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DOI: 10.1148/rg.281065721
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RadioGraphics 2008;28:81-99
© RSNA, 2008

EDUCATION EXHIBIT

Multimodality Imaging Following 90Y Radioembolization: A Comprehensive Review and Pictorial Essay1

Bassel Atassi, MD, Affaan K. Bangash, DO, Ammar Bahrani, BS, Giuseppi Pizzi, MD, Robert J. Lewandowski, MD, Robert K. Ryu, MD, Kent T. Sato, MD, Vanessa L. Gates, MS, Mary F. Mulcahy, MD, Laura Kulik, MD, Frank Miller, MD, Vahid Yaghmai, MD, Ravi Murthy, MD, Andrew Larson, PhD, Reed A. Omary, MD, MS, and Riad Salem, MD, MBA

1 From the Department of Radiology, Section of Interventional Radiology (B.A., A.K.B., A.B., R.J.L., R.K.R., K.T.S., V.L.G., F.M., V.Y., A.L., R.A.O., R.S.), and the Department of Medicine (L.K.), Division of Hematology and Oncology (M.F.M.), Robert H. Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, 676 N St Clair, Suite 800, Chicago, IL 60611; Department of Diagnostic and Interventional Radiology, Istituto Regina Elena, National Cancer Institute, Rome, Italy (G.P.); and Division of Diagnostic Imaging, Section of Interventional Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, Tex (R.M.). Received July 14, 2006; revision requested August 31; final revision received July 31, 2007; accepted July 31. M.F.M. received a research grant from MDS Nordion; R.M. received a research grant from Sirtex Medical; R.S. received a research grant from and is a consultant with MDS Nordion; all other authors have no financial relationships to disclose. Address correspondence to R.S. (e-mail: r-salem{at}northwestern.edu).


   Abstract
Top
 Abstract
Introduction
 Technical Considerations
 Criteria for the Assessment...
 Other Posttherapy Findings
 Complications
 Discussion
 Conclusions
 References
 
Radioembolization with yttrium 90 (90Y) microspheres represents an emerging transarterial therapy for the treatment of liver malignancies that continues to generate interest in the medical community. The classic indication of treatment response is a reduction in tumor size; however, parenchymal changes (eg, necrosis, lack of enhancement, specific findings at positron emission tomography and functional magnetic resonance imaging) and other benign findings (pleural effusions, perivascular edema, contralateral hypertrophy, ring enhancement, perihepatic fluid, fibrosis) may occur following treatment, requiring proper image interpretation. With classic imaging findings and surrogates (time to progression, duration of response, disease-free interval), response rates range from 20% to 80% in patients treated for hepatocellular carcinoma or metastatic disease to the liver. Complications of 90Y radioembolization include cholecystitis, abscess, and bilomas and should be recognized early in the imaging follow-up of these patients. Radiologists who are involved in the posttreatment assessment of patients undergoing 90Y radioembolization should be familiar with the imaging findings and potential imaging pitfalls associated with this therapy.

© RSNA, 2008


   Introduction
Top
 Abstract
 Introduction
Technical Considerations
 Criteria for the Assessment...
 Other Posttherapy Findings
 Complications
 Discussion
 Conclusions
 References
 
The prognosis for both primary and metastatic liver cancer is generally poor. Therapeutic modalities for primary and metastatic solid tumors of the liver have been evaluated in numerous randomized control trials (1,2). To date, the only potentially curative measure has been surgical resection. Unfortunately, the extent and pattern of liver involvement, advanced cirrhosis or portal vein invasion, and metastatic disease from various primary tumors exclude the majority of patients from curative surgical resection.

Over the past 2 decades, studies have been conducted to evaluate the benefits of several treatment modalities, including surgical (tumor resection, transplantation), percutaneous (ethanol injections, radiofrequency ablation, cryoablation), and transarterial interventions. Until recently, arterial options for the treatment of hepatic malignancy have been for the most part limited to transarterial chemoembolization (TACE) or bland particle embolization (3). Over the past several years, a new form of embolotherapy has been developed (4–11). This treatment is known as radioembolization and involves the transarterial administration of micron-sized radioactive particles featuring yttrium 90 (90Y), a pure beta emitter. Once these particles lodge in the arterioles, they impart a very intense local radiotherapeutic effect (4,5,12–16), with the 90Y penetrating an area of tissue approximately 1 cm in diameter before decaying to inactive zirconium 90. The infusion of microspheres containing 90Y into the hepatic artery allows the administration of 125–150 Gy to specific target areas of the liver, with tumors receiving well over 150 Gy (17). 90Y microspheres (TheraSphere: MDS Nordion, Ottawa, Ontario, Canada; SIR-Spheres: Sirtex Medical, Lane Cove, Australia) deliver internal radiation directly to tumors, which constitutes a form of brachytherapy when delivery is via the hepatic artery. These microspheres range from 20 to 60 µm in diameter and differ in terms of the relationship of the 90Y to the carrier. The radioactive element 90Y is either directly bound to the resin (SIR-Spheres) or an integral constituent of the glass (TheraSphere). The predominance of arterial (as opposed to portal venous) blood supply to hepatic tumors allows the preferential deposition of microspheres in the tumors rather than the normal parenchyma, thereby maximizing tumor irradiation (18).

Radioembolization is unlike any other therapy applied in the liver (eg, radiofrequency ablation and transarterial chemoembolization, in which heat and ischemic principles apply, respectively). Consequently, given the combination of radiation and embolization, the imaging findings differ significantly from those seen with other therapies, thereby mandating further investigation. As a result, without a complete understanding of the expected imaging findings, the use of standard clinical and radiologic follow-up in these patients may be inaccurate (19).

Patient selection criteria for radioembolization include (a) unresectable hepatocellular carcinoma or chemorefractory liver-dominant metastases, (b) nonsurgical candidate, (c) the presence of Eastern Cooperative Oncology Group stage 0–2, (d) noncompromised pulmonary function, (e) the ability to undergo angiography and selective visceral catheterization, (f) adequate hematologic findings (granulocyte count ≥1.5 x109/L, platelet count ≥50 x109/L) and renal function (creatinine level ≤2.0 mg/dL), and (g) adequate liver function (bilirubin level ≤2.0 mg/dL). Exclusion criteria include (a) significant extrahepatic disease (life expectancy <3 months), (b) evidence of uncorrectable flow to the gastrointestinal tract observed at angiography or technetium-99m macroaggregated albumin scintigraphy, and (c) more than 30 Gy (16.5 mCi) estimated to be delivered to the lungs in a single dose or more than 50 Gy in multiple doses (15). Given the promising outcomes and good quality of life following treatment, radioembolization is now replacing TACE in some centers as the first-line therapy in selected patients with unresectable hepatocellular carcinoma (8,20,21). Furthermore, given the controversial outcomes of TACE for metastatic colorectal cancer to the liver, radioembolization is now being applied clinically in these settings (22,23).

In a manner analogous to patients’ receiving systemic therapeutic agents, response following radioembolization should be assessed with anatomic imaging (computed tomography [CT], conventional magnetic resonance [MR] imaging) performed at 2–3-month intervals, functional imaging (positron emission tomography [PET], diffusion-weighted MR imaging), and biologic markers (eg, {alpha}-fetoprotein, carcinoembryonic antigen [CEA], CA 19-9).

The imaging findings in 130 of 137 patients with metastatic disease to the liver (332 target lesions) who were treated with 90Y glass microspheres were reviewed by two board-certified radiologists (follow-up imaging data were not available for seven patients) (Table 1). To our knowledge, the study described in this article represents the first comprehensive review of the imaging findings that are encountered following treatment with this novel therapy. In this article, we review the technical considerations in 90Y radioembolization and discuss criteria for the assessment of response (decrease in tumor size, necrosis, angiographic avascularity, imaging complete response, metabolic activity at fluorine 18 fluorodeoxyglucose [FDG] PET, tumor volume reduction, tumor marker reduction, increased water diffusion) (Table 2). In addition, we discuss and illustrate other posttherapy findings (peritumoral edema and hemorrhage; ring enhancement; hypertrophy; transient perivascular edema; capsular retraction, hepatic fibrosis, and portal hypertension; perihepatic fluid and pleural effusion) as well as possible complications (hepatic abscess, biliary dyskinesia and radiation-induced cholecystitis, biloma and biliary necrosis, radiation hepatitis, gastrointestinal ulceration) (Table 3). Table 4 summarizes the primary malignancies in all 137 patients with metastatic liver disease.


