Currently, inoperable hepatocellular carcinoma (HCC) is treated by both transarterial radioembolization (TARE) and transarterial chemoembolization (TACE). However, their relative efficacy and outcomes remain unclear. This meta-analysis aimed to compare TARE and TACE to evaluate their safety and efficacy in treating inoperable HCC patients.

Relevant studies were identified by searching the Web of Science, PubMed, and Wanfang databases. Pooled analyses were used to compare treatment response rates, complications, and overall survival (OS) outcomes between the TARE and TACE groups.

This analysis selected 8 studies comprising 1026 and 358 patients that respectively underwent TACE and TARE treatment. The results revealed that the TARE group had significantly higher pooled total response, disease control, and 1-year OS rates compared to the TACE group (P = 0.04, 0.003, and 0.02, respectively), with a corresponding increase in OS (P = 0.0002). Furthermore, rates of complications including fever and abdominal pain were also reduced in the TARE group (P = 0.006 and 0.02, respectively). Moreover, there were no significant differences in the pooled analyses of complete response rates, fatigue, nausea/vomiting, 3-year OS, or 5-year OS between these groups (P = 0.24, 0.69, 0.15, 0.73, and 0.38, respectively). Significant heterogeneity was detected for endpoints including fatigue, nausea/vomiting, fever, abdominal pain, OS duration, and 3-year OS (I2 = 89%, 82%, 72%, 90%, 96%, and 66%, respectively). All endpoints exhibited no significant risk of publication bias.

This study revealed that relative to TACE, TARE performed using 90Y can yield significantly higher treatment response rates and prolong HCC patient survival with fewer treatment-related side effects.The PRISMA guidelines were used to guide the execution and publication of this meta-analysis. The study is registered at INPLASY.COM (No. INPLASY202380017).

INPLASY.COM, identifier INPLASY202380017.

Stereotactic body radiation therapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC), which provides excellent local control (LC) and prolongs overall survival (OS). However, in current guidelines, transcatheter arterial chemoembolization (TACE) has been proposed as a key treatment option for patients with early- and intermediate-stage HCC, whereas SBRT is not. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials and retrospective studies using the propensity score (PS) to compare the outcomes of SBRT and TACE for HCC in a balanced manner. We systematically searched the PubMed, Cochrane, EMBASE, and Web of Science databases to identify randomized controlled trials and studies comparing SBRT and TACE using PS analysis. The hazard ratios (HRs) for OS and LC were pooled. The heterogeneity between the data collected from these studies was also assessed. SBRT led to a comparable OS (HR: 0.83; 95 % confidence interval (CI): 0.52-1.34; p = 0.44) to TACE, and significantly improved LC (HR: 0.25; 95 % CI: 0.09-0.67; p = 0.006). Considerable heterogeneity was observed in the HR of OS and LC. Although there was no significant difference in the rate of grade 3 or higher toxicities between TACE and SBRT, or between studies, liver toxicity was identified as a common adverse event associated with both SBRT and TACE. Compared to TACE, SBRT showed a comparable OS and improved LC without serious toxicity. Therefore, SBRT should be considered an effective treatment option for various stages of HCC, depending on the tumor factors and pretreatment liver function.

Selective internal radiation therapy (SIRT) represents an endovascular treatment option for patients with hepatocellular carcinoma (HCC). Its use is widely recognized in the intermediate and advanced HCC, but it has become more prevalent in recent years in different Barcelona Clinic Liver Cancer (BCLC) stages. The aim of this review is to summarize the role of SIRT and its clinical implications through different stages of HCC.

A literature review of papers on this topic was performed using PubMed MEDLINE, focusing exclusively on the role of yttrium-90 SIRT across all BCLC stages and comparing it with other treatments. Only English-language papers currently available until September 2023 were considered.

Many studies have shown that SIRT is a promising tool with multiple uses, such as tumour control in the context of bridge-to-liver transplantation or resection, tumour downstaging, and curative therapy in selected patients. Therefore, according to the recent update of BCLC staging system criteria, SIRT now emerges as a potential curative treatment for early-stage HCC patients, serving as an alternative when ablation or resection is not feasible. It is also a promising treatment compared to transarterial chemoembolization (TACE) as well as in combination with immunotherapies.

SIRT is a safe and effective treatment for selected patients at all BCLC stages of HCC. Therefore, due to its numerous advantages, SIRT may prove useful in many complex HCC treatment situations in the near future.

Hepatocellular carcinoma (HCC); radioembolization; yttrium-90 (90Y); selective internal radiation therapy (SIRT); transarterial radioembolization (TARE).

Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking.

To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US.

This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024.

Patient demographic characteristics and disease factors.

All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type.

Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs <20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434).

This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.

Hepatocellular carcinoma (HCC) treatment often requires transarterial chemoembolization (TACE). However, TACE efficacy is controversial in the presence of portal vein thrombosis (PVT). Although transarterial radioembolization (TARE) benefit was previously documented in PVT, neither the objective tumor response (OTR) after TARE with Iodine-131-lipiodol (131I-lipiodol) nor the PVT effect on the results of locoregional therapies was accurately measured in prospective clinical trials. The aim of this study was to compare OTR and survival obtained by TARE with 131I-lipiodol versus TACE in patients with cirrhosis and HCC, as well as between those with and without PVT.

33 patients were included, from whom 38 tumors were assessed. OTR was quantified by a special algorithm to measure hypervascular HCC tissue.

