DOI: 10.1148/rg.284075170
RadioGraphics 2008;28:1131-1145
© RSNA, 2008
Neuroendocrine Tumors: Role of Interventional Radiology in Therapy1
Michael J. Steward, MRCP,
Victoria S. Warbey, FRCR,
Anmol Malhotra, FRCR,
Martyn E. Caplin, MD, FRCP,
John R. Buscombe, FRCR, and
Dominic Yu, FRCR
1 From the Departments of Radiology (M.J.S., A.M., D.Y.), Gastroenterology (M.E.C.), and Nuclear Medicine (V.S.W., J.R.B.), Royal Free Hospital, Pond Street, London NW3 2QG, England. Recipient of a Certificate of Merit award for an education exhibit at the 2006 RSNA Annual Meeting. Received August 10, 2007; revision requested September 28; final revision received December 17; accepted January 2, 2008. All authors have no financial relationships to disclose.
Address correspondence to M.J.S. (e-mail: MichaelSteward{at}doctors.net.uk).
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Abstract
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The management of neuroendocrine tumors (NETs) is complex. Although NETs can affect a variety of organ systems, hepatic metastatic disease in particular lends itself to a wide range of interventional treatment options. Prior detailed radiologic assessment and careful patient selection are required. Curative surgery should always be considered but is rarely possible. Embolization, radionuclide therapy, or ablative techniques may then be undertaken. Transcatheter arterial embolization (TAE) may be used alone or in combination with transcatheter arterial chemoembolization (TACE). NET type and extent of hepatic involvement are factors that can help predict the success of either TAE or TACE. Embolization techniques can also be useful in patients with nonhepatic NETs. Radionuclide therapy is emerging as a valuable adjunct and is dependent on positive somatostatin receptor status. Therapeutic radiopeptides may be delivered arterially. Ablative techniques have been shown to play a role in the palliation of symptoms and principally involve radiofrequency ablation. Hepatic cryotherapy and percutaneous ethanol injection have also been used. A multidisciplinary approach to treatment and follow-up is important. Imaging should involve dual-phase multidetector computed tomography and contrast material–enhanced magnetic resonance imaging. The role of the interventional radiologist will continue to expand as imaging techniques become more refined.
© RSNA, 2008
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LEARNING OBJECTIVES
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After reading this article and taking the test, the reader will be able to:
- Describe the initial assessment required and the current role of interventional radiology in the management of neuroendocrine tumors.
- List the therapies currently in clinical use for neuroendocrine tumors.
- Discuss the importance of follow-up and a multidisciplinary approach in patients with neuroendocrine tumors.
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Introduction
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Neuroendocrine tumors (NETs) are a rare but diverse group of malignancies that arise in a wide range of organ systems. Gut-derived NETs arise from the diffuse endocrine system and, according to the 2002 World Health Organization classification system (1), are most simply classified based on their site of origin as either "functional" (symptomatic hormone secretion) or "nonfunctional" (no symptomatic hormones). Many investigators still find it practical to use the categorization of NETs based on embryologic origin into foregut tumors (bronchi, stomach, pancreas, gallbladder, duodenum), midgut tumors (jejunum, ileum, appendix, right colon), and hindgut tumors (left colon, rectum). Although there has been continued improvement in detection, NETs (most commonly, midgut NETs) have frequently metastasized to the liver by the time of diagnosis. A diverse range of imaging modalities can be used for the assessment of NETs.
The treatment of patients with liver metastases is complex, and there are often several factors that must be taken into account. Curative surgery should always be considered but is rarely possible due to the diffuse nature of the disease. NETs are relatively slow-growing tumors; therefore, patients can survive for several years with current treatment strategies. Interventional radiology has played an increasingly important role. In this article, we discuss and illustrate the assessment of NETs; radiologic treatment options and patient selection; and the various adjunct options that have become available for NET management, including embolization, radionuclide therapy, and ablative techniques. In addition, we briefly discuss posttherapeutic evaluation.
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Assessment of NETs
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Many patients present with metastatic disease with no known primary tumor site. Opinion is divided as to whether locating the primary tumor changes the prognosis.
A multimodality approach is optimal for detecting the primary tumor and metastases and can include multidetector computed tomography (CT) (Fig 1a), functional imaging (Fig 1b), magnetic resonance (MR) imaging (Fig 2), ultrasonography (US) (Fig 3), endoscopy, digital subtraction angiography, and venous sampling.
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Figure 1a. Primary liver tumor. (a) Multidetector CT scan shows a small hepatic lesion (arrow). (b) Single photon emission CT (SPECT) image shows the lesion with increased uptake of 111In-pentetreotate (arrow).
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Figure 1b. Primary liver tumor. (a) Multidetector CT scan shows a small hepatic lesion (arrow). (b) Single photon emission CT (SPECT) image shows the lesion with increased uptake of 111In-pentetreotate (arrow).
