Douglas Coldwell

Radioembolization for the treatment of liver tumors: General principles

Radioembolization aims to selectively target radiation to all liver tumors while limiting the dose to normal liver parenchyma. The deposition of yttrium-90 (90Y) microspheres delivered through the hepatic artery are preferentially implanted within liver tumors in a 3:1 to 20:1 ratio compared with a normal liver. The principles and mode of action of radioembolization are fundamentally different from the conventional embolization of liver tumors through transarterial embolization or chemoembolization. A meticulous work-up, involving computed tomography scanning, contrast-enhanced magnetic resonance imaging, and transfemoral hepatic angiogram, is essential to assess the appropriateness of the patient for treatment. A simulation of the treatment, done with technetium-99m-labeled macroaggregated albumin particles, which approximate the size of microspheres, is used to identify the shunting of microparticles to the lungs or gastrointestinal tract, thus helping to determine patient selection. Whole-liver or unilobar treatment approaches are chosen according to the anatomic distribution of the tumors, concomitant factors affecting liver function, and institutional preferences. Optimal periprocedural care, discharge planning, and follow-up care are essential to assess treatment response and ensure that short-term side effects of radioembolization are adequately managed. The expanding literature on radioembolization shows that this is an effective treatment for the management of both primary and metastatic tumors.

Radioembolization for hepatocellular carcinoma: A review of the evidence and treatment recommendations

Treatment decisions for hepatocellular carcinoma involve the evaluation of multiple factors including tumor size, location, and morphology; comorbidity and/or extrahepatic disease; health status; patient preferences; and the treating physicians expertise and skill. For patients who are not candidates for transplant or resection, and for whom other therapies (radiofrequency ablation, systemic chemotherapies, transarterial embolization or chemoembolization), may have limited efficacy, an urgent need for bridging procedures, to enable surgery or ablation, or meet transplantation criteria, has led to investigations with radioembolization. A number of recent reports have supported the effectiveness of Yttrium-90 (90Y) labeled microspheres to treat intermediate and advanced disease in patients with good overall functional status and liver reserve; patients with portal vein involvement and in a limited role to treat unresectable early-stage disease. This review addresses response rates and survival benefit following radioembolization in different patient populations, in centers throughout Europe, North America, and Asia, and across the spectrum of patients presenting with various prognostic factors. By using stringent selection criteria and conservative models for calculating radiation dosage, radioembolization can be performed safely even in cirrhotic patients, without postembolization syndrome or radiation-induced liver disease, and even with multiple treatments to whole or part of the liver.

General selection criteria of patients for radioembolization of liver tumors: an international working group report.

A combined treatment approach that incorporates surgical resection, ablation, chemotherapy, targeted agents, and radiotherapy has augmented the management of liver tumors (both primary and metastatic). The challenge that remains is how to reduce the burden of liver disease and thus enable greater patient eligibility for resection as well as lengthened survival for those who remain unsuitable for surgery. Radioembolization can deliver high doses of radiation preferentially to liver tumors and is a valuable treatment option that should be considered as part of a multimodal treatment approach for the management of patients in whom the liver is the sole or dominant site of disease. Essential in this consideration is a careful assessment by a multidisciplinary team of the individuals most likely to benefit from this treatment modality. Along with the clinical benefits, integration of radioembolization into the treatment paradigm can provide added options of using systemic chemotherapy synergistically as a radiosensitizer and to control extrahepatic metastases, permitting a reduction in hepatic disease and conserving remaining liver function. If successful, the possibility of improved patient survival and quality of life is increased.

A novel biliary stent loaded with 125I seeds in patients with malignant biliary obstruction: Preliminary results versus a conventional biliary stent

BACKGROUND & AIMS Stenting is a palliative therapy method for relieving malignant biliary obstruction. The aim of this study was to evaluate the safety and effectiveness of an irradiation stent compared to a conventional biliary stent in patients with biliary obstruction caused by both primary and metastatic adenocarcinomas. METHODS Participants were randomly assigned to receive treatment with a biliary irradiation stent (irradiation stent group) or a conventional biliary stent (control group). After stent implantation, the outcomes were measured in terms of relief of obstructive jaundice, survival time, complications related to the procedure. A p value of less than 0.05 indicated a significant difference. RESULTS The stents were successfully placed in all the 23 patients. The obstructive jaundice was relieved in all patients except three in the control group. The median and mean overall survivals in the irradiation stent group were higher than those in the control group (7.40 months versus 2.50 months, 8.03 months versus 3.36 months, p=0.006). The patients with stent patent at 3, 6, and 12 months in the irradiation stent group were 11 (91.7%), 7 (58.3%), and 1 (8.3%), respectively. While in the control group, 4 (36.4%), 1 (9.1%), and 0 (0%), respectively. There were no significant differences in the complications related to stent insertion between the two groups. CONCLUSIONS This interim analysis shows that treatment with the biliary intraluminal irradiation stent in patients with biliary obstruction caused by adenocarcinomas appears safe and technically feasible, has benefits in relieving jaundice, and seems to extend survival when compared to a conventional biliary stent.