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  		Table 1. Characteristics of Follow-up Imaging in 130 Patients

 

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  		Table 2. Tumor Response at Imaging in 130 Patients with 332 Lesions

 

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  		Table 3. Imaging Complications in 130 Patients

 

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  		Table 4. Primary Malignancies in 137 Patients with Metastatic Liver Disease

 

   Technical Considerations
Top
 Abstract
 Introduction
 Technical Considerations
Criteria for the Assessment...
 Other Posttherapy Findings
 Complications
 Discussion
 Conclusions
 References
 
Once a patient has been selected as a candidate for radioembolization, mesenteric angiography must be performed. The proper sequence in which vessels are to be evaluated has been published previously (24,25). This evaluation is performed primarily to document the visceral anatomy, identify anatomic variants, and isolate the hepatic circulation by occluding extrahepatic vessels (26) and includes abdominal aortography followed by selective visceral angiography. Superior mesenteric arteriography is performed to assess for the presence of accessory or replaced hepatic arteries. Venous phase imaging (usually cross-sectional imaging) is also performed to evaluate the status and patency of the portal vein. The celiac trunk is selectively catheterized to evaluate the hepatic arterial supply of the tumors. Right and left hepatic angiography is performed to identify variant mesenteric anatomy and to prompt subsequent prophylactic embolization of extrahepatic (eg, right gastric, gastroduodenal) vessels. Treatment is usually performed with microcatheters on a lobar basis, with microsphere infusion proceeding at flow rates similar to that of the native hepatic artery. Follow-up imaging and treatment of the second lobe are usually performed 30–60 days later and at regular 3-month intervals thereafter.


   Criteria for the Assessment of Response
Top
 Abstract
 Introduction
 Technical Considerations
 Criteria for the Assessment...
Other Posttherapy Findings
 Complications
 Discussion
 Conclusions
 References
 
Methods for assessing response following oncologic therapies continue to evolve. Although tumor size remains the standard of reference, surrogates for assessing response and treatment effect have been adopted. These surrogates include time to progression, duration of response, and disease-free interval. However, with the advent of localized therapies and cytostatic (as opposed to cytotoxic) biologics, methods for assessing therapeutic effect must be refined. For radioembolization, which is an intraarterially based radiation therapy, response may be evaluated on the basis of standard size criteria as well as other novel surrogates. The latter include necrosis, angiographic avascularity, tumor disappearance, reduced metabolic activity at FDG PET, tumor volume reduction, tumor marker reduction, and increased water diffusion at diffusion-weighted MR imaging. All of these criteria are discussed in the following sections.

Decrease in Tumor Size
In our study, treatment efficacy was evaluated with use of the World Health Organization (WHO) criteria (27). Tumor response was determined at CT for all measurable lesions (>1 cm), in which pre- and posttreatment cross products were calculated by multiplying the maximum diameter by the maximum perpendicular dimension. For multiple lesions, the sums of the pre-and posttreatment cross products in individual lesions were compared. Partial response was defined as a greater than 50% reduction in cross product, complete response as complete disappearance of the tumor, and disease progression as a greater than 25% increase in cross product. Lesions that did not meet any of these criteria were categorized as stable disease (27,28). A decrease in tumor size is the characteristic imaging finding in tumors following effective treatment for cancer (27). Similarly, with radioembolization, a decrease in tumor size represents a response to treatment (Fig 1). In our study, partial or complete response was seen in 42.8% of cases on the basis of size criteria.


Figure 1A
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  		Figure 1a.  Decrease in tumor size. (a) Gadolinium-enhanced fat-suppressed portal venous phase T1-weighted MR image shows a poorly enhanced, inhomogeneous nodule with a thin enhancing ring in segment VI of the liver. The lesion measured 7.5 cm prior to radioembolization. (b) Portal venous phase CT scan obtained 12 months after treatment of the right lobe shows an interval decrease of nearly 75% (to 1.9 cm) in the size of the lesion, a finding that should be interpreted as a treatment response. Note the hypertrophic left lobe.

 

Figure 1B
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  		Figure 1b.  Decrease in tumor size. (a) Gadolinium-enhanced fat-suppressed portal venous phase T1-weighted MR image shows a poorly enhanced, inhomogeneous nodule with a thin enhancing ring in segment VI of the liver. The lesion measured 7.5 cm prior to radioembolization. (b) Portal venous phase CT scan obtained 12 months after treatment of the right lobe shows an interval decrease of nearly 75% (to 1.9 cm) in the size of the lesion, a finding that should be interpreted as a treatment response. Note the hypertrophic left lobe.

 
Necrosis
Ablative type therapies such as radiofrequency ablation and percutaneous ethanol ablation create an area of coagulative necrosis and relative avascularity with variable reduction in tumor size (29–31). This postablation finding of necrosis and avascularity, previously endorsed as a measure of treatment response, also occurs following radioembolization (Fig 2) (7,10,19,31–33). The high doses of radiation delivered directly to the tumor provide a lethal insult to the cancer cells, destroying the vasculature and resulting in cell death and tumor necrosis. In our study, a response rate of 75.4% was achieved when necrosis was used as a criterion.


Figure 2A
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  		Figure 2a.  Necrosis. (a) MR image demonstrates a tumor in the right hepatic lobe (arrow). (b) Posttreatment MR image shows a slight decrease in tumor size but significant necrosis (arrow). Tumor marker decreased by 99%.

 

Figure 2B
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  		Figure 2b.  Necrosis. (a) MR image demonstrates a tumor in the right hepatic lobe (arrow). (b) Posttreatment MR image shows a slight decrease in tumor size but significant necrosis (arrow). Tumor marker decreased by 99%.

 
Angiographic Complete Response
Prior to undergoing therapy with 90Y microspheres, all patients undergo baseline angiography to evaluate the hepatic vasculature and to identify any aberrant or collateral vessels. When anatomic variants are present, infusion techniques must be tailored to ensure safe and accurate delivery of 90Y microspheres to the target tumors (15,19). Given that 90Y microspheres are delivered via the hepatic vasculature with preferential flow into the tumor, it is possible for the malignant vasculature to become obliterated with preservation of normal parenchymal flow. Elimination of vascularity is a clinical endpoint that is routinely used in the follow-up of TACE patients. The same principle applies to radioembolization (Fig 3).


Figure 3A
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  		Figure 3a.  Angiographic complete response. (a) Superselective digital subtraction angiogram of a left hepatic artery branch supplying segment III of the liver shows a hypervascular lesion. (b) Angiogram obtained 45 days following treatment shows complete absence of the vessels supplying the lesion and preservation of hepatic parenchymal flow. (c) Pretreatment CT scan shows an enhancing neuroendocrine lesion in segment III (arrow). (d) Posttreatment CT scan shows an area of necrosis and nonenhancement, but with obliteration of the hepatic vasculature (arrow). Although angiographically these findings represent a complete response, they represent a partial response according to cross-sectional imaging size criteria.

 

Figure 3B
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  		Figure 3b.  Angiographic complete response. (a) Superselective digital subtraction angiogram of a left hepatic artery branch supplying segment III of the liver shows a hypervascular lesion. (b) Angiogram obtained 45 days following treatment shows complete absence of the vessels supplying the lesion and preservation of hepatic parenchymal flow. (c) Pretreatment CT scan shows an enhancing neuroendocrine lesion in segment III (arrow). (d) Posttreatment CT scan shows an area of necrosis and nonenhancement, but with obliteration of the hepatic vasculature (arrow). Although angiographically these findings represent a complete response, they represent a partial response according to cross-sectional imaging size criteria.

 

Figure 3C
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  		Figure 3c.  Angiographic complete response. (a) Superselective digital subtraction angiogram of a left hepatic artery branch supplying segment III of the liver shows a hypervascular lesion. (b) Angiogram obtained 45 days following treatment shows complete absence of the vessels supplying the lesion and preservation of hepatic parenchymal flow. (c) Pretreatment CT scan shows an enhancing neuroendocrine lesion in segment III (arrow). (d) Posttreatment CT scan shows an area of necrosis and nonenhancement, but with obliteration of the hepatic vasculature (arrow). Although angiographically these findings represent a complete response, they represent a partial response according to cross-sectional imaging size criteria.

 

Figure 3D
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  		Figure 3d.  Angiographic complete response. (a) Superselective digital subtraction angiogram of a left hepatic artery branch supplying segment III of the liver shows a hypervascular lesion. (b) Angiogram obtained 45 days following treatment shows complete absence of the vessels supplying the lesion and preservation of hepatic parenchymal flow. (c) Pretreatment CT scan shows an enhancing neuroendocrine lesion in segment III (arrow). (d) Posttreatment CT scan shows an area of necrosis and nonenhancement, but with obliteration of the hepatic vasculature (arrow). Although angiographically these findings represent a complete response, they represent a partial response according to cross-sectional imaging size criteria.

 
Imaging Complete Response
Although uncommon, complete disappearance of tumor following radioembolization may occasionally be seen (Fig 4).


