Radioembolization Research Articles

Optimization of the Clinical Effectiveness of Radioembolization in Hepatocellular Carcinoma with Dosimetry and Patient-Selection Criteria.

Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response and the patient outcome when the tumor-absorbed dose was assessed by nuclear medicine imaging. Dosimetry plays a key role in predicting the clinical response and can be optimized using a personalized method of activity planning (multi-compartmental dosimetry). This paper reviews the main clinical results of SIRT in HCC and emphasizes the central role of dosimetry for improving it effectiveness. Moreover, some patient and tumor characteristics predict a worse outcome, and toxicity related to SIRT treatment of advanced HCC patient selection based on the performance status, liver function, tumor characteristics, and tumor targeting using technetium-99m macro-aggregated albumin scintigraphy can significantly improve the clinical performance of SIRT.

Long-term survival of a patient with liver metastases from clear cell gastric adenocarcinoma after multimodality treatment including interventional oncology techniques: case report

BackgroundGastric cancer (GC) is the fourth most common cancer and the third leading cancer-related cause of death worldwide since most patients are diagnosed at an advanced stage. The majority of GCs are adenocarcinomas (ACs), and the poorly characterized clear cell AC represents a unique subgroup of GCs and is an independent marker of poor prognosis. Even though the prognosis for patients with advanced GC is poor we present a report of a patient with long-term survival despite having liver metastases from clear cell gastric AC.Case presentationA 45-year-old male with clear cell gastric AC underwent subtotal gastrectomy and postoperative chemoradiation. Only a year and a half after his initial treatment the disease spread to his liver. He received two lines of chemotherapy treatment within the next two years before a right hepatectomy was suggested. Due to an initially insufficient future liver remnant (FLR), transarterial chemoembolization (TACE) and portal vein embolization (PVE) were performed, which made the surgical procedure possible. Shortly after a disease progression in the remaining liver was detected. In the following three years the patient was treated with a carefully planned combination of systemic therapy and different interventional oncology techniques including selective internal radiation therapy (SIRT) and TACE. And as illustrated, an attentive, patient-tailored, multimodality treatment approach can sometimes greatly benefit our patients as he had an overall survival of 88 months despite the poor prognosis of his disease.ConclusionTo the best of our knowledge, this report is the first to describe a patient with liver metastases from clear cell gastric AC treated with interventional oncology techniques (PVE, TACE, and SIRT) in combination with other locoregional and systemic therapies thereby presenting that these interventional oncology techniques can be successfully integrated into long-term management of non-conventional liver tumors.

Pure laparoscopic major liver resection after yttrium90 radioembolization: a case-matched series analysis of feasibility and outcomes

BackgroundLiver surgery after radioembolization (RE) entails highly demanding and challenging procedures due to the frequent combination of large tumors, severe RE-related adhesions, and the necessity of conducting major hepatectomies. Laparoscopic liver resection (LLR) and its associated advantages could provide benefits, as yet unreported, to these patients. The current study evaluated feasibility, morbidity, mortality, and survival outcomes for major laparoscopic liver resection after radioembolization.Material and methodsIn this retrospective, single-center study patients diagnosed with hepatocellular carcinoma, intrahepatic cholangiocarcinoma or metastases from colorectal cancer undergoing major laparoscopic hepatectomy after RE were identified from institutional databases. They were matched (1:2) on several pre-operative characteristics to a group of patients that underwent major LLR for the same malignancies during the same period but without previous RE.ResultsFrom March 2011 to November 2020, 9 patients underwent a major LLR after RE. No differences were observed in intraoperative blood loss (50 vs. 150 ml; p = 0.621), operative time (478 vs. 407 min; p = 0.135) or pedicle clamping time (90.5 vs 74 min; p = 0.133) between the post-RE LLR and the matched group. Similarly, no differences were observed on hospital stay (median 3 vs. 4 days; p = 0.300), Clavien–Dindo ≥ III complications (2 vs. 1 cases; p = 0.250), specific liver morbidity (1 vs. 1 case p = 1.000), or 90 day mortality (0 vs. 0; p = 1.000).ConclusionThe laparoscopic approach for post radioembolization patients may be a feasible and safe procedure with excellent surgical and oncological outcomes and meets the current standards for laparoscopic liver resections. Further studies with larger series are needed to confirm the results herein presented.

