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Arterial Changes Due to Chemoembolization of Hepatocellular Carcinoma Impacting Subsequent Radioembolization
LETTERS TO THE EDITOR Arterial Changes Due to Chemoembolization of Hepatocellular Carcinoma Impacting Subsequent Radioembolization From: Pooja Patel, BS Hearns W. Charles, MD James Park, MD Amy R. Deipolyi, MD, PhD Division of Vascular and Interventional Radiology Department of Radiology (P.P., H.W.C., A.R.D.), and Division of Gastroenterology, Department of Medicine (J.P.) New York University Medical Center 660 First Ave., 7th Floor New York, NY 10016
Editor: Current hepatocellular carcinoma (HCC) treatment algorithms prescribe transarterial chemoembolization but have not yet incorporated transarterial radioembolization. The relative superiority and optimal order of therapies are not known. Given its embolic nature, chemoembolization results in occlusive vascular changes that may interfere with subsequent delivery of therapeutic agents, such as yttrium-90 microspheres. Here we present a patient with HCC treated with transarterial chemoembolization and radioembolization. Case reports at our institution are exempt from institutional review board review. A 66-year-old woman with hepatitis C cirrhosis and previous percutaneous ablation and conventional transarterial chemoembolization treatments for HCC involving segments IV, VI, VII, and VIII presented with new HCCs in segments IV and VIII on magnetic resonance (MR) imaging, prompting another transarterial chemoembolization session. The HCCs were identified and targeted by arteriography and cone-beam computed tomography (CT; Fig a, b). Selective chemoembolization was performed to segments IV and VIII with 65 mg of doxorubicin loaded onto 100–300-μm drugeluting embolic particles (BTG International, West Conshohocken, Pennsylvania) to an endpoint of nearstasis. Liver MR imaging 2 months later showed residual disease in segments IV and VIII, prompting the decision to proceed with radioembolization. A mapping study before radioembolization (Fig c) showed occlusion of the previously treated segment VIII artery, with intense gallbladder uptake and no uptake in the superolateral right liver on a technetium-99m
None of the authors have identified a conflict of interest. http://dx.doi.org/10.1016/j.jvir.2016.04.029
macroaggregated albumin scan. Given these findings, arterial redistribution was considered based on the theoretical possibility of consolidating arterial supply by embolizing arterial collateral vessels (1). When the patient returned for left hepatic radioembolization, coil embolization of the cystic artery was performed to redistribute blood flow from the cystic to the hepatic arteries. Right inferior phrenic artery (RIPA) arteriography showed collateral arterial supply to segment VIII, prompting RIPA embolization with 700– 900-μm microspheres (Embosphere; Merit Medical, South Jordan, Utah) to an endpoint of stasis. Radioembolization was performed via the left hepatic artery with 1-GBq TheraSphere particles (Nordion, Kanata, Ontario, Canada). One month later, the right hepatic artery was treated with 1.1-GBq TheraSphere particles, but no uptake in segment VIII was seen on single-photon emission CT/CT (Fig d). MR imaging 3 months later demonstrated interval enlargement of the segment VIII HCC. No treatment-related complications occurred. Morphologic changes in arterial anatomy after transarterial chemoembolization range from stenosis to occlusion, are progressive with multiple sessions and increasing chemotherapy dose, and are associated with extensive extrahepatic collateralization (2). By redistributing arterial supply, chemoembolization may impact the ability to deliver therapeutic agents to targeted tumors, reducing the perfusion of systemic and liverdirected therapies. Here we show no uptake of radiotracer in a large HCC as a result of occlusion of a previously treated segmental artery despite efforts to redistribute arterial supply by occluding extra- and intrahepatic collateral vessels (1). In this case, even though arterial injury from traumatic catheterization or previous ablation were considered, the segment VIII artery had been catheterized without difficulty, no dissection had been noted, and the vessel became occluded at the site of administration of the drugeluting embolic agents, suggesting a