Figure 4A
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  		Figure 4a.  Imaging complete response. (a) Gadolinium-enhanced fat-suppressed T1-weighted MR image shows a well-defined tumor in the left hepatic lobe (arrow). (b) Gadolinium-enhanced fat-suppressed T1-weighted MR image obtained 6 months after 90Y treatment shows complete response (ie, disappearance of the tumor) (arrow).

 

Figure 4B
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  		Figure 4b.  Imaging complete response. (a) Gadolinium-enhanced fat-suppressed T1-weighted MR image shows a well-defined tumor in the left hepatic lobe (arrow). (b) Gadolinium-enhanced fat-suppressed T1-weighted MR image obtained 6 months after 90Y treatment shows complete response (ie, disappearance of the tumor) (arrow).

 
Metabolic Activity at FDG PET
Functional imaging with PET provides diagnostic information based on the metabolic activity of malignant tissue. The utility of PET with radioembolization has been described by previous investigators, who demonstrated that PET provides enhanced tumor response data compared with cross-sectional anatomic imaging (CT, MR imaging) (34,35). This is consistent with the standard oncologic practice of using PET for follow-up of treated patients with lymphoma (36) or gastrointestinal stromal tumors (37). Recent studies suggest that the conventional treatment of patients with colorectal cancer has changed due to the capacity of PET to help detect recurrent or metastatic lesions more accurately than CT (22,38). The same is true with radioembolization (Fig 5).


Figure 5A
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  		Figure 5a.  Use of PET to measure treatment response. (a) Pretreatment contrast-enhanced CT scan of the liver shows a right lobe tumor. (b) Contrast-enhanced CT scan obtained 3 months after radioembolization shows only minimal response according to imaging criteria. (c) Pretreatment whole-body PET scan shows increased radiotracer uptake in the right hepatic lobe. (d) Whole-body PET scan obtained 3 months after treatment shows uniform normal activity throughout the liver, a finding that represents near-complete response.

 

Figure 5B
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  		Figure 5b.  Use of PET to measure treatment response. (a) Pretreatment contrast-enhanced CT scan of the liver shows a right lobe tumor. (b) Contrast-enhanced CT scan obtained 3 months after radioembolization shows only minimal response according to imaging criteria. (c) Pretreatment whole-body PET scan shows increased radiotracer uptake in the right hepatic lobe. (d) Whole-body PET scan obtained 3 months after treatment shows uniform normal activity throughout the liver, a finding that represents near-complete response.

 

Figure 5C
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  		Figure 5c.  Use of PET to measure treatment response. (a) Pretreatment contrast-enhanced CT scan of the liver shows a right lobe tumor. (b) Contrast-enhanced CT scan obtained 3 months after radioembolization shows only minimal response according to imaging criteria. (c) Pretreatment whole-body PET scan shows increased radiotracer uptake in the right hepatic lobe. (d) Whole-body PET scan obtained 3 months after treatment shows uniform normal activity throughout the liver, a finding that represents near-complete response.

 

Figure 5D
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  		Figure 5d.  Use of PET to measure treatment response. (a) Pretreatment contrast-enhanced CT scan of the liver shows a right lobe tumor. (b) Contrast-enhanced CT scan obtained 3 months after radioembolization shows only minimal response according to imaging criteria. (c) Pretreatment whole-body PET scan shows increased radiotracer uptake in the right hepatic lobe. (d) Whole-body PET scan obtained 3 months after treatment shows uniform normal activity throughout the liver, a finding that represents near-complete response.

 
Tumor Volume Reduction
In 2000, investigators published the Response Evaluation Criteria in Solid Tumors (RECIST). This document established the RECIST criteria for the assessment of tumors following treatment (27). In brief, it discussed the three current methods of assessing pre- and posttreatment tumor size, namely, measuring (a) the maximum diameter (RECIST), (b) the cross product of the maximum diameter and the maximum perpendicular dimension (WHO), and (c) tumor volume. Although the first two methods are the most straightforward, inconsistencies arise in measuring tumors that are geometrically irregular. Because the measurement of multilobed tumors cannot be reproduced from one institution to another, interobserver variability may be unacceptably high. Therefore, the standard of reference for tumor response should be a reduction in volume (27). Although tedious to perform, the determination of tumor volume takes into account and corrects for the geometric configuration of the tumor. A volume reduction of 65% represents a partial response according to standard oncologic criteria (Fig 6) (27).


Figure 6A
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  		Figure 6a.  Volume reduction. (a) Contrast-enhanced portal venous phase CT scan shows a lobulated, geometrically irregular hepatic lesion with an area of 186.7 cm2 and a volume of 112.3 mL. The lesion represents metastatic colorectal disease to the liver. (b) On a posttreatment CT scan, the area and volume of the lesion have decreased to 96.9 cm2 and 38.9 mL (65% volume reduction), respectively, findings that represent partial response. Volume measurements help correct for irregularly shaped lesions.

 

Figure 6B
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  		Figure 6b.  Volume reduction. (a) Contrast-enhanced portal venous phase CT scan shows a lobulated, geometrically irregular hepatic lesion with an area of 186.7 cm2 and a volume of 112.3 mL. The lesion represents metastatic colorectal disease to the liver. (b) On a posttreatment CT scan, the area and volume of the lesion have decreased to 96.9 cm2 and 38.9 mL (65% volume reduction), respectively, findings that represent partial response. Volume measurements help correct for irregularly shaped lesions.

 
Tumor Marker Reduction
Imaging findings often do not correlate with findings related to tumor markers. In our study, tumor markers decreased in many patients (Table 2), a decrease that did not correlate with imaging findings.

Changes at Diffusion-weighted MR Imaging
Decreased cellularity and compromised cell membrane integrity in necrotic tissues allow locally increased diffusion of water molecules (39). Diffusion-weighted MR imaging can help detect increased diffusion in tumors following TACE and 90Y microsphere therapy (40,41). The signal intensity of tissues with increased water diffusion is suppressed on diffusion-weighted images. In addition, diffusion-weighted MR imaging may help differentiate posttreatment regions of reactive edema from neighboring tumor tissues (Fig 7).


Figure 7A
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  		Figure 7a.  Use of diffusion-weighted MR imaging to measure treatment response. (a) Contrast-enhanced gradient-echo T1-weighted MR image obtained in a 66-year-old patient shows an infiltrative tumor in the right hepatic lobe (arrows). (b) Posttreatment contrast-enhanced gradient-echo T1-weighted MR image shows no significant change in lesion size (arrows), making interpretation of response difficult. (c) Pretreatment diffusion-weighted MR image (b =500 sec/mm2) demonstrates restricted water diffusion in the region of interest (arrows and inset [magnified view]). (d) Diffusion-weighted MR image (b =500 sec/ mm2) obtained following 90Y therapy shows increased water mobility (decreased signal intensity) in the treated area (arrows and inset [magnified view]), a finding that represents response.

 

Figure 7B
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  		Figure 7b.  Use of diffusion-weighted MR imaging to measure treatment response. (a) Contrast-enhanced gradient-echo T1-weighted MR image obtained in a 66-year-old patient shows an infiltrative tumor in the right hepatic lobe (arrows). (b) Posttreatment contrast-enhanced gradient-echo T1-weighted MR image shows no significant change in lesion size (arrows), making interpretation of response difficult. (c) Pretreatment diffusion-weighted MR image (b =500 sec/mm2) demonstrates restricted water diffusion in the region of interest (arrows and inset [magnified view]). (d) Diffusion-weighted MR image (b =500 sec/ mm2) obtained following 90Y therapy shows increased water mobility (decreased signal intensity) in the treated area (arrows and inset [magnified view]), a finding that represents response.

 

Figure 7C
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  		Figure 7c.  Use of diffusion-weighted MR imaging to measure treatment response. (a) Contrast-enhanced gradient-echo T1-weighted MR image obtained in a 66-year-old patient shows an infiltrative tumor in the right hepatic lobe (arrows). (b) Posttreatment contrast-enhanced gradient-echo T1-weighted MR image shows no significant change in lesion size (arrows), making interpretation of response difficult. (c) Pretreatment diffusion-weighted MR image (b =500 sec/mm2) demonstrates restricted water diffusion in the region of interest (arrows and inset [magnified view]). (d) Diffusion-weighted MR image (b =500 sec/ mm2) obtained following 90Y therapy shows increased water mobility (decreased signal intensity) in the treated area (arrows and inset [magnified view]), a finding that represents response.

