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302 The use of postprocedural imaging in the medical management of patients
Lhommel, R. et al. (2009). Yttrium-90 TOF PET
scan demonstrates high-resolution biodistribution after liver SIRT. Eur J Nucl Med Mol
Imaging 36:1696.
Mascarenhas, N., Ryu, R., Salem, R. (2011).
Hepatic radioembolization complicated by
abscess. Semin Intervent Radiol 28:222–225.
Miller, F.H. et al. (2007). Response of liver metas-
tases after treatment with yttrium-90 microspheres: Role of size, necrosis, and PET. AJR
Am J Roentgenol 188:776 –783.
Miller, A.B., Hoogstraten, B., Staquet, M.,
Winkler, A. (1981). Reporting results of cancer
treatment. Cancer 47:207–214.
Minocha, J., Lewandowski, R. (2011).
Radioembolization for hepatocellular carcinoma complicated by biliary stricture. Semin
Intervent Radiol 28:226–229.
Neperud, J. (2013). Can imaging patterns of
neuroendocrine hepatic metastases predict
response yttruim-90 radioembolotherapy?
WJR 5:241.
Northover, J.M., Terblanche, J. (1979). A new
look at the arterial supply of the bile duct in
man and its surgical implications. Br J Surg
66:379–384.
Pasciak, A.S. et al. (2015). The impact of an antire-
ux catheter on target volume particulate distribution in liver-directed embolotherapy: A
pilot study. J Vasc Interv Radiol. 26:660–669.
Piduru, S.M. et al. (2012). Prognostic value of
18f-uorodeoxyglucose positron emission
tomography-computed tomography in predicting survival in patients with unresectable
metastatic melanoma to the liver undergoing
yttrium-90 radioembolization. J Vasc Interv
Radiol 23:943–948.
Poon, R.T.-P., Fan, S.T., Tsang, F.H.-F., Wong, J.
(2002). Locoregional therapies for hepatocellular carcinoma: A critical review from the surgeon’s perspective. Ann Surg 235:466–486.
Reiner, C.S. et al. (2014). Early treatment
response evaluation after yttrium-90 radioembolization of liver malignancy with CT perfusion. J Vasc Interv Radiol 25:747–759.
Rhee, T.K. et al. (2008). Tumor response after
yttrium-90 radioembolization for hepatocellular carcinoma: Comparison of diffusionweighted functional MR imaging with
anatomic MR imaging. J Vasc Interv Radiol
19:118 0 –1186.
Riaz, A. (2014). Side effects of yttrium-90 radio-
embolization. Front Oncol 4:198.
Sacks, A. et al. (2011). Value of PET/CT in the
management of liver metastases, Part 1. Am J
Roentgenol 197:W256–W259.
Sag, A.A., Savin, M.A., Lal, N.R., Mehta, R.R.
(2014). Yttrium-90 radioembolization of malignant tumors of the liver: Gallbladder effects.
Am J Roentgenol 202:1130–113 5.
Salem, R. et al. (2002). Yttrium-90 microspheres:
Radiation therapy for unresectable liver cancer. J Vasc Interv Radiol 13:S223–S229.
Salem, R. et al. (2008). Incidence of radiation
pneumonitis after hepatic intra-arterial
radiotherapy with yttrium-90 microspheres
assuming uniform lung distribution. Am J Clin
Oncol 31:431–438.
Salem, R. et al. (2010). Radioem bolization for he pa-
tocellula r carcinoma usi ng yttriu m-90 microspheres: A comprehensive report of long-term
outcomes. Gastroenterology 138:52– 64.
Salem, M.E. et al. (2013a). Radiographic param-
eters in predicting outcome of patients
with hepatocellular carcinoma treated with
yttrium-90 microsphere radioembolization.
ISRN Oncol 2013:1–8.
Salem, R., Mazzaferro, V., Sangro, B. (2013b).
Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: Biological
lessons, current challenges, and clinical perspectives. Hepatology 58:2188–2197.
Salem, R., Thurston, K.G. (2006).
Radioembolization with 90yttrium microspheres: A state-of-the-art brachytherapy
treatment for primary and secondary
liver malignancies. J Vasc Interven Radiol
17:1251–1278.
Sangro, B. et al. (2006). Radioembolization using
90Y-resin microspheres for patients with
advanced hepatocellular carcinoma. Radiat
Oncol Biol 66:792–800.
Sangro, B. et al. (2008). Liver disease induced
by radioembolization of liver tumors:
Description and possible risk factors. Cancer
112:1538–1546.
Sato, K. et al. (2006). Treatment of unre-
sectable primary and metastatic liver
cancer with yttrium-90 microspheres
(TheraSphere®): Assessment of hepatic
arterial embolization. Cardiovasc Intervent
Radiol 29:522–529.
References 303
Schlaak, J. (2013). Choi criteria are superior in
evaluating tumor response in patients treated
with transarterial radioembolization for hepatocellular carcinoma. Oncol Lett 6:1707–1712.
Shim, J.H. et al. (2012). Which response criteria
best help predict survival of patients with
hepatocellular carcinoma following chemoembolization? A validation study of old and new
models. Radiology 262:708 –718.
Singh, P., Anil, G. (2013). Yttrium-90 radioemboli-
zation of liver tumors: What do the images tell
us? Cancer Imaging 13 :645– 6 57.
Smith, M.T., Johnson, D.T., Gipson, M.G. (2015).
Skin necrosis resulting from nontarget
embolization of the falciform artery during transarterial chemoembolization with
drug-eluting beads. Semin Intervent Radiol
32:22–25.
Smits, M.L.J. et al. (2013). Clinical and laboratory
toxicity after intra-arterial radioembolization with 90Y-microspheres for unresectable
liver metastases Aravindan N, ed. PLoS One
8:e69448.
Soydal, C. et al. (2013). The prognostic value of
quantitative parameters of 18F-FDG PET/CT
in the evaluation of response to internal radiation therapy with yttrium-90 in patients with
liver metastases of colorectal cancer. Nucl
Med Commun 34:501–506.
Strigari, L. et al. (2010). Efcacy and toxicity
related to treatment of hepatocellular carcinoma with 90Y-SIR spheres: Radiobiologic
considerations. J Nucl Med 51:1377–1385.
Thera sse, P. et al. (20 00). New guidelin es to evaluate
the resp onse to treatmen t in solid tumors .
European Organization for Research and
Treatment of Cancer, National Cancer Institute
of the Unite d States, National C ancer Insti tute of
Canada. J Natl Cancer Inst 92:205 –216.
Veloso, N. et al. (2013). Gastroduodenal ulcer-
ation following liver radioembolization with
yttrium-90. Endoscopy 45:E108–E109.
Vouche, M. et al. (2015). Clinical imaging. J Clin
Imaging 39:454–462.
Wang, L.M., Jani, A.R., Hill, E.J., Sharma, R.A.
(2013). Anatomical basis and histopathological changes resulting from selective internal
radiotherapy for liver metastases. J Clin
Pathol 6 6:205–211.
Willowson, K., Tapner, M., Bailey, D. (2015).
A multicentre comparison of quantitative
90Y PET/CT for dosimetric purposes after
radioembolization with resin microspheres.
Eur J Nucl Med Mol Imaging:1–21.
Wondergem, M. et al. (2013). 99mTc-mac-
roaggregated albumin poorly predicts
the intrahepatic distribution of 90Y resin
microspheres in hepatic radioembolization. J Nucl Med 54:1294–1301. Available at:
http://jnm.snmjournals.org/cgi/doi/10.2967/
jnumed.112.117614.
Wright, C.L. et al. (2012). Radiation pneumonitis
following yttrium-90 radioembolization: Case
report and literature review. J Vasc Interv
Radiol 23:669– 674.