causative role of chemoembolization in the vascular damage. Transarterial chemoembolization and radioembolization may have similar efficacy for management of HCC, and the impact of performing one after the other is not known. Given that radioembolization is relatively nonembolic, it may not preclude or reduce efficacy of future liver-directed therapies as a result of arterial occlusion. However, transarterial radioembolization can cause radiation-induced liver failure, fibrosis in nontumoral liver, and venoocclusive disease (3), which may complicate subsequent embolization therapies. Previous and concomitant systemic therapies may increase the risk of vascular injury and liver dysfunction after transarterial chemoembolization and radioembolization, and would impact clinical decisions
1452
’
Letters to the Editor
Patel et al
’
JVIR
Figure. (a) Superior mesenteric arteriogram demonstrates replaced right and left hepatic arteries, typical corkscrew-like appearance of hepatic arteries in cirrhotic patients (arrowhead), and a patent segment VIII artery (white arrow). An area of Lipiodol (Guerbet, Roissy, France) deposition (black arrow) is the result of conventional transarterial chemoembolization performed remotely. (b) Because the HCCs were not apparent on conventional arteriography, cone-beam CT was performed with an injection of the segment VIII artery and demonstrated supply to the segment VIII HCC (arrow). This was then treated with drug-eluting embolic chemoembolization. (c) Proper hepatic arteriogram 4 months following chemoembolization demonstrates multiple changes, including decreased caliber and eventual truncation of the previously treated segment VIII artery (black arrow) with corresponding loss of arterial vascularity to the superolateral right liver (asterisks), arterial stenosis (white arrow), and increased tortuosity (black arrowhead). There has been interval increase in cystic arterial flow (white arrowhead), with new collateral supply to the adjacent liver from the cystic artery. The cystic artery and RIPA were embolized to promote redistribution of blood flow. Coil embolization of the gastroduodenal artery was performed (star). (d) One month after left hepatic radioembolization, right hepatic artery treatment was performed. Single-photon emission CT/CT image immediately following right hepatic radioembolization shows lack of radiotherapeutic agent uptake in segment VII/VIII (white asterisk) despite the previous attempts to redistribute flow by eliminating collateral supply.
regarding which locoregional therapy is indicated. Many factors beyond the treatments’ effects on hepatic vasculature and function, such as cost and insurance support; expertise and availability; multiplicity, location, and size of tumors; and preference of referring providers, may influence potential treatment decisions, making the incorporation of transarterial radioembolization into HCC treatment algorithms challenging (4). Further
research is warranted to assess the relative benefits of managing HCC initially with transarterial radioembolization or chemoembolization, particularly in patients who must be “bridged” for longer periods of time until liver transplantation. An optimal HCC algorithm would prescribe liver-directed therapies in a fashion that minimizes vascular and nontumoral hepatic damage, allowing for repeated treatments as needed.
Volume 27
’
Number 9
’
September
’
2016
REFERENCES 1. Abdelmaksoud MH, Louie JD, Kothary N, et al. Consolidation of hepatic arterial inflow by embolization of variant hepatic arteries in preparation for yttrium-90 radioembolization. J Vasc Interv Radiol 2011; 22:1364–1371.e1. 2. Suh CH, Shin JH, Yoon HM, et al. Angiographic evaluation of hepatic arterial injury after cisplatin and Gelfoam-based transcatheter arterial chemoembolization for hepatocellular carcinoma in a 205 patient cohort during a 6-year follow-up. Br J Radiol 2014; 87:20140054. 3. Dhingra S, Schwartz M, Kim E, et al. Histological changes in nontumoral liver secondary to radioembolization of hepatocellular carcinoma with yttrium 90-impregnated microspheres: report of two cases. Semin Liver Dis 2014; 34:465–468. 4. Rostambeigi N, Dekarske AS, Austin EE, Golzarian J, Cressman EN. Cost effectiveness of radioembolization compared with conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Vasc Interv Radiol 2014; 25:1075–1084.