 

Figure 7D
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  		Figure 7d.  Use of diffusion-weighted MR imaging to measure treatment response. (a) Contrast-enhanced gradient-echo T1-weighted MR image obtained in a 66-year-old patient shows an infiltrative tumor in the right hepatic lobe (arrows). (b) Posttreatment contrast-enhanced gradient-echo T1-weighted MR image shows no significant change in lesion size (arrows), making interpretation of response difficult. (c) Pretreatment diffusion-weighted MR image (b =500 sec/mm2) demonstrates restricted water diffusion in the region of interest (arrows and inset [magnified view]). (d) Diffusion-weighted MR image (b =500 sec/ mm2) obtained following 90Y therapy shows increased water mobility (decreased signal intensity) in the treated area (arrows and inset [magnified view]), a finding that represents response.

 

   Other Posttherapy Findings
Top
 Abstract
 Introduction
 Technical Considerations
 Criteria for the Assessment...
 Other Posttherapy Findings
Complications
 Discussion
 Conclusions
 References
 
Peritumoral Edema and Hemorrhage
Given the intense radiation effects of 90Y, the CT equivalent of an inflammatory response may be observed following treatment. This finding may include peritumoral edema and hemorrhage, lesion enlargement, and apparent disease progression if assessment is made on the basis of lesion size alone. This represents a pitfall analogous to the blooming artifact that may be seen with PET (Fig 8) (42).


Figure 8A
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  		Figure 8a.  Image interpretation pitfall owing to an increase in lesion size. (a) Contrast-enhanced portal venous phase CT scan shows a large right lobe metastasis from colorectal cancer. The lesion straddles both lobes and hence derives its blood supply from both the right and left hepatic arteries. (b) Pretreatment FDG PET scan shows uptake (CEA =40 units/mL) in two liver lesions. (c) Posttreatment contrast-enhanced portal venous phase CT scan shows the lesion with necrosis and possible intratumoral hemorrhage, which result in a slight interval increase in overall lesion size and an incorrect interpretation as disease progression. (d) Posttreatment PET scan shows a decrease in uptake in the right lobe with a decrease in CEA to 20 units/mL despite the increase in size seen at CT, findings that support the clinical interpretation of response.

 

Figure 8B
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  		Figure 8b.  Image interpretation pitfall owing to an increase in lesion size. (a) Contrast-enhanced portal venous phase CT scan shows a large right lobe metastasis from colorectal cancer. The lesion straddles both lobes and hence derives its blood supply from both the right and left hepatic arteries. (b) Pretreatment FDG PET scan shows uptake (CEA =40 units/mL) in two liver lesions. (c) Posttreatment contrast-enhanced portal venous phase CT scan shows the lesion with necrosis and possible intratumoral hemorrhage, which result in a slight interval increase in overall lesion size and an incorrect interpretation as disease progression. (d) Posttreatment PET scan shows a decrease in uptake in the right lobe with a decrease in CEA to 20 units/mL despite the increase in size seen at CT, findings that support the clinical interpretation of response.

 

Figure 8C
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  		Figure 8c.  Image interpretation pitfall owing to an increase in lesion size. (a) Contrast-enhanced portal venous phase CT scan shows a large right lobe metastasis from colorectal cancer. The lesion straddles both lobes and hence derives its blood supply from both the right and left hepatic arteries. (b) Pretreatment FDG PET scan shows uptake (CEA =40 units/mL) in two liver lesions. (c) Posttreatment contrast-enhanced portal venous phase CT scan shows the lesion with necrosis and possible intratumoral hemorrhage, which result in a slight interval increase in overall lesion size and an incorrect interpretation as disease progression. (d) Posttreatment PET scan shows a decrease in uptake in the right lobe with a decrease in CEA to 20 units/mL despite the increase in size seen at CT, findings that support the clinical interpretation of response.

 

Figure 8D
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  		Figure 8d.  Image interpretation pitfall owing to an increase in lesion size. (a) Contrast-enhanced portal venous phase CT scan shows a large right lobe metastasis from colorectal cancer. The lesion straddles both lobes and hence derives its blood supply from both the right and left hepatic arteries. (b) Pretreatment FDG PET scan shows uptake (CEA =40 units/mL) in two liver lesions. (c) Posttreatment contrast-enhanced portal venous phase CT scan shows the lesion with necrosis and possible intratumoral hemorrhage, which result in a slight interval increase in overall lesion size and an incorrect interpretation as disease progression. (d) Posttreatment PET scan shows a decrease in uptake in the right lobe with a decrease in CEA to 20 units/mL despite the increase in size seen at CT, findings that support the clinical interpretation of response.

 
Ring Enhancement
Ring enhancement is a possibility, given the preferential flow of blood vessels to the periphery of the tumors as well as the subsequent intense radiation effect exerted by the microspheres once they have become lodged in the arterioles (43). Although posttreatment ring enhancement has been described as residual viable tissue, this is not necessarily the case with 90Y microsphere therapy (32). Previous reports have shown that this finding following 90Y therapy represents fibrous rather than neoplastic tissue (33). Other investigators have pointed out that ring enhancement may persist for months and does not necessarily imply residual tumor (Fig 9) (44,45).


Figure 9A
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  		Figure 9a.  Persistent ring enhancement in multiple liver tumors. (a) Contrast-enhanced arterial phase CT scan shows well-defined lesions with thick borders and inhomogeneous enhancement. (b) Contrast-enhanced arterial phase CT scan obtained 30 days after treatment with 90Y shows no change in lesion size. However, decreased intralesional enhancement, intralesional necrosis, and thin peripheral ring enhancement are noted. (c) Contrast-enhanced arterial phase CT scan obtained 7 months after treatment shows persistent ring enhancement without a significant decrease in lesion size. The patient survived for 3 years after undergoing only one treatment with 90Y and no other therapy.

 

Figure 9B
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  		Figure 9b.  Persistent ring enhancement in multiple liver tumors. (a) Contrast-enhanced arterial phase CT scan shows well-defined lesions with thick borders and inhomogeneous enhancement. (b) Contrast-enhanced arterial phase CT scan obtained 30 days after treatment with 90Y shows no change in lesion size. However, decreased intralesional enhancement, intralesional necrosis, and thin peripheral ring enhancement are noted. (c) Contrast-enhanced arterial phase CT scan obtained 7 months after treatment shows persistent ring enhancement without a significant decrease in lesion size. The patient survived for 3 years after undergoing only one treatment with 90Y and no other therapy.

 

Figure 9C
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  		Figure 9c.  Persistent ring enhancement in multiple liver tumors. (a) Contrast-enhanced arterial phase CT scan shows well-defined lesions with thick borders and inhomogeneous enhancement. (b) Contrast-enhanced arterial phase CT scan obtained 30 days after treatment with 90Y shows no change in lesion size. However, decreased intralesional enhancement, intralesional necrosis, and thin peripheral ring enhancement are noted. (c) Contrast-enhanced arterial phase CT scan obtained 7 months after treatment shows persistent ring enhancement without a significant decrease in lesion size. The patient survived for 3 years after undergoing only one treatment with 90Y and no other therapy.

 
Hypertrophy
Unilateral portal vein embolization is a well-established method for stimulating contralateral liver hypertrophy in preparation for partial hepatic resection (46). Patients receiving 90Y microsphere treatment may also demonstrate contralateral liver hypertrophy following treatment while maintaining normal liver function (10). Hypertrophy of the untreated lobe and concomitant atrophy of the treated lobe may be due to alterations in blood flow and radiation effects, respectively. The exact cause of liver hypertrophy is unclear but has been linked to alterations in portal venous blood flow (47). Hypertrophy may also be observed in the caudate lobe following 90Y therapy (Figs 1b, 10).


Figure 10A
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  		Figure 10a.  Hypertrophy. (a) Contrast-enhanced portal venous phase CT scan obtained prior to treatment of the right lobe shows multiple hypoattenuating lesions, which represent multiple bilo-bar metastases from a primary colorectal tumor. (b) Posttreatment CT scan shows an interval decrease in the size of the lesions. Note the hypertrophic left lobe.

 

Figure 10B
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  		Figure 10b.  Hypertrophy. (a) Contrast-enhanced portal venous phase CT scan obtained prior to treatment of the right lobe shows multiple hypoattenuating lesions, which represent multiple bilo-bar metastases from a primary colorectal tumor. (b) Posttreatment CT scan shows an interval decrease in the size of the lesions. Note the hypertrophic left lobe.

 
Transient Perivascular Edema
The mechanism of 90Y administration is transarterial. Hence, it is possible for radiation to affect the liver parenchyma in a distribution that mimics blood flow and (perivascular) microsphere distribution. These radiation effects are analogous to the secondary effects on the liver that have historically been seen in patients undergoing external irradiation for breast cancer (48). These findings are transient and should not be misinterpreted as infiltrative disease or hepatic attenuation defects from vascular phenomena (Fig 11).