19 tumors received each therapy. Nine subjects (27%) had PVT, most of them in the TARE group (p = 0.026). Mean OTR according to the tumor volumes was 24.2% ± 56% after TARE and 32.8% ± 48.9% after TACE, with no difference between the treatments (p = 0.616). Similar values were also observed between those with and without PVT (p = 0.704). Mean survival was 340 days and did not differ between the two treatments (p = 0.596), but was 194 days in PVT cases (p = 0.007).

This is the first study in which OTR obtained by TARE with 131I-lipiodol is accurately measured. Additionally, PVT impact on survival after TARE and TACE was precisely documented. Although the TARE group had more PVT subjects (who had shorter survival), TARE and TACE achieved similar OTR and OS rates.

Due to a lack of data, there is an ongoing debate regarding the optimal frontline interventional therapy for unresectable hepatocellular carcinoma (HCC). The aim of the study is to compare the results of transarterial radioembolization (TARE) as the first-line therapy and as a subsequent therapy following prior transarterial chemoembolization (TACE) in these patients.

A total of 83 patients were evaluated, with 38 patients having undergone at least one TACE session prior to TARE [27 male; mean age 67.2 years; 68.4% stage Barcelona clinic liver cancer (BCLC) B, 31.6% BCLC C]; 45 patients underwent primary TARE (33 male; mean age 69.9 years; 40% BCLC B, 58% BCLC C). Clinical [age, gender, BCLC stage, activity in gigabecquerel (GBq), Child-Pugh status, portal vein thrombosis, tumor volume] and procedural [overall survival (OS), local tumor control (LTC), and progression-free survival (PFS)] data were compared. A regression analysis was performed to evaluate OS, LTC, and PFS.

No differences were found in OS (95% CI: 1.12, P = 0.289), LTC (95% CI: 0.003, P = 0.95), and PFS (95% CI: 0.4, P = 0.525). The regression analysis revealed a relationship between Child-Pugh score (P = 0.005), size of HCC lesions (>10 cm) (P = 0.022), and OS; neither prior TACE (Child-Pugh B patients; 95% CI: 0.120, P = 0.729) nor number of lesions (>10; 95% CI: 2.930, P = 0.087) correlated with OS.

Prior TACE does not affect the outcome of TARE in unresectable HCC.

Hepatocellular carcinoma (HCC) accounts for majority of primary liver cancer. Use of preoperative neoadjuvant transarterial chemoembolization (PN-TACE) may result in tumor shrinkage and improve resectability. This study aims to summarize the outcomes of PN-TACE versus upfront liver resection (Up-LR) in large HCC (≥5 cm).

PubMed, Embase, The Cochrane Library, and Scopus were systematically searched till September 2022 for studies comparing PN-TACE versus Up-LR. The primary study outcomes were overall survival (OS), disease-free survival (DFS), and recurrence. Our secondary outcomes were postoperative morbidity and mortality.

There were 12 studies with 15 data sets including 3960 patients (PN-TACE n = 2447, Up-LR n = 1513). Majority (89.5%, n = 1250/1397) of patients had Child's A liver cirrhosis. Incidence of Child's B cirrhosis was higher in PN-TACE compared to Up-LR (Odds ratio (OR) 1.69, 95% CI: 1.18, 2.41, p = 0.004). Pooled hazard ratio (HR) for OS showed no significant difference between PN-TACE and Up-LR (HR 0.87, 95% CI: 0.64, 1.18, p = 0.37), but DFS was superior in PN-TACE (HR 0.79, 95% CI: 0.63, 0.99, p = 0.04). Subgroup analysis based on study design failed to show any significant effect in randomized controlled trials (n = 2/15 data sets). However, operating time (mean difference (MD) 31.94 min, 95% CI: 2.42, 61.45, p = 0.03) and blood loss (MD 190.93 ml, 95% CI: 10.22, 317.65, p = 0.04) were higher in PN-TACE. Intrahepatic and extrahepatic recurrence, post-operative morbidity and in-hospital mortality were comparable between PN-TACE and Up-LR.

In retrospective studies, PN-TACE resulted in superior DFS compared to Up-LR. However, this may be confounded by selection bias.

The aim of this study was (a) to optimise the99mTc-SPECT reconstruction parameters for the pre-treatment dosimetry of90Y-selective internal radiation therapy (SIRT) and (b) to compare the accuracy of clinical dosimetry methods with full Monte-Carlo dosimetry (fMCD) performed with Gate.

To optimise the reconstruction parameters, two hundred reconstructions with different parameters were performed on a NEMA phantom, varying the number of iterations, subsets, and post-filtering. The accuracy of the dosimetric methods was then investigated using an anthropomorphic phantom. Absorbed dose maps were generated using (1) the Partition Model (PM), (2) the Dose Voxel Kernel (DVK) convolution, and (3) the Local Deposition Method (LDM) with known activity restricted to the whole phantom (WP) or to the liver and lungs (LL). The dose to the lungs was calculated using the "multiple DVK" and "multiple LDM" methods.

Optimal OSEM reconstruction parameters were found to depend on object size and dosimetric criterion chosen (Dmean or DVH-derived metric). The Dmean of all three dosimetric methods was close (≤ 10%) to the Dmean of fMCD simulations when considering large segmented volumes (whole liver, normal liver). In contrast, the Dmean to the small volume (∅=31) was systemically underestimated (12%-25%). For lungs, the "multiple DVK" and "multiple LDM" methods yielded a Dmean within 20% for the WP method and within 10% for the LL method.

All three methods showed a substantial degradation of the dose-volume histograms (DVHs) compared to fMCD simulations. The DVK and LDM methods performed almost equally well, with the "multiple DVK" method being more accurate in the lungs.