Yu, J.-S. et al. (2002). Predisposing factors of
bile duct injury after transcatheter arterial chemoembolization (TACE) for hepatic
malignancy. Cardiovasc Intervent Radiol
25:270–274.
PART 5
New Horizons
15 Future directions in radioembolization 307
Alexander S. Pasciak, J. Mark McKinney, and Yong C. Bradley
15
Future directions in radioembolization
ALEXANDER S. PASCIAK, J. MARK MCKINNEY, AND YONG C. BRADLEY
15.1 Introduction 307
15.2 Background 308
15.3 Toward improved treatment
planning 309
15.4 Improving efcacy and safety 311
15.4.1 Enhancement of T:N 311
15.4.2 Alternative methods to
enhance tumor targeting 314
15.1 INTRODUCTION
From the perspective of medical physicists,
nuclear medicine radiologists, and radiation
oncologists involved in radioembolization, the
ideal direction of the future of this therapy may
appear dierent than it does to interventional
radiologists. is is primarily due to the dierences in the common procedures in which each of
these groups normally participate. Interventional
radiologists focus on procedures that, while technically demanding, normally do not involve the
physics, mathematics, or the related precision
commonly employed in radiation oncology and
nuclear medicine. Further, while the technical
considerations involved in a complex vascular
intervention necessitate careful review of pretreatment structural and angiographic imaging,
most nuclear medicine procedures are completely imaging based, focusing on both function
and structure to diagnose and treat the patient.
e distinction between these two groups and
the ownership that interventional radiologists
15.5 Toward improved posttreatment
imaging 315
15.5.1 New tracers and methods 315
15.5.2 Image analysis 316
15.6 Toward extrahepatic tumor
radioembolization 318
15.7 Conclusions 318
References 319
normally have over patients undergoing radioembolization therapy have largely driven the
radioembolization technical process in the
past. Evidence for this can be seen in Chapters
4 and5, where the manufacturer-recommended
treatment-planning methods for radioembolization are largely based on simple empiric calculations that are only patient specic at the simplest
level. For example, recall the specics of the
body surface area (BSA) model oen employed
for treatment planning using resin microspheres.
In this model, the impact of height and weight
on the prescribed dosage exceed the impact of
relative tumor burden. Additionally, the tumor
type, vascularity, prior treatment, homogeneity
of uptake, and any other patient-specic factors
are not considered. While BSA is widely used in
medicine for determining dosages for medications such as chemotherapy, it certainly makes
more sense for a systemic administration than
for a local brachytherapy such as radioembolization. It is for these reasons that many medical
physicists, nuclear medicine radiologists, and
radiation oncologists new to radioembolization
307
308 Future directions in radioembolization
nd themselves immediately frustrated with the
seeming lack of precision associated with the current standard of care in radioembolization treatment planning. It should be noted that this brief
discussion of the commonly employed BSA treatment planning method for resin microspheres is
not unique in its lack of tumor specicity—the
recommended method for glass microspheres is
even less tumor specic and does not account for
tumor burden at all. ose looking for a more
detailed review of these methods should refer to
Chapter 5.
While these treatment-planning methodologies
may be simplistic , radioembolization is st ill successful and benecial for many patients. Nevertheless,
improving the treatment-planning process for both
glass and resin microspheres is one way that the
future of radioembolization may be shaped. As the
subject of this text would suggest, radioembolization is an inherently multidisciplinary eld requiring not only an interventional radiologist but also
the skills of many other medical specialties. ere
are numerous necessary steps required to perform
a safe and eective radioembolization and with so
many potential hands involved, the task can sometimes seem overwhelming. While covered in some
detail in the previous chapters, a summary list of
tasks required and potential specialties involved
are shown below, with a particular focus on the
tasks necessary for the audience of this text.