Figure 11A
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  		Figure 11a.  Transient perivascular edema. (a) Contrast-enhanced portal venous phase CT scan shows relatively normal right posterior portal vein branches. No tumor nodules are seen at this level. (b) CT scan obtained 14 weeks after treatment with 90Y shows perivascular edema (arrow) parallel to the right portal vein. (c) CT scan obtained 6 months after treatment shows complete resolution of the perivascular edema. (d) Pretreatment CT scan obtained in a patient with metastatic colorectal cancer shows metastatic deposits. (e) On a posttreatment CT scan, the lesions have decreased in size, but significant perivascular edema has developed (arrows). The latter finding should not be interpreted as infiltrative metastatic disease but as a reversible sequela of treatment with 90Y.

 

Figure 11B
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  		Figure 11b.  Transient perivascular edema. (a) Contrast-enhanced portal venous phase CT scan shows relatively normal right posterior portal vein branches. No tumor nodules are seen at this level. (b) CT scan obtained 14 weeks after treatment with 90Y shows perivascular edema (arrow) parallel to the right portal vein. (c) CT scan obtained 6 months after treatment shows complete resolution of the perivascular edema. (d) Pretreatment CT scan obtained in a patient with metastatic colorectal cancer shows metastatic deposits. (e) On a posttreatment CT scan, the lesions have decreased in size, but significant perivascular edema has developed (arrows). The latter finding should not be interpreted as infiltrative metastatic disease but as a reversible sequela of treatment with 90Y.

 

Figure 11C
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  		Figure 11c.  Transient perivascular edema. (a) Contrast-enhanced portal venous phase CT scan shows relatively normal right posterior portal vein branches. No tumor nodules are seen at this level. (b) CT scan obtained 14 weeks after treatment with 90Y shows perivascular edema (arrow) parallel to the right portal vein. (c) CT scan obtained 6 months after treatment shows complete resolution of the perivascular edema. (d) Pretreatment CT scan obtained in a patient with metastatic colorectal cancer shows metastatic deposits. (e) On a posttreatment CT scan, the lesions have decreased in size, but significant perivascular edema has developed (arrows). The latter finding should not be interpreted as infiltrative metastatic disease but as a reversible sequela of treatment with 90Y.

 

Figure 11D
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  		Figure 11d.  Transient perivascular edema. (a) Contrast-enhanced portal venous phase CT scan shows relatively normal right posterior portal vein branches. No tumor nodules are seen at this level. (b) CT scan obtained 14 weeks after treatment with 90Y shows perivascular edema (arrow) parallel to the right portal vein. (c) CT scan obtained 6 months after treatment shows complete resolution of the perivascular edema. (d) Pretreatment CT scan obtained in a patient with metastatic colorectal cancer shows metastatic deposits. (e) On a posttreatment CT scan, the lesions have decreased in size, but significant perivascular edema has developed (arrows). The latter finding should not be interpreted as infiltrative metastatic disease but as a reversible sequela of treatment with 90Y.

 

Figure 11E
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  		Figure 11e.  Transient perivascular edema. (a) Contrast-enhanced portal venous phase CT scan shows relatively normal right posterior portal vein branches. No tumor nodules are seen at this level. (b) CT scan obtained 14 weeks after treatment with 90Y shows perivascular edema (arrow) parallel to the right portal vein. (c) CT scan obtained 6 months after treatment shows complete resolution of the perivascular edema. (d) Pretreatment CT scan obtained in a patient with metastatic colorectal cancer shows metastatic deposits. (e) On a posttreatment CT scan, the lesions have decreased in size, but significant perivascular edema has developed (arrows). The latter finding should not be interpreted as infiltrative metastatic disease but as a reversible sequela of treatment with 90Y.

 
Capsular Retraction, Hepatic Fibrosis, and Portal Hypertension
Capsular retraction has an unknown etiology, but it is thought that chemotherapy may cause shrinkage of the tumor with resultant scar formation and nodularity developing in uninvolved areas (49). In addition, confluent hepatic fibrosis, oriental cholangiohepatitis, and bile duct necrosis have been associated with retraction of the liver capsule. We postulate that, in the context of 90Y microsphere therapy, capsular retraction may arise from (a) necrosis within the liver tumor distorting the tumor margin and, consequently, the liver capsule; and (b) radiation effect on the hepatic parenchyma, resulting in fibrosis and cicatrization. Hepatic fibrosis causes attenuation of the intrahepatic portal and hepatic venous branches and reduction of the hepatic vascular bed (50). Hepatic fibrosis, as well as the chronic effects of systemic chemotherapy on the hepatic parenchyma, may result in imaging features of portal hypertension, including splenomegaly and recanalized umbilical vein (Fig 12). These findings have been described previously (51–53).


Figure 12A
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  		Figure 12a.  Hepatic fibrosis. (a) Pretreatment CT scan obtained in a patient with metastatic colorectal cancer shows the hepatic parenchyma with a normal shape and contour. (b) CT scan obtained 2 years after treatment shows hepatic fibrosis as well as caudate and left lobe hypertrophy. Liver function test results remained normal, and a positive response to treatment was observed.

 

Figure 12B
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  		Figure 12b.  Hepatic fibrosis. (a) Pretreatment CT scan obtained in a patient with metastatic colorectal cancer shows the hepatic parenchyma with a normal shape and contour. (b) CT scan obtained 2 years after treatment shows hepatic fibrosis as well as caudate and left lobe hypertrophy. Liver function test results remained normal, and a positive response to treatment was observed.

 
Perihepatic Fluid and Pleural Effusion
Although the vast majority of 90Y microspheres are distributed to hypervascular areas, adjacent structures may also be exposed to radiation, including the Glisson capsule and the right pleural space (15,19). This exposure can result in reactive perihepatic fluid and pleural effusions (Fig 13), particularly following right lobe treatment. In the absence of other findings, small amounts of perihepatic fluid should not be misinterpreted as radiation hepatitis.


Figure 13A
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  		Figure 13a.  (a) Perihepatic fluid. CT scan obtained following treatment with 90Y demonstrates perihepatic fluid anteriorly (arrow). (b) Pleural effusion. CT scan of the liver and lung base obtained in an asymptomatic patient shows a reactive pleural effusion in the right lung (arrow). The numerous metastatic breast cancer lesions are necrotic and have responded to therapy.

 

Figure 13B
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  		Figure 13b.  (a) Perihepatic fluid. CT scan obtained following treatment with 90Y demonstrates perihepatic fluid anteriorly (arrow). (b) Pleural effusion. CT scan of the liver and lung base obtained in an asymptomatic patient shows a reactive pleural effusion in the right lung (arrow). The numerous metastatic breast cancer lesions are necrotic and have responded to therapy.

 

   Complications
Top
 Abstract
 Introduction
 Technical Considerations
 Criteria for the Assessment...
 Other Posttherapy Findings
 Complications
Discussion
 Conclusions
 References
 
Hepatic Abscess
Microorganisms access the hepatic parenchyma by means of ascending cholangitis, chronic biliary colonization, or portal pyemia. Hepatic interventions resulting in hepatic abscess, such as radiofrequency ablation, bland particle embolization, and TACE, have been described (54–56). 90Y therapy can also result in hepatic abscess, particularly in patients with an incompetent ampulla of Vater (eg, hepaticoenterostomy). The clinical manifestation of a suspected liver abscess includes right upper quadrant abdominal pain, right shoulder pain, nausea, vomiting, fever and chills, chest pain, shortness of breath, and, in some patients, cough and weight loss (Fig 14) (57).


Figure 14
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  		Figure 14.  Hepatic abscess in a patient with metastatic pancreatic cancer to the right hepatic lobe. The patient had a history of Whipple surgery. Posttreatment contrast-enhanced CT scan shows a focal, peripherally enhancing lesion (arrow) containing fluid and air, a finding that raised suspicion for a hepatic abscess. The patient was successfully treated with percutaneous drainage and antibiotics.

 
Biliary Dyskinesia and Radiation-induced Cholecystitis
Gallbladder complications may result from 90Y microsphere therapy when the cystic artery receives some of the microspheres in the vascular bed that was treated. In some patients, symptoms of biliary dyskinesia following 90Y therapy may include right upper quadrant and postprandial pain. In more serious cases involving gallbladder injury and cholecystitis, patients may exhibit fever, nausea, and vomiting. Radiation-induced cholecystitis has been reported with 90Y microsphere therapy (58). Imaging of the gallbladder following radioembolization may depict mural enhancement, disruption or discontinuity of the gallbladder wall, and pericholecystic fluid (15,19). There is no correlation between imaging findings and clinical symptoms of cholecystitis following 90Y therapy (15,19). Treatment for radiation-induced cholecystitis depends on the severity of the disease and the patient’s symptoms (Fig 15a, 15b). Treatment options include antibiotics or cholecystectomy, depending on the clinical scenario (59). The majority of the patients in our study who exhibited imaging features of radiation-induced cholecystitis were clinically asymptomatic and did not require surgery (Fig 15c). In addition, segmental biliary dilatation may occur in the infused vascular territory.


