Rare Malignant Indications for Liver Transplantation: A Collaborative Transplant Study Report

Introduction: Hepatocellular carcinoma (HCC) is by far the leading malignant indication for liver transplantation (LT). Few other malignancies, including cholangiocellular carcinoma (CCC), metastases from neuroendocrine tumors (NET), and sarcomas of the liver (LSAR), also are commonly accepted indications for LT. However, there is limited information on their outcome after LT.Methods: Graft and patient survival in 14,623 LTs performed in patients with hepatocellular carcinoma, CCC, NET, and LSAR from 1988 to 2017 and reported to the Collaborative Transplant Study were analyzed.Results: The study group consisted of 13,862 patients who had HCC (94.8%), 498 (3.4%) who had CCC, 100 (0.7%) who had NET, and 163 (1.1%) who had LSAR. CCC patients showed a 5-year graft survival rate of 32.1%, strikingly lower than the 63.2% rate in HCC, 51.6% rate in NET, and 64.5% rate in LSAR patients (P < 0.001 for all vs. CCC). Multivariable Cox regression analysis revealed a significantly higher risk of graft loss and death due to cancer during the first five post-transplant years in CCC vs. HCC patients (HR 1.77 and 2.56; P < 0.001 for both). The same risks were increased also in NET and LSAR patients but did not reach statistical significance.Conclusion: Among patients with rare malignant indications for LT, CCC patients showed significantly impaired graft as well as patient survival compared to HCC patients. The observed differences might challenge traditional decision-making processes for LT indication and palliative treatment in specific hepatic malignancies.

Current Approach to Planning Angiography and MAA Administration

Transarterial radioembolization of primary and secondary hepatic malignancies utilizing yttrium-90 microspheres is a commonly performed treatment by interventional radiologists. Traditionally performed as a two-part procedure, a diagnostic angiography is performed 1 to 3 weeks prior to treatment with the injection of technetium-99m-macroaggregated albumin followed by planar scintigraphy in the nuclear medicine department. Careful attention must be paid to the details during the diagnostic angiography to ensure the delivery of a safe and optimal dose to the diseased liver and to minimize radiation-induced damage to both unaffected liver and adjacent structures. In this article, we will review the steps and considerations that must be made during the angiography planning and discuss current and future areas of research.

Radioembolization of Secondary Hepatic Malignancies

Cancer has become the leading cause of mortality in America, and the majority of patients eventually develop hepatic metastasis. As liver metastases are frequently unresectable, the value of liver-directed therapies, such as transarterial radioembolization (TARE), has become increasingly recognized as an integral component of patient management. Outcomes after radioembolization of hepatic malignancies vary not only by location of primary malignancy but also by tumor histopathology. This article reviews the outcomes of TARE for the treatment of metastatic colorectal cancer, metastatic breast cancer, and metastatic neuroendocrine tumors, as well as special considerations when treating metastatic disease with TARE.

Radiation Lobectomy: An Overview of Concept and Applications, Technical Considerations, Outcomes

Surgical resection has long been considered curative for patients with early-stage hepatocellular carcinoma (HCC). However, inadequate future liver remnant (FLR) renders many patients not amenable to surgery. Recently, lobar administration of yttrium-90 (Y90) radioembolization has been utilized to induce FLR hypertrophy while providing disease control, eventually facilitating resection in patients with hepatic malignancy. This has been termed “radiation lobectomy (RL).” The concept is evolving, with modified approaches combining RL and high-dose curative-intent radioembolization (radiation segmentectomy) to achieve tumor ablation. This article provides an overview of the concept and applications of RL, including technical considerations and outcomes in patients with hepatic malignancies.

Quality of Life and Cost Considerations: Y-90 Radioembolization

Objective Transarterial radioembolization (TARE) offers a minimally invasive and safe treatment option for primary and metastatic hepatic malignancies. The benefits of TARE are manifold including prolonged overall survival, low associated morbidities, and improved time to progression allowing prolonged treatment-free intervals. The rapid development of new systemic therapies including immunotherapy has radically changed the treatment landscape for primary and metastatic liver cancer. Given the current climate, it is critical for interventional oncologists to understand the benefits of TARE relative to these other therapies. Therefore, this report aims to review quality-of-life outcomes and the cost comparisons of TARE as compared with systemic therapies.