Radioembolization in the treatment of unresectable liver tumors: experience across a range of primary cancers.

Radioembolization is a proven treatment to slow disease progression and improve survival in patients with colorectal cancer liver metastases and hepatocellular carcinoma. Accumulating evidence supports its use in metastases from neuroendocrine tumors and breast cancer. Cancers with radiobiologic profiles similar to those of colorectal and breast cancer, including melanoma, lung cancer, and nodular cholangiocarcinoma, are being studied as candidates for radioembolization. This treatment modality has also been shown to downsize hepatic tumors for potentially curative ablation in patients with breast, pancreatic, and colorectal cancer. Radioembolization using either yttrium-90 (90Y)-labeled resin or glass microspheres represents a promising therapy for liver-only or liver-predominant tumors in patients with 1 or more variables, including adequate or sufficient functional liver reserve, good performance status, and absence of other significant comorbidities. Therapeutic efficacy and safety can be best achieved by use of careful dosimetric techniques and treatment planning. Radioembolization could be considered after progression of liver metastases during treatment hiatus, at an early therapeutic line in tumors that respond poorly to chemotherapy, or in treatment-refractory disease.

Integrating Radioembolization (90Y Microspheres) Into Current Treatment Options for Liver Tumors: Introduction to the International Working Group Report

Liver-directed therapies for unresectable cancers in the liver are evolving with increased efficacy and decreasing toxicity. One of these approaches uses radioactive microspheres delivered to hepatic tumors via the hepatic artery system—radioembolization. Use of this therapy is rapidly increasing worldwide with over 20,000 patients treated thus far. Therefore, greater understanding of its potential and optimal positioning of this therapy in the multimodality management of cancers affecting the liver is needed. This task has been undertaken by a group of the most experienced clinicians in radioembolization from multiple disciplines involved in this therapy.

Integrating radioembolization with chemotherapy in the treatment paradigm for unresectable colorectal liver metastases

Clinical decisions regarding the treatment of metastatic colorectal cancer require consideration of current and evolving modalities to best achieve prolonged patient survival. Clinical trials have established that for first-line treatment of patients with or without extrahepatic metastases, radioembolization augments the response produced by chemotherapy in patients with unresectable liver metastases. This includes progression-free and overall survivals that compare favorably with phase II to III data of current chemotherapy regimens. The increased response rate with radioembolization and first-line chemotherapy may improve the likelihood for potentially curative hepatic lesion resection or ablation. Application of an innovative multidisciplinary treatment approach that integrates radioembolization and local ablative therapy may enable the benefits of curative hepatic resection to be extended to a broader group of patients.

Radioembolization in the Treatment of Neuroendocrine Tumor Metastases to the Liver

Surgical excision remains the preferred treatment for resectable hepatic metastases of neuroendocrine tumors. In cases of more disseminated hepatic disease, transarterial radioembolization with Yttrium-90- (90Y-) labeled microspheres has been demonstrated as a viable option for symptom and locoregional tumor control. On an outpatient basis, radioembolization can be utilized from early line to salvage phases, in various combinations with systemic therapies. Review of available data shows encouraging safety and efficacy profiles for the intraarterial application of 90Y for the treatment of mNETs of the liver. Symptom control and decrease in somatostatin analog use can be achieved, as well as prolonged survival.

Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review

Selective internal radiation therapy (or radioembolization) by intra‐arterial injection of radioactive yttrium‐90‐loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high‐dose beta‐radiation penetrates an average of only 2.5 mm from the source, thus limiting its effects to the site of delivery. However, the off‐target diversion of yttrium‐90 microspheres to tissues other than the tumor may lead to complications. The most prominent of these complications include radiation gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radioembolization‐induced liver disease, which may occur despite careful pretreatment planning. Thus, selective internal radiation therapy demands an expert multidisciplinary team approach in order to provide comprehensive care for patients. This review provides recommendations to multidisciplinary teams on the optimal medical processes in order to ensure the safe delivery of selective internal radiation therapy. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis, and management of potential radiation injury to the liver and to other organs. (Hepatology 2017;66:969–982).

Review of pelvic collateral pathways in aorto-iliac occlusive disease: demonstration by CT angiography.

The pelvic collateral system is a robust network of communicating vessels that provide the functional reserve to withstand chronic aorto-iliac occlusive disease. For establishment of collateral circulation, the afferent vessel must originate proximal to the occlusion and anastomose with vessel/s distal to the occlusion. These collateral pathways can be classified as viscero–systemic, systemic–systemic, and visceral–visceral. CT angiography (CTA) is often the initial modality for evaluating patients with atherosclerotic vascular disease, because it is non-invasive and has been shown to be comparable to conventional angiography. Most collateral pathways are well demonstrated on CTA, which therefore is a useful tool for preoperative planning and regional interventional procedures.