Figure 15A
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  		Figure 15a.  (a, b) Radiation-induced cholecystitis in a 45-year-old woman with breast cancer metastatic to the liver. (a) Contrast-enhanced CT scan obtained 4 weeks after radioembolization with 90Y microspheres shows radiation-induced disruption and discontinuity in the enhancement of the gallbladder wall. The patient required cholecystectomy. (b) Photomicrograph shows hemorrhage within the gallbladder wall. Arrow indicates a microsphere. (c) CT scan obtained in a patient with pancreatic cancer metastatic to the liver who had undergone 90Y treatment 1 month earlier shows gallbladder wall edema and disruption (arrow). Despite this worrisome imaging finding, the patient had no symptoms of cholecystitis and did not require intervention.

 

Figure 15B
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  		Figure 15b.  (a, b) Radiation-induced cholecystitis in a 45-year-old woman with breast cancer metastatic to the liver. (a) Contrast-enhanced CT scan obtained 4 weeks after radioembolization with 90Y microspheres shows radiation-induced disruption and discontinuity in the enhancement of the gallbladder wall. The patient required cholecystectomy. (b) Photomicrograph shows hemorrhage within the gallbladder wall. Arrow indicates a microsphere. (c) CT scan obtained in a patient with pancreatic cancer metastatic to the liver who had undergone 90Y treatment 1 month earlier shows gallbladder wall edema and disruption (arrow). Despite this worrisome imaging finding, the patient had no symptoms of cholecystitis and did not require intervention.

 

Figure 15C
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  		Figure 15c.  (a, b) Radiation-induced cholecystitis in a 45-year-old woman with breast cancer metastatic to the liver. (a) Contrast-enhanced CT scan obtained 4 weeks after radioembolization with 90Y microspheres shows radiation-induced disruption and discontinuity in the enhancement of the gallbladder wall. The patient required cholecystectomy. (b) Photomicrograph shows hemorrhage within the gallbladder wall. Arrow indicates a microsphere. (c) CT scan obtained in a patient with pancreatic cancer metastatic to the liver who had undergone 90Y treatment 1 month earlier shows gallbladder wall edema and disruption (arrow). Despite this worrisome imaging finding, the patient had no symptoms of cholecystitis and did not require intervention.

 
Biloma and Biliary Necrosis
A biloma represents a contained rupture of small biliary radicles. Because the peribiliary plexus supplies the blood to the biliary tree and consists of vessels 30–50 µm in size, it is not unexpected that some effect on the biliary tree might occasionally be seen with 90Y microspheres, likely as a result of ischemic and radiation injury to the small bile ducts. Bilomas can also occur following bland particle embolization, chemoembolization, or liver transplantation (60). Typical signs and symptoms of biloma include abdominal pain and fever. Hyperbilirubinemia may also occur. Although bilomas may resolve spontaneously, some may require percutaneous drainage.

Radiation Hepatitis
A possible complication following treatment with 90Y microspheres is radiation-induced liver disease, also known as radiation hepatitis. Radiation hepatitis may be induced when the normal hepatic parenchyma is exposed to excessive doses of radiation. This phenomenon was initially reported by Ingold et al (61), who described ascites, elevated alkaline phosphatase levels, and thrombocytopenia with external beam radiation doses to the liver exceeding 50 Gy. Treatment is usually medical (steroids, anti-inflammatory drugs), although some investigators have had success treating this condition with transjugular intrahepatic portosystemic shunts. Typical radiologic findings include intraparenchymal edema and transient hepatomegaly. Ultimately, subcapsular edema and ascites ensue, and liver failure with associated smooth peripheral cholangitis becomes evident (62). Radiation-induced liver disease can be attributed to 90Y therapy in the context of lack of disease progression, improvement seen at PET or with tumor markers, and absence of biliary obstruction.

Gastrointestinal Ulceration
Peptic ulceration and gastritis are known complications of radioactive 90Y microsphere treatment (24,63). When deposited outside the desired location, 90Y can cause ulceration. Patients will usually experience pain, food intolerance, and weight loss. There are no imaging findings of gastrointestinal ulceration unless deep ulceration and perforation occur. Endoscopy is required for definitive diagnosis.


   Discussion
Top
 Abstract
 Introduction
 Technical Considerations
 Criteria for the Assessment...
 Other Posttherapy Findings
 Complications
 Discussion
Conclusions
 References
 
It seems clear that image interpretation following arterial or ablative therapies in cancer patients is complex. Radioembolization, an emerging therapy, is no different, and this mode of action poses specific challenges and difficulties in the assessment of response.

Tumor size is the universally recognized measure of response (27). This variable has been validated by the oncology community and is in fact the single most commonly assessed variable in the radiologic follow-up of cancer patients. Radiologists interpreting images obtained following radioembolization should not only assess this variable, but should also recognize and note the degree of avascularity and necrosis, findings that have been well accepted as criteria for response assessment following ablative therapies (31). In the presence of obvious subjectivity in measuring the length and width of a lesion following treatment, radiologists may consider the use of tumor volume as a criterion. The appropriate regions of interest surrounding the lesion must be demarcated, the tumor volume determined, and the appropriate percentage decrease in volume used to assess response. This procedure eliminates operator variability and subjectivity in cases of irregularly shaped lesions. If no changes in size, shape, or vascularity are noted, functional MR imaging may allow a more sensitive measure of response prior to anatomic changes (41). Furthermore, the treating clinician may reconcile a confusing clinical scenario on the basis of change in tumor markers.

PET is becoming increasingly important in the assessment of tumor response. This modality should be used when standard criteria yield conflicting or inconclusive information. For example, irrespective of size-related findings following radioembolization, an improvement seen at PET as determined on the basis of visual criteria or standard uptake values represents a response to therapy (34,38,64,65).

However, the interpretation of images following 90Y therapy is fraught with pitfalls. Paradoxical increases in size are the rule rather than the exception with ablative therapies such as radiofrequency ablation. This phenomenon may also occur with radioembolization if the necrotic response is augmented (radiation effect) and should not be interpreted as simply disease progression. This possibility should be recognized prospectively and reconciled with findings obtained with other available clinical tools such as PET, functional MR imaging, and tumor markers. Ring enhancement is another imaging finding that raises suspicion for active disease more often than it is taken to represent fibrous or granulation tissue. This phenomenon has been described with radioembolization and, if it appears uniformly smooth and enhancing, has been shown to represent scar tissue rather than active disease (15,19,32). False-positive findings of malignant "ring enhancement" have also been documented in the literature (33). Other pitfalls include the biliary sequelae that are addressed later.

Miscellaneous imaging findings such as contralateral lobar hypertrophy may also occur following radioembolization. Although the mechanism of this finding is not known, the end result is analogous to what is seen following portal vein embolization. The radiation effect of the microspheres lodged at the arteriolar level may result in perivascular edema, a finding that is reversible given sufficient follow-up (months). Long-term effects of radiation on the parenchyma may result in hepatic cicatrization and the development of a fibrotic appearance of the liver. These findings should not be interpreted as cirrhosis, since there is no intrinsic hepatocytic dysfunction but rather only benign secondary effects of radiation on the interstitium. Benign findings such as pleural effusions and perihepatic fluid may also result from attenuated radiation.

The findings seen at follow-up imaging and the source information from which this analysis is derived are shown in Tables 1–3. Most of the patients in our study had more than three target lesions, with a mean follow-up of 159 days. Necrosis, perivascular edema, and biliary changes accounted for the majority of imaging findings. Necrosis appeared to better reflect a positive treatment response (75.4% of cases) than did size criteria alone (42.8%). The time to partial response as determined on the basis of size criteria was 133 days, a figure that is consistent with findings from other studies involving radioembolization (10,33). The median time to progression was 462 days (15.4 months), a value nearly identical to that found in previous studies (4). The median duration of response was 433 days (14.4 months). The highest response rate was achieved with PET (nearly 90%), a result that is consistent with those described in earlier studies and that reaffirms the importance of PET in the follow-up of this type of therapy (34,38,64–66). On the other hand, tumor marker changes did not necessarily parallel imaging findings. This discrepancy is explained in part by the presence of minimal extrahepatic disease, a finding not uncommon in this 137-patient cohort.