Computational study of a novel catheter for liver radioembolization.

Radioembolization (RE) is a medical treatment for primary and secondary liver cancer that involves the transcatheter intraarterial delivery of micron‐sized and radiation‐emitting microspheres, with the goal of improving microsphere deposition in the tumoral bed while sparing healthy tissue. An increasing number of in vitro and in silico studies on RE in the literature suggest that the particle injection velocity, spatial location of the catheter tip and catheter type are important parameters in particle distribution. The present in silico study assesses the performance of a novel catheter design that promotes particle dispersion near the injection point, with the goal of generating a particle distribution that mimics the flow split to facilitate tumour targeting. The design is based on two factors: the direction and the velocity at which particles are released from the catheter. A series of simulations was performed with the catheter inserted at an idealised hepatic artery tree with physiologically realistic boundary conditions. Two longitudinal microcatheter positions in the first generation of the tree were studied by analysing the performance of the catheter in terms of the outlet‐to‐outlet particle distribution and split flow matching. The results show that the catheter with the best performance is one with side holes on the catheter wall and a closed frontal tip. This catheter promotes a flow‐split‐matching particle distribution, which improves as the injection crossflow increases.

Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma.

Simple SummaryDespite recent progress on the treatment of metastatic uveal melanoma (mUM), prognosis remains dismal for the majority of patients. Directed liver therapies including selective internal radiation therapy (SIRT) have been the pillar of hepatic metastases management. Independently, immune checkpoint blockade by combination of ipilimumab plus nivolumab has demonstrated a median survival slightly superior to 1 year. However, the benefit of sequential ipilimumab plus nivolumab immunotherapy and SIRT has not been elucidated.To assess the safety and efficacy of ipilimumab plus nivolumab around selective internal radiation therapy (SIRT) in patients with metastatic uveal melanoma (mUM). We present a retrospective, single center study of 32 patients with mUM divided into two groups based on the treatment received between April 2013 and April 2021. The SIRT_IpiNivo cohort was treated with Yttrium-90 microspheres and ipilimumab plus nivolumab before or after the SIRT (n = 18). The SIRT cohort underwent SIRT but did not receive combined immunotherapy with ipilimumab plus nivolumab (n = 14). Twelve patients (66.7%) of the SIRT_IpiNivo arm received SIRT as first-line treatment and six patients (33.3%) received ipilimumab plus nivolumab prior to SIRT. In the SIRT group, seven patients (50.0%) received single-agent immunotherapy. One patient treated with combined immunotherapy 68 months after the SIRT was included in this group. At the start of ipilimumab plus nivolumab, 94.4% (n = 17) presented hepatic metastases and 72.2% (n = 13) had extra liver disease. Eight patients (44.4%) of the SIRT_IpiNivo group experienced grade 3 or 4 immune related adverse events, mainly colitis and hepatitis. Median overall survival from the diagnosis of metastases was 49.6 months (95% confidence interval (CI); 24.1-not available (NA)) in the SIRT_IpiNivo group compared with 13.6 months (95% CI; 11.5-NA) in the SIRT group (log-rank p-value 0.027). The presence of extra liver metastases at the time of SIRT, largest liver lesion more than 8 cm (M1c) and liver tumor volume negatively impacted the survival. This real-world cohort suggests that a sequential treatment of ipilimumab plus nivolumab and SIRT is a well-tolerated therapeutic approach with promising survival rates.

Levels of Alpha-Fetoprotein and Association with Mortality in Hepatocellular Carcinoma of HIV-1-Infected Patients.