The Utility of Unilobar Technetium-99m Macroaggregated Albumin to Predict Pulmonary Toxicity in Bilobar Hepatocellular Carcinoma prior to Yttrium-90 Radioembolization From: Joseph R. Kallini, MD Ahmed Gabr, MD Laura Kulik, MD Riad Salem, MD, MBA Robert J. Lewandowski, MD Department of Radiology, Section of Interventional Radiology (J.R.K, A.G., R.S., R.J.L.) Northwestern University 676 N. St. Clair, Suite 800 Chicago, Illinois 60611; Department of Medicine, Division of Hematology and Oncology (R.S.) Robert H. Lurie Comprehensive Cancer Center Northwestern University Chicago, Illinois; Department of Medicine, Division of Hepatology (L.K.) Northwestern University Chicago, Illinois; and Department of Surgery, Division of Transplantation (R.S.) Comprehensive Transplant Center Northwestern University Chicago, Illinois
Editor: Yttrium-90 (90Y) radioembolization is a minimally invasive procedure widely utilized during the last decade for inoperable liver cancers. Glass or resin microspheres impregnated with the radioisotope 90Y are injected into the hepatic vasculature and subsequently lodge in tumor-
L.K. receives personal fees from BTG (West Conshohocken, Pennsylvania) and Bayer/Onyx (Leverkusen, Germany). R.S. receives personal fees from BTG. R.J.L. receives personal fees from BTG. Neither of the other authors have any conflict of interest. http://dx.doi.org/10.1016/j.jvir.2016.06.004
1453
feeding capillary beds. Liver tumors, particularly hepatocellular carcinoma (HCC), have a tendency to form arteriovenous communications that bypass tumoral capillary beds such that injected microspheres may circumnavigate the liver, enter the lungs, and induce pulmonary toxicity. Current standard practice involves a planning hepatic angiogram prior to radioembolization in which technetium-99m macroaggregated albumin (99mTcMAA) is injected into the hepatic arterial (HA) vasculature perfusing the tumor(s) of interest. This technique mimics catheter placement for subsequent radioembolization. This is done to assess splanchnic and pulmonary shunting. Given the similarities in sizes of 90Y microspheres (20 to 40 μm) and 99mTc-MAA (20 to 50 μm), the pattern of 99mTc-MAA deposition on high-resolution single photon emission computerized tomography (SPECT/CT) demonstrates how 90Y will localize during treatment. The lung shunt fraction (LSF) is determined from 99mTc-MAA and provides predictive value of potential lung toxicity with subsequent treatment. LSF is calculated by dividing the geometric mean of the net counts from the lungs by the sum of the geometric mean of the net counts from the lungs and the liver: LSF ¼
total lung counts total lung counts þ total abdomen counts
For glass microspheres, a lung dose greater than 30 Gy per treatment or cumulative lung dose of 50 Gy (derived from LSF) places the patient at increased risk of radiation pneumonitis after radioembolization (1). For resin microspheres, the radioembolization dose must be modified for LSF Z 10%; patients are not candidates for treatment if LSF 4 20% (2). The proper hepatic artery (PHA) bifurcates into the left hepatic artery (LHA) and right hepatic artery (RHA) to supply the respective lobes of the liver. Liver tumors can either be confined to 1 lobe (unilobar) or involve both lobes of the liver (bilobar). In order to mimic the radioembolization procedure and accurately determine the LSF, most operators will inject 99mTc-MAA into both lobes of the liver (“bilobar 99mTc-MAA”) when tumors are bilobar. One technique is to administer the 99mTc-MAA into the PHA (Fig a). Although simple to perform, this lends itself to the possibility of nontarget extrahepatic 99mTc-MAA delivery (eg to a right gastric artery off the proximal LHA in approximately 15% or RHA in approximately 10% of cases), potentially complicating treatment planning. To avoid this scenario, some operators perform sequential 99mTc-MAA administrations. A microcatheter is first advanced into the LHA, and 99mTc-MAA is infused into the left hepatic lobe (Fig b). Under fluoroscopy, the operator then retracts the microcatheter into the PHA and gently advances it into the RHA. Once in the RHA, the remainder of the 99mTc-MAA is infused (Fig c). This