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Figure 2a. NET metastases. Precontrast T1-weighted (a), arterial phase T1-weighted (b), venous phase T1-weighted (c), and T2-weighted (d) MR images show multiple NET metastases. Note the hypointensity of the metastasis in c, compared with its hyperintensity in d (arrow).
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Figure 2b. NET metastases. Precontrast T1-weighted (a), arterial phase T1-weighted (b), venous phase T1-weighted (c), and T2-weighted (d) MR images show multiple NET metastases. Note the hypointensity of the metastasis in c, compared with its hyperintensity in d (arrow).
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Figure 2c. NET metastases. Precontrast T1-weighted (a), arterial phase T1-weighted (b), venous phase T1-weighted (c), and T2-weighted (d) MR images show multiple NET metastases. Note the hypointensity of the metastasis in c, compared with its hyperintensity in d (arrow).
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Figure 2d. NET metastases. Precontrast T1-weighted (a), arterial phase T1-weighted (b), venous phase T1-weighted (c), and T2-weighted (d) MR images show multiple NET metastases. Note the hypointensity of the metastasis in c, compared with its hyperintensity in d (arrow).
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For the evaluation of liver metastases, the use of triple-phase multidetector CT and contrast material–enhanced MR imaging is suggested to establish a baseline, which can help assess disease extent and allow posttreatment comparison. The arterial anatomy of the liver and portal vein patency can also be determined. Liver metastases have low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted images. In a recent study by Dromain et al (2), MR imaging was compared with multidetector CT and scintigraphy in the detection of liver metastases from endocrine tumors. Liver metastases were present in 40 patients, and the three aforementioned modalities helped detect 394, 325, and 204 metastases, respectively. The study recommended MR imaging for the detection of liver metastases, with both MR imaging and multidetector CT used for initial evaluation. In addition, T2-weighted sequences were shown to help detect the most lesions when contrast agents could not be given (2).
Unfortunately, highly differentiated NETs do not show increased uptake of fluorine 18 (18F)–fluorodeoxyglucose (FDG). A specific radiotracer, 5-hydroxytryptophan (5-HTP), a serotonin precursor, has been labeled with carbon 11 (11C), and recent studies have shown increased uptake of 11C-5-HTP in NETs. This imaging method is more sensitive than somatostatin receptor (SSTR) scintigraphy and CT in detecting small NETs. In a study by Orlefors et al (3), the sensitivities for positron emission tomography (PET), SSTR scintigraphy, and CT were 95%, 87%, and 76%, respectively.
Many tumors in humans, including NETs, are SSTR positive. A variety of somatostatin analogs have been developed that bind with varying affinity to the five different receptor subtypes. Indium 111 (111In)–pentetreotide is the most important and commonly used somatostatin analog; it binds specifically to SSTR2 with high affinity, and with a lesser affinity to SSTR5.
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Radiologic Treatment Options and Patient Selection
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Curative surgery for hepatic NET metastases should always be considered as a treatment option. Recent retrospective studies have compared surgery with medical therapy or embolization. Eighty-three percent of patients treated with surgical resection survived for 3 years, compared with 31% of patients treated with medical therapy or embolization (4). Unfortunately, less than 20% of patients present with surgically manageable disease (5). Most patients present with extensive bilobar disease or bulky tumor that requires alternative therapy.
Liver metastases can result in debilitating hormonal symptoms. Symptomatic residual disease can be treated initially with a trial of somatostatin analog therapy. Nonprogressive asymptomatic disease may also be simply observed initially. Refractory, unresectable, or recurrent disease with hepatic predominance is the domain of the interventional radiologist.
Local treatment strategies such as embolization, chemoembolization, and targeted radionuclide therapy are increasingly being used (6). Local ablative techniques such as radiofrequency (RF) ablation, cryotherapy, and percutaneous ethanol injection (PEI) are also important adjuncts. It is becoming recognized that an aggressive approach to management increases survival time when less than 50% of the liver is involved (7).
Careful patient selection is needed, as is tailoring of the treatment to the therapeutic goal in a given patient. This goal may be palliation of hormonal symptoms, reduction of tumor bulk, or even conversion to resectable status. Performance status and extent of hepatic disease involvement should also be evaluated.
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Transcatheter Arterial Embolization and Transcatheter Arterial Chemoembolization
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The liver has a dual vascular supply that lends itself to the use of hepatic transcatheter arterial embolization (TAE). The hepatic artery is the primary supplier of hypervascular liver metastases. Embolization induces ischemia of tumor cells, thereby reducing hormone output and causing liquefaction. Transcatheter arterial chemoembolization (TACE) has been developed based on the principle that ischemia of tumor cells increases sensitivity to chemotherapeutic substances.
Other possible advantages of TACE over TAE include regional delivery of chemotherapy and the increased intratumoral drug concentration and exposure time that result from reduced blood flow with embolization (Fig 4). TACE preparation and technique can vary. The method used at our institution is shown in Table 1.