Globally, primary liver cancer is the third leading cause of cancer-related deaths, with approximately 830 000 deaths worldwide in 2020, accounting for 8.3% of total deaths from all cancer types (1). This disease disproportionately affects those in countries with low or medium Human Development Index scores in Eastern Asia, South-Eastern Asia, and Northern and Western Africa (2). Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often develops in the background of chronic liver disease, caused by hepatitis B or C virus, non-alcoholic steatohepatitis (NASH), or other diseases that cause cirrhosis. Prognosis can vary dramatically based on number, size, and location of tumors. Hepatic synthetic dysfunction and performance status (PS) also impact survival. The Barcelona Clinic Liver Cancer (BCLC) staging system best accounts for these variations, providing a reliable prognostic stratification. Therapeutic considerations of this complex disease necessitate a multidisciplinary approach and can range from curative-intent surgical resection, liver transplantation or image-guided ablation to more complex liver-directed therapies like transarterial chemoembolization (TACE) and systemic therapy. Recent advances in the understanding of the tumor biology and microenvironment have brought new advances and approvals for systemic therapeutic agents, often utilizing immunotherapy or VEGF-targeted agents to modulate the immune response. This review will discuss the current landscape in the treatments available for early, intermediate, and advanced stage HCC.

Patients with un-resectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) are a diverse group with varying overall survival (OS). Despite the availability of several scoring systems for predicting OS, one of the unsolved problems is identifying patients who might not benefit from TACE. We aim to develop and validate a model for identifying HCC patients who would survive <6 months after their first TACE.

Patients with un-resectable HCC, BCLC stage 0-B, who received TACE as their first and only treatment between 2007 and 2020 were included in this study. Before the first TACE, demographic data, laboratory data, and tumor characteristics were obtained. Eligible patients were randomly allocated in a 2:1 ratio to training and validation sets. The former was used for model development using stepwise multivariate logistic regression, and the model was validated in the latter set.

A total of 317 patients were included in the study (210 for the training set and 107 for the validation set). The baseline characteristics of the two sets were comparable. The final model (FAIL-T) included AFP, AST, tumor sIze, ALT, and Tumor number. The FAIL-T model yielded AUROCs of 0.855 and 0.806 for predicting 6-month mortality after TACE in the training and validation sets, respectively, while the "six-and-twelve" score showed AUROCs of 0.751 (P < 0.001) in the training set and 0.729 (P = 0.099) in the validation sets for the same purpose.

The final model is useful for predicting 6-month mortality in naive HCC patients undergoing TACE. HCC patients with high FAIL-T scores may not benefit from TACE, and other treatment options, if available, should be considered.

The targeted delivery of anti-cancer drugs and isotopes is one of the most pursued goals in anti-cancer therapy. One of the prime examples of such an application is the intra-arterial injection of microspheres containing cytostatic drugs or radioisotopes during hepatic embolization procedures. Therapy based on the application of microspheres revolves around vascular occlusion, complemented with local therapy in the form of trans-arterial chemoembolization (TACE) or radioembolization (TARE). The broadest implementation of these embolization strategies currently lies within the treatment of untreatable hepatocellular cancer (HCC) and metastatic colorectal cancer. This review aims to describe the state-of-the-art TACE and TARE technologies investigated in the clinical setting for HCC and addresses current trials and new developments. In addition, chemical properties and advancements in microsphere carrier systems are evaluated, and possible improvements in embolization therapy based on the modification of and functionalization with therapeutical loads are explored.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies, recurrence rates remain high. In contrast to first-line treatment for HCC, which relies on several factors, including clinical staging, tumor burden, and liver function, there is no consensus or general treatment recommendations for recurrent HCC (R-HCC). Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC. Herein, we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.

There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC).

To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization.

This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) < 70 Gy for non-segmental therapies. Single compartment dose of 200 Gy was used for segmentectomies. Prescribed Y90 activity minus scout activity was administered for therapeutic Y90 followed by Y90-PET/CT. Sureplan® (MIM Software, Cleveland, OH) was used for dosimetry analysis. Treatment response was evaluated at 3 and 6 months. Receiver operating characteristic curve determined TD response threshold for objective response (OR) and complete response (CR) as well as non-tumor liver dose (NTLD) threshold that predicted AEs.

N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p < 0.001). A mean TD of 337 Gy predicted a CR with 83% sensitivity and 89% specificity (AUC = 0.845, p < 0.001). A mean NTLD of 81 and 87 Gy predicted grade 3 AEs with 100% sensitivity and 100% specificity in the non-segmental cohort at 3- and 6-month post Y90, respectively.

In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes.

NCT04172714.

To evaluate the relationship between non-tumor liver (NTL) dose and adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with glass-based Yttrium-90 radioembolization (Y90-RE).

A retrospective analysis of patients with HCC treated with Y90-RE between 2013 and 2018 was performed. Baseline characteristics including demographics and Y90-RE treatment approach were captured. Common Terminology Criteria for Adverse Events v5 was assessed at months 3 and 6 post-treatment. Using voxel-based dosimetry with MIM Software V. 6.9, dose-volume histograms of treated area of liver were created. Receiver operator characteristic curve was used to determine NTL dose threshold predicting AEs. Multivariate analysis was used to determine independent clinical factors of predicting severe AEs. Chi-square analysis was used to compare proportions.

