Hepatopulmonary Shunt Fraction Research Articles

Non-Invasive Imaging Biomarkers to Predict the Hepatopulmonary Shunt Fraction Before Transarterial Radioembolization in Patients with Hepatocellular Carcinoma.

To identify disease-specific profiles comprising patient characteristics and imaging biomarkers on contrast-enhanced (CE)-computed tomography (CT) that enable the non-invasive prediction of the hepatopulmonary shunt fraction (HPSF) in patients with hepatocellular carcinoma (HCC) before resin-based transarterial radioembolization (TARE). This institutional review board-approved (EA2/071/19) retrospective study included 56 patients with HCC recommended for TARE. All patients received tri-phasic CE-CT within 6 weeks prior to an angiographic TARE evaluation study using technetium-99m macroaggregated albumin. Imaging biomarkers representative of tumor extent, morphology, and perfusion, as well as disease-specific clinical parameters, were used to perform data-driven variable selection with backward elimination to generate multivariable linear regression models predictive of HPSF. Results were used to create clinically applicable risk scores for patients scheduled for TARE. Additionally, Cox regression was used to identify independent risk factors for poor overall survival (OS). Mean HPSF was 13.11% ± 7.6% (range: 2.8- 35.97%). Index tumor diameter (p = 0.014) or volume (p = 0.034) in combination with index tumor non-rim arterial phase enhancement (APHE) (p < 0.001) and washout (p < 0.001) were identified as significant non-invasive predictors of HPSF on CE-CT. Specifically, the prediction models revealed that the HPSF increased with index lesion diameter or volume and showed higher HPSF if non-rim APHE was present. In contrast, index tumor washout was associated with decreased HPSF levels. Independent risk factors of poorer OS were radiogenomic venous invasion and ascites at baseline. The featured prediction models can be used for the initial non-invasive estimation of HPSF in patients with HCC before TARE to assist in clinical treatment evaluation while potentially sparing ineligible patients from the angiographic shunt evaluation study.

Abstract No. 557 Transarterial chemoembolization prior to Y-90 radioembolization as a risk factor for elevated hepatopulmonary shunt fraction

Abstract No. 557 Transarterial chemoembolization prior to Y-90 radioembolization as a risk factor for elevated hepatopulmonary shunt fraction

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.

Hybrid angiography-CT for transarterial radioembolization: a pictorial essay.

Although hybrid angiography-CT (Angio-CT) has a long history of use for interventional oncology procedures, its applications for transarterial radioembolization (TARE) are not as well described in the literature. This pictorial essay demonstrates a single-institution experience with the utilization of an Angio-CT system for TARE treatment of hepatocellular carcinoma. Procedural images and clinical data for twenty-four patients who underwent initial angiographic mapping with hepatopulmonary shunt fraction assessment and or administration of Yttrium-90 (Y-90) microspheres using the Angio-CT system to date were reviewed. Cases were reviewed for examples that highlight the specific utility of Angio-CT. Three representative TARE cases were selected which illustrate unique advantages and applications of the Angio-CT system when performing TARE. These include the ability to optimally delineate hepatic vascular anatomy, accurately calculate liver volumes for dosimetry, and improve the detection and characterization of equivocal lesions. Angio-CT has unique advantages which can be applied to TARE treatment of patients with HCC. The technology has potential to be an especially effective tool for those who aim to be at the cutting edge of the rapidly growing field of interventional oncology.

Analysis of failed therapy evaluations in radioembolization of primary and secondary liver cancers

PurposeTo analyze patients’ characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after 99mTc-labeled macroaggregated albumin (99mTc-MAA) evaluation.MethodsIn this retrospective single-center cohort, all patients undergoing 99mTc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either “TARE” or “no TARE” group. Patients’ characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed.Results436 patients [male = 248, female = 188, median age 62 (23–88) years] with 99mTc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in “no TARE” compared to “TARE” group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of 99mTc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031).ConclusionA substantial number of patients are precluded from TARE following 99mTc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.