●
Patient recruitment and selection (interven-
tional radiologist, oncologist)
●
Vascular treatment planning (interventional
radiologist)
●
Evaluating lung shunt fraction (interventional
radiologist, nuclear medicine radiologist)
●
Dosimetric treatment planning (nuclear medi-
cine radiologist, radiation oncologist, medical
physicist, interventional radiologist)
●
Safely preparing the radioembolization dosage
(technologist, radiopharmacy, medical physi-
cist, health physicist)
●
Preparing the angiographic suite (technologist,
health physicist)
●
Controlling entry and exit into the treatment
room (technologist, health physicist, medical
physicist)
●
Delivering the dosage (interventional
radiologist)
●
Determining delivered dose (medical physicist,
technologist)
●
Posttreatment yttrium-90 (90Y) imaging
(nuclear medicine radiologist, medical physicist, technologist)
●
Surveying and clearing radioactive contamination (technologist, health physicist)
●
Releasing the patient and providing release
instructions (health physicist, medical physicist, technologist)
●
Using posttreatment 90Y imaging to plan future
treatments (interventional radiologist, nuclear
medicine radiologist, radiation oncologist,
medical physicist)
In this chapter, we will discuss how the future
of radioembolization will be aected by improvements related to some of the above tasks. e
authors acknowledge that radioembolization is a
eld that has grown tremendously in recent years
but is still relatively young compared with alternative treatments for liver cancer.
15.2 BACKGROUND
e use of 90Y and other radionuclides with localized energy deposition in the percutaneous treatment of disease has a more lengthy history than
one might initially suspect. Before the widespread
use of hepatic radioembolization, simpler percutaneous procedures were being performed clinically for patients with chronic synovitis due, in
part, to hypertrophy of the synovial membrane.
Ansell etal. (1963) used a gold-198 (
loid percutaneously injected into the synovial
space to destroy the supercial luminal layers of
the synovial membrane. However, as this form of
therapy expanded, 90Y in various chemical forms
soon replaced
198
Au (Oka et al., 1971; Prosser et
al., 1993; Stucki et al., 1993; Asavatanabodee et
al., 1997; Jahangier et al., 1997; Taylor et al., 1997;
Jacob et al., 2003; Oztürk et al., 2008; omas
et al., 2011).
Radiation synovectomy using 90Y is a treatment that has seen some clinical use, particularly for chronic synovitis that is refractory to
traditional intra-articular steroid injections.
Treatment traditionally has been used for
198
Au) col-
15.3 Toward improved treatment planning 309
rheumatoid arthritis, osteoarthritis (Taylor et al.,
1997), psoriatic arthritis (Stucki et al., 1993), and
hemophilic arthritis (omas et al., 2011) unresponsive to systemic medical therapy. 5mCi of
90
Y silicate or 90Y resin-colloid injected into the
knee is capable of producing an absorbed dose in
the synovium at a depth of 1 mm exceeding 50
Gy (Oka et al., 1971). e goal of radiation synovectomy is to create brosis in the hypertrophic
areas of the synovium. 90Y has been used extensively for knees; however, for smaller joints, that
is, elbows and shoulders,
186
Re is preferred due
to the lower beta energy (Kavakli et al., 2008).
However, the downside of
186
Re is the gamma
component of the decay, which could result in
radiation dose to sensitive tissues near the injection site (e.g., lymph nodes).
Moving in the direction of endovascular
therapy, vascular disease, one of the most common diseases in the world, has also been treated
with internal emitters. Percutaneous transluminal angioplasty (PTA) is one of the most common treatments for vascular stenosis. However,
the durability of PTA is largely determined by
restenosis rates, which can be high. Prophylactic
endovascular brachytherapy (EVBT), as a preventative tool for restenosis due to intimal hyperplasia (Amols, 1999), has been used successfully for
a number of years with various radionuclides and
in various parts of the body (Minar, 2012). While
early uses of EVBT were based on iridium-192
192
(
Ir), a low-energy gamma emitter (Schopohl
et al., 1996; Reynaert et al., 2001; Piermattei
et al., 2002), some newer techniques use highenergy beta particles from phosphorus-32 (32P)
(Piermattei et al., 2003), rhenium-188 (
188
Re)
(Werner et al., 2012), strontium-90 (90Sr), or 90Y
(Coucke, 2009). e advantage of pure beta emitters is, of course, the markedly reduced radiation
safety concerns associated with the procedure.