Finally, imaging complications may occur following radioembolization, the most common being biliary in nature. Although the majority of these complications are benign and are not associated with any clinical sequelae, their development is noteworthy. Small fluid-filled and necrotic structures in the liver were seen in 11 of 130 patients (8.5%). Although these structures may have represented small unrecognized micrometastases successfully treated with radioembolization, they were assumed to represent small bilomas from injury to the peribiliary plexus that developed in patients who had been heavily treated with systemic chemotherapy. Through the same mechanism, areas of peripheral biliary obstruction were noted in some cases; these areas were assumed to be biliary strictures from radiation injury to the bile ducts. The most serious complications were large bilomas (requiring drainage) and radiation-induced cholecystitis (requiring cholecystectomy). One patient developed hyperbilirubinemia without disease progression and was assumed to have radiation hepatitis. Two patients developed gastrointestinal ulceration, one of whom required surgery.


   Conclusions
Top
 Abstract
 Introduction
 Technical Considerations
 Criteria for the Assessment...
 Other Posttherapy Findings
 Complications
 Discussion
 Conclusions
References
 
Radioembolization therapy to liver tumors results in unique imaging findings. Although the classic indication of treatment response is a reduction in tumor size, changes occur in the parenchyma that require proper interpretation of anatomic and functional images.

These parenchymal changes include necrosis, lack of enhancement, and specific findings at PET and functional MR imaging. Other benign findings that can occur include pleural effusions, perivascular edema, contralateral hypertrophy, ring enhancement, perihepatic fluid, and fibrosis. Complications of radioembolization, including cholecystitis, abscess, and bilomas, should be recognized early in the imaging follow-up of these patients.With classic imaging findings and surrogates, response rates range from 20% to 80% in patients treated for hepatocellular carcinoma or metastatic disease to the liver (10,22,23,33,66,67).

90Y microspheres represent an emerging transarterial therapy for the treatment of liver malignancies. Because these microspheres are micron-sized, rely on tumor hypervascularity, flow through the hepatic vasculature, and impart intense radiation, this mode of action results in unique imaging findings. Hence, it is incumbent on radiologists involved in the posttreatment assessment of patients undergoing radioembolization to be familiar with the imaging findings and potential pitfalls. Ultimately, the appropriate imaging and clinical follow-up of these patients requires information obtained with anatomic and functional imaging and tumor markers.To our knowledge, the study described in this article represents the first comprehensive review of the imaging findings that are encountered following treatment with this novel therapy.


   Acknowledgments
 
The authors would like to acknowledge the efforts of the Interventional Oncology team at Northwestern Memorial Hospital: Karen Marshall, Sharon Coffey, Krystina Salzig, and Peggy Gilbertsen.


   Footnotes
 

Abbreviations: CEA = carcinoembryonic antigen, FDG = fluorodeoxyglucose, RECIST = Response Evaluation Criteria in Solid Tumors, TACE = transarterial chemoembolization, WHO = World Health Organization


   References
Top
 Abstract
 Introduction
 Technical Considerations
 Criteria for the Assessment...
 Other Posttherapy Findings
 Complications
 Discussion
 Conclusions
 References
 