90Y radioembolization dosimetry using a simple semi-quantitative method in intrahepatic cholangiocarcinoma: Glass versus resin microspheres

IntroductionThere are two different types of 90Y Microspheres, glass and resin, in the market for 90Y radioembolization (90Y-RE). This study aimed to investigate the dose of radiation delivered through glass vs. resin-based 90Y-RE to intrahepatic cholangiocarcinoma (ICC). MethodsIn this retrospective study, 10 patients with ICC underwent 90Y-RE, five underwent glass (Glass group) and other 5 resin (Resin group) microspheres. Technetium-99m macro-aggregated albumin (Tc-99m MAA) shunt study was performed two weeks before 90Y-RE. Within 2 h from 90Y-RE, Bremsstrahlung SPECT/CT was obtained. Regions of interest (ROIs) were segmented around the targeted tumor and the liver. Tumor and liver volumes, corresponding radioactive counts, and tumor to liver count ratio were calculated using MIM software and compared between Glass and Resin groups. ResultsMean hepatopulmonary shunt fraction was 7.1 vs. 6.2% for the Glass and Resin groups (p = 0.83), with no extrahepatic activity. There was no difference in the activity and tumor uptake of administered Tc-99m MAA between both groups (p = 0.71 and p = 0.63). Mean administered activity of 90Y in the Glass group was higher than the Resin group (73.2 ± 24.3 vs. 44.5 ± 18.2 mCi, p < 0.001). The tumor 90Y uptake was significantly higher in the Glass group compared to the Resin group (41.3% vs. 33.5%, p < 0.001), corresponding to the mean tumor dose of 205.7 ± 19.7 vs. 128.9 ± 10.6 Gy, respectively (p < 0.001). The tumor to normal liver parenchyma 90Y dose ratio was significantly higher in the Glass group compared to the Resin group, 4.9 ± 0.7 versus 2.4 ± 0.3 respectably (p < 0.001). ConclusionsBoth 90Y glass and resin-based microsphere 90Y-RE are feasible and safe in patients with ICC, while 90Y glass microsphere delivers higher dose of 90Y to the targeted tumors. Advances in knowledgeWhile both 90Y glass and resin-based microsphere yttrium-90 radioembolization are feasible and safe treatment options for in patients with intrahepatic cholangiocarcinoma, 90Y glass microsphere delivers higher dose of 90Y to the targeted tumors. Implications for patient careBoth of 90Y glass and resin-based microsphere can be safely and feasibly used for treatment of intrahepatic cholangiocarcinoma, difference in dose of 90Y delivered to the targeted tumors should be clinically considered while choosing the microsphere type.

Patient and tumor characteristics predictive of an elevated hepatopulmonary shunt fraction before radioembolization of hepatic tumors.

To determine whether any patient or hepatic tumor characteristics are predictive of hepatopulmonary shunt fraction when performed before radioembolization. A retrospective review was performed on 190 patients who underwent preradioembolization hepatic arteriography with calculation of hepatopulmonary shunt fraction using technetium-99m-labeled macroaggregated albumin perfusion scintigraphy. Patient and tumor characteristics including imaging features were reviewed for correlation with absolute shunt fraction, shunt fraction greater than 10%, and shunt fraction greater than 20%. Most tumor types showed some cases of elevated shunt fraction greater than 10%. Six patients had a shunt fraction greater than 20%: four were hepatocellular carcinoma and two were neuroendocrine tumor metastases. Univariate analysis showed that dominant tumor diameter, hepatic tumor burden, vascular invasion, hepatic venous invasion, and hypervascularity on angiography were associated with a shunt fraction greater than 10%. Only dominant tumor diameter and vascular invasion were associated with a shunt fraction greater than 20%. On multivariate analysis, only tumor diameter (odds ratio 1.2) and hepatic venous invasion (odds ratio 23.0) were associated independently with an increased shunt fraction greater than 10%. Multiple patient and tumor-related characteristics were significantly correlated with the hepatopulmonary shunt fraction on univariate analysis. However, on multivariate analysis, only the dominant tumor diameter and presence of hepatic venous invasion were associated independently with a greater than 10% shunt fraction.