Methods This is a retrospective cohort study on patients living with HIV-1 infection (PLWH) followed at the Division of Infectious Diseases of the San Raffaele Hospital, with cirrhosis and HCC diagnosed between 1999 and 2018 and with an available AFP value at HCC diagnosis. The area under the receiver operating characteristic curve (AUC) was used to estimate the accuracy of baseline AFP in predicting death. Factors associated with the risk of death were identified using multivariable Cox proportional-hazards regression models. Results Overall, 53 PLWH were evaluated: 18 patients received a curative treatment (9 liver transplantation, 5 liver resections and 4 radiofrequency ablation) and 35 a noncurative treatment (17 chemo or radio embolization, 10 sorafenib and 8 best supportive care). Baseline AFP was predictive of death [AUC 0.71, 95% confidence interval (CI) 0.54–0.83], and the optimal cut-off was 28.8 ng/mL. At multivariable analysis, BL AFP ≥28.8 ng/mL was associated with death [adjusted hazard ratio (aHR) 7.05, 95% CI 1.94–25.71 P = 0.003]. Other factors were HBV infection (aHR 8.57, 95% CI 1.47–50.08, P = 0.017) and treatment allocation (curative vs. noncurative, aHR 0.08, 95% CI 0.02–0.40, P = 0.0004). Conclusions Our findings suggest that in PLWH AFP serum levels ≥28.8 ng/mL, HBV coinfection and treatment allocation represent predictive markers for death at the time of HCC diagnosis.

Locoregional Liver-Directed Therapies to Treat Unresectable Colorectal Liver Metastases: A Review

An estimated 70% of patients with colorectal cancer will develop liver metastases during the course of their disease. While the first-line treatment for hepatic metastases is resection, most patients with colorectal liver-only or liver-dominant metastases (CRLM) present with unresectable disease and are not surgical candidates. In the past decade, locoregional liver-directed therapies have demonstrated safety and efficacy in the treatment of patients with unresectable CRLM and chemotherapy-refractory disease. These treatments can be used to attempt conversion to surgical resectability, can control local disease progression, and have the potential to prolong survival. However, they have not yet become the standard of care in many practices. Each treatment has unique risks, and the clinical data are heterogeneous and thus difficult to interpret. In this article, we will review the most recent, high-impact literature on 3 common locoregional therapies used in the treatment of patients with unresectable CRLM: hepatic artery infusion pump chemotherapy, stereotactic body radiation therapy, and selective internal radiation therapy with yttrium-90 embolization. Ultimately, for this patient population, clinical decision-making requires a multidisciplinary discussion which should take into account individual patient characteristics and clinical expertise available at the treatment facility.

A new animal model of atrophy\u2013hypertrophy complex and liver damage following Yttrium-90 lobar selective internal radiation therapy in rabbits

Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy–hypertrophy complex after SIRT. Three groups of 5–8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with different activities (0.3, 0.6 and 1.2 GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2 GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6 GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced significant toxicity. Cranial SIRT with 0.3 GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2 GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3 GBq groups developed moderate damage with inflammation and portal fibrosis at 15 days, partially recovering at 30 days. There was no difference in the expression of hepatocyte function and differentiation genes between 0.3 GBq and control groups. Cranial SIRT with 0.3 GBq of 90Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy–hypertrophy complex and liver damage without toxicity.

Facteurs prédictifs de la toxicité hépatique de la radio-embolisation par microsphères marquées à l’Yttrium-90 dans les hépatocarcinomes

IntroductionThe toxicity associated with hepatic radioembolization (RE) by microspheres labeled with Yttrium 90 (90Y) has a very variable incidence between studies and depends on a multitude of parameters. The objective of this study is to assess the various predictive factors of this toxicity, inherent of the patient or the type of procedure. Patients and methodsSingle-center retrospective study including 85 patients with hepatocarcinoma treated by hepatic RE. The medico-technical and clinical-biological parameters were studied over a defined time interval and the toxicity of the latter graded according to the Common Terminology Criteria for Adverse Events. Dosimetry was carried out on the basis of the 90Y PET/CT using the “Simplicit90Y” software and the statistical analysis using the “SAS” software. ResultsPost-RE hepatotoxicity observed in 77.7% of our population with maximum grade 3 toxicity in 10.6% of cases. The presence post-RE of hyperbilirubinemia and ascites were detected in 32.1% (only grade 1-2) and 27.1% (4.7% grade 3) of patients, respectively. The pre-therapeutic presence of cirrhosis and/or hyperbilirubin are predictive of post-RE toxicity. Other biological elements studied are less relevant in practice. Radioembolization-induced liver disease (REILD) was observed in 15.3% of cases, mainly of moderate form (13.0%). No impact of the dosimetric approach was observed. ConclusionA personalized dosimetric approach does not generate additional side effects, while maximizing the tumor dose and therefore the therapeutic effect. The presence of cirrhosis and hyperbilirubinemia pre-RE seem to be the two predominant in the appearance of REILD.

