Single-cell transcriptomic analysis of endometriosis.

Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled transcriptomes of >370,000 individual cells from endometriomas (n = 8), endometriosis (n = 28), eutopic endometrium (n = 10), unaffected ovary (n = 4) and endometriosis-free peritoneum (n = 4), generating a