Metastatic colorectal cancer (mCRC) remains largely an incurable condition. Although progress has been made in expanding the number of available systemic agents, treatment after initial therapy has limited benefit. Radioembolization (RE) with radiolabeled microspheres is an emerging treatment modality for mCRC. Given the potential benefit of chemotherapy to control systemic disease and act as a radiosensitizer, there is high enthusiasm for studying RE and chemotherapy combinations, particularly after initial systemic therapy for patients with liver dominant or confined disease. This manuscript reviews the rationale for this approach, summarizes recently reported clinical trials, and provides a perspective for everyday practice and future unanswered research questions.

Debulking neuroendocrine hepatic metastases is commonplace as both symptoms and disease are better controlled. The challenge in clinical decision making includes patient selection, timing and procedure. Extirpation, radiofrequency ablation, hepatic artery chemoembolization, bland embolization and radioembolization are techniques widely available in the U.S. For patients undergoing intrahepatic therapies, procedure selection is based not only on disease bulk but also on disease location. From 8 published studies, the outcomes of 281 patients who underwent radioembolization were reviewed. Symptomatic improvement occurs within 3 months in approximately half the patients. Partial biochemical responses (>50% reduction from baseline) using chromogranin A occur in two thirds of subjects as 2 centers have observed. Disease control (complete + partial + stable responses) is reported in 50-100% of patients. The median time to progression is 11.1 months in one report. Six centers report a median survival ranging from 14 to 70 months. One, 2 and 3 year survival ranges from 2 reports are 86-100%, 57-58% and 47-57%, respectively As more choices become available in controlling neuroendocrine disease, optimally combining debulking procedures such as radioembolization with systemic therapy is challenging. Using infusional 5-FU with radioembolization can be done safely but added benefit remains uncertain. Prior hepatic artery chemoembolization may not be a contraindication to radioembolization. Future trials are needed to guide the practitioner in using radiation sensitizers with radioembolization.

Within the setting of hepatic neoplasia [primary and secondary], selective internal radiation therapy [SIRT], also known as radioembolization has become an accepted procedure, incorporated into the armamentarium of multidisciplinary oncologic care. The procedure itself requires understanding of mesenteric anatomy, tumor vascular patterns, liver metabolism, and chemotherapy. Given the complex nature of the treatment, unique toxicities, and complications may develop from multiple etiologies. Reduction of toxicities and complications as they relate to this procedure can be stratified into two broad categories: factors involving vascularity/vascularization, and factors involving compromise to the underlying liver parenchyma. The purpose of this manuscript is to provide the reader with a systematic review of the most commonly presented toxicities, their etiologies, prevention strategies, and suggested therapeutic options in a practical, and concise manner. A brief discussion on the common misconceptions regarding toxicities will be included.

Selective internal radiation therapy (SIRT), otherwise known as radio embolization is now becoming a common procedure performed for those patients with primary hepatic neoplasia [such as hepatocellular carcinoma], and liver dominant metastatic disease [such as in near endocrine disease, and colorectal carcinoma]. The current technology platforms incorporate the use of yttrium 90, a pure beta emitter loaded on either a resin microsphere, or ceramic microsphere. Although clinical outcomes have been encouraging with both technology platforms, second-generation radioembolic devices [utilizing either new processes of microsphere synthesis, or different radioactive isotopes] are currently under development, or clinical study. The purpose of this manuscript is to provide the reader with some perspectives regarding the next generation of radioembolic devices, and discussing the advantages and disadvantages of both current, and future platforms.

The commonest cause of death from advanced colorectal cancer is disease progression of hepatic metastases. A number of technologies are in clinical development to improve local control of liver metastases and potentially improve overall survival. Radio-embolization (RE) is a technique for administering resin or glass microspheres that contain yttrium-90 to unresectable primary or secondary hepatic malignancies internally via the liver's arterial supply in a single procedure. Clinical trials of RE used with concomitant radiosensitizing chemotherapy have shown promising results in patients with metastatic colorectal cancer. In this article, the evidence base for combining RE with systemic chemotherapy in the first line therapy of metastatic colorectal cancer is appraised and the scientific rationale for combining RE with chemotherapy in first and subsequent lines of therapy is outlined. Clinical trials of RE and chemotherapy currently recruiting patients with metastatic colorectal cancer are discussed in detail and practical recommendations offered on how best to combine RE and systemic chemotherapy.