4:03 PMAbstract No. 343 - 3D quantification of viable tumor volume in patients with hepatocellular carcinoma predicts the hepato-pulmonary shunt fraction before Y90 radioembolization.

4:03 PMAbstract No. 343 - 3D quantification of viable tumor volume in patients with hepatocellular carcinoma predicts the hepato-pulmonary shunt fraction before Y90 radioembolization.

Management of High Hepatopulmonary Shunting in Patients Undergoing Hepatic Radioembolization

PurposeTo review the safety of hepatic radioembolization (RE) in patients with high (≥ 10%) hepatopulmonary shunt fraction (HPSF) using various prophylactic techniques. Materials and MethodsA review was conducted of 409 patients who underwent technetium 99m–labeled macroaggregated albumin scintigraphy before planned RE. Estimated pulmonary absorbed radiation doses based on scintigraphy and hepatic administered activity were calculated. Outcomes from dose reductions and adjunctive catheter-based prophylactic techniques used to reduce lung exposure were assessed. ResultsThere were 80 patients with HPSF ≥ 10% who received RE treatment (41 resin microspheres for metastases, 39 glass microspheres for hepatocellular carcinoma). Resin microspheres were used in 17 patients according to consensus guideline–recommended dose reduction; 38 patients received no dose reduction because the expected lung dose was < 30 Gy. Prophylactic techniques were used in 25 patients (with expected lung dose ≤ 74 Gy), including hepatic vein balloon occlusion, variceal embolization, or bland arterial embolization before, during, or after RE delivery. Repeated scintigraphy after prophylactic techniques to reduce HPSF in seven patients demonstrated a median change of −40% (range, +32 to −69%). Delayed pneumonitis developed in two patients, possibly related to radiation recall after chemoembolization. Response was lower in patients treated with resin spheres with dose reduction, with an objective response rate of 13% and disease control rate of 47% compared with 56% and 94%, respectively, without dose reduction (P = .023, P = .006). ConclusionsDose reduction recommendations for HPSF may compromise efficacy. Excessive shunting can be reduced by prophylactic catheter-based techniques, which may improve the safety of performing RE in patients with high HPSF.

(90)Y Radioembolization: Multimodality Imaging Pattern Approach with Angiographic Correlation for Optimized Target Therapy Delivery.

Primary and metastatic liver cancers are responsible for considerable morbidity and mortality, and many patients are not curable at presentation. Therefore, new therapies such as radioembolization with yttrium 90 ((90)Y)-labeled microspheres are an alternative method to treat patients with unresectable primary or secondary liver tumors. Patient selection, treatment technique, and early recognition of potential complications are the keys for successful patient outcomes. The activity of administered (90)Y microspheres depends on multiple variables, including the tumor burden, the volume of the liver lobe to be treated, the type of (90)Y microspheres, and the hepatopulmonary shunt fraction. Preprocedural planning relies on the results of cross-sectional imaging to determine the extent of disease, tumoral and nontumoral liver volumes, patency of the portal vein, and the degree of extrahepatic disease. A multidisciplinary approach that combines expertise in cross-sectional imaging, nuclear medicine, and flow dynamics is critical to adequately target malignant tissue. Preprocedural multimodality imaging, particularly combined single photon emission computed tomography (SPECT) and computed tomography (CT) imaging (SPECT/CT), may be used to identify nontarget imaging patterns that, if recognized, can potentially be corrected with either branch vessel embolization or catheter repositioning. Postprocedural multimodality imaging is also useful to confirm the appropriate delivery of (90)Y microspheres, enabling early identification of potential complications and the adequacy of microsphere distribution, thereby optimizing planning for subsequent therapies.