In Vivo Comparison of Micro-Balloon Interventions (MBI) Advantage: A Retrospective Cohort Study of DEB-TACE Versus b-TACE and of SIRT Versus b-SIRT.

The purpose of this study was to evaluate in vivo the role of the micro-balloon by comparing trans-arterial chemoembolization (DEB-TACE) and selective internal radiotherapy (SIRT) procedures performed with and without balloon micro-catheter (b-DEB-TACE and DEB-TACE/SIRT and b-SIRT) for the treatment of hepatocellular carcinoma (HCC). The impact of a balloon micro-catheter on trans-arterial loco-regional treatment was analyzed using non-enhanced post-procedural cone-beam CT (Ne-CBCT) by comparing the attenuation values in the embolized area and the surrounding liver tissue before and after DEB-TACE versus b-DEB-TACE and by comparing 2D/3D dosimetry in single-photon emission computed tomography after SIRT versus b-SIRT, and by comparing the histological count of the beads following orthotopic liver transplantation in the DEB-TACE versus b-DEB-TACE subgroup. We treated 84 HCC patients using trans-arterial loco-regional therapy. Fifty-three patients (26 DEB-TACE and 27 b-DEB-TACE) were analyzed in the TACE group. Contrast, signal-to-noise ratio, and contrast-to-noise ratio were all significantly higher in b-DEB-TACE subgroup than DEB-TACE (182.33 HU [CI95% 160.3-273.5] vs. 124 HU [CI95% 80.6-163.6]; 8.3 [CI95% 5.7-10.1] vs. 4.5 [CI95% 3.7-6.0]; 6.9 [CI95% 4.3-7.8] vs. 3.1 [CI95% 2.2-5.0] p < 0.05). Thirty-one patients (24 SIRT and 7 b-SIRT) were analyzed in the SIRT group. 2D dosimetry profile evaluation showed an activity intensity peak significantly higher in the b-SIRT than in the SIRT subgroup (987.5 ± 393.8 vs. 567.7 ± 302.2, p = 0.005). Regarding 3D dose analysis, the mean dose administered to the treated lesions was significantly higher in the b-SIRT than in the SIRT group (151.6Gy ± 53.2 vs. 100.1Gy ± 43.4, p = 0.01). In histological explanted liver analysis, there was a trend for higher intra-tumoral localization of embolic microspheres for b-DEB-TACE in comparison with DEB-TACE. Due to the use of three different methods, the results of this study demonstrate in vivo, a better embolization profile of oncological intra-arterial interventions performed with balloon micro-catheter regardless of the embolic agent employed.

Treatment of Intrahepatic Cholangiocarcinoma-A Multidisciplinary Approach.

Simple SummaryThis review discusses multimodality treatment strategies for intrahepatic cholangiocarcinoma (iCC). Surgical resection remains the only potentially curative therapeutic option and the central cornerstone of treatment. Adjuvant systemic treatment will be recommended after resection or in the palliative setting. Increasing knowledge of phenotypic subclassification and molecular profiling allows investigation of targeted therapies as (neo-)adjuvant treatment. High-dose brachytherapy, internal radiation therapy, and transarterial chemoembolization are among the interventional treatment options being evaluated for unresectable iCC. Given the multiple options of multidisciplinary management, any treatment strategy should be discussed in a multidisciplinary tumor board and treatment should be directed by a specialized treatment center.Intrahepatic cholangiocarcinoma (iCC) is distinguished as an entity from perihilar and distal cholangiocarcinoma and gallbladder carcinoma. Recently, molecular profiling and histopathological features have allowed further classification. Due to the frequent delay in diagnosis, the prognosis for iCC remains poor despite major technical advances and multimodal therapeutic approaches. Liver resection represents the therapeutic backbone and only curative treatment option, with the functional residual capacity of the liver and oncologic radicality being deciding factors for postoperative and long-term oncological outcome. Furthermore, in selected cases and depending on national guidelines, liver transplantation may be a therapeutic option. Given the often advanced tumor stage at diagnosis or the potential for postoperative recurrence, locoregional therapies have become increasingly important. These strategies range from radiofrequency ablation to transarterial chemoembolization to selective internal radiation therapy and can be used in combination with liver resection. In addition, adjuvant and neoadjuvant chemotherapies as well as targeted therapies and immunotherapies based on molecular profiles can be applied. This review discusses multimodal treatment strategies for iCC and their differential use.