Enlarged extracellular vesicles are a negative prognostic factor in patients undergoing TACE for primary or secondary liver cancer–a case series

Background Transarterial chemoembolization (TACE) has evolved as a standard treatment option in patients with intermediate stage, unresectable HCC [Barcelona Clinic Liver Cancer (BCLC) stage B] as well as in patients with liver metastases, when surgery or systemic therapy is considered not appropriate. Concentration and sizes of extracellular vesicles (EVs) recently emerged as novel diagnostic and prognostic biomarkers in patients with liver cancer, but no data on its prognostic relevance in the context of TACE exists. Here, we evaluate pre-interventional EVs as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies. Methods Vesicle size distribution and concentration were measured by nanoparticle tracking analysis (NTA) in patient sera before and after TACE in 38 patients. Results Extracellular vesicle size distribution measured before TACE is of prognostic significance with respect to overall survival in patients after TACE. Overall survival is significantly reduced when initial vesicle size (X50) is in the upper quartile (>145.65nm). Median overall survival in patients in the upper quartile was only 314 days, compared to 799 days in patients with vesicle size in the first to third quartile (<145.65nm; p = 0.007). Vesicle size was also shown to be a significant prognostic marker for overall survival in Cox regression analysis [HR 1.089, 95% CI: 1.021–1.162, p = 0.010]. In addition, a significant correlation was observed between initial EVs concentration/BMI (rS = 0.358, p = 0.029), X50/IL-8-concentration (rS = 0.409, p = 0.011) and X50/CRP-concentration (rS = 0.404, p = 0.016). In contrast, with regard to immediate tumor response after TACE, EVs concentration and size did not differ. Summary Sizes (but not concentrations) of EVs represent a novel prognostic marker in patients receiving TACE for primary and secondary hepatic malignancies since patients with enlarged EVs display a significantly impaired prognosis after TACE.

Road to becoming Y-90 authorized user as an integrated vascular and interventional radiology resident (NRC alternate pathway)

Yttrium-90 (Y-90) radioembolization, also called transarterial radioembolization (TARE), is a catheter-directed therapy for direct delivery of internal radiation to tumors in the form of microspheres. It is currently available in two forms, either as a constituent of glass microspheres called TheraSphere® (BTG Ltd., London, UK [now Boston Scientific, Marlborough, MA, USA]) or as a biocompatible resin-based microsphere called SIR-Spheres® (Sirtex Medical Ltd., Woburn, MA, USA). Once these microspheres are delivered to the tumor through an arterial pathway, they are embedded within the tumor microcirculation and emit β-radiation at therapeutic levels. TARE is a commonly used treatment for unresectable primary or secondary hepatic malignancies and has led to improved survival rates and increased success rates in downstaging patients before liver resection or transplantation. Immediately following the pre-treatment angiogram, each patient undergoes a nuclear medicine study, otherwise known as technetium (99mTc) macroaggregated albumin scan, to determine the amount of radiotracer that has accumulated in the lungs (lung shunt fraction). Finally, after several calculations, the appropriate radiation dose to be delivered to the tumor is determined. While the technical aspects of radioembolization are quite complex, the collective clinical experience presented in the literature supports the use of Y-90 radioembolization for unresectable hepatic malignancies. Those ordering and administering radioembolization particles must be deemed an authorized user (AU) by the Nuclear Regulatory Commission (NRC). The NRC defines an AU as the individual responsible for ensuring that radioactive materials are handled and used safely and following NRC regulations and the terms and conditions of the NRC license. The NRC has published licensing guidance on Y-90 brachytherapy with the 10th revision released on November 8, 2019. This guidance has outlined specific requirements for obtaining a license for the use of TheraSphere and SIR-Spheres. Following the revised licensure guidelines from the NRC on Y-90 usage, a conditional authorization has been obtained at our institution by the PGY-6 interventional radiology/diagnostic radiology (IR/DR) resident. While the full guidelines and extensive alternative requirements can be found online, we will highlight the specific guidelines applicable to and fulfilled by IR/DR residents. The traditional ABR pathway takes approximately 18 months after graduation, including passing the ABR certification examination to become an AU. With the proposed alternate pathway, trainees will potentially become AU immediately after graduation. The primary aim of this submission is to describe the process for obtaining conditional authorization for Y-90 microspheres for PGY-6 IR/DR residents.

Radioembolization for Rare Metastatic Disease

Radioembolization has become a widespread treatment modality for both primary and metastatic hepatic malignancies. Although the majority of data and indication for yttrium-90 radioembolization have been for hepatocellular carcinoma and metastatic colorectal cancer, radioembolization with yttrium-90 has rapidly expanded into the treatment options for multiple tumor types with metastases to the liver. This article reviews the clinical data and expanding utilization of radioembolization for rare metastatic diseases with an emphasis on efficacy and safety.