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

BACKGROUND: Liver 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 METHODS: In 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. RESULTS: From 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). CONCLUSION: The 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.

Transarterial radioembolization in patients with hepatocellular carcinoma of intermediate B2 substage.

PURPOSE: Patients with hepatocellular carcinoma (HCC) of intermediate stage (BCLC-B according to the Barcelona Clinic Liver Cancer classification) are a heterogeneous group with different degrees of liver function impairment and tumour burden. The recommended treatment is transarterial chemoembolization (TACE). However, patients in this group may be judged as poor candidates for TACE because the risk-benefit ratio is low. Such patients may receive transarterial radioembolization (TARE) only by entering a clinical trial. Experts have proposed that the stage could be further divided into four substages based on available evidence of treatment benefit. We report here, for the first time, the outcome in patients with BCLC-B2 substage HCC treated with TARE. METHODS: A retrospective analysis of the survival of 126 patients with BCLC-B2 substage HCC treated with TARE in three European hospitals was performed. RESULTS: Overall median survival in patients with BCLC-B2 substage was not significantly different in relation to tumour characteristics; 19.35 months (95% CI 8.27-30.42 months) in patients with a single large (>7 cm) HCC, and 18.43 months (95% CI 15.08-21.77 months) in patients with multinodular HCC (p = 0.27). However, there was a higher proportion of long-term survivors at 36 months among those with a single large tumour (29%) than among those with multiple tumours (16.8%). CONCLUSION: Given the poor efficacy of TACE in treating patients with BCLC-B2 substage HCC, TARE treatment could be a better choice, especially in those with a large tumour.

Prevention and treatment of complications of selective internal radiation therapy: Expert guidance and systematic review.

Selective internal radiation therapy (or radioembolization) by intra-arterial injection of radioactive yttrium-90-loaded microspheres is increasingly used for the treatment of patients with liver metastases or primary liver cancer. The high-dose beta-radiation penetrates an average of only 2.5 mm from the source, thus limiting its effects to the site of delivery. However, the off-target diversion of yttrium-90 microspheres to tissues other than the tumor may lead to complications. The most prominent of these complications include radiation gastritis and gastrointestinal ulcers, cholecystitis, radiation pneumonitis, and radioembolization-induced liver disease, which may occur despite careful pretreatment planning. Thus, selective internal radiation therapy demands an expert multidisciplinary team approach in order to provide comprehensive care for patients. This review provides recommendations to multidisciplinary teams on the optimal medical processes in order to ensure the safe delivery of selective internal radiation therapy. Based on the best available published evidence and expert opinion, we recommend the most appropriate strategies for the prevention, early diagnosis, and management of potential radiation injury to the liver and to other organs. (Hepatology 2017;66:969-982).

The Post-SIR-Spheres Surgery Study (P4S): Retrospective Analysis of Safety Following Hepatic Resection or Transplantation in Patients Previously Treated with Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres.

BACKGROUND: Reports show that selective internal radiation therapy (SIRT) may downsize inoperable liver tumors to resection or transplantation, or enable a bridge-to-transplant. A small-cohort study found that long-term survival in patients undergoing resection following SIRT appears possible but no robust studies on postsurgical safety outcomes exist. The Post-SIR-Spheres Surgery Study was an international, multicenter, retrospective study to assess safety outcomes of liver resection or transplantation following SIRT with yttrium-90 (Y-90) resin microspheres (SIR-Spheres®; Sirtex). METHODS: Data were captured retrospectively at participating SIRT centers, with Y-90 resin microspheres, surgery (resection or transplantation), and follow-up for all eligible patients. Primary endpoints were perioperative and 90-day postoperative morbidity and mortality. Standard statistical methods were used. RESULTS: The study included 100 patients [hepatocellular carcinoma: 49; metastatic colorectal cancer (mCRC): 30; cholangiocarcinoma, metastatic neuroendocrine tumor, other: 7 each]; 36% of patients had one or more lines of chemotherapy pre-SIRT. Sixty-three percent of patients had comorbidities, including hypertension (44%), diabetes (26%), and cardiopathy (16%). Post-SIRT, 71 patients were resected and 29 received a liver transplant. Grade 3+ peri/postoperative complications and any grade of liver failure were experienced by 24 and 7% of patients, respectively. Four patients died <90 days postsurgery; all were trisectionectomies (mCRC: 3; cholangiocarcinoma: 1) and typically had one or more previous chemotherapy lines and presurgical comorbidities. CONCLUSIONS: In 100 patients undergoing liver surgery after receiving SIRT, mortality and complication rates appeared acceptable given the risk profile of the recruited patients.