Two hundred and twenty-nine consecutive patients (115(50.2%) lobar and 114(49.8%) segmental) were included. At 3 months, there was a lower rate of any grade AE (55(46%) segmental and 36(31%) lobar, p = 0.009) and increased rate of severe AEs for lobar compared to segmental (2(2%) segmental and 9(8%) lobar, p = 0.029). At 6 months, severe AEs were greater for lobar than segmental (1(1%) segmental vs 10(9%) lobar, p = 0.005). For lobar Y90-RE, mean NTL dose of 112 Gy predicted severe AE (89% sensitivity and 91% specificity (AUC = 0.95, p =  < 0.0001) at 3 and 6 months. For the segmental group, no significant association was found between NTL dose and severe treatment-related AE at 3 and 6 months.

In patients with HCC undergoing glass-based lobar Y90-RE, NTL dose of > 112 Gy is associated with severe treatment-related AEs at 3-6 months.

Transarterial chemoembolization (TACE) has been demonstrated to provide a survival benefit for patients with unresectable hepatocellular carcinoma (HCC). However, conventional TACE still faces limitations associated with complications, side effects, unsatisfactory tumor responses, repeated treatment, and narrow indications. For further improvement of TACE, additional beneficial functions such as degradability, drug-loading and releasing properties, detectability, targetability, and multiple therapeutic modalities were introduced. The purpose here is to provide a comprehensive overview of current and emerging particulate embolization technology with respect to materials. Therefore, this review systematically identified and described typical features, various functions, and practical applications of recently emerging micro/nano materials as particulate embolic agents for TACE. Besides, new insights into the liquid metals-based multifunctional and flexible embolic agents were highlighted. The current development routes and future outlooks of these micro/nano embolic materials were also presented to promote advancement in the field.

According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the optimal strategy for patients with multiple HCC within the Milan Criteria is liver transplantation (LT). However, LT cannot be offered to all the patients due to organ shortages and long waiting lists, as well as because of the advanced disease carrying a high risk of poor outcomes. For early stages, liver resection (LR) or thermal ablation (TA) can be proposed, while trans-arterial chemoembolization (TACE) still remains the treatment of choice for intermediate stages (BCLC-B). Asian guidelines and the National Comprehensive Cancer Network suggest LR for resectable multinodular HCCs, even beyond Milan criteria. In this scenario, a growing body of evidence shows better outcomes after surgical resection when compared with TACE. Trans-arterial radioembolization (TARE) and stereotaxic body radiation therapy (SBRT) can also play an important role in this setting. Furthermore, the role of minimally invasive liver surgery (MILS) specifically for patients with multiple HCC is still not clear. This review aims to summarize current knowledge about the best therapeutical strategy for multiple HCC while focusing on the role of minimally invasive surgery and on the most attractive future perspectives.

The treatment and management of hepatic malignancies can be complex because it encompasses a variety of primary and metastatic malignancies and an assortment of local and systemic treatment options. When to use each of these treatments is critical to ensure the most appropriate care for patients. Interventional radiologists have a key role to play in the delivery of a variety of liver directed treatments including percutaneous ablation, transarterial embolization with bland embolic particles alone, transarterial chemoembolization (TACE) with injection of a chemotherapeutic emulsion, and transarterial radioembolization (TARE). Based on 9 clinical variants, the appropriateness of each treatment is described in this document. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Transarterial radioembolization (TARE) is increasingly used as an alternative to transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). We aimed to perform an overall and individual patient data (IPD) meta-analysis of studies comparing TACE and TARE.

We performed a systematic literature search using pre-specified keywords with the aid of an informationist for articles from inception to 3/2020. The primary endpoint was overall survival (OS), and the secondary endpoint was time to progression (TTP).

Seventeen studies met inclusion criteria with 2465 unique patients, with one randomized trial, 4 prospective studies and 12 retrospective studies. Barcelona Clinic Liver Cancer (BCLC) stage B (42.8%) was the most common stage followed by BCLC A (30.3%) and BCLC C (29.0%). There was no difference in OS between the two modalities (-0.55 months, 95% CI -1.95 to 3.05). In three studies with available TTP data, TARE resulted in a longer TTP than TACE (mean TTP 17.5 vs. 9.8 months; mean TTP difference 4.8 months, 95% CI 1.3-8.3 months). IPD-level meta-analysis of 311 patients from three studies showed no difference in overall OS between the two modalities including among subgroups stratified by tumor stage and liver function. Limitations of the current literature include inconsistent length of follow-up, inconsistency in response criteria, and safety reporting.

Current data suggest TARE provides significantly longer TTP than TACE, although the two treatments do not significantly differ in terms of OS. Given limitations of the current data, there is rationale for prospective studies comparing these modalities.

Embolization with microspheres is a therapeutic strategy based on the selective occlusion of the blood vessels feeding a tumor. This procedure is intraarterially performed in the clinical setting for the treatment of liver cancer. The practice has evolved over the last decade through the incorporation of drug loading ability, biodegradability and imageability with the subsequent added functionality for the physicians and improved clinical outcomes for the patients. This review highlights the evolution of the embolization systems developed through the analysis of the marketed embolic microspheres for the treatment of malignant hepatocellular carcinoma, namely the most predominant form of liver cancer. Embolic microspheres for the distinct modalities of embolization (i.e., bland embolization, chemoembolization and radioembolization) are here comprehensively compiled with emphasis on material characteristics and their impact on microsphere performance. Moreover, the future application of the embolics under clinical investigation is discussed along with the scientific and regulatory challenges ahead in the field. STATEMENT OF SIGNIFICANCE: Embolization therapy with microspheres is currently used in the clinical setting for the treatment of most liver cancer conditions. The progressive development of added functionalities on embolic microspheres (such as biodegradability, imageability or drug and radiopharmaceutical loading capability) provides further benefit to patients and widens the therapeutic armamentarium for physicians towards truly personalized therapies. Therefore, it is important to analyze the possibilities that advanced biomaterials offer in the field from a clinical translational perspective to outline the future trends in therapeutic embolization.