  1. Blum HE. Hepatocellular carcinoma: therapy and prevention. World J Gastroenterol 2005;11(47): 7391–7400.[Medline]
  2. Mulcahy MF, Benson AB 3rd. Bevacizumab in the treatment of colorectal cancer. Expert Opin Biol Ther 2005;5(7):997–1005.[CrossRef][Medline]
  3. Ramsey DE, Kernagis LY, Soulen MC, Geschwind JF. Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol 2002;13(9 pt 2): S211–S221.[CrossRef][Medline]
  4. Gray B, Van Hazel G, Hope M, et al. Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer. Ann Oncol 2001;12(12):1711–1720.[Abstract/Free Full Text]
  5. Van Hazel G, Blackwell A, Anderson J, et al. Randomised phase 2 trial of SIR-Spheres plus fluorouracil/leucovorin chemotherapy versus fluorouracil/leucovorin chemotherapy alone in advanced colorectal cancer. J Surg Oncol 2004;88(2):78–85.[CrossRef][Medline]
  6. Carr BI. Hepatocellular carcinoma: current management and future trends. Gastroenterology 2004;127(5 suppl 1):S218–S224.[CrossRef][Medline]
  7. Carr BI. Hepatic arterial 90Yttrium glass microspheres (Therasphere) for unresectable hepatocellular carcinoma: interim safety and survival data on 65 patients. Liver Transpl 2004;10(2 suppl 1): S107–S110.[CrossRef][Medline]
  8. Geschwind JF, Salem R, Carr BI, et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology 2004;127(5 suppl 1):S194–S205.[CrossRef][Medline]
  9. Popperl G, Helmberger T, Munzing W, Schmid R, Jacobs TF, Tatsch K. Selective internal radiation therapy with SIR-Spheres in patients with nonresectable liver tumors. Cancer Biother Radiopharm 2005;20(2):200–208.[CrossRef][Medline]
  10. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 2005;16(12):1627–1639.[Medline]
  11. Stubbs RS, Cannan RJ, Mitchell AW. Selective internal radiation therapy (SIRT) with 90Yttrium microspheres for extensive colorectal liver metastases. Hepatogastroenterology 2001;48(38):333–337.[Medline]
  12. Gray BN, Anderson JE, Burton MA, et al. Regression of liver metastases following treatment with yttrium-90 microspheres. Aust N Z J Surg 1992; 62(2):105–110.[Medline]
  13. Gray BN, Burton MA, Kelleher D, Klemp P, Matz L. Tolerance of the liver to the effects of Yttrium-90 radiation. Int J Radiat Oncol Biol Phys 1990;18(3):619–623.[Medline]
  14. Gray BN, Burton MA, Kelleher DK, Anderson J, Klemp P. Selective internal radiation (SIR) therapy for treatment of liver metastases: measurement of response rate. J Surg Oncol 1989;42(3): 192–196.[CrossRef][Medline]
  15. Salem R, Thurston KG. Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. I. Technical and methodologic considerations. J Vasc Interv Radiol 2006;17(8): 1251–1278. [Published correction appears in J Vasc Interv Radiol 2006;17(10):1594.][CrossRef][Medline]
  16. Salem R, Thurston KG. Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. II. Special topics. J Vasc Interv Radiol 2006;17(9):1425–1439.[CrossRef][Medline]
  17. Goin JE, Salem R, Carr BI, et al. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol 2005;16(2 pt 1):205–213.[Medline]
  18. Andrews JC, Walker SC, Ackermann RJ, Cotton LA, Ensminger WD, Shapiro B. Hepatic radioembolization with yttrium-90 containing glass microspheres: preliminary results and clinical follow-up. J Nucl Med 1994;35(10):1637–1644.[Abstract/Free Full Text]
  19. Murthy R, Nunez R, Szklaruk J, et al. Yttrium-90 microsphere therapy for hepatic malignancy: devices, indications, technical considerations, and potential complications. RadioGraphics 2005; 25(suppl 1):S41–S55.[Abstract/Free Full Text]
  20. Salem R, Hunter RD. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma: a review. Int J Radiat Oncol Biol Phys 2006;66(2 suppl):S83–S88.[CrossRef][Medline]
  21. Salem R, Thurston KG. Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. III. Comprehensive literature review and future direction. J Vasc Interv Radiol 2006;17(10):1571–1593.[CrossRef][Medline]
  22. Lewandowski RJ, Thurston KG, Goin JE, et al. 90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135–150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging. J Vasc Interv Radiol 2005; 16(12):1641–1651.[Medline]
  23. Sharma RA, Van Hazel GA, Morgan B, et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 2007; 25(9):1099–1106.[Abstract/Free Full Text]
  24. Liu DM, Salem R, Bui JT, et al. Angiographic considerations in patients undergoing liver-directed therapy. J Vasc Interv Radiol 2005;16(7): 911–935.[Medline]
  25. Lewandowski RJ, Sato KT, Atassi B, et al. Radioembolization with (90)Y microspheres: angiographic and technical considerations. Cardiovasc Intervent Radiol 2007;30(4):571–592.[CrossRef][Medline]
  26. Covey AM, Brody LA, Maluccio MA, Getrajdman GI, Brown KT. Variant hepatic arterial anatomy revisited: digital subtraction angiography performed in 600 patients. Radiology 2002;224(2): 542–547.[Abstract/Free Full Text]
  27. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92(3):205–216.[Abstract/Free Full Text]
  28. Rhee TK, Larson AC, Prasad PV, et al. Feasibility of blood oxygenation level-dependent MR imaging to monitor hepatic transcatheter arterial embolization in rabbits. J Vasc Interv Radiol 2005; 16(11):1523–1528.[Medline]
  29. Pompili M, Mirante VG, Rondinara G, et al. Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: assessment of efficacy at explant analysis and of safety for tumor recurrence. Liver Transpl 2005;11(9):1117–1126.[CrossRef][Medline]
  30. Ebied OM, Federle MP, Carr BI, et al. Evaluation of responses to chemoembolization in patients with unresectable hepatocellular carcinoma. Cancer 2003;97(4):1042–1050.[CrossRef][Medline]
  31. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35(3):421–430.[CrossRef][Medline]
  32. Kulik LM, Mulcahy MF, Hunter RD, Nemcek AA Jr, Abecassis MM, Salem R. Use of yttrium-90 microspheres (TheraSphere) in a patient with unresectable hepatocellular carcinoma leading to liver transplantation: a case report. Liver Transpl 2005;11(9):1127–1131.[CrossRef][Medline]
  33. Kulik LM, Atassi B, van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: down-staging to resection, RFA and bridge to transplantation. J Surg Oncol 2006;94(7):572–586.[CrossRef][Medline]
  34. Wong CY, Qing F, Savin M, et al. Reduction of metastatic load to liver after intraarterial hepatic yttrium-90 radioembolization as evaluated by [18F]fluorodeoxyglucose positron emission tomographic imaging. J Vasc Interv Radiol 2005;16(8): 1101–1106.[Medline]
  35. Bienert M, McCook B, Carr BI, et al. Sequential FDG PET/CT in 90Y microsphere treatment of unresectable colorectal liver metastases. Eur J Nucl Med Mol Imaging 2005;32(6):723.[CrossRef][Medline]
  36. Bucerius J, Herkel C, Joe AY, et al. (18F)-FDG PET and conventional imaging for assessment of Hodgkin’s disease and non Hodgkin’s lymphoma: an analysis of 193 patient studies. Nuklearmedizin 2006;45(3):105–110.[Medline]
  37. Reddy MP, Reddy P, Lilien DL. F-18 FDG PET imaging in gastrointestinal stromal tumor. Clin Nucl Med 2003;28(8):677–679.[CrossRef][Medline]
  38. Wong CY, Salem R, Qing F, et al. Metabolic response after intraarterial 90Y-glass microsphere treatment for colorectal liver metastases: comparison of quantitative and visual analyses by 18FFDG PET. J Nucl Med 2004;45(11):1892–1897.[Abstract/Free Full Text]
  39. Lang P, Wendland MF, Saeed M, et al. Osteogenic sarcoma: noninvasive in vivo assessment of tumor necrosis with diffusion-weighted MR imaging. Radiology 1998;206(1):227–235.[Abstract/Free Full Text]
  40. Deng J, Miller FH, Rhee TK, et al. Diffusion-weighted MR imaging for determination of hepatocellular carcinoma response to yttrium-90 radioembolization. J Vasc Interv Radiol 2006;17(7): 1195–1200.[CrossRef][Medline]
  41. Kamel IR, Bluemke DA, Ramsey D, et al. Role of diffusion-weighted imaging in estimating tumor necrosis after chemoembolization of hepatocellular carcinoma. AJR Am J Roentgenol 2003;181(3): 708–710.[Free Full Text]
  42. Shreve PD, Anzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. RadioGraphics 1999; 19(1):61–77.[Abstract/Free Full Text]
  43. Kennedy AS, Nutting C, Coldwell D, Gaiser J, Drachenberg C. Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers. Int J Radiat Oncol Biol Phys 2004;60(5):1552–1563.[CrossRef][Medline]
  44. Keppke AL, Salem R, Reddy D, et al. Imaging of hepatocellular carcinoma after treatment with yttrium-90 microspheres. AJR Am J Roentgenol 2007;188(3):768–775.[Abstract/Free Full Text]
  45. Miller FH, Keppke AL, Reddy D, et al. Response of liver metastases after treatment with yttrium-90 microspheres: role of size, necrosis, and PET. AJR Am J Roentgenol 2007;188(3):776–783.[Abstract/Free Full Text]
  46. Murthy R, Xiong H, Nunez R, et al. Yttrium 90 resin microspheres for the treatment of unresectable colorectal hepatic metastases after failure of multiple chemotherapy regimens: preliminary results. J Vasc Interv Radiol 2005;16(7):937–945.[Medline]
  47. Gerunda GE, Bolognesi M, Neri D, et al. Preoperative selective portal vein embolization (PSPVE) before major hepatic resection: effectiveness of Doppler estimation of hepatic blood flow to predict the hypertrophy rate of non-embolized liver segments. Hepatogastroenterology 2002;49(47): 1405–1411.[Medline]
  48. Ricke J, Wust P, Stohlmann A, et al. CT-guided interstitial brachytherapy of liver malignancies alone or in combination with thermal ablation: phase I–II results of a novel technique. Int J Radiat Oncol Biol Phys 2004;58(5):1496–1505.[CrossRef][Medline]
  49. Young ST, Paulson EK, Washington K, Gulliver DJ, Vredenburgh JJ, Baker ME. CT of the liver in patients with metastatic breast carcinoma treated by chemotherapy: findings simulating cirrhosis. AJR Am J Roentgenol 1994;163(6):1385–1388.[Abstract/Free Full Text]
  50. Awaya H, Mitchell DG, Kamishima T, Holland G, Ito K, Matsumoto T. Cirrhosis: modified caudate–right lobe ratio. Radiology 2002;224(3): 769–774.[Abstract/Free Full Text]
  51. Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006; 24(13):2065–2072.[Abstract/Free Full Text]
  52. Ayav A, Habib N, Jiao LR. Portal hypertension secondary to 90Yttrium microspheres: an unknown complication. J Clin Oncol 2005;23(32): 8275–8276.[Free Full Text]
  53. Rubbia-Brandt L, Audard V, Sartoretti P, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004;15(3):460–466.[Abstract/Free Full Text]
  54. Xia J, Ren Z, Ye S, et al. Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. Eur J Radiol 2006;59(3): 407–412.[CrossRef][Medline]
  55. Kim W, Clark TW, Baum RA, Soulen MC. Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv Radiol 2001; 12(8):965–968.[Medline]
  56. Geschwind JF, Kaushik S, Ramsey DE, Choti MA, Fishman EK, Kobeiter H. Influence of a new prophylactic antibiotic therapy on the incidence of liver abscesses after chemoembolization treatment of liver tumors. J Vasc Interv Radiol 2002;13(11): 1163–1166.[CrossRef][Medline]
  57. Kim MH, Choi MS, Choi YS, et al. Clinical features of liver abscess developed after radiofrequency ablation and transarterial chemoembolization for hepatocellular carcinoma [in Korean]. Korean J Hepatol 2006;12(1):55–64.[Medline]
  58. Lewandowski R, Salem R. Incidence of radiation cholecystitis in patients receiving Y-90 treatment for unresectable liver malignancies [abstr]. J Vasc Interv Radiol 2004;15(2 pt 2):S162.
  59. Xu Z, Wang L, Zhang N, Ling X, Hou C, Zhou X. Chemical ablation of the gallbladder: clinical application and long-term observations. Surg Endosc 2005;19(5):693–696.[CrossRef][Medline]
  60. Cheng YF, Huang TL, Chen TY, et al. Impact of pre-operative transarterial embolization on the treatment of hepatocellular carcinoma with liver transplantation. World J Gastroenterol 2005; 11(10):1433–1438.[Medline]
  61. Ingold JA, Reed GB, Kaplan HS, Bagshaw MA. Radiation hepatitis. Am J Roentgenol Radium Ther Nucl Med 1965;93:200–208.[Medline]
  62. Kida H, Hasuike Y, Fukuchi N, et al. A case report of hepatocellular carcinoma (Vp4): an attempt to reduce residual tumor thrombus using combination therapy (hepatic arterial infusion, hepatic arterial embolization and radiation) [in Japanese]. Gan To Kagaku Ryoho 2005;32(11): 1812–1814.[Medline]
  63. Dancey JE, Shepherd FA, Paul K, et al. Treatment of nonresectable hepatocellular carcinoma with intrahepatic 90Y-microspheres. J Nucl Med 2000;41(10):1673–1681.[Abstract/Free Full Text]
  64. Wong CY, Salem R, Raman S, Gates VL, Dworkin HJ. Evaluating 90Y-glass microsphere treatment response of unresectable colorectal liver metastases by [18F]FDG PET: a comparison with CT or MRI. Eur J Nucl Med Mol Imaging 2002; 29(6):815–820.[CrossRef][Medline]
  65. Wong CY, Savin M, Sherpa KM, et al. Regional yttrium-90 microsphere treatment of surgically unresectable and chemotherapy-refractory metastatic liver carcinoma. Cancer Biother Radiopharm 2006;21(4):305–313.[CrossRef][Medline]
  66. Kennedy AS, Coldwell D, Nutting C, et al. Resin 90Y-microsphere brachytherapy for unresectable colorectal liver metastases: modern USA experience. Int J Radiat Oncol Biol Phys 2006;65(2): 412–425.[CrossRef][Medline]
  67. Sangro B, Bilbao JI, Boan J, et al. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2006;66(3):792–800.[Medline]




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