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Figure 4. Results of TACE. Whole-body 111In-pente-treotide images (only abdomen shown) obtained after TACE show a large hepatic metastasis with central photopenia (arrow), a finding that confirms the presence of post-TACE tumor necrosis. Ant = anterior, Lat = lateral, Post = posterior.
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TAE has included the use of polyvinyl alcohol and gel foam (8,9). The latter study showed a clinical response in 80% of symptomatic patients undergoing embolization. A radiographic partial response rate of 48% was also demonstrated. Median overall survival time was 36 months from the time of initial embolization (9). Mixtures of cyanoacrylate (a liquid glue) and lipiodol have also been shown to be safe and effective permanent embolic agents (10). It is suggested that this mixture is superior in that peripheral embolization and, therefore, more complete tumor ischemia is more likely to be achieved. Comparative evidence-based data for identifying an optimal embolization technique have not been obtained.
Similarly, the therapeutic benefit of TACE over TAE is still not clear. Many studies have used a variety of types of chemotherapy, embolic agents, and techniques (11–14). More recently, evidence has emerged that the addition of intraarterial chemotherapy to TAE does not improve outcome in patients with carcinoid tumors but does benefit those with islet cell carcinomas (15). This study was conducted by Gupta et al (15) and included 123 patients, 69 with carcinoid tumors and 54 with pancreatic islet cell carcinomas. Univariate and multivariate analyses were used to assess prognostic variables. In patients with carcinoid tumors, TAE had a higher response rate than TACE (P = .004). In contrast, patients with islet cell carcinomas treated with TACE had a prolonged overall survival time and improved response rate (50%) compared with those treated with TAE (25%). This was not an unexpected result, since carcinoid tumors have a lower response rate to systemic chemotherapy than do islet cell tumors. In addition, it was observed that an intact primary tumor, extensive liver disease, and bone metastases were associated with reduced survival time in patients with islet cell carcinomas. The use of octreotide analogs was also considered and, although it was not found to be a statistically significant variable in predicting response or survival time in either group of patients, it was marginally predictive for progression-free survival time in patients with carcinoid tumors (P = .06).
There are still several unanswered questions concerning TACE technique. The question of whether embolization should be performed early or late in the clinical course of the disease is unresolved. Tumor burden and the quantity of liver to be embolized at each session are also factors that require further attention. Optimal tumor response has been shown to occur with a minimum of two TACE sessions (16).
It is generally accepted that embolization of the entire liver at a single treatment session should not be attempted. In the majority of patients, one hepatic lobe is embolized per session—usually the lobe with the greatest tumor burden (Figs 5, 6). Indeed, tumor burden is the only predictor of tumor response (17). It has been shown that patients with more than 75% of the liver involved by metastatic disease generally have worse outcomes (15).
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Figure 5a. Multiple treatments of metastases. (a) Multidetector CT scan shows bilobar disseminated NET metastases to the liver (arrows). (b) Angiogram shows an enlarged left hepatic artery (arrow) supplying a large tumor deposit. (c) Posttherapeutic images obtained after selective infusion of 90Y-octreotate into the left hepatic artery show good uptake in the left tumor (arrow). Ant = anterior, Post = posterior. (d) On posttherapeutic images obtained with selective infusion of 90Y-octreotate after subsequent treatment of the right metastases, the metastases show good uptake (arrow). Ant = anterior, Post = posterior.
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Figure 5b. Multiple treatments of metastases. (a) Multidetector CT scan shows bilobar disseminated NET metastases to the liver (arrows). (b) Angiogram shows an enlarged left hepatic artery (arrow) supplying a large tumor deposit. (c) Posttherapeutic images obtained after selective infusion of 90Y-octreotate into the left hepatic artery show good uptake in the left tumor (arrow). Ant = anterior, Post = posterior. (d) On posttherapeutic images obtained with selective infusion of 90Y-octreotate after subsequent treatment of the right metastases, the metastases show good uptake (arrow). Ant = anterior, Post = posterior.
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Figure 5c. Multiple treatments of metastases. (a) Multidetector CT scan shows bilobar disseminated NET metastases to the liver (arrows). (b) Angiogram shows an enlarged left hepatic artery (arrow) supplying a large tumor deposit. (c) Posttherapeutic images obtained after selective infusion of 90Y-octreotate into the left hepatic artery show good uptake in the left tumor (arrow). Ant = anterior, Post = posterior. (d) On posttherapeutic images obtained with selective infusion of 90Y-octreotate after subsequent treatment of the right metastases, the metastases show good uptake (arrow). Ant = anterior, Post = posterior.