To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry.

A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland-Altman analysis.

A linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r2 > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r2 = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10-12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland-Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively.

The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose-response relationship, which could ultimately improve future patient outcomes.

Prognosis prediction in patient with hepatocellular carcinoma (HCC) after transarterial radioembolization (TARE) remains difficult. The aim of this study was to develop a prognostic model to aid in the decision to use TARE.

A total of 174 patients in Korea who underwent TARE for HCC as the initial treatment were included. We developed a prediction model for overall survival (OS) based on independent risk factors for OS and validated the model by bootstrap method.

The median maximal size of the tumors was 8.2 cm, the median number of tumors was 2, and the median albumin level was 4.0 g/dL. Portal vein tumor thrombosis was found in 46.0% (Vp1-3 [39.7%] and Vp4 [6.3%]). Four independent risk factors associated with OS (maximal tumor size, tumor number, albumin, and portal vein tumor thrombosis) were used to develop the SNAP-HCC score. Bootstrap validation of the scoring index determined that the Harrell's c-index for OS was 0.756 (95% confidence interval: 0.729-0.783). Patients grouped based on their SNAP-HCC (scores 0-5) were well discriminated, with significant differences between the groups (all P < 0.05). Patients with SNAP-HCC < 3 showed significantly longer OS than patients with SNAP-HCC ≥ 3 (P < 0.001). The respective survival probabilities at years 1 and 3 were 0.81 and 0.73 in the low-risk (SNAP-HCC < 3) and 0.32 and 0.14 in the high-risk (SNAP-HCC ≥ 3) patients.

The SNAP-HCC scoring system predicted the outcome of HCC patients undergoing TARE as an initial treatment. This model could be helpful for initial planning the treatment of HCC patients.

Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.

Typical clinical dosimetry models for trans-arterial radioembolization (TARE) assume uniform dose distribution in each tissue compartment. We performed simple voxel-based dosimetry using post-treatment 90Y PET following TARE with 90Y-resin microspheres and investigated its prognostic value in a pilot cohort.

Ten patients with 14 hepatocellular carcinoma lesions who underwent TARE with 90Y-resin microspheres were retrospectively included. The partition model-based expected target tumor dose (TDp) was calculated using a pretreatment 99mTc-macroaggregated albumin scan. From post-treatment 90Y-microsphere PET and voxel-wise S-value kernels, voxel-based dose maps were produced and the absorbed dose of each lesion (TDv) was calculated. Heterogeneity of intratumoral absorbed doses was assessed using the SD and coefficient of variation of voxel doses. The response of each lesion was determined based on contrast-enhanced MRI or CT, or both. Lesion responses were classified as local control success or failure. Prognostic values of dosimetry parameters and clinicopathological factors were evaluated in terms of progression-free survival (PFS) of each lesion.

TDv was significantly different between local control success and failure groups, whereas tumor size, TDp and intratumoral dose heterogeneity were not. Univariate survival analysis identified serum aspartate transaminase level ≥40 IU/L, tumor size ≥66 mm and TDv <81 Gy as significant prognostic factors for PFS. However, only TDv was an independent predictive factor in the multivariate analysis (P = 0.022). There was a significant correlation between TDv and PFS (P = 0.009; r = 0.669).

In TARE, voxel-based dose index TDv can be estimated on post-treatment 90Y PET using a simple method. TDv was a more effective prognostic factor for TARE than TDp and clinicopathologic factors in this pilot study. Further studies are warranted on the role of voxel-based dose and dose distribution in TARE.

Recently, selective internal radiation therapy using yttrium-90 (Y90) glass microspheres (TheraSphere™) was approved for reimbursement by health authorities in France. The PROACTIF study aims to gather data on effectiveness, patient quality of life, and safety with use of Y90 glass microspheres in real-world clinical settings in France.

Patient with a diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCC), and/or metastatic colorectal cancer (mCRC) who was treated with a dose of Y90 glass microspheres that has been reimbursed in France and who do not oppose use of their personal medical data.

If data collection is opposed, treatment is reimbursed but not administered, or treatment is administered but not reimbursed.

Primary outcome measures include overall survival from time of Y90 glass microsphere treatment and quality of life, as assessed using the Functional Assessment of Cancer Therapy- Hepatobiliary questionnaire.

This is an open study and there is no set number of patients; 115 have already been enrolled.

Analyses will be stratified by disease state (HCC, iCC, or mCRC). Subgroups to be analyzed include age group, unilobar/bilobar disease at baseline, Eastern Cooperative Oncology Group (ECOG) status at baseline, liver tumor burden at baseline, target lesion size, and standard versus multi-compartment personalized dosimetry treatment.

Recruitment includes patients who are prescribed and treated with a commercial vial of Y90 glass microspheres between 01 January 2019 and 31 December 2024.

ClinicalTrials.gov Identifier: NCT04069468.

Intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) are the most common primary liver cancers (PLCs). Differences in their clinical features and outcomes are open for investigation in a large-scale study. We aim to investigate the differences in clinical features and outcomes between iCCA and HCC.