Pilot randomized trial of selective internal radiation therapy vs. chemoembolization in unresectable hepatocellular carcinoma.

BACKGROUND & AIMS: To compare selective internal radiation therapy (SIRT) with transarterial chemoembolization (TACE), the standard-of-care for intermediate-stage unresectable, hepatocellular carcinoma (HCC), as first-line treatment. METHODS: SIRTACE was an open-label multicenter randomized-controlled pilot study, which prospectively compared primarily safety and health-related quality of life (HRQoL) changes following TACE and SIRT. Patients with unresectable HCC, Child-Pugh ≤B7, ECOG performance status ≤2 and ≤5 liver lesions (≤20 cm total maximum diameter) without extrahepatic spread were randomized to receive either TACE (at 6-weekly intervals until tumour enhancement was not observed on MRI or disease progression) or single-session SIRT (yttrium-90 resin microspheres). RESULTS: Twenty-eight patients with BCLC stage A (32.1%), B (46.4%) or C (21.4%) received either a mean of 3.4 (median 2) TACE interventions (N = 15) or single SIRT (N = 13). Both treatments were well tolerated. Despite SIRT patients having significantly worse physical functioning at baseline, at week-12, neither treatment had a significantly different impact on HRQoL as measured by Functional Assessment of Cancer Therapy-Hepatobiliary total or its subscales. Both TACE and SIRT were effective for the local control of liver tumours. Best overall response-rate (RECIST 1.0) of target lesions were 13.3% and 30.8%, disease control rates were 73.3% and 76.9% for TACE and SIRT, respectively. Two patients in each group were down-staged for liver transplantation (N = 3) or radiofrequency ablation (N = 1). CONCLUSIONS: Single-session SIRT appeared to be as safe and had a similar impact on HRQoL as multiple sessions of TACE, suggesting that SIRT might be an alternative option for patients eligible for TACE.

Radioembolization of hepatocellular carcinoma activates liver regeneration, induces inflammation and endothelial stress and activates coagulation.

BACKGROUND & AIMS: Radioembolization may rarely induce liver disease resulting in a syndrome that is similar to veno-occlusive disease complicating bone marrow transplantation where inflammation, endothelial cell activation and thrombosis are likely involved. We hypothesized that similar mechanisms could be implicated in radioembolization-induced liver disease (REILD). Moreover, lobar radioembolization may induce hypertrophy of the non-treated hemiliver most probably by inducing liver regeneration. METHODS: In patients with hepatocellular carcinoma, we prospectively studied serum levels of markers of liver regeneration, oxidative stress, pro-inflammatory pathways, endothelial activation and coagulation parameters over 2 months after radioembolization. RESULTS: Although REILD did not occur among 14 treated patients, a decrease in effective liver blood flow was observed. Radioembolization was followed by a persistent increase in pro-inflammatory (interleukin 6 and 8) and oxidative stress (malondyaldehide) markers, an induction of endothelial injury markers (vW factor and PAI-1) and an activation of the coagulation cascade (factor VIII, PAI-1, D-Dimer) as well as a significant increase in factors related to liver regeneration (FGF-19 and HGF). CONCLUSION: Radioembolization activates liver regeneration, produces oxidative stress, activates inflammatory cytokines and induces endothelial injury with partial activation of the coagulation cascade. These findings may have implications in the pathogenesis, prevention and therapy of REILD and in the development of new therapies to enhance hypertrophy with a surgical perspective.

Prognostic factors and prevention of radioembolization-induced liver disease.

UNLABELLED: Radioembolization (RE)-induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low-dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P<0.0001). Treatment efficacy was not jeopardized since 3-month disease control rates were virtually identical in both groups (66.7% and 67.2%, P=0.93). Exposure to chemotherapy in the 2-month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume<1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. CONCLUSION: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD.

Partial Splenic Embolization in Paediatric Sickle Cell Disease Patients with Hypersplenism.

PURPOSE: To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD). MATERIAL AND METHODS: This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6 months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma. RESULTS: The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05 g/dL vs. 6.31 g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline. CONCLUSION: PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions.

Predictive Factors for Adverse Event Outcomes After Transarterial Radioembolization with Yttrium-90 Resin Microspheres in Europe: Results from the Prospective Observational CIRT Study.