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Figure 5d. Multiple treatments of metastases. (a) Multidetector CT scan shows bilobar disseminated NET metastases to the liver (arrows). (b) Angiogram shows an enlarged left hepatic artery (arrow) supplying a large tumor deposit. (c) Posttherapeutic images obtained after selective infusion of 90Y-octreotate into the left hepatic artery show good uptake in the left tumor (arrow). Ant = anterior, Post = posterior. (d) On posttherapeutic images obtained with selective infusion of 90Y-octreotate after subsequent treatment of the right metastases, the metastases show good uptake (arrow). Ant = anterior, Post = posterior.
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Figure 6a. NET metastases fed by an accessory right hepatic artery. (a) Multidetector CT scan helps confirm the extent of disease. (b) Angiogram helps confirm the vascular anatomy (arrow). (c) Posttherapeutic images obtained after injection of 90Y-octreotate into the accessory right hepatic artery show good retention of radiotracer in the tumors (arrow). Ant = anterior, Post = posterior.
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Figure 6b. NET metastases fed by an accessory right hepatic artery. (a) Multidetector CT scan helps confirm the extent of disease. (b) Angiogram helps confirm the vascular anatomy (arrow). (c) Posttherapeutic images obtained after injection of 90Y-octreotate into the accessory right hepatic artery show good retention of radiotracer in the tumors (arrow). Ant = anterior, Post = posterior.
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Figure 6c. NET metastases fed by an accessory right hepatic artery. (a) Multidetector CT scan helps confirm the extent of disease. (b) Angiogram helps confirm the vascular anatomy (arrow). (c) Posttherapeutic images obtained after injection of 90Y-octreotate into the accessory right hepatic artery show good retention of radiotracer in the tumors (arrow). Ant = anterior, Post = posterior.
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Factors that do not contribute to treatment outcome include site of primary tumor, tumor differentiation, previous treatment, and size of liver metastases (17,18).
Data concerning long-term outcome with TAE or TACE are limited. Retrospective data suggest that overall survival time after either procedure in patients with NETs is approximately 3.5 years (19). An unresected primary tumor or the presence of extrahepatic metastasis should not limit the use of either technique.
TAE and TACE are both associated with complications (Table 1). Postembolization syndrome (including nausea, vomiting, abdominal pain, and fever) is the most common side effect. These symptoms are readily controlled, but patients should be made aware that they may persist for several days. Major complications such as renal and liver failure, gallbladder perforation (Fig 7), abscess formation, and peptic ulcer hemorrhage have been observed but are rare (16). With the increasing use of multiple TACE sessions, local complications such as hepatic artery stenosis should also be considered, especially in potential candidates for liver transplantation.
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Figure 7a. Complications of TACE. (a) US image obtained 2 days after TACE shows an edematous gallbladder wall (arrow), a finding that is consistent with ischemia. The patient was treated conservatively but continued to be symptomatic. (b) Multidetector CT scan obtained 2 days later shows gallbladder wall perforation (arrow).
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Figure 7b. Complications of TACE. (a) US image obtained 2 days after TACE shows an edematous gallbladder wall (arrow), a finding that is consistent with ischemia. The patient was treated conservatively but continued to be symptomatic. (b) Multidetector CT scan obtained 2 days later shows gallbladder wall perforation (arrow).
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Portal vein embolization is another interventional technique used for NETs (Fig 8). It is usually selected for use in patients who are candidates for extended hepatectomy to increase the volume of potential liver remnant (20,21). Interventional radiology is also useful in the management of complications of NETs, such as hemorrhage and pseudoaneurysm formation (Fig 9).
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Figure 8a. Portal vein embolization for NET. (a, b) MR images obtained before (a) and after (b) embolization of the right portal vein show hypertrophy of the left hepatic lobe (arrow in b). (c) Multidetector CT scan obtained after resection shows a hypertrophic liver remnant (arrow).
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Figure 8b. Portal vein embolization for NET. (a, b) MR images obtained before (a) and after (b) embolization of the right portal vein show hypertrophy of the left hepatic lobe (arrow in b). (c) Multidetector CT scan obtained after resection shows a hypertrophic liver remnant (arrow).
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Figure 8c. Portal vein embolization for NET. (a, b) MR images obtained before (a) and after (b) embolization of the right portal vein show hypertrophy of the left hepatic lobe (arrow in b). (c) Multidetector CT scan obtained after resection shows a hypertrophic liver remnant (arrow).
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Figure 9a. Pseudoaneurysm within a NET metastasis to the liver. The pseudoaneurysm was presumed to be biopsy related. (a) Multidetector CT scan obtained prior to embolization shows the pseudoaneurysm (arrow). (b) Angiogram obtained after placement of a microcatheter in a branch of the replaced right hepatic artery arising from the superior mesenteric artery shows filling of the pseudoaneurysm (arrow). (c) Angiogram obtained after the deployment of coils (arrow) shows successful embolization. (d) On a postembolization multidetector CT scan, the pseudoaneurysm (arrow) shows no enhancement.