The Surveillance, Epidemiology, and End Results Program 18 Database (2000-2017) was used to extract demographic and clinical features of HCC and iCCA patients. Logistic regression analysis was performed to identify factors associated with iCCA diagnosis versus HCC. Cox regression analysis was used to assess factors affecting overall survival (OS). There were 13,611 iCCA and 96,151 HCC patients. Half of iCCA (50.7%) and three quarters of HCC (76.3%) patients were male. Diagnosis in recent year, age (<50 or ≥65), female sex, non-Hispanic White race, higher income, rural area, and higher tumor burden were independently associated with iCCA diagnosis versus HCC. Patients with iCCA had worse OS than those with HCC (9 vs. 13 months; P < 0.001). However, OS was comparable between iCCA and HCC in multivariable analysis (adjusted hazard ratio [aHR] = 1.02; 95% CI = 0.99-1.05). In subgroup analyses, iCCA was associated with better OS than HCC in patients with tumor ≥5 cm (aHR = 0.83; 95% CI = 0.80-0.86), lymph node involvement (aHR = 0.76; 95% CI = 0.72-0.81), distant metastasis (aHR = 0.76; 95% CI = 0.73-0.79), poorly/undifferentiated tumors (aHR = 0.88; 95% CI = 0.83-0.94), and those receiving noncurative treatment (aHR = 0.96; 95% CI = 0.93-0.98).

We identified the demographic, socioeconomic, and clinical features associated with iCCA diagnosis over HCC among patients with PLC. Although iCCA patients presented at an advanced stage, OS was similar between iCCA and HCC in multivariable analysis. iCCA was associated with longer OS for subgroups with poor prognostic features.

¹⁸ F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is a functional image technique that can inform clinical decisions related to prognosis. We investigated the predictive role of ¹⁸ F-fluorodeoxyglucose PET/CT in patients with hepatocellular carcinoma (HCC) undergoing Yttrium-90 (Y-90) transarterial radioembolization (TARE).

Patients with HCC treated with TARE and pre-TARE PET/CT scan were recruited between 2009 and 2013. Maximum standardized uptake value and tumor-to-non-tumorous liver uptake ratio (TLR) were measured. Tumor response was evaluated in accordance with modified RECIST criteria at 3-month intervals after Y-90 TARE.

Forty patients were included in the final analysis. The median age was 56.5 years and male predominant. Disease control in treated lesion was achieved in 82.5% (n = 33) of patients. During median 18.3-month follow-up, 27.5% (n = 11) of patients achieved progression-free survival. The cutoff of TLR, which was related to the median value, did not affect disease control rate, progression-free survival, and overall survival in patients with Y-90 TARE.

The TLR-based stratification may be a simple method, but our study did not show the usefulness in predicting prognosis in HCC patients with Y-90 TARE. Further studies with large number of patients are needed.

While dexamethasone has been applied following transcatheter arterial chemoembolization (TACE) for years, its clinical effects have not been determined. In the current study, we aimed to evaluate the efficacy of dexamethasone in preventing adverse events induced by TACE.

Literature retrieval was conducted using globally recognized online databases, namely MEDLINE, EMBASE, and Cochrane Central, to identify randomized controlled trials (RCTs) of dexamethasone application in patients undergoing TACE. The relative odds ratios (ORs) of incidence rates of three adverse events, namely, fever, abdominal pain and nausea/vomiting, were calculated. The value of I was applied to evaluate the heterogeneity of the trials, and the overall publication bias was assessed with Egger test.

Four RCTs containing 350 subjects were included for the pooled estimation. Dexamethasone significantly reduced the incidence rate of TACE-induced adverse events (OR = 1.237, 95% CI: 1.170-1.308, P < .001) with moderate heterogeneity (I = 46.0%). The result of Egger test revealed a publication bias for the included studies.

The current meta-analysis confirmed the efficacy of dexamethasone in preventing TACE-induced adverse events. To confirm the practicality of dexamethasone use with TACE, further studies with large sample sizes are warranted to update the evidence-based analyses.

It is not known whether percutaneous radiofrequency ablation (PRFA) has the same treatment efficacy and fewer complications than laparoscopic resection in patients with small centrally located hepatocellular carcinoma (HCC).

To compare the effectiveness of PRFA with classical laparoscopic resection in patients with small HCC and document the safety parameters.

In this retrospective study, 85 patients treated with hepatic resection (HR) and 90 PRFA-treated patients were enrolled in our hospital from July 2016 to July 2019. Treatment outcomes, including major complications and survival data, were evaluated.

The results showed that minor differences existed in the baseline characteristics between the patients in the two groups. PRFA significantly increased cumulative recurrence-free survival (hazard ratio 1.048, 95%CI: 0.265-3.268) and overall survival (hazard ratio 0.126, 95%CI: 0.025-0.973); PRFA had a lower rate of major complications than HR (7.78% vs 20.0%, P < 0.05), and hospital stay was shorter in the PRFA group than in the HR group (7.8 ± 0.2 d vs 9.5 ± 0.3 d, P < 0.001).

Based on the data obtained, we conclude that PRFA was superior to HR and may reduce complications and hospital stay in patients with small HCC.

Hepatocellular carcinoma (HCC) is the fourth-leading cause of cancer-related mortality worldwide and the fastest-rising cause of cancer-related death in the United States. Given the strong association between tumor stage and prognosis, HCC surveillance is recommended in high-risk patients, including patients with cirrhosis from any etiology. The diagnosis can be made based on characteristic imaging findings, with histologic confirmation primarily reserved for patients with atypical imaging findings. Over the last 2 decades, the treatment landscape for HCC has experienced significant advances. Curative therapies, including liver transplantation and surgical resection, are available to patients with early-stage HCC; however, recent data have expanded the potentially eligible patient population. Locoregional therapies, including transarterial chemoembolization and transarterial radio-embolization, continue to be standard therapies for patients with intermediate-stage disease. The greatest advances have been observed for patients with advanced HCC, where there are now multiple first- and second-line options that can prolong survival by up to 2 years when used sequentially. The increasing complexity of HCC treatment options underlies the necessity for multidisciplinary care, which has been associated with increased survival. This article reviews data on best practices for early detection and diagnosis of HCC and the current status of treatment options.