BACKGROUND: Using data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours. METHODS: We analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS). RESULTS: All-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade ≥ 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p = 0.0045), 1 tumour nodule (0.0081), > 1 TARE treatment (p = 0.0224), no prophylactic embolization (p = 0.0211), partition model dosimetry (p = 0.0007) and unilobar treatment target (0.0032). For ICC, > 1 TARE treatment was associated with an increase in AEBS (p = 0.0224), and for colorectal liver metastases, ECOG 0 (p = 0.0188), > 2 prior systemic treatments (p = 0.0127), and 1 tumour nodule (p = 0.0155) were associated with an increased AEBS. CONCLUSION: Our study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.

Liver Resection and Transplantation Following Yttrium-90 Radioembolization for Primary Malignant Liver Tumors: A 15-Year Single-Center Experience.

Radioembolization (RE) may help local control and achieve tumor reduction while hypertrophies healthy liver and provides a test of time. For liver transplant (LT) candidates, it may attain downstaging for initially non-candidates and bridging during the waitlist. METHODS: Patients diagnosed with HCC and ICC treated by RE with further liver resection (LR) or LT between 2005-2020 were included. All patients selected were discarded for the upfront surgical approach for not accomplishing oncological or surgical safety criteria after a multidisciplinary team assessment. Data for clinicopathological details, postoperative, and survival outcomes were retrospectively reviewed from a prospectively maintained database. RESULTS: A total of 34 patients underwent surgery following RE (21 LR and 13 LT). Clavien-Dindo grade III-IV complications and mortality rates were 19.0% and 9.5% for LR and 7.7% and 0% for LT, respectively. After RE, for HCC and ICC patients in the LR group, 10-year OS rates were 57% and 60%, and 10-year DFS rates were 43.1% and 60%, respectively. For HCC patients in the LT group, 10-year OS and DFS rates from RE were 51.3% and 43.3%, respectively. CONCLUSION: Liver resection after RE is safe and feasible with optimal short-term outcomes. Patients diagnosed with unresectable or high biological risk HCC or ICC, treated with RE, and rescued by LR may achieve optimal global and DFS rates. On the other hand, bridging or downstaging strategies to LT with RE in HCC patients show adequate recurrence rates as well as long-term survival.

Radioembolization for hepatocellular carcinoma.

Radioembolization is a form of brachytherapy in which intra-arterially injected (90)Y-loaded microspheres serve as sources for internal radiation purposes. It produces average disease control rates above 80% and is usually very well tolerated. Main complications do not result from the microembolic effect, even in patients with portal vein occlusion, but rather from an excessive irradiation of non-target tissues including the liver. All the evidence that support the use of radioembolization in HCC is based on retrospective series or non-controlled prospective studies. However, reliable data can be obtained from the literature, particularly since the recent publication of large series accounting for nearly 700 patients. When compared to the standard of care for the intermediate and advanced stages (transarterial embolization and sorafenib), radioembolization consistently provides similar survival rates. Two indications seem particularly appealing in the boundaries of these stages for first-line radioembolization. First, the treatment of patients straddling between the intermediate and advanced stages (intermediate patients with bulky or bilobar disease that are considered poor candidates for TACE, and advanced patients with solitary tumors invading a segmental or lobar branch of the portal vein). Second, the treatment of patients that are slightly above the criteria for resection, ablation or transplantation, for which downstaging could open the door for a radical approach. Radioembolization can also be used to treat patients progressing to TACE or sorafenib. With a number of clinical trials underway, the available evidence shows that it adds a significant value to the therapeutic weaponry against HCC of tertiary care centers dealing with this major cancer problem.

A new animal model of atrophy-hypertrophy 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.

Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study.

PURPOSE: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in combination with a PD-1 inhibitor in patients with unresectable hepatocellular carcinoma (uHCC) and liver-only disease ineligible for chemoembolization. PATIENTS AND METHODS: NASIR-HCC is a single-arm, multicenter, open-label, phase 2 trial that recruited from 2017 to 2019 patients who were naïve to immunotherapy and had tumors in the BCLC B2 substage (single or multiple tumors beyond the up-to-7 rule), or unilobar tumors with segmental or lobar portal vein invasion (PVI); no extrahepatic spread; and preserved liver function. Patients received SIRT followed 3 weeks later by nivolumab (240 mg every 2 weeks) for up to 24 doses or until disease progression or unacceptable toxicity. Safety was the primary endpoint. Secondary objectives included objective response rate (ORR), time to progression (TTP), and overall survival (OS). RESULTS: 42 patients received SIRT (31 BCLC-B2, 11 with PVI) and were followed for a median of 22.2 months. 27 patients discontinued and 1 never received Nivolumab. 41 patients had any-grade adverse events (AE) and 21 had serious AEs (SAE). Treatment-related AEs and SAEs grade 3-4 occurred in 8 and 5 patients, respectively. Using RECIST 1.1 criteria, ORR reported by investigators was 41.5% (95% CI 26.3% to 57.9%). Four patients were downstaged to partial hepatectomy. Median TTP was 8.8 months (95% CI 7.0 to 10.5) and median OS was 20.9 months (95% CI 17.7 to 24.1). CONCLUSIONS: The combination of SIRT and nivolumab has shown an acceptable safety profile and signs of antitumor activity in the treatment of patients with uHCC that were fit for SIRT. TRIAL REGISTRATION NUMBER: NCT03380130.

