Authors: Riad Salem, Guy E Johnson, Edward Kim...

BACKGROUND AND AIMS

Locoregional therapies, including yttrium-90 radioembolization, play an important role in the treatment of unresectable HCC. The aim of the LEGACY (Local radioEmbolization using Glass Microspheres for the Assessment of Tumor Control with Y-90) study was to evaluate objective response rate (ORR) and duration of response (DoR) in patients with solitary unresectable HCC treated with yttrium-90 glass microspheres.

APPROACH AND RESULTS

LEGACY is a multicenter, single-arm, retrospective study conducted at three sites that included all eligible, consecutive patients with HCC treated with radioembolization between 2014 and 2017. Eligibility criteria included solitary HCC ≤ 8 cm, Child-Pugh A cirrhosis, and Eastern Cooperative Oncology Group performance status 0-1. Primary endpoints were ORR and DoR based on modified Response Evaluation Criteria in Solid Tumors in the treated area (localized), as evaluated by blinded, independent, central review. Radioembolization was performed with intent of ablative-level dosimetry in a selective fashion when possible. Overall survival was evaluated using Kaplan-Meier and multivariate Cox proportional hazards. Among the 162 patients included, 60.5% were Eastern Cooperative Oncology Group 0, and the median tumor size was 2.7 cm (range: 1-8) according to blinded, independent, central review. Radioembolization served as neoadjuvant therapy for transplantation or resection in 21.0% (34 of 162) and 6.8% (11 of 162) of patients, respectively, and as primary treatment for all others. Median follow-up time was 29.9 months by reverse Kaplan-Meier. ORR (best response) was 88.3% (CI: 82.4-92.4), with 62.2% (CI: 54.1-69.8) exhibiting a DoR ≥ 6 months. Three-year overall survival was 86.6% for all patients and 92.8% for those neoadjuvant patients with resected or transplanted liver.

CONCLUSIONS

In this multicenter study of radioembolization, clinical meaningful response rates and prolonged DoR were observed in the treatment of unresectable, solitary HCC ≤ 8 cm.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brachytherapy; Carcinoma, Hepatocellular; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Liver Transplantation; Male; Microspheres; Middle Aged; Neoadjuvant Therapy; Radiopharmaceuticals; Retrospective Studies; Treatment Outcome; Young Adult; Yttrium Radioisotopes

PubMed: 33739462
DOI: 10.1002/hep.31819

Review

Authors: Coskun O Demirtas, Antonio D'Alessio, Lorenza Rimassa...

Hepatocellular carcinoma (HCC) usually arises in the context of a chronically damaged liver. Liver functional estimation is of paramount importance in clinical decision making. The Child-Pugh score (CPS) can be used to categorise patients into 3 classes (A to C) based on the severity of liver functional impairment according to 5 parameters (albumin, bilirubin, prothrombin time, presence of ascites and hepatic encephalopathy). The albumin-bilirubin (ALBI) grade has emerged as an alternative, reproducible and objective measure of liver functional reserve in patients with HCC, defining worsening liver impairment across 3 grades (I to III). The ALBI score can identify different subgroups of patients with different prognoses across the diverse Barcelona Clinic Liver Cancer stages and CP classes, making it an appealing clinical predictor. In patients treated with potentially curative approaches (resection, transplantation, radiofrequency ablation, microwave ablation), ALBI grade has been shown to correlate with survival, tumour relapse, and post-hepatectomy liver failure. ALBI grade also predicts survival, toxicity and post-procedural liver failure in patients treated with transarterial chemoembolisation, radioembolisation, external beam radiotherapy as well as multi-kinase inhibitors (sorafenib, lenvatinib, cabozantinib, regorafenib) and immune checkpoint inhibitor therapy. In this review, we summarise the body of evidence surrounding the role of ALBI grade as a biomarker capable of optimising patient selection and therapeutic sequencing in HCC.

PubMed: 34505035
DOI: 10.1016/j.jhepr.2021.100347

Review

Authors: Kristina Prachanronarong, Edward Kim

Radiation segmentectomy is an yttrium-90 transarterial radioembolization treatment where a high radiation dose is administered to a small volume of liver to achieve a high tumoricidal dose to a target with anatomic surgical precision while sparing surrounding parenchyma. This therapeutic modality is often used to treat hepatocellular carcinoma, and recent studies have demonstrated that radiation segmentectomy is an effective treatment as a neoadjuvant to transplant, resection, or as a standalone treatment. This article provides a review of radiation segmentectomy, indications for treatment, recent outcome data, and guidelines for postprocedural management.