Hepatocellular carcinoma (HCC) is responsible for 1% of deaths worldwide, and the incidence continues to increase. Despite surveillance programs, 70% of HCC patients are not suitable for curative options at diagnosis, and therefore, non-curative treatments are essential to modern clinical practice. There are many novel treatments, though their roles are not well defined. This study aimed to contrast Selective Internal Radiation Therapy (SIRT) and Drug Eluting Bead Transarterial Chemoembolisation (DEB-TACE) to further define their roles.

This was a retrospective multicentre cohort study. Factors included for analysis were type of HCC treatment, number of lesions, lesion size, multiple disease severity scores, cirrhosis and vascular invasion. The primary endpoint was transplant-free survival.

Transplant-free survival was similar between the two cohorts (p = 0.654), despite a variation in median lesion size, SIRT: 54.5 mm, DEB-TACE: 34 mm (p ≤ 0.001). A univariate Cox proportional hazard model utilising treatment modality as the covariate showed no significant difference in survival (DEB-TACE HR 1.4 (95%CI 0.85-2.15 p = 0.207). The size of the largest lesion was the best predictor of 3-year survival (p = 0.035). Lesion size was inversely associated with survival (HR 1.01 (95%CI 1-1.02, p = 0.025)) on multivariate analysis.

This study is the first to catalogue the experience of using SIRT in HCC in a real-world Australian population. It has demonstrated no difference in survival outcomes between DEB-TACE and SIRT. Further, it has shown SIRT to be a reasonable alternative to DEB-TACE especially in larger lesions and has demonstrated that DEB-TACE has a role in select patients with advanced disease.

Transarterial radioembolization (TARE) with yttrium-90 microspheres has become widely utilized in managing hepatocellular carcinoma (HCC). The utility of TARE is expanding with new insights through experiences from real-world practice and clinical trials, and recently published data suggest that TARE in combination with sorafenib may improve the overall survival in selected patients. Here, we report a case of advanced stage HCC that was successfully treated with TARE and sorafenib. The patient achieved complete response (CR) at 12 months after the initial treatment with TARE and sorafenib, followed by additional transarterial chemoembolization and proton beam therapy for local tumor recurrence at 19-month post-TARE. The patient was followed up every 3 months thereafter and still achieved CR both biochemically and radiologically for the following 12 months. A combination strategy of TARE and systemic therapy may be a useful alternative treatment option for selected patients with advanced stage HCC.

Hepatocellular carcinoma is the most common type of primary liver cancer. Treatment choice is dependent on underlying liver dysfunction and cancer stage. Treatment options include conventional transarterial therapies for patients with intermediate-stage disease and systemic therapy [e.g. sorafenib (Nexavar®; Bayer plc, Leverkusen, Germany)] for patients with advanced-stage disease. Selective internal radiation therapies deliver radiation to liver tumours via microspheres that are injected into the hepatic artery. There are three selective internal radiation therapies: TheraSphere™ [BTG Ltd, London, UK (now Boston Scientific, Marlborough, MA, USA)], SIR-Spheres® (Sirtex Medical Ltd, Woburn, MA, USA) and QuiremSpheres® (Quirem Medical BV, Deventer, the Netherlands).

To assess the clinical effectiveness and cost-effectiveness of selective internal radiation therapies for treating patients with unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma.

A search was undertaken to identify clinical effectiveness literature relating to selective internal radiation therapies and relevant comparators for the treatment of hepatocellular carcinoma. Studies were critically appraised and summarised. The network of evidence was mapped to estimate the relative effectiveness of the different selective internal radiation therapies and comparator treatments. An economic analysis evaluated the cost-effectiveness.

Twenty studies were included in the clinical effectiveness review. Two large randomised controlled trials rated as having a low risk of bias [SARAH: Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled Phase 3 trial. Lancet Oncol 2017;18:1624-36; and SIRveNIB: Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 2018;36:1913-21] found no significant difference in overall survival or progression-free survival between SIR-Spheres and sorafenib (systemic therapy) in an advanced population, despite greater tumour response in the SIR-Spheres arm of both trials. There were some concerns regarding generalisability of the SARAH and SIRveNIB trials to UK practice. All other studies of SIR-Spheres, TheraSphere or QuiremSpheres were either rated as being at a high risk of bias or caused some concerns regarding bias. A network meta-analysis was conducted in adults with unresectable hepatocellular carcinoma who had Child-Pugh class A liver cirrhosis and were ineligible for conventional transarterial therapies. The analysis included the SARAH and SIRveNIB trials as well as a trial comparing lenvatinib (Kisplyx®; Eisai Ltd, Tokyo, Japan) (systemic therapy) with sorafenib. There were no meaningful differences in overall survival between any of the treatments. The base-case economic analysis suggested that TheraSphere may be cost-saving relative to both SIR-Spheres and QuiremSpheres. However, incremental cost differences between TheraSphere and SIR-Spheres were small. In a fully incremental analysis, which included confidential Patient Access Scheme discounts, lenvatinib was the most cost-effective treatment and dominated all selective internal radiation therapies. In pairwise comparisons of sorafenib with each selective internal radiation therapy, sorafenib also dominated all selective internal radiation therapies.