Yttrium-90 microspheres radioembolization has shown to be an effective modality of treatment in patients with primary or metastatic liver tumours [1-4]. It is usually offered to patients with advanced liver cancers. However, surgical experience after radioembolization is very limited to anecdotal cases mainly related to hepatocellular carcinoma. We have treated patients with hepatocellular carcinoma or liver metastasis mainly from colon, breast, melanoma and neuroendocrine tumours. In our experience after such treatment we were able to downstage the tumour to surgery only in the case of hepatocellular carcinoma. Five patients had liver transplantation and 1 had right hepatic resection after Yttrium-90 microspheres radioembolization. Of note 2 patients had neoplastic infiltration of a portal vein branch which resolved after treatment with Yttrium-90 microspheres radioembolization. The extra-hepatic spread was ruled out and later they were both transplanted. Here we report our initial single center experience with Yttrium-90 microspheres radioembolization as downstaging and bridging method for hepatocellular carcinoma prior liver surgery, resection or liver transplantation.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality. Radioembolization is a form of selective internal radiation therapy that is increasingly used to treat patients with HCC, particularly those with more advanced disease. This review will try to answer some of the most frequently asked questions regarding the use of radioembolization to treat HCC patients and provide supporting evidence. Rather than a new form of transarterial chemoembolization (TACE), radioembolization is a form of brachytherapy that has a highly localized effect on liver tumors. The two devices that are available (glass and resin microspheres) are similar in size (25 to 35 microns), but differ in the amount of isotope loaded onto each microsphere and the number of spheres injected in a single treatment. Despite this, the evidence seems to indicate that the antitumor effect and safety profiles of these two devices in HCC are similar. Liver cirrhosis frequently underlies HCC. Despite the higher chance for relevant liver toxicity, there is now good evidence from large studies to show that radioembolization can be safely and effectively performed in cirrhotic patients with HCC. With no randomized controlled trials published so far, there is recent scientific evidence that allows comparison between radioembolization and other treatment options including TACE and the systemic, agent sorafenib. Radioembolization appears to have similar efficacy to TACE in patients that are ideal candidates for locoregional therapy and has shown encouraging results in patients that have failed TACE or who are poor candidates for this therapy. Survival in comparable sorafenib- and radioembolizationtreated HCC patients is quite similar. The indication for radioembolization has to be balanced against the risk of liver decompensation and the natural history of the disease, based on tumor burden and liver function. Patients with inadequate liver functional reserve and diffuse tumors affecting either lobes, or portal vein thrombosis that reaches the main trunk should probably not be treated with this procedure.

Introduction: Hepatic brachytherapy using either resin or glass 90Y microspheres is an established therapy for unresectable primary and metastatic tumors. Unlike conventional brachytherapy, microsphere brachytherapy has no software currently available for pretreatment evaluation and radiation planning. A non-MIRD radiation dose calculation approach is desired to accurately utilize spatial relationships in the liver and tumor distribution. Materials and methods: A newly developed software tool employing the technetium-99m macro aggregated albumin (99mTc-MAA) SPECT 3-D dataset and CT scan was used to estimate the likely absorbed dose in normal liver and tumor tissue from 90Y microsphere brachytherapy (radioembolization). Monte Carlo algorithms were utilized to maximize true 3D dose estimates for each patient's unique liver and tumor geometry. Clinical correlation was completed regarding toxicity, imaging response, and complications as an independent measure of the software's usefulness in predicting radiation effects. Comparisons were made to MIRD, Body Surface Area method, and physician prescription for 90Y activity. Results: The software performed accurately in estimating absorbed dose in phantom testing. Patient data from 50 consecutive patients with metastatic tumors (26 colon, 24 neuroendocrine) to the liver receiving 59 radioembolization treatments were studied. The software estimate of median normal liver and tumor absorbed doses were 27.6 Gy and 41.2 Gy, respectively. Conclusions: The use of pretreatment 99mTc-MAA SPECT co-registered to a CT scan provides useful and unique data for a newly developed non-MIRD, Monte Carlo-based radiation dosimetry software program in 90Y microsphere brachytherapy. Software estimates of radiation dose preserving critical spatial information in the liver and tumors appeared reasonable based on clinical outcomes. Further testing and refinement of the software interface is ongoing with plans to distribute it to research organizations.

The number of patients afflicted with liver tumors continues to rise being a major concern of international healthcare. Yttrium-90 microsphere radioembolization can be an effective and safe treatment of unresectable primary and secondary liver tumors, and has the potential to be a forefront treatment option for tumor-afflicted patients. Computational fluid-particle dynamics is a powerful research tool that can be used to understand the underlying physics of Yttrium-90 microsphere transport and deposition, leading to improved clinical strategies and ultimately to a better treatment of tumor-afflicted patients. Two representative, patient-inspired three-dimensional geometries of the hepatic arterial system with assumed connections to liver tumors have been considered. Experimentallyvalidated computational fluid-particle dynamics modeling results have shown the significant influence of vessel morphology, downstream resistance to flow, catheter radial and axial location associated with microsphere injection time interval, and injection velocity on microsphere transport through the hepatic arterial system. Moreover, the computational investigations have identified the ability to preferentially deliver microspheres to a specific arterial vessel outlet, presumably connected to a tumor, by selecting appropriate temporal and spatial parameters of the microsphere injection. As the computational findings are extended to additional experiments as well as nextgeneration smart micro-catheters, clinicians can implement a refined set of treatment strategies that utilize the aforementioned physical phenomena. Computational fluid-particle dynamics models have thus provided valuable physical insight as well as suggestions for the improvement of current Yttrium-90 microsphere radioembolization treatment. Additional computational investigations are needed to create more encompassing conclusions from a large collection of patient-specific analyses plus the design, prototyping, and testing of a new smart micro-catheter and high-resolution imaging devices that give radiation and interventional oncologists new degrees of control and precision when administering Yttrium-90 microsphere radioembolization.

Adequate patient selection and treatment planning is crucial for a safe and cost-effective administration of selective internal radiotherapy (SIRT) of malignant liver disease using 90Y-labelled microspheres. It requires the implementation of multimodality imaging, integrating metabolic, functional and structural characteristics. A multidisciplinary approach is a prerequisite for SIRT, bringing together the knowhow and expertise of radiologists, nuclear medicine physicians, medical physicists, imaging engineers, and radiotherapists. This review discusses the available radiologic (CT/MRI) and nuclear (SPECT/PET) imaging modalities and their specific utility in the different diagnostic phases related to SIRT: whole body and intrahepatic pre-treatment disease staging, CT and MRI-based angiography, liver-lung shunt assessment, treatment simulation, predictive dosimetry, post-treatment imaging, and SIRT response assessment.