Editor: Current hepatocellular carcinoma (HCC) treatment algorithms prescribe transarterial chemoembolization but have not yet incorporated transarterial radioembolization. The relative superiority and optimal order of therapies are not known. Given its embolic nature, chemoembolization results in occlusive vascular changes that may interfere with subsequent delivery of therapeutic agents, such as yttrium-90 microspheres. Here we present a patient with HCC treated with transarterial chemoembolization and radioembolization. Case reports at our institution are exempt from institutional review board review. A 66-year-old woman with hepatitis C cirrhosis and previous percutaneous ablation and conventional transarterial chemoembolization treatments for HCC involving segments IV, VI, VII, and VIII presented with new HCCs in segments IV and VIII on magnetic resonance (MR) imaging, prompting another transarterial chemoembolization session. The HCCs were identified and targeted by arteriography and cone-beam computed tomography (CT; Fig a, b). Selective chemoembolization was performed to segments IV and VIII with 65 mg of doxorubicin loaded onto 100–300-μm drugeluting embolic particles (BTG International, West Conshohocken, Pennsylvania) to an endpoint of nearstasis. Liver MR imaging 2 months later showed residual disease in segments IV and VIII, prompting the decision to proceed with radioembolization. A mapping study before radioembolization (Fig c) showed occlusion of the previously treated segment VIII artery, with intense gallbladder uptake and no uptake in the superolateral right liver on a technetium-99m
None of the authors have identified a conflict of interest. http://dx.doi.org/10.1016/j.jvir.2016.04.029
macroaggregated albumin scan. Given these findings, arterial redistribution was considered based on the theoretical possibility of consolidating arterial supply by embolizing arterial collateral vessels (1). When the patient returned for left hepatic radioembolization, coil embolization of the cystic artery was performed to redistribute blood flow from the cystic to the hepatic arteries. Right inferior phrenic artery (RIPA) arteriography showed collateral arterial supply to segment VIII, prompting RIPA embolization with 700– 900-μm microspheres (Embosphere; Merit Medical, South Jordan, Utah) to an endpoint of stasis. Radioembolization was performed via the left hepatic artery with 1-GBq TheraSphere particles (Nordion, Kanata, Ontario, Canada). One month later, the right hepatic artery was treated with 1.1-GBq TheraSphere particles, but no uptake in segment VIII was seen on single-photon emission CT/CT (Fig d). MR imaging 3 months later demonstrated interval enlargement of the segment VIII HCC. No treatment-related complications occurred. Morphologic changes in arterial anatomy after transarterial chemoembolization range from stenosis to occlusion, are progressive with multiple sessions and increasing chemotherapy dose, and are associated with extensive extrahepatic collateralization (2). By redistributing arterial supply, chemoembolization may impact the ability to deliver therapeutic agents to targeted tumors, reducing the perfusion of systemic and liverdirected therapies. Here we show no uptake of radiotracer in a large HCC as a result of occlusion of a previously treated segmental artery despite efforts to redistribute arterial supply by occluding extra- and intrahepatic collateral vessels (1). In this case, even though arterial injury from traumatic catheterization or previous ablation were considered, the segment VIII artery had been catheterized without difficulty, no dissection had been noted, and the vessel became occluded at the site of administration of the drugeluting embolic agents, suggesting a causative role of chemoembolization in the vascular damage. Transarterial chemoembolization and radioembolization may have similar efficacy for management of HCC, and the impact of performing one after the other is not known. Given that radioembolization is relatively nonembolic, it may not preclude or reduce efficacy of future liver-directed therapies as a result of arterial occlusion. However, transarterial radioembolization can cause radiation-induced liver failure, fibrosis in nontumoral liver, and venoocclusive disease (3), which may complicate subsequent embolization therapies. Previous and concomitant systemic therapies may increase the risk of vascular injury and liver dysfunction after transarterial chemoembolization and radioembolization, and would impact clinical decisions