The existing evidence cannot provide decision-makers with clear guidance on the comparative effectiveness of treatments in early- and intermediate-stage hepatocellular carcinoma or on the efficacy of TheraSphere or QuiremSpheres.

In the advanced-stage hepatocellular carcinoma population, two large randomised trials have shown that SIR-Spheres have similar clinical effectiveness to sorafenib. None of the selective internal radiation therapies was cost-effective, being more costly and less effective than lenvatinib, both at list price and with Patient Access Scheme discounts.

Future studies may wish to include early- and intermediate-stage hepatocellular carcinoma patients and the low tumour burden/albumin-bilirubin 1 subgroup of advanced-stage patients. Future high-quality studies evaluating alternative selective internal radiation therapies would be beneficial.

This study is registered as PROSPERO CRD42019128383.

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 48. See the NIHR Journals Library website for further project information.

Few studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC.

Patients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed.

Seventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2-112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8-11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75-1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p < 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01-1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03-1.25, p = 0.018).

Pre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

Transarterial radioembolization with radionuclide-labeled microspheres is successfully used in hepatocellular carcinoma (HCC) treatment, but the non-biodegradability and rapid settlement of the microsphere material are associated with unsatisfied distribution and unable for multiple administrations. In this study, a novel biodegradable chitosan-collagen composite microsphere (CCM) with ideal settlement rate is prepared. The Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) results indicate CCMs have desirable shapes with diameters around 10 µm, and considerable biodegradability within 12 weeks. These CCMs are successfully radiolabeled with ¹³¹ I and processed efficiency of 70.4 MBq mg^-1 of microspheres as well as favorable stability in vitro. Then, ¹³¹ I-CCMs are injected into rats with orthotopic HCC via the hepatic artery which effectively improves the median overall survival from 19 to 44 days (p < 0.05). Single photon emission computed tomography (SPECT/CT) imaging and immunohistochemical analysis indicate well-localized biodistribution and consistent stability of ¹³¹ I-CCMs in the liver over 28 days. Magnetic resonance imaging (MRI) and gross specimens monitoring confirm the inhibited tumor growth after ¹³¹ I-CCMs treatment. In conclusion, these biodegradable ¹³¹ I-CCMs exhibit optimal radiolabeling efficiency, stability, and favorably radioembolization effect for orthotopic HCC in a rodent model, suggesting potential for interventional cancer therapy.

Yttrium-90 transarterial radioembolization (TARE) is a safe, effective modality of locoregional therapy for intermediate and advanced-stage hepatocellular carcinoma (HCC). We aim to identify novel predictors of important outcomes of TARE therapy.

A single-center retrospective study of 166 patients treated with TARE for HCC at Mayo Clinic Rochester between 2005-2015 and followed until December 2017. Multivariate logistic and stepwise regression analysis models were used to identify variables associated with overall survival (OS) and progression-free survival (PFS).

The median OS and the median PFS were12.9  (95% CI: 11.0-17.3), and 8 months (95% CI: 6-11), respectively. Macrovascular invasion (HR: 1.9 [1.3-2.8]), Child-Pugh score (CPS) B or C vs. A (HR: 1.8 [1.2-2.7]), Eastern Cooperative Oncology Group Performance status (ECOG-PS) 2 or 1 vs. 0 (HR: 1.6 [1.1-2.4]) and activity (A) of administered radiation dose (HR: 1.005[1.00-1.010), independently correlated with poorer OS. Infiltrative HCC (HR: 2.4 [1.3-4.5), macrovascular invasion (HR: 1.6 [1.1-2.7]), and high activity of administered radiation dose (HR: 1.005 [1.00-1.010) were associated with worse PFS.

In HCC patients treated with TARE; macrovascular invasion, the activity of radiation dose, CPS, ECOG-PS, and infiltrative HCC predict OS and PFS.

In randomized clinical trials, no survival benefit has been observed for selective internal radiation therapy (SIRT) over sorafenib in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess, through a metaanalysis, whether overall survival (OS) with SIRT, as monotherapy or followed by sorafenib, is noninferior to sorafenib and to compare safety profiles for patients with advanced HCC. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library up to February 2019 to identify randomized clinical trials comparing SIRT, as monotherapy or followed by sorafenib, with sorafenib monotherapy among patients with advanced HCC. The main outcomes were OS and frequency of treatment-related severe adverse events (≥grade 3). The per-protocol population was the primary analysis population. A noninferiority margin of 1.08 in terms of hazard ratio was prespecified for the upper boundary of 95% confidence interval for OS. Prespecified subgroup analyses were performed. Results: Three randomized clinical trials, involving 1,243 patients, comparing sorafenib with SIRT (SIRveNIB and SARAH) or SIRT followed by sorafenib (SORAMIC), were included. After randomization, 411 of 635 (64.7%) patients allocated to SIRT and 522 of 608 (85.8%) allocated to sorafenib completed the studies without major protocol deviations. Median OS with SIRT, whether or not followed by sorafenib, was noninferior to sorafenib (10.2 and 9.2 mo [hazard ratio, 0.91; 95% confidence interval, 0.78-1.05]). Treatment-related severe adverse events were reported in 149 of 515 patients (28.9%) who received SIRT and 249 of 575 (43.3%) who received sorafenib only (P < 0.01). Conclusion: SIRT as initial therapy for advanced HCC is noninferior to sorafenib in terms of OS and offers a better safety profile.