembolization without
99m
Tc-MAA 81
per 100 mL/min had a sensitivity of 100% and a
specicity of 89% for predicting therapy response.
In a single-center retrospective study of 70
patients with HCC, inltrative morphologic
structure, tumor burden greater than 50%, portal vein invasion, and arterioportal shunting
were signicantly associated with high (>20%)
LSF in multivariate analysis (Gaba et al., 2014).
Similarly, in a study using pretreatment multiphase CT, strong tumor contrast enhancement
was found to be associated with a signicantly
larger LSF than in tumors with little enhancement (11.7% vs. 8.3%; p < .001). In addition,
patients with compression (LSF = 13.9%) or
tumor thrombosis (15.8%) of a major portal
vein branch had a signicantly higher LSF than
patients with a normal portal vein (8.1%) (both p
< .001) (Powerski et al., 2015).
Finally, in a multivariate analysis of ndings
on CT (n = 134) or MRI (n = 18) among patients
with primary and secondary hepatic tumors, early
hepatic vein opacication and hepatic vein tumor
thrombus or occlusion were associated with a signicantly higher LSF. Sensitivity and specicity of
early hepatic vein opacication originating from
the tumor were 78% and 93%, respectively (positive
likelihood ratio, 10.5), for predicting high (>20%)
LSF (Olorunsola et al., 2015).
4.6.2 USEFULNESS OF C-ARM CBCT
IN ENHANCING SAFETY
With the ability of modern angiographic units to
acquire C-arm cone beam CT (CBCT) images,
multiplanar evaluation of the tumor, background
liver, and extrahepatic enhancement can now be
evaluated during planning angiography (Pellerin
et al., 2013). is technique has demonstrated
increased sensitivity in the detection of extrahepatic enhancement when compared with digital
subtraction angiography or
in a small cohort (Louie et al., 2009). A larger study
evaluated the utility of pretreatment CBCT to correctly identify the presence of extrahepatic NTE.
is eort found that CBCT prior to radioembolization was associated with a negative predictive
value for extrahepatic shunting of 95% (van den
Hoven et al., 2016). Despite these positive ndings,
there is no single standard C-arm CBCT protocol
in use. In an attempt to optimize a protocol for
99m
Tc-MAA imaging
identication of extrahepatic shunting and parenchymal enhancement in radioembolization, van
den Hoven et al. (2016) conducted a prospective
development study. e authors found that the
variable contrast and scan delay determined using
timing parenchymal enhancement on digital subtraction angiography were more eective than the
contrast and scan delay determined with a protocol that used either a xed 6-s delay and 10-s scan
or a 5-s low-dose scan setting applied to reduce
breathing artifacts in combination with a variable
delay (van den Hoven et al., 2016).
In the future, multispin/multiphase CBCT may
be used during planning to identify features associated with safe and favorable clinical outcomes
and to aid in modifying required 90Y dose activity. CBCT may also be used to predict high LSF
and tumor enhancement characteristics that are
unlikely to produce desired outcomes, thus allowing for modication of the treatment plan to other
forms of embolization in the same session.
4.6.3 IS RADIOEMBOLIZATION
WITHOUT
99m
TC-MAA
INJECTION FEASIBLE?
In a major proportion of patients who undergo
radioembolization, LSF is estimated to be signicantly less than 20%. As described in Sections
4.6.1 and 4.6.2, there are several ndings on CT/
MRI and pretreatment angiography that are associated with a high lung shunt. In addition, CBCT
is increasingly used during planning angiography, which has improved our ability to prevent
inadvertent extrahepatic uptake in the abdomen,
thus reducing our reliance on
imaging. Hence, obtaining such information
before injection of
99m
Tc-MAA might help clinicians to predict which patients are likely to have
a high LSF.
Among the most recent 39 patients at e
Cleveland Clinic to undergo treatment planning
99m
using
Tc-MAA injection for right lobe HCC, the
highest evaluate LSF was 12.1%. At this maximum
lung shunt, a radioembolization absorbed dose of
120 Gy to a typical right liver lobe measuring 1000
cc in volume would result in 17.1 Gy to the lungs,
well within aforementioned safety limits. Using a
predetermined target liver volume, a single-session
planning angiogram immediately followed by 90Y
99m
Tc-MAA SPECT
Соседние файлы в папке Библиотека им академика М.И. Перельмана