The relationship between the percentage of lung shunting on Tc-99m macroaggregated albumin (Tc-99m MAA) scan and the grade of hepatocellular carcinoma vascularity

BackgroundHepatocellular carcinoma (HCC) stands for the majority of primary liver malignancy. HCC has variable grade of vascularity according to the histological tumor grade and underlying liver damage. Yttrium-90 radioembolization is a promising catheter-based hepatic intra-arterial therapy for HCC that necessitates proper planning. Technetium-99m macroaggregated albumin (Tc-99m MAA), a simulation of the treatment, is used to identify the shunting of microspheres to the lungs or gastrointestinal tract. ObjectiveTo evaluate the relationship between the percentage of lung shunting on Tc-99m MAA scan performed in treatment planning of Yttrium-90 (Y-90) microsphere selective internal radiation therapy (SIRT) for HCC and the grade of tumor vascularity shown on digital subtraction hepatic angiography. Materials and methodsThis study was conducted on 19 patients diagnosed to have HCC, based on typical computed tomography (CT) criteria and/or elevated alpha-fetoprotein (AFP) ⩾200ng/ml, and planned for Y-90 therapy. They were injected by Tc-99m MAA into the hepatic arterial territory with prior digital subtraction angiography. Tc-99m MAA scan was reviewed for extrahepatic shunting within the abdomen. Additionally, the hepatopulmonary shunt (HPS) fraction or the lung shunting (LS) percentage was calculated and further evaluated in relation to the grade of tumor vascularity shown on digital subtraction hepatic angiography. ResultsThere was no extrahepatic accumulation of Tc-99m MAA related to umbilical, gastroduodenal or splenic shunting. The LS percentage assorted among patients and ranged between 0.8% and 42.9% with a median of 5.5%. LS more than 20% occurred in only 1 patient. Subsequent therapy plan was changed accordingly in 5% of patients. The more vascular the lesion was, the higher lung shunting percentage was detected. ConclusionTc-99m MAA scan is fundamental prior to Y-90 microsphere SIRT as it minimizes the risk of post-radioembolization complications, hence, enhancing the safety of Y-90 microsphere subsequent administration. Moreover, the percentage of lung shunting varies considerably among patients with HCC relying on the grade of tumor vascularity.

Radiographic Parameters in Predicting Outcome of Patients with Hepatocellular Carcinoma Treated with Yttrium-90 Microsphere Radioembolization

Background. In patients with hepatocellular carcinoma, selection criteria for transarterial hepatic selective internal radiotherapy are imprecise. Additionally, radiographic parameters to predict outcome of transarterial hepatic selective internal radiotherapy have not been fully characterized. Patients and methods. Computed tomography (CT) scans of 23 patients with unresectable primary hepatocellular carcinoma before and after transarterial hepatic selective internal radiotherapy with yttrium-90 microspheres were retrospectively reviewed. Selected radiographic parameters were evaluated and correlated with progression-free survival and overall survival. Response to treatment was assessed with Response RECIST 1.1 and Morphology, Attenuation, Size, and Structure (MASS) criteria. Results. On the post-SIRT CT, 68% of tumors demonstrated decreased size (median decrease of 0.8 cm, P = 0.3); 64% had decreased attenuation (median decrease 5.7 HU, P = 0.06), and 48% demonstrated increased tumor necrosis (P < 0.001). RECIST-defined partial response was seen in 10% patients, stable disease in 80%, and 10% had disease progression. Median progression-free survival was 3.9 months (range, 3.3 to 7.3), and median overall survival was 11.2 months (7.1 to 31.1). Pretreatment lower hepatopulmonary shunt fraction, central hypervascularity, and well-defined tumor margins were associated with improved progression-free survival. Conclusion. In patients with unresectable hepatocellular carcinoma, pretreatment CT parameters may predict favorable response to SIRT and improve patient selection.