However, despite clinical ecacy, the technical
diculty of EVBT has hindered its widespread
clinical use in favor of alternatives such as drugeluting stents for the management of restenosis.
Radioembolization also has a more lengthy
clinical history than one might initially expect.
Ariel and Padula (1978a, 1978b) in 1978 reported
the rst cases of the clinical use of 90Y microspheres in the intra-arterial treatment of colorectal metastases to the liver. Ariel combined
intra-arterial infusion of resin 90Y microspheres
with chemotherapy in the form of 5-uorouracil. Ariel’s patients received relatively large dosages of 90Y, ranging from 100 to 150 mCi (3.7–5.5
GBq) that led to improved response in their 65
patient cohort. Interestingly, Ariel infused 90Y
microspheres into these patients using both percutaneous delivery and delivery through open
laparotomy with a catheter inserted directly into
the hepatic artery. Since this initial experience,
the techniques and sophistication involved in
the manufacture and treatment with 90Y microspheres have tremendously improved.
e therapeutic percutaneous uses of endovas-
cular brachytherapy and radioembolization using
90
Y and other radionuclides have lengthy and interesting histories. However, this chapter will look to
the future of radioembolization.
15.3 TOWARD IMPROVED
TREATMENT PLANNING
Treatment planning in 90Y radioembolization
lacks much of the detail and patient specicity
required for external beam radiation therapy.
is is logical since there is an element of control in external beam radiation therapy and even
in conventional brachytherapy that is lacking
in radioembolization—namely, physical ow
dynamics that determine the nal location of the
microspheres. While this process cannot be controlled, it can be predicted to a limited extent.
As discussed extensively in Chapters 4 and 5,
technetium-99m (
min (MAA) single-photon emission computed
tomography/computed tomography (SPECT/CT)
can be used as a standard component of treatment
planning using the partition model. Many authors
have examined the validity of MAA as a radioembolization surrogate, with no clear consensus
(Knesaurek et al., 2010; Kao et al., 2012; Lam and
Smits, 2013; Lam et al., 2013; Wondergem et al.,
2013; Garin et al., 2014; Lam and Sze, 2014) as to
its accuracy in the modeling of hepatic distribution. e position of the catheter tip during both
infusion of MAA and radioembolization is among
the most critical factors to the prognostic utility of
tumor to normal uptake ratio (T:N) measurements
99m
Tc)-macroaggregated albu-
310 Future directions in radioembolization
made from
99m
Tc-MAA SPECT/CT. Positioning of
the catheter tip becomes especially critical when
it is near a bifurcation or when it is positioned in
a tortuous vessel (Jiang et al., 2012; Wondergem
etal., 2013). However, in spite of variable correlation between MAA and 90Y microspheres in the
literature, many authors agree that MAA is an
excellent option for treatment planning and predictive dosimetry. is has been discussed in detail
in Chapters 4 through 6.
e use of
99m
Tc-MAA as a treatment- planning
guide certainly has potential utility in the prognostication of lung shunt fraction, intrahepatic
dose distribution, and presence of gastroduodenal
nontarget embolization (NTE). Due to a handful
of publications describing the diculty of managing patients with ulcerations from gastroduodenal NTE, the majority of radioembolization
treatment centers carefully examine post-MAA
nuclear imaging to look for the presence of NTE.