1452
’
Letters to the Editor
Patel et al
’
JVIR
Figure. (a) Superior mesenteric arteriogram demonstrates replaced right and left hepatic arteries, typical corkscrew-like appearance of hepatic arteries in cirrhotic patients (arrowhead), and a patent segment VIII artery (white arrow). An area of Lipiodol (Guerbet, Roissy, France) deposition (black arrow) is the result of conventional transarterial chemoembolization performed remotely. (b) Because the HCCs were not apparent on conventional arteriography, cone-beam CT was performed with an injection of the segment VIII artery and demonstrated supply to the segment VIII HCC (arrow). This was then treated with drug-eluting embolic chemoembolization. (c) Proper hepatic arteriogram 4 months following chemoembolization demonstrates multiple changes, including decreased caliber and eventual truncation of the previously treated segment VIII artery (black arrow) with corresponding loss of arterial vascularity to the superolateral right liver (asterisks), arterial stenosis (white arrow), and increased tortuosity (black arrowhead). There has been interval increase in cystic arterial flow (white arrowhead), with new collateral supply to the adjacent liver from the cystic artery. The cystic artery and RIPA were embolized to promote redistribution of blood flow. Coil embolization of the gastroduodenal artery was performed (star). (d) One month after left hepatic radioembolization, right hepatic artery treatment was performed. Single-photon emission CT/CT image immediately following right hepatic radioembolization shows lack of radiotherapeutic agent uptake in segment VII/VIII (white asterisk) despite the previous attempts to redistribute flow by eliminating collateral supply.
regarding which locoregional therapy is indicated. Many factors beyond the treatments’ effects on hepatic vasculature and function, such as cost and insurance support; expertise and availability; multiplicity, location, and size of tumors; and preference of referring providers, may influence potential treatment decisions, making the incorporation of transarterial radioembolization into HCC treatment algorithms challenging (4). Further
research is warranted to assess the relative benefits of managing HCC initially with transarterial radioembolization or chemoembolization, particularly in patients who must be “bridged” for longer periods of time until liver transplantation. An optimal HCC algorithm would prescribe liver-directed therapies in a fashion that minimizes vascular and nontumoral hepatic damage, allowing for repeated treatments as needed.
Volume 27
’
Number 9
’
September
’
2016
REFERENCES 1. Abdelmaksoud MH, Louie JD, Kothary N, et al. Consolidation of hepatic arterial inflow by embolization of variant hepatic arteries in preparation for yttrium-90 radioembolization. J Vasc Interv Radiol 2011; 22:1364–1371.e1. 2. Suh CH, Shin JH, Yoon HM, et al. Angiographic evaluation of hepatic arterial injury after cisplatin and Gelfoam-based transcatheter arterial chemoembolization for hepatocellular carcinoma in a 205 patient cohort during a 6-year follow-up. Br J Radiol 2014; 87:20140054. 3. Dhingra S, Schwartz M, Kim E, et al. Histological changes in nontumoral liver secondary to radioembolization of hepatocellular carcinoma with yttrium 90-impregnated microspheres: report of two cases. Semin Liver Dis 2014; 34:465–468. 4. Rostambeigi N, Dekarske AS, Austin EE, Golzarian J, Cressman EN. Cost effectiveness of radioembolization compared with conventional transarterial chemoembolization for treatment of hepatocellular carcinoma. J Vasc Interv Radiol 2014; 25:1075–1084.