Neoadjuvant Hemi-Liver Directed Selective Internal Radiation Therapy (SIRT) Followed by Portal Vein and Liver Vein Embolization Could Make Non-Operable Patients with Liver Cancer Eligible for Curative Intended Major Liver Resection

Introduction: The majority of patients with liver cancer is non-operable due to high tumor burden and/or impaired liver function with low regenerative potential of the liver tissue. Selective internal radiation therapy (SIRT) applicated to one liver lobe can control the liver cancer there, buy time for hypertrophy and induce hypertrophy in the contra-lateral future liver remnant (FLR). Still hypertrophy could be insufficient for liver resection. Portal vein embolization (PVE) combined with liver vein embolization (LVE) boost liver hypertrophy and patients could become eligible for curative intended major liver resections. Aim of the multi-center European SIR Spheres Surgical Registry (ESSURE) is to evaluate if the concept of hemi-liver SIRT followed by liver resection is feasible for patients that were initially non-operable. Methods: First data analysis of patients enrolled to ESSURE Results: 14 patients were recruited (9 HCC in cirrhosis, 1HCC without cirrhosis, 2 iCCC with fibrosis,1 CRLM,1 NET). All received successful SIRT to the right liver lobe without major complications. SIRT dose was 1.4-2.4 Gbq. 5 patients received additional PVE & LVE to the right liver lobe. The increase of future liver remnant after SIRT was 22%, after additional PVE & LVE 34%. Finally in 5/14 (36%) patients major liver resection could be performed (3 HCC,2 iCCC). 1 patient died, the other 4 patients showed an uncomplicated post-operative course (no complications >3a Clavien-Dindo). Conclusion: Neoadjuvant hemi-Liver SIRT followed by portal vein and liver vein embolization seems feasible and could make selected, initially non-operable patients eligible for curative intended liver resection.

POSA134 Evaluating the Economic Effects of Flexible Radionuclide Delivery Timing and Same-Day Work-up and Radioembolization in Patients with Unresectable Liver Tumors Undergoing Selective Internal Radiation Therapy

The nature of radioactive decay means that the administration of medical interventions that utilize radionuclides is time sensitive and requires careful planning. For techniques such as selective internal radiation therapy (SIRT), pre-treatment work-up procedures are also required to assess the vascular anatomy of the liver, potentially occlude certain hepatic blood vessels, and establish the hepatopulmonary shunt fraction. The aim of the present study was to evaluate the effect of the SIR-Spheres Y-90 resin microspheres FLEXdose and Order-Map-Treat radionuclide delivery and procedure planning programs on the cost of performing SIRT. The effects of the FLEXdose and Order-Map-Treat programs on costs were evaluated from the perspective of the UK Department of Health (DoH). The FLEXdose program allows for delivery of SIR-Spheres Y-90 resin microspheres at multiple timepoints prior to the planned treatment, while the complementary Order-Map-Treat program enables both the work-up and procedure to be performed on the same day. Costs of work-up and treatment were calculated based on 2018-19 NHS Reference Costs, and the cost reduction was assumed to arise from the avoidance of one day case admission per patient treated with SIRT. Assuming the complementary FLEXdose and Order-Map-Treat programs would together enable work-up and treatment to be performed in a single day, the anticipated cost savings relative to administering SIR-Spheres Y-90 resin microspheres without the two programs would be GBP 2,619 per patient, corresponding to a cost reduction of 19.8% from GBP 13,237 to GBP 10,619 per patient treated. The present analysis showed that the FLEXdose and Order-Map-Treat programs would result in cost savings from the UK DoH perspective versus performing SIRT without either of the programs. The additional flexibility afforded by the FLEXdose and Order-Map-Treat programs may also increase flexibility of interventional radiology suite scheduling, which may in turn bring about benefits beyond cost alone.

