Manon N.G.J.A. Braat

⁹⁰Y Hepatic Radioembolization : An Update on Current Practice and Recent Developments

Radioembolization is an established treatment modality that has been subjected to many improvements over the last decade. Developments are occurring at a high pace, affecting patient selection and treatment. The aim of this review is therefore to provide an overview of current practice, with a focus on recent developments in the field of radioembolization. Several practical issues and recommendations in the application of radioembolization will be discussed, ranging from patient selection to treatment response and future applications.

Radioembolization-induced liver disease: a systematic review.

Radioembolization (RE) is a relatively novel treatment modality for primary and secondary hepatic malignancies. Microspheres embedded with a &bgr;-emitting radioisotope are injected into the hepatic artery, resulting in microsphere deposition in the tumor arterioles and normal portal triads. Microsphere deposition in nontumorous parenchyma can result in radiation-induced liver injury, with lethal RE-induced liver disease (REILD) at the outer end of the spectrum. The primary aim of this study was to evaluate RE-related hepatotoxicity and present an overview of the currently applied definitions and clinically relevant characteristics of REILD. A systematic literature search on REILD was performed. Studies after the introduction of the term REILD (2008) were screened for definitions of REILD. Hepatotoxicity and applied definitions of REILD were compared. Liver biochemistry test abnormalities occur in up to 100% of patients after RE, mostly self-limiting. The incidence of symptomatic REILD varied between 0 and 31%, although in most reports, the incidence was 0–8%, with a lethal outcome in 0–5%. With the exception of bilirubin, the presentation of hepatotoxicity and REILD was similar for cirrhotic and noncirrhotic patients. No uniform definition of REILD was established in the current literature. Here, we propose a unifying definition and grading system for REILD. RE-related hepatotoxicity is a common phenomenon; symptomatic REILD, however, is rare. Currently, reporting of REILD is highly variable, precluding reliable comparison between studies, identification of risk factors, and treatment developments.

The peri‐esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri‐esophageal fascias have not been described and it is unclear whether this layer can be visualized by non‐invasive imaging. This study aimed to provide a comprehensive description of the peri‐esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2‐weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri‐esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion‐triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named ‘aorto‐esophageal ligament’ and the layer connecting aorta to the right pleural reflection ‘aorto‐pleural ligament’. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named ‘peri‐esophageal compartment’ and the posterior compartment ‘para‐aortic compartment’. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long‐standing paradigm that no such structure exists. A comprehensive, detailed description of the peri‐esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI.

The role of (90)Y-radioembolization in downstaging primary and secondary hepatic malignancies: a systematic review.

Radioembolization (RE) is an emerging treatment strategy for patients with primary hepatic malignancies and metastatic liver disease. Though RE is primarily performed in the palliative setting, a shift toward the curative setting is seen. Currently, hepatic resection and in selected cases liver transplantation are the only curative options for patients with a hepatic malignancy. Unfortunately, at diagnosis most patients are not eligible for liver surgery due to the imbalance between the necessary liver resection and the remaining liver remnant. However, in borderline resectable cases, tumor volume reduction and/or increasing the future liver remnant can lead to a resectable situation. The combination of selective tumor treatment, the induction of hypertrophy of untreated liver segments, and its favourable toxicity profile make RE an appealing strategy for downstaging. The present review discusses the possibilities for RE in the preoperative setting as a downstaging tool or as a bridge to liver transplantation.

Efficacy of radioembolization with holmium-166 microspheres in salvage patients with liver metastases: a phase 2 study.

Radioembolization of liver malignancies with 166Ho-microspheres has been shown to be safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy of 166Ho radioembolization. Methods: In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. The primary outcome was a response by 2 target lesions on triphasic liver CT scans 3 mo after therapy, as assessed using RECIST, version 1.1. Secondary outcomes included overall tumor response, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI. Results: Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27 (73%) of 37 patients, the target lesions showed complete response, partial response, or stable disease (disease control) at 3 mo (95% confidence interval [CI], 57%–85%). The median overall survival was 14.5 mo (95% CI, 8.6–22.8 mo). For colorectal cancer patients (n = 23), the median overall survival was 13.4 mo (95% CI, 8.2–15.7 mo). Grade 3 or 4 toxic events after treatment (according to the Common Terminology Criteria for Adverse Events, version 4.03) included abdominal pain (in 18% of patients), nausea (8%), ascites (3%), fatigue (3%), gastric stenosis (3%), hepatic failure (3%), liver abscesses (3%), paroxysmal atrial tachycardia (3%), thoracic pain (3%), upper gastrointestinal hemorrhage (3%), and vomiting (3%). On SPECT, 166Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3% ± 7.1% in the liver. Conclusion: Radioembolization with 166Ho-microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.