PubMed: 34629709
DOI: 10.1055/s-0041-1735529

Review

Authors: Pouya Entezari, Ahsun Riaz

Cholangiocarcinoma is the second most common primary malignancy of the liver. This review will focus on the mass-forming intrahepatic type of this disease and discuss the role of medical, surgical, and radiation oncology in managing this difficult disease. A global understanding to the management of intrahepatic cholangiocarcinoma (ICC) can help the interventional radiologist understand the role of locoregional therapies such as ablation, transarterial chemoembolization, and radioembolization in the management of ICC.

PubMed: 33328703
DOI: 10.1055/s-0040-1719188

Review

The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

Authors: M Ducreux, G K Abou-Alfa, T Bekaii-Saab...

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

Topics: Humans; Carcinoma, Hepatocellular; Gastrointestinal Neoplasms; Liver Neoplasms; Practice Guidelines as Topic

PubMed: 37263081
DOI: 10.1016/j.esmoop.2023.101567

Comparative Study Randomized Controlled Trial

Authors: Riad Salem, Andrew C Gordon, Samdeep Mouli...

BACKGROUND & AIMS

Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC.

METHODS

From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child-Pugh A) or cTACE (n = 21; 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan-Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses.

RESULTS

Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027-0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3-not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4-32.5) (P = .99).

CONCLUSIONS

In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.

Topics: Aged; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Diarrhea; Disease Progression; Disease-Free Survival; Ethiodized Oil; Female; Humans; Hypoalbuminemia; Intention to Treat Analysis; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Necrosis; Neoplasm Staging; Prospective Studies; Survival Rate; Yttrium Radioisotopes

PubMed: 27575820
DOI: 10.1053/j.gastro.2016.08.029

Review

Authors: Gajan Sivananthan, Nora E Tabori

Radioembolization has become a mainstay therapy in the treatment of primary and secondary liver cancers. This article will specifically discuss a brief history of yttrium treatment as well as an overview of the physical properties of the currently available devices. A discussion of the mechanism of action will be followed by a discussion on patient selection for this treatment.

PubMed: 34629704
DOI: 10.1055/s-0041-1735606

Review

Authors: Mitchell Rice, Matthew Krosin, Paul Haste...

Transarterial radioembolization with yttrium-90 ( Y) is a mainstay for the treatment of liver cancer. Imaging the distribution following delivery is a concept that dates back to the 1960s. As β particles are created during Y decay, bremsstrahlung radiation is created as the particles interact with tissues, allowing for imaging with a gamma camera. Inherent qualities of bremsstrahlung radiation make its imaging difficult. SPECT and SPECT/CT can be used but suffer from limitations related to low signal-to-noise bremsstrahlung radiation. However, with optimized imaging protocols, clinically adequate images can still be obtained. A finite but detectable number of positrons are also emitted during Y decay, and many studies have demonstrated the ability of commercial PET/CT and PET/MR scanners to image these positrons to understand Y distribution and help quantify dose. PET imaging has been proven to be superior to SPECT for quantitative imaging, and therefore will play an important role going forward as we try and better understand dose/response and dose/toxicity relationships to optimize personalized dosimetry. The availability of PET imaging will likely remain the biggest barrier to its use in routine post- Y imaging; thus, SPECT/CT imaging with optimized protocols should be sufficient for most posttherapy subjective imaging.

PubMed: 34629714
DOI: 10.1055/s-0041-1735569

Review

Authors: A A Alsultan, A J A T Braat, M L J Smits...

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments.

Topics: Brachytherapy; Humans; Liver Neoplasms

PubMed: 33358630
DOI: 10.1016/j.clon.2020.12.003

Review

Authors: Remco Bastiaannet, S Cheenu Kappadath, Britt Kunnen...

Radioembolization is an established treatment for chemoresistant and unresectable liver cancers. Currently, treatment planning is often based on semi-empirical methods, which yield acceptable toxicity profiles and have enabled the large-scale application in a palliative setting. However, recently, five large randomized controlled trials using resin microspheres failed to demonstrate a significant improvement in either progression-free survival or overall survival in both hepatocellular carcinoma and metastatic colorectal cancer. One reason for this might be that the activity prescription methods used in these studies are suboptimal for many patients.In this review, the current dosimetric methods and their caveats are evaluated. Furthermore, the current state-of-the-art of image-guided dosimetry and advanced radiobiological modeling is reviewed from a physics' perspective. The current literature is explored for the observation of robust dose-response relationships followed by an overview of recent advancements in quantitative image reconstruction in relation to image-guided dosimetry.This review is concluded with a discussion on areas where further research is necessary in order to arrive at a personalized treatment method that provides optimal tumor control and is clinically feasible.

PubMed: 30386924
DOI: 10.1186/s40658-018-0221-z