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Figure 9b. Pseudoaneurysm within a NET metastasis to the liver. The pseudoaneurysm was presumed to be biopsy related. (a) Multidetector CT scan obtained prior to embolization shows the pseudoaneurysm (arrow). (b) Angiogram obtained after placement of a microcatheter in a branch of the replaced right hepatic artery arising from the superior mesenteric artery shows filling of the pseudoaneurysm (arrow). (c) Angiogram obtained after the deployment of coils (arrow) shows successful embolization. (d) On a postembolization multidetector CT scan, the pseudoaneurysm (arrow) shows no enhancement.
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Figure 9c. Pseudoaneurysm within a NET metastasis to the liver. The pseudoaneurysm was presumed to be biopsy related. (a) Multidetector CT scan obtained prior to embolization shows the pseudoaneurysm (arrow). (b) Angiogram obtained after placement of a microcatheter in a branch of the replaced right hepatic artery arising from the superior mesenteric artery shows filling of the pseudoaneurysm (arrow). (c) Angiogram obtained after the deployment of coils (arrow) shows successful embolization. (d) On a postembolization multidetector CT scan, the pseudoaneurysm (arrow) shows no enhancement.
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Figure 9d. Pseudoaneurysm within a NET metastasis to the liver. The pseudoaneurysm was presumed to be biopsy related. (a) Multidetector CT scan obtained prior to embolization shows the pseudoaneurysm (arrow). (b) Angiogram obtained after placement of a microcatheter in a branch of the replaced right hepatic artery arising from the superior mesenteric artery shows filling of the pseudoaneurysm (arrow). (c) Angiogram obtained after the deployment of coils (arrow) shows successful embolization. (d) On a postembolization multidetector CT scan, the pseudoaneurysm (arrow) shows no enhancement.
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Radionuclide Therapy
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Peptide receptor radionuclide therapy is an emerging treatment modality for NETs. Candidates include patients with inoperable NETs, progressive disease, or symptoms that are not controlled with medication. The tumor needs to be SSTR positive as determined with 111In-pentetreotide scintigraphy. This radiolabeled somatostatin analog has proved very useful in tumors expressing SSTR2. It is known that there is a high sensitivity for this radiopeptide in a rangeis of NETs. In NETs of hindgut origin (eg, classic carcinoid tumors), nearly 90% of all tumors are receptor positive. However, this percentage can drop to 50% in NETs of pancreatic origin, especially insulinomas, which have low expression of SSTR2 (22,23). To determine whether a patient could benefit from radionuclide therapy, diagnostic 111In-pentetreotide scanning is performed. For a patient to be eligible for treatment, activity at sites of known tumor must be more intense than in the normal liver (23,24). The majority of patients will have disseminated disease, but there will be a subgroup in whom all or nearly all of the tumor lies within the liver. In these patients, infusing the therapeutic radiopeptide slowly into the liver via the hepatic artery may allow the radiation dose to be delivered without the risk of systemic side effects. The peptides that have been used include octreotide, octreotate, and lanreotide, all modified with the addition of the metal chelator tetraazacyclododecanetetraacetic acid (DOTA). This has allowed the use of a variety of radionuclides, although yttrium 90 (90Y) and lutetium 177 are the most commonly used (25,26). These therapies are not applicable solely to hepatic treatment (Fig 10), and certain inclusion and exclusion criteria are applicable prior to treatment (Table 2).
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Figure 10a. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10b. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10c. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10d. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10e. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10f. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10g. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10h. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10i. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10j. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10k. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10l. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Figure 10m. Metastatic NET in the sacrum in a young woman. (a–c) Whole-body image (a) and transverse (b) and sagittal (c) SPECT images show increased uptake of 111In-pentetreotide in the sacrum (arrow). Ant = anterior, Post = posterior. (d, e) Angiograms show blood being supplied to the tumor from both internal iliac arteries and the median sacral artery (arrow in d), along with a large tumor blush (arrow in e). (f, g) Angiograms obtained prior to embolization show rich blood supply to the tumor via the internal iliac arteries (arrow in f). (h) Angiogram shows that the median sacral artery has been catheterized (arrow) and 90Y-DOTA-octreotate instilled. (i, j) Angiograms obtained at the end of the procedure show greatly reduced blood flow to the sacral tumor (arrow in i) and a much smaller tumor blush (arrow in j). (k, l) Transverse (k) and sagittal (l) 111In-pentetreotide SPECT images obtained 6 weeks later help confirm the presence of central necrosis in the tumor (arrow). (m) Posttreatment T2-weighted MR image also helps confirm the presence of central necrosis (arrow).
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Most of the published work has involved the intraarterial administration of 90Y-lanreotide, resulting in a doubling (as measured radiologically) of the efficacy of 90Y-lanreotide administered intravenously (6,27). This technique has also been applied to other anatomic structures (Fig 10).
The role of PET in the evaluation of patients with NETs has not yet been determined. The low metabolic rate of these tumors means that 18F-FDG uptake is often reduced and may not be higher than background. An inverse relationship between SSTR imaging and 18F-FDG imaging has been reported: Tumors that are positive with one agent tend to be negative with the other (28).