Abstract No. 385 - Clinical correlation between hepatic vein opacification and hepatopulmonary shunt fraction for 90Y evaluation

Purpose Hepatopulmonary shunt (HPS) fraction ≥20% is one of the occasional criteria preventing 90Y therapy. This study aimed to identify if there is clinical correlation between hepatic vein (HV) opacification and HPS during initial evaluation for 90Y therapy. Materials and Methods We collected 90Y candidates from 2004 to 2011. Patient’s underlying disease, imaging, arteriograms, and HPS calculations were retrospectively reviewed. If the HV was opacified during visceral arteriogram, the time between contrast injection and HV visualization was recorded. Statistical analysis with unpaired t-test compared the time of HV visualization in patients with and without an elevated HPS fraction. Results Total of 151 initial 90Y work up studies in 149 patients were included. The diagnoses included 75 HCC, 53 neuroendocrine tumor metastases, 14 colorectal metastases, 3 cholangiocarcinoma and 4 other metastases. Imaging revealed multifocal disease(n=117, 77%), bilobar disease(102, 68%) and macrovascular invasion (41, 27%). Macrovascular invasions included 4 HV and IVC, 2 HV and portal vein (PV), 1 IVC, 11 main PV, 1 right main PV, 16 right PV branch, 2 left main PV and 4 left PV branch. Mean maximum tumor diameter was 6.9±3.6 cm. Twenty-nine patients (19%) did not complete Y90 therapy; due to (18) high HPS, (5) unfavorable vascular anatomy, (2) declining liver function, (1) gastric uptake, (1) extrahepatic tumor, (1) poor tumor localization and (1) misdiagnosis. HV opacification was noted in 15 studies. Nine out of 15 studies showed HPS fraction ≥20%. PPV and NPV of HV opacification as a predictor of high HPS fraction were 60% and 94%. Average time until visualized HV in patients whom HPS fraction ≥20% and Conclusion The results demonstrated that visualization of the HV during initial arteriogram alone may not be sufficient to predict high HPS. We found that HV opacifications were seen on arteriograms earlier in the patients with high HPS (≥20%) than the patients with shunt

8:16 AM Abstract No. 61 - Splenomegaly-associated thrombocytopenia after hepatic Yttrium-90 radioembolization

Purpose Thrombocytopenia is often observed after Yttrium-90 hepatic radioembolization (RE). Mechanisms may include direct radiation toxicity in the blood compartment, marrow suppression, or sequestration. We sought to identify the causative factors by retrospective analysis. Materials and Methods All patients with complete baseline and 3 month post-RE imaging and lab data were included in the analysis. Uni- and multivariate regression analysis were performed on clinical, procedural and imaging data, including white and red blood cell counts, administered Yttrium-90 activity and absorbed dose, territory treated, pre-existing cirrhosis, hepatopulmonary shunt fraction, and hepatic and splenic volumes. Results A total of 116 patients with complete datasets were identified (65 M, 51 F; median age 63; 46 primary, 70 secondary liver malignancy, 86 resin, 30 glass microspheres, median activity 1.85 GBq, median liver dose 45 Gy, 83 whole liver treatments). Median thrombocyte decrease was -20.2%, leading to new or increased grade of thrombocytopenia in 43 patients, by CTCAE-NCI version 4.02 criteria. One patient suffered grade 4 thrombocytopenia requiring transfusions. Independent risk factors for decrease in thrombocyte count included change in spleen volume (median change +17.5%; p Conclusion Post-RE treatment increase of spleen volume is correlated to decrease in peripheral thrombocyte count, suggesting a mechanism of increased portal hypertension and sequestration being responsible for thrombocytopenia.

Chemoembolic Hepatopulmonary Shunt Reduction to Allow Safe Yttrium-90 Radioembolization Lobectomy of Hepatocellular Carcinoma

Yttrium-90 ((90)Y) radioembolization represents an emerging transcatheter treatment option for the management of hepatocellular carcinoma (HCC). Elevation of the hepatopulmonary shunt fraction risks nontarget radiation to the lungs and may limit the use of (90)Y therapy in patients with locally advanced disease with vascular invasion, who often demonstrate increased shunting. We present two cases in which patients with HCC and portal vein invasion resulting in elevated hepatopulmonary shunt fractions underwent chemoembolic shunt closure to allow safe (90)Y radioembolization. Both patients demonstrated excellent tumor response and patient survival. On this basis, we propose a role for chemoembolic reduction of the lung shunt fraction before (90)Y radioembolization in patients with extensive tumor-related hepatopulmonary shunting.