The Utility of Unilobar Technetium-99m Macroaggregated Albumin to Predict Pulmonary Toxicity in Bilobar Hepatocellular Carcinoma prior to Yttrium-90 Radioembolization From: Joseph R. Kallini, MD Ahmed Gabr, MD Laura Kulik, MD Riad Salem, MD, MBA Robert J. Lewandowski, MD Department of Radiology, Section of Interventional Radiology (J.R.K, A.G., R.S., R.J.L.) Northwestern University 676 N. St. Clair, Suite 800 Chicago, Illinois 60611; Department of Medicine, Division of Hematology and Oncology (R.S.) Robert H. Lurie Comprehensive Cancer Center Northwestern University Chicago, Illinois; Department of Medicine, Division of Hepatology (L.K.) Northwestern University Chicago, Illinois; and Department of Surgery, Division of Transplantation (R.S.) Comprehensive Transplant Center Northwestern University Chicago, Illinois
Editor: Yttrium-90 (90Y) radioembolization is a minimally invasive procedure widely utilized during the last decade for inoperable liver cancers. Glass or resin microspheres impregnated with the radioisotope 90Y are injected into the hepatic vasculature and subsequently lodge in tumor-
L.K. receives personal fees from BTG (West Conshohocken, Pennsylvania) and Bayer/Onyx (Leverkusen, Germany). R.S. receives personal fees from BTG. R.J.L. receives personal fees from BTG. Neither of the other authors have any conflict of interest. http://dx.doi.org/10.1016/j.jvir.2016.06.004
1453
feeding capillary beds. Liver tumors, particularly hepatocellular carcinoma (HCC), have a tendency to form arteriovenous communications that bypass tumoral capillary beds such that injected microspheres may circumnavigate the liver, enter the lungs, and induce pulmonary toxicity. Current standard practice involves a planning hepatic angiogram prior to radioembolization in which technetium-99m macroaggregated albumin (99mTcMAA) is injected into the hepatic arterial (HA) vasculature perfusing the tumor(s) of interest. This technique mimics catheter placement for subsequent radioembolization. This is done to assess splanchnic and pulmonary shunting. Given the similarities in sizes of 90Y microspheres (20 to 40 μm) and 99mTc-MAA (20 to 50 μm), the pattern of 99mTc-MAA deposition on high-resolution single photon emission computerized tomography (SPECT/CT) demonstrates how 90Y will localize during treatment. The lung shunt fraction (LSF) is determined from 99mTc-MAA and provides predictive value of potential lung toxicity with subsequent treatment. LSF is calculated by dividing the geometric mean of the net counts from the lungs by the sum of the geometric mean of the net counts from the lungs and the liver: LSF ¼
total lung counts total lung counts þ total abdomen counts
For glass microspheres, a lung dose greater than 30 Gy per treatment or cumulative lung dose of 50 Gy (derived from LSF) places the patient at increased risk of radiation pneumonitis after radioembolization (1). For resin microspheres, the radioembolization dose must be modified for LSF Z 10%; patients are not candidates for treatment if LSF 4 20% (2). The proper hepatic artery (PHA) bifurcates into the left hepatic artery (LHA) and right hepatic artery (RHA) to supply the respective lobes of the liver. Liver tumors can either be confined to 1 lobe (unilobar) or involve both lobes of the liver (bilobar). In order to mimic the radioembolization procedure and accurately determine the LSF, most operators will inject 99mTc-MAA into both lobes of the liver (“bilobar 99mTc-MAA”) when tumors are bilobar. One technique is to administer the 99mTc-MAA into the PHA (Fig a). Although simple to perform, this lends itself to the possibility of nontarget extrahepatic 99mTc-MAA delivery (eg to a right gastric artery off the proximal LHA in approximately 15% or RHA in approximately 10% of cases), potentially complicating treatment planning. To avoid this scenario, some operators perform sequential 99mTc-MAA administrations. A microcatheter is first advanced into the LHA, and 99mTc-MAA is infused into the left hepatic lobe (Fig b). Under fluoroscopy, the operator then retracts the microcatheter into the PHA and gently advances it into the RHA. Once in the RHA, the remainder of the 99mTc-MAA is infused (Fig c). This