Alternative methods of imaging have included use of 11C-5-HTP, a method that has been shown to have high sensitivity in a range of NETs. For example, in a series of 42 patients with NETs, the sensitivity of 11C-5-HTP imaging was 85%, compared with 87% for 111In-pentetreotide imaging (3). However, the use of 11C as a radiolabel restricts the use of 11C-5-HTP imaging to those centers with specialized radiochemistry facilities, including a cyclotron. Yet another alternative has been the development of gallium 68 (68Ga) DOTA–labeled SSTR imaging, which combines the sensitivity and specificity of SSTR imaging with the spatial resolution of PET. Early studies suggest that it is superior to 111In-pentetreotide imaging (29). A further advantage is that 68Ga is a generator-produced PET isotope and therefore has a greater availability.
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Ablative Techniques
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Ablative techniques rely on the principle that decreasing the volume of viable tumor or preventing new growth may lead to longer survival. If local ablation can decrease hormone production, significant symptomatic relief can be obtained.
RF ablation is the most commonly used ablative technique in metastatic NETs (Fig 11). This technique involves converting RF waves into heat. A high-frequency alternating current is passed from an uninsulated electrode into surrounding tissues. This results in friction heating between tumor particles surrounding the electrodes and produces cellular destruction. Options include open, laparoscopic, and percutaneous approaches. Unfortunately, studies of the use of RF ablation in NETs are few in number.
Surgery remains the standard of reference for liver metastases (30). However, indications for imaging-guided ablation have been suggested (31), including (a) need for an adjunct to surgical resection, (b) treatment of patients with unresectable tumor, (c) palliation of tumor-related symptoms, and (d) treatment of recurrent disease after surgical resection or prior ablation.
The largest study to date involved 34 patients with 234 liver metastases (32). Symptomatic relief was classified as either complete or significant and was achieved in 80% of symptomatic patients, lasting for an average of 10 months (32).
Other groups have reported similar success. Although the study group in a report by Henn et al (33) was smaller, 71% of patients experienced symptomatic relief. More recently, 25 patients with 189 liver metastases were treated with either 30 sessions of laser ablation or 36 sessions of RF ablation (34). Symptomatic relief was achieved in 69% of cases and disease control in 74% (34).
Other evidence shows that rate-limiting factors include the size and number of liver metastases. The lesions should generally be less than 3.5 cm in size and less than five in number (16). Tumors lying adjacent to large hepatic vessels should also be carefully evaluated prior to treatment. Although studies have shown promising results with combined RF ablation and TACE in patients with large hepatocellular carcinomas (HCCs), this combination approach has not been applied to NETs. It may be that the combination of the two techniques is superior to either technique alone. Surgical debulking of more than 90% of tumor (35) has provided short-term symptomatic relief, but this symptomatic benefit may also be applicable to RF ablation.
Like embolization techniques, RF ablation is associated with the release of hormones during the procedure. Therefore, it is important to consider prophylactic treatment with somatostatin analogs. Major complications such as hemorrhage or abscess formation are rare (36,37).
Hepatic cryotherapy involves the alternate freezing and thawing of liver tumors by means of a cryoprobe inserted into the tumors. Intra- and extracellular ice formation occurs, leading to tumor destruction. Hepatic cryotherapy has been an accepted adjunct to open surgery for many years (38) and can be performed repeatedly. Successful results have been demonstrated, with symptomatic control and objective tumor responses (39,40). The only disadvantages of cryotherapy are the higher complication rates seen with larger hepatic lesions and a tendency toward risk of hemorrhage when a large-diameter probe is used (41).
PEI can also be used in the treatment of metastatic NETs. Its mechanism of action causes coagulative necrosis and the formation of fibrous tissue with thrombosis of small vessels. It was used with good effect in patients with hepatic NET metastases in one study (42); however, this study involved only 14 patients. PEI is more frequently used in the treatment of HCC (43), although a lack of controlled studies and series with large numbers of patients have made interpretation of results in NETs more difficult. This is especially true because the degree of liver cirrhosis in HCC is different than that in NET. Cirrhosis in HCC can actually help limit the diffusion of ethanol out of the tumor into the remainder of the liver, which is quite cirrhotic. This phenomenon may not be seen in patients with a relatively cirrhosis-free liver, as in those with NET metastases.
Indeed, RF ablation has somewhat superseded PEI as the technique of choice in HCC. It is possible that PEI may be used for lesions unsuitable for RF ablation; the response rate for PEI has been shown to be higher in smaller HCC lesions (<3 cm in diameter) (43).
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Posttherapeutic Evaluation
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The management and follow-up of NETs requires a multidisciplinary approach. Subsequent therapy will depend on clinical status as well as biochemical, radiologic, and histologic findings.