However, the majority of treatment centers perform only planar imaging of
99m
Tc-MAA, as this
is the most common method used to determine
the lung shunt fraction and is recommended in
the package insert for both resin and glass 90Y
microspheres. Many institutions can improve
both the sensitivity and specicity of
99m
TcMAA for the determination of NTE with several simple protocol modications. As discussed
in Chapter 14, there is a substantial increase in
the prognostic utility of MAA as a predictor for
extrahepatic NTE with the use of SPECT/CT
compared with planar imaging. A detailed study
by Ahmadzadehfar et al. (2010) suggested that
the relative sensitivity of detecting extrahepatic
NTE increased from 32% to 100% when SPECT/
CT was used compared with planar imaging. at
said, however, an increase in sensitivity may lead
to exclusion of patients from treatment owing to
false positives, such as free technetium. In Chapter
4, there is a detailed discussion of the biological
half-life of MAA, binding eciency, and eects of
free
99m
(
99m
TcO
Tc. Free
4
99m
–
) will show a strong uptake in the gas-
Tc in the form of pertechnetate
tric mucosa, potentially leading to false positives
when MAA is used to assess NTE. Standard of
care prophylaxis should include oral administration of sodium perchlorate (NaClO4) as a blocking
agent to prevent the uptake of
99m
TcO
–
in gastro-
4
duodenal tissues. Sodium perchlorate has been
shown to substantially increase the specicity of
99m
Tc-MAA as a tool for prognostication of gas-
troduodenal NTE (Sabet et al., 2011).
Stepping away from the standard of care
99m
TcMAA for evaluating lung shunt fraction and treatment simulation, there have been several attempts
to identify alternative tracers that can be applied to
this purpose. Mathias and Green (2008) described
a simple method for the production of gallium-68
(68Ga) MAA from the elutant of a conventional
germanium-68/68Ga generator. e size range of
MAA did not change with the binding of 68Ga and
binding eciency exceeded 99% (Mathias and
Green, 2008). 68Ga is a convenient positron emission tomography (PET) radiotracer that provides
fully quantitative imaging with a superior resolu-
99m
tion to
Tc SPECT. 68Ga MAA may have utility in
conventional pulmonary perfusion studies, evaluation of lung shunt fraction for radioembolization,
and, potentially, improved intrahepatic treatment
planning given the improved resolution and quantication of PET/CT.
It is likely, however, that the largest source
of error in the use of
99m
Tc-MAA as a 90Y microsphere surrogate is in particulate deposition differences rather than SPECT resolution limits.
erefore, the greatest advances in pretreatment
simulation may come from replacing MAA with
a superior particle, rather than identication of a
radionuclide with superior imaging characteristics
99m
to
Tc. Biodegradable human serum albumin
(HSA) microspheres have been proposed for use
in pulmonary perfusion studies labeled with
99m
Tc
or 86Y. HSA microspheres have also been proposed
as an alternative form of radioembolization when
labeled with
188
Re or 90Y (Schiller et al., 2008). A
potential benet of HSA microspheres over MAA
is that the size and surface characteristics of the
microsphere much more closely approximate
those of 90Y microspheres, as shown in Figure 1 of
Schiller et al. (2008). Naturally, the specic gravity
of an HSA microsphere will also closely approximate that of 90Y resin microspheres. As a tool for
pretreatment simulation, the biodegradability of
HSA microspheres has a favorable characteristic
since it may be degraded and removed from the
hepatic vasculature prior to 90Y radioembolization.
Currently, there are multiple clinical trials underway to evaluate the utility of alternative microspheres for pretreatment planning,
both in biodegradable and permanent physical form. Potential imaging modalities for these
15.4 Improving efcacy and safety / 15.4.1 Enhancement of T:N 311
/
/
Y,normal
normal
AV
AV
Y,tumor
A
Y,normal
A
microspheres primarily include SPECT or PET,
but in some cases have extended to magnetic
resonance imaging (MRI). Holmium-166 (
166
Ho)
microspheres (Quiremspheres, Quirem Medical,
e Netherlands) are relatively unique in radioembolization for their multimodality imaging
and therapy potential.
