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Yoneoka et al. Hepatoma Res 2020;6:67  I  http://dx.doi.org/10.20517/2394-5079.2020.57                                       Page 3 of 11

               imaging tests were done 3 months after treatment. This retrospective chart and imaging review study
               was approved by the Institutional Review Board at the Queen’s Medical Center and was determined to be
               exempt from needing informed consent.

               The diagnosis of HCC was made with histologic confirmation of HCC with biopsy or with contrast-
               enhanced imaging (CT or MRI) which demonstrated liver mass or masses with LI-RADS 5 criteria,
               an arterial phase hyperenhancement and one or more of the following, “washout” on venous phase, an
               enhancing capsule or threshold growth. These criteria were also consistent with the Organ Procurement
               and Transplantation class 5 criteria.


               Pre-treatment imaging was performed using either CT or MRI. Pre-treatment tumor size was defined as
               the sum of the diameters of all enhancing lesions. All images were taken within 6 months prior to TARE.
               All patients were evaluated by an interventional radiologist, hepatologist and surgeon and cases were
               discussed at a multidisciplinary hepatobiliary conference. Patients were not candidates for TARE if they
               had a total bilirubin above 2.0 mg/dL or evidence of extrahepatic spread of disease. A Y90 arterial mapping
               procedure was performed to identify the tumor(s), vascular branches supplying the tumor and degree of
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               lung shunting with  Tc-macroaggregated albumin. Patients with greater than 10% lung shunting were not
               candidates for TARE.

               Radioembolization was performed with Y90 delivered via glass microspheres (TheraSphere, Boston
               Scientific, USA) or resin microspheres (SIR-Spheres, Sirtex Medical, Australia). All procedures were
               performed by one of seven interventional radiologists who comprise the only group that performs complex
               hepatobiliary interventions in Hawaii.

               Post-treatment imaging was performed at approximately 3-month and 6-month intervals. Response to
               TARE was determined using mRECIST. Patients with complete response (CR) or partial response (PR)
               according to mRECIST were further classified into a response group, while patients with stable disease (SD)
               or progressive disease (PD) were classified into a non-response group. For patients who received both a
               3-month and 6-month scan, the 6-month scan was used to determine overall response to treatment.

               Data collected
               Collected demographic information included patient age, sex and race. Medical history included height,
               weight, body mass index, diabetes mellitus, hyperlipidemia, hypertension, infection with hepatitis B or
               hepatitis C, significant alcohol use (> 2 alcoholic beverages daily for 10 years), smoking history, non-
               alcoholic fatty liver disease, non-alcoholic steatohepatitis, ascites, encephalopathy, cirrhosis, AFP and
               normal AFP (< 20 ng/mL).

               Laboratory studies included prothrombin time, international normalized ratio, creatinine, aspartate
               transaminase, alanine aminotransferase, bilirubin, albumin, white blood cell count, neutrophil count,
               lymphocyte count and platelet count. Laboratory values were obtained prior to TARE and approximately
               2 weeks, 3 months and 6 months post-treatment. NLR was defined as the ratio between the absolute
               neutrophil count and the absolute lymphocyte count. PLR was defined as the ratio between the absolute
               platelet count and the absolute lymphocyte count. Date of laboratory draws were used to determine
               temporal trends in NLR and PLR following treatment. Albumin-bilirubin (ALBI) grade and Child-Pugh
               class were calculated from baseline laboratory values.

               After identifying patients and collecting baseline data from the prospectively collected database, individual
               charts were queried to obtain detailed imaging reports. Imaging was reviewed and measured retrospectively
               by a single physician. Collected imaging data included pre-treatment tumor size, post-treatment tumor
               size, mRECIST, and dates of imaging and treatment.
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