Dual-phase multidetector CT and contrast-enhanced MR imaging play a central role in long-term assessment and follow-up. They are usually performed at 4-month intervals initially after intervention. If patients are shown to have stable disease for more than 1 year, they are then routinely monitored with biochemical analysis and imaging every 6 months. Evidence of extrahepatic disease should be sought, since it may preclude further targeted hepatic therapy. A suggested algorithm for treatment is shown in Figure 12.
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Figure 12. Diagram illustrates a suggested algorithm for the treatment of gastroenteropancreatic NETs. IA = intraarterial, IV = intravenous, OLT = orthotopic liver transplantation, Panc = pancreatic, SMS = somatostatin, STZ = streptozocin.
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Conclusions
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Interventional radiology already plays an important role in the palliation and treatment of metastatic NETs. This role will continue to expand with earlier diagnosis of NETs and the development of new techniques. Further studies are needed to assess which embolization techniques are most suitable for particular tumor types and which chemotherapy combination offers the best chance of increased survival time.
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Footnotes
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Abbreviations: DOTA = tetraazacyclododecanetetraacetic acid, FDG = fluorodeoxyglucose, HCC = hepatocellular carcinoma, HTP = hydroxytryptophan, NET = neuroendocrine tumor, RF = radiofrequency, PEI = percutaneous ethanol injection, SSTR = somatostatin receptor, TACE = transcatheter arterial chemoembolization, TAE = transcatheter arterial embolization
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References
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|---|
- Socia E, Kloppel G, Sobin LH, et al. Histologic typing of endocrine tumors. In: WHO international histological classification of tumors. Heidelberg, Germany: Springer Verlag, 2000.
- Dromain C, de Baere T, Lumbroso J, et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol 2005;23: 70–78.[Abstract/Free Full Text]
- Orlefors H, Sundin A, Garske U, et al. Whole-body (11)C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed tomography. J Clin Endocrinol Metab 2005;90(6): 3392–3400.[Abstract/Free Full Text]
- Musunuru S, Chen H, Rajpal S, et al. Metastatic neuroendocrine hepatic tumors: resection improves survival. Arch Surg 2006;141:1000–1004.[Abstract/Free Full Text]
- Hodul P, Malafa M, Choi J, Kvols L. The role of cytoreductive hepatic surgery as an adjunct to the management of metastatic neuroendocrine carcinomas. Cancer Control 2006;13(1):61–71.[Medline]
- McStay MK, Maudgil D, Williams M, et al. Large-volume liver metastases from neuroendocrine tumors: hepatic intraarterial 90Y-DOTA-lanreotide as effective palliative therapy. Radiology 2005;237: 718–726.[Abstract/Free Full Text]
- Touzios JG, Kiely JM, Pitt SC, et al. Neuroendocrine hepatic metastases: does aggressive management improve survival? Ann Surg 2005;241: 776–785.[CrossRef][Medline]
- Brown KT, Koh BY, Brody LA, et al. Particle embolization of hepatic neuroendocrine metastases for control of pain and hormonal symptoms. J Vasc Interv Radiol 1999;10:397–403.[Medline]
- Strosberg JR, Choi J, Cantor AB, Kvols LK. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control 2006;13(1): 72–78.[Medline]
- Loewe C, Schindl M, Cejna M, Niederle B, Lammer J, Thurnher S. Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: assessment of mid- and long-term results. AJR Am J Roentgenol 2003;180:1379–1384.[Abstract/Free Full Text]
- Moertel CG, Johnson CM, McKusick MA, et al. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 1994;120(4):302–309.[Abstract/Free Full Text]
- Yao KA, Talamonti MS, Nemcek A, et al. Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors. Surgery 2001;130: 677–685.[CrossRef][Medline]
- Perry LJ, Stuart K, Stokes KR, Clouse ME. Hepatic arterial chemoembolization for metastatic neuroendocrine tumors. Surgery 1994;116: 1111–1117.[Medline]
- Eriksson BK, Larsson EG, Skogseid BM, Lofberg AM, Lorelius LE, Oberg KE. Liver embolizations of patients with malignant neuroendocrine gastrointestinal tumors. Cancer 1998;83:2293–2301.[CrossRef][Medline]
- Gupta S, Johnson MM, Murthy R, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival. Cancer 2005;104:1590–1602.[CrossRef][Medline]
- O’Toole D, Ruszniewski P. Chemoembolization and other ablative therapies for liver metastases of gastrointestinal endocrine tumors. Best Pract Res Clin Gastroenterol 2005;19(4):585–594.[CrossRef][Medline]