Two Cases of Severe Hypercalcaemia Associated with Cholangiocarcinoma Successfully Treated by Resection in One and Selective Internal Radiation Therapy (SIRT) in the Other

Introduction: Humoral hypercalcaemia of malignancy (HHM) in patients with cholangiocarcinoma is rarely reported with only 36 cases reported in the literature. We present two patients with marked hypercalcaemia both associated with large intrahepatic cholangiocarcinoma without bony metastases.

Uloga stereotaksične radioterapije u lečenju metastaza u jetri kolorektalnog karcinoma

Colorectal cancer is third most common malignant disease and second leading cause of cancer-related deaths worldwide. In 2020, there were 5900 new cases in Serbia and around 3300 number of deaths related to this disease. Metastatic disease is most frequently located in liver. Surgery is first option if complete resection of liver metastases is achievable. Since liver metastases are resectable in 10 - 20% of cases, there is a possibility of implementation of other treatment modality. Alternative for surgery in local treatment of unresectable metastases are stereotactic body radiation therapy (SBRT), interstitial and intraluminal brachytherapy, transarterial chemoembolization, hepatic arterial infusion chemotherapy, selective internal radiation therapy with yttrium-90 resin microspheres, cryoablation, radiofrequency, chemical, and microwave ablation. Candidates for SBRT are patients with unresectable liver metastatic disease and patients with comorbidities which disable surgical treatment, with adequate function of uninvolved liver tissue. Respiration induced motion of target volume can be reduced by introduction of motion management strategies such as infrared markers, deep inspiration breath hold, abdominal compression, respiratory tracking and gating. CyberKnife, TomoTherapy machine and modified linear accelerators are used for delivering SBRT. These units allow us to deliver dose more precisely and to make dose escalation. Different regimes of fractionation are optional, from single fraction to hypo fractionation regimes, and doses are typically around 30 - 60 Gy in 3 fractions. Low toxicity rates in patients with liver metastases treated with SBRT are in relation with precise treatment planning, dose prescription and fractionation. Results of research suggest that delivery of large doses can provide high rate of local response, but on the other hand there is possibility of disease progression out of target volumes. With adequate selection of patients with unresectable liver metastases, the implementation of SBRT, especially in combination with effective systematic treatment modalities, can provide better local control with extension of survival.

Comparing efficacies of different treatment regimens in patients with hepatocellular carcinoma accompanied by portal vein tumor thrombus using network meta-analysis.

Although various treatment regimens have been introduced for hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT), comprehensive and direct comparisons between them are limited. Thus, the purpose of this study was to perform a network meta-analysis (NMA) to compare the efficacies of different treatment regimens for HCC accompanied by PVTT. A systematic review was conducted to identify studies comparing 2 or more treatment regimens for HCC accompanied by PVTT without extrahepatic metastasis and reporting each overall survival (OS). Endpoints of this NMA were to hazard ratios with confidential intervals for OS and mean survival time difference of each treatment regimen comparison using a random-effects model. Each treatment regimen was then ranked using the P-score to assess the probability of the superiority of each one. Eleven studies involving 1,623 patients that yielded 16 comparisons were identified and enrolled in this NMA. There were 12 different treatment regimens as comparators, including sorafenib therapy alone (reference treatment). The NMA suggested that the following 4 treatment regimens improved OS compared to sorafenib: surgical resection followed by portal vein chemotherapy (SR plus PVC), SR, radiofrequency ablation plus sorafenib, and transarterial chemoembolization combined with selective internal radiation therapy. SR plus PVC was ranked the best treatment regimen for OS (P-score, 93.9%). Comparative efficacy based on this NMA may help clinicians select treatment for HCC accompanied by PVTT. If amenable, aggressive locoregional treatment regimens such as SR plus PVC should be considered for HCC accompanied by PVTT.

Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial

Introduction: This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC). Methods: A phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m² and cisplatin 25 mg/m² on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy. Results: Total 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1–8). The median OS was 13.6 months (95% CI: 5.4–21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3–25.2) and the median PFS was 9 months (95% CI: 3.2–13.1). The response rate was 25% (95% CI: 3.8–46.2%), and the disease control rate was 75% (95% CI: 53.8–96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7–42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n = 4), underlying treatment unrelated comorbidities (n = 2), and withdrawal of consent due to personal reasons (n = 2). Conclusions: Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.

Evaluation of staging systems to predict prognosis in hepatocellular carcinoma patients treated with radioembolization

PurposeTo compare the prognostic accuracy of nine staging systems, some of which are well-known and some of which have only been more recently described, for patients with unresectable HCC treated with radioembolization (RE). Materials and methodsIndividual scores or classes for the following staging systems were recorded or calculated for patients (n = 89) with unresectable HCC who underwent RE at a single tertiary care center from January 2008 to October 2016: Eastern Cooperative Oncology Group, Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, Okuda, Cancer of the Liver Italian Program (CLIP), Model for End Stage Liver Disease, Child-Pugh (CP) Categorical and Numeric, and Albumin-Bilirubin. For each staging system, a cox proportional hazards regression model was fit to the data and log-rank test statistics, concordance indices, Akaike Information Criteria (AIC) and other diagnostic statistics were calculated. ResultsOf the nine staging systems analyzed, the basic discriminatory ability assessed with the log-rank test (rejected at the α = .05-level) was significant for two of the systems: CP Numeric (p < .001) and CLIP (p < .05). Out of these two systems, CP Numeric system had a higher prognostic accuracy than CLIP with the lowest AIC (464.90), the highest optimism-corrected pseudo R2 (0.16), and the highest estimated concordance index (0.64). ConclusionAs applied to our patient population, the CP Numeric system contained the most predictive prognostic information for patients with HCC undergoing radioembolization. However, all evaluated staging systems performed suboptimally, and the relative superiority of any of the systems remains unclear when ranking them according to common practice. Further evaluation of current ranking methodologies is recommended.

P32 Price Analysis of Cancer Therapies for the Treatment of Patients with Unresectable Hepatocellular Carcinoma

The price of cancer therapy for the treatment of adult US patients with hepatocellular carcinoma (HCC) remains unknown. This study estimated the price of systemic therapies (ST) compared to selective internal radiotherapy (SIRT) for the treatment of HCC from the payer and provider perspectives.

The Cost-Effectiveness of Selective Internal Radiation Therapies Compared With Sorafenib for Treating Advanced Unresectable Hepatocellular Carcinoma in the United Kingdom

ObjectivesTo assess the cost-effectiveness of selective internal radiation therapy (SIRT) compared with sorafenib for the treatment of patients with advanced hepatocellular carcinoma in the United Kingdom, including a selected subgroup of patients who have been identified as benefiting from treatment with SIRT. MethodsA de novo economic model was developed comparing SIRT with sorafenib using data from two large randomized controlled trials. The model structure comprised a decision tree representing the outcome of the work-up procedure, transitioning into a 3-state partitioned survival model to project long-term survival outcomes. Cost-effectiveness in a post hoc defined subgroup with low tumor burden and good liver function was explored. ResultsAt list price, SIRT was predicted to be less costly but less effective than sorafenib with an estimated saving of £156 089 per quality-adjusted life-year forgone, with cost savings of £4589 and 0.029 fewer quality-adjusted life-years than sorafenib. Accounting for existing confidential discounts for sorafenib, two SIRTs were cost-effective at a £30 000 willingness-to-pay threshold compared with sorafenib when a discount for the technologies was introduced. In the subgroup with low tumor burden and good liver function, SIRT may be associated with greater survival benefits and cost savings. ConclusionsAccounting for confidential discounts, on average, SIRT technologies represent value for money in the whole advanced hepatocellular carcinoma population, being less effective but less costly than sorafenib. Results from a subgroup with low tumor burden and good liver function suggest that the cost-effectiveness of SIRTs may be maximized in this group, but further research is required to demonstrate the validity of effectiveness benefits.