Prognosis of hepatocellular carcinoma in relation to treatment across BCLC stages.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system recommends first-line therapy for each tumor stage. We evaluated the effect of compliance with BCLC treatment allocation on the prognosis of patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 359 consecutive, newly diagnosed HCC patients treated in our Liver Unit during a 14-year period. For each stage, survival was compared according to whether treatment matched the BCLC recommendation. We also compared the survival of patients in the same BCLC stage who received different treatments, and patients in different BCLC stages receiving the same treatment. RESULTS: BCLC-A patients treated with radical therapies (66%) survived longer (117 vs. 20 months; p < 0.001) than patients (33%) who received locoregional or systemic therapies. Survival of BCLC-B patients treated with locoregional treatments (57%) was shorter (24 vs. 71 months; p < 0.001) than that of patients receiving radical therapies (32%). BCLC-C patients treated with systemic therapy or supportive care survived shorter (6 vs. 11 months; p = 0.003) than those receiving locoregional therapies (39%). Survival of BCLC-D patients receiving systemic therapies or supportive care was significantly lower than that of patients treated by liver transplantation (5 vs. 137 months; p < 0.001). CONCLUSIONS: In addition to BCLC stage, actual treatment determines survival in patients with HCC.

Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis.

PURPOSE: Intraarterial delivery of yttrium-90 ((90)Y)-bound microspheres (ie, radioembolization) is a promising treatment for hepatocellular carcinoma (HCC). An early concern was the "embolic" nature of the microspheres, and their potential to reduce hepatic arterial blood flow in patients with compromised portal blood flow secondary to portal vein thrombosis/occlusion (PVT). In this situation, the risk of liver failure could be enhanced, particularly in patients with cirrhosis who have increased hepatic arterial blood flow. This retrospective analysis was undertaken to assess the safety and clinical benefits of radioembolization with (90)Y resin microspheres in HCC with branch or main PVT. MATERIALS AND METHODS: A total of 25 patients presenting with unresectable HCC and compromised portal flow received segmental, lobar, or whole-liver infusion of (90)Y resin microspheres. For the analysis of tumor response, changes in target lesions, appearance of new lesions, and changes in portal vein thrombus were studied. Controlled disease was defined by absence of progression in all these components. RESULTS: Globally, controlled disease was achieved in 66.7% of patients at 2 months and 50% of patients at 6 months. No significant changes were observed in liver-related toxicities according to Common Toxicity Criteria (version 3.0) at 1 and 2 months after treatment. Median survival time was 10 months (95% CI, 6.6-13.3 months). CONCLUSIONS: Radioembolization of unresectable HCC and branch or main PVT with (90)Y resin microspheres was associated with minimal toxicity and a favorable median survival time. Further prospective studies are warranted to validate the findings in this clinically challenging patient population.

Liver Radioembolization: An Analysis of Parameters that Influence the Catheter-Based Particle-Delivery via CFD.

Radioembolization (RE) is a valuable treatment for liver cancer. It consists of administering radioactive microspheres by an intra-arterially placed catheter with the aim of lodging these microspheres, which are driven by the bloodstream, in the tumoral bed. Even though it is a safe treatment, some radiation-induced complications may arise. In trying to detect or solve the possible incidences that cause nontarget irradiation, simulating the particle- hemodynamics in hepatic arteries during RE by computational fluid dynamics (CFD) tools has become a valuable approach. This paper reviews the parameters that influence the outcome of RE and that have been studied via numerical simulations. In this numerical approach, the outcome of RE is regarded as successful if particles reach the artery branches that feed tumor-bearing liver segments. Up to 10 parameters have been reviewed. The variation of each parameter actually alters the hemodynamic pattern in the vicinities of the catheter tip and locally alters the incorporation of the particles into the bloodstream. Therefore, in general, the local influences of these parameters should result in global differences in terms of particle distribution in the hepatic artery branches. However, it has been observed that under some (qualitatively described) appropriate conditions where particles align with blood streamlines, the local influence resulting from a variation of a given parameter vanishes and no global differences are observed. Furthermore, the increasing number of CFD studies on RE suggests that numerical simulations have become an invaluable research tool in the study of RE.