- Roche A, Girish BV, De Baere T, et al. Transcatheter arterial chemoembolization as first-line treatment for hepatic metastases from endocrine tumors. Eur Radiol 2003;13:136–140.[Medline]
- Therasse E, Breittmayer F, Roche A, et al. Transcatheter chemoembolization of progressive carcinoid liver metastases. Radiology 1993;189: 541–547.[Abstract/Free Full Text]
- Ho AS, Picus J, Darcy MD, et al. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol 2007;188:1201–1207.[Abstract/Free Full Text]
- Madoff DC, Abdalla EK, Gupta S, et al. Transhepatic ipsilateral right portal vein embolization extended to segment IV: improving hypertrophy and resection outcomes with spherical particles and coils. J Vasc Interv Radiol 2005;16(2 pt 1): 215–225.[Medline]
- Madoff DC, Abdalla EK, Vauthey JN. Portal vein embolization in preparation for major hepatic resection: evolution of a new standard of care. J Vasc Interv Radiol 2005;16:779–790.[Medline]
- Teunissen JJ, Kwekkeboom DJ, de Jong M, Esser JP, Valkema R, Krenning EP. Peptide receptor radionuclide therapy. Best Pract Res Clin Gastroenterol 2005;19(4):595–616.[CrossRef][Medline]
- Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993;20:716–731.[Medline]
- Krenning EP, Teunissen JJ, Valkema R, deHerder WW, de Jong M, Kwekkeboom DJ. Molecular radiotherapy with somatostatin analogs for (neuro-) endocrine tumors. J Endocrinol Invest 2005;28 (11 suppl):146–150.[Medline]
- Forrer F, Valkema R, Kwekkeboom DJ, de Jong M, Krenning EP. Neuroendocrine tumors: peptide receptor radionuclide therapy. Best Pract Res Clin Endocrinol Metab 2007;21(1):111–129.[CrossRef][Medline]
- Valkema R, Pauwels S, Kvols LK, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0, Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2006;36(2): 147–156.[CrossRef][Medline]
- Virgolini I, Britton K, Buscombe J, Moncayo R, Paganelli G, Riva P. In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial. Semin Nucl Med 2002;32:148–155.[CrossRef][Medline]
- Belhocine T, Foidart J, Rigo P, et al. Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67. Nucl Med Commun 2002;23:727–734.[CrossRef][Medline]
- Groves AM, Win T, Haim SB, Ell PJ. Non-18F-FDG PET in clinical oncology. Lancet Oncol 2007;8:822–830.[CrossRef][Medline]
- Chamberlain RS, Canes D, Brown KT, et al. Hepatic neuroendocrine metastases: does intervention alter outcome? J Am Coll Surg 2000;190:432–445.[CrossRef][Medline]
- Atwell TD, Charboneau, Que FG, et al. Treatment of neuroendocrine cancer metastatic to the liver: the role of ablative techniques. Cardiovasc Intervent Radiol 2005;28:409–421.[CrossRef][Medline]
- Berber E, Flesher N, Siperstein AE. Laparoscopic radiofrequency ablation of neuroendocrine liver metastases. World J Surg 2002;26:985–990.[CrossRef][Medline]
- Henn AR, Levine EA, McNulty W, Zagoria RJ. Percutaneous radiofrequency ablation of hepatic metastases for symptomatic relief of neuroendocrine syndromes. AJR Am J Roentgenol 2003;181: 1005–1010.[Abstract/Free Full Text]
- Gillams A, Cassoni A, Conway G, et al. Radiofrequency ablation of neuroendocrine liver metastases: the Middlesex experience. Abdom Imaging 2005;30:435–441.[CrossRef][Medline]
- McEntee GP, Nagorney DM, Kvols LK, et al. Cytoreductive hepatic surgery for neuroendocrine tumors. Surgery 1990;108:1091–1096.[Medline]
- Ramage JK, Davies AH, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumors. Gut 2005;54(suppl 4):iv1–iv16.[Free Full Text]
- Plockinger U, Rindi G, Arnold R, et al. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumors. Neuroendocrinology 2004; 80:394–424.[CrossRef][Medline]
- Cozzi PJ, Englund R, Morris DL. Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors. Cancer 1995;76: 501–509.[CrossRef][Medline]
- Sheen AJ, Poston GJ, Sherlock DJ. Cryotherapeutic ablation of liver tumours. Br J Surg 2002;89: 1396–1401.[CrossRef][Medline]
- Tait IS, Yong SM, Cuschieri SA. Laparoscopic in situ ablation of liver cancer with cryotherapy and radiofrequency ablation. Br J Surg 2002;89: 1613–1619.[CrossRef][Medline]
- Madoff DC, Gupta S, Ahrar K, Murthy R, Yao JC. Update on the management of neuroendocrine hepatic metastases. J Vasc Interv Radiol 2006;17: 1235–1250.[CrossRef][Medline]
- Livraghi T, Vettori C, Lazzaroni S. Liver metastases: results of percutaneous ethanol injection in 14 patients. Radiology 1991;179:709–712.[Abstract/Free Full Text]
- Giovannini M. Percutaneous alcohol ablation for liver metastases. Semin Oncol 2002;29(2): 192–195.[CrossRef][Medline]
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Abstract
LEARNING OBJECTIVES