166
Ho decays with the emission of a two medium-energy beta particles at a
high yield with average energies of 654 and 691
166
keV.
Ho also emits an 80 keV gamma ray with a
lower yield (approximately 6.5 per 100 transformations) that can be eectively imaged using SPECT.
Finally, Holmium is strongly paramagnetic, resulting in convenient visualization using MRI with
high contrast and resolution. Examples of direct
imaging of
166
Ho by both MRI and SPECT are
shown in Figure 1.1, in Chapter 1. e clinical pro-
tocol for
166
Ho radioembolization takes advantage
of multimodality imaging and includes pretreatment infusion of a low-activity dosage of
166
Ho
radioembolization as a tool for treatment planning
and evaluation of lung shunt fraction via nuclear
imaging. is process eliminates MAA altogether
166
in the
Ho radioembolization treatment process.
Many current and previous investigations have
focused on improving pretreatment imaging and
simulation for radioembolization in an eort
to improve treatment planning. However, while
these tools can help to predict tumor and normal
liver tissue absorbed doses, this is just part of the
treatment-planning equation. Patient-specic
treatment planning also requires a precise knowledge of tumoricidal dose thresholds, which will
vary at a minimum on tumor type, size, vascularity, previous therapy, and use of glass or resin
microspheres. e diculty of obtaining these
data has been compounded in the past by the limited availability of postradioembolization quantitative imaging; however, some excellent sources
do exist particularly for hepatocellular carcinoma
(HCC) (Strigari et al., 2010). Going forward, the
discovery of 90Y PET/CT will open up the door to
precisely dening toxicity thresholds for radioembolization. An international clinical trial sponsored by SIRTeX medical (SIR-Spheres®, SIRTex
Technology Pty, Lane Cove, NSW, Australia) will
use postradioembolization 90Y PET/CT to elucidate dose–response thresholds based on tumor
type for metastatic breast and colon cancer. Some
initial data from this eort have already been published (Willowson et al., 2015).
15.4 IMPROVING EFFICACY
AND SAFETY
15.4.1 ENHANCEMENT OF T:N
As discussed in detail in Chapters 5 and 8, the success of radioembolization depends on delivering
sucient dosage to the tumor to elicit a therapeutic response while sparing uninvolved liver tissue from excessive toxicity. In conventional lobar
therapy, it is the T:N that in many ways will dene
the balance between sucient absorbed dose to the
tumor and limitation of dose to normal liver tissue.
T:N is dened in Equation 15.1:
90
where,
is the 90Y activity (MBq) deposited
90
in the tumor and
Y,tumor
90
90
ited in uninvolved liver tissue. V
are the respective volumes of each. Tumor type,
size, burden, prior treatments, and other patientspecic physiological factors signicantly aect
T:N, leading to a range of clinical values which
can vary from nearly 15:1 to less than 1. Table5.2
in Chapter 5 lists some typical T:N values from
the literature. While there are many factors in
addition to T:N that determine the success or failure of a radioembolic therapy, lower T:Ns make a
robust clinical response dicult to achieve. e
premise behind the diculty of successful radioembolization in the setting of a low T:N (<2:1)
can be linked back to the fundamental fallacy of
treating liver cancer with external beam radiation
therapy: the radiation toxicity threshold for uninvolved liver tissue is low—potentially lower than
the absorbed dose necessary for eective tumor
control.
Several methods of prophylactically increasing T:N are available and may improve ecacy in
certain classes of patients receiving lobar therapy.
Patients with low T:N (<2:1), or patients with moderate T:N (<3:1) in the setting of underlying liver
disease and/or tumors that require large absorbed
doses, may benet from these techniques. Both
pharmaceutical and physical techniques can be
used to prophylactically increase T:N prior to
radioembolization in patients who fall into either
of these categories.
tumor
(15.1)
is the activity depos-
and V
normal
tumor
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