On the importance of spiral-flow inflow boundary conditions when using idealized artery geometries in the analysis of liver radioembolization: A parametric study.

In the last decades, the numerical studies on hemodynamics have become a valuable explorative scientific tool. The very first studies were done over idealized geometries, but as numerical methods and the power of computers have become more affordable, the studies tend to be patient specific. We apply the study to the numerical analysis of tumor-targeting during liver radioembolization (RE). RE is a treatment for liver cancer, and is performed by injecting radiolabeled microspheres via a catheter placed in the hepatic artery. The objective of the procedure is to maximize the release of radiolabeled microspheres into the tumor and avoid a healthy tissue damage. Idealized virtual arteries can serve as a generalist approach that permits to separately analyze the effect of a variable in the microsphere distribution with respect to others. However, it is important to use proper physiological boundary conditions (BCs). It is not obvious, the need to account for the effect of tortuosity when using an idealized virtual artery. We study the use of idealized geometry of a hepatic artery as a valid research tool, exploring the importance of using realistic spiral-flow inflow BC. By using a literature-based cancer scenario, we vary two parameters to analyze the microsphere distribution through the outlets of the geometry. The parameters varied are the type of microspheres injected and the microsphere injection velocity. The results with realistic inlet velocity profile showed that the particle distribution in the liver segments is not affected by the analyzed injection velocity values neither by the particle density. NOVELTY STATEMENT: In this article, we assessed the use of idealized geometries as a valid research tool and applied the use of an idealized geometry to the case of an idealized hepatic artery to study the particle-hemodynamics during radioembolization (RE). We studied three different inflow boundary conditions (BCs) to assess the usefulness of the geometry, two types of particle injection velocities and two types of commercially available microspheres for RE treatment. In recent years, the advent in computational resources allowed for more detailed patient-specific geometry generation and discretization and hemodynamics simulations. However, general studies based on idealized geometries can be performed in order to provide medical doctors with some basic and general guidelines when using a given catheter for a given cancer scenario. Moreover, using an idealized geometry can be a reasonable approach which allows us to isolate a given parameter and control other parameters, so that parameters can be independently assessed. Even though an idealized geometry does not match any patient's geometry, the use of an idealized geometry can be valid when drawing general conclusions that may be useful in patient-specific cases. However, we believe that even if an idealized hepatic artery geometry is used for the study, it is necessary to account for the upstream and downstream tortuosity of vessels through the BCs. In this work, we highlighted the need of modeling the tortuosity of upstream and downstream vasculatures through the BCs.

Clinical Application of Radioembolization in Hepatic Malignancies: Protocol for a Prospective Multicenter Observational Study.

BACKGROUND: Radioembolization, also known as transarterial radioembolization or selective internal radiation therapy with yttrium-90 (90Y) resin microspheres, is an established treatment modality for patients with primary and secondary liver tumors. However, large-scale prospective observational data on the application of this treatment in a real-life clinical setting is lacking. OBJECTIVE: The main objective is to collect data on the clinical application of radioembolization with 90Y resin microspheres to improve the understanding of the impact of this treatment modality in its routine practice setting. METHODS: Eligible patients are 18 years or older and receiving radioembolization for primary and secondary liver tumors as part of routine practice, as well as have signed informed consent. Data is collected at baseline, directly after treatment, and at every 3-month follow-up until 24 months or study exit. The primary objective of the Cardiovascular and Interventional Radiological Society of Europe Registry for SIR-Spheres Therapy (CIRT) is to observe the clinical application of radioembolization. Secondary objectives include safety, effectiveness in terms of overall survival, progression-free survival (PFS), liver-specific PFS, imaging response, and change in quality of life. RESULTS: Between January 2015 and December 2017, 1047 patients were included in the study. The 24-month follow-up period ended in December 2019. The first results are expected in the third quarter of 2020. CONCLUSIONS: The CIRT is the largest observational study on radioembolization to date and will provide valuable insights to the clinical application of this treatment modality and its real-life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02305459; https://clinicaltrials.gov/ct2/show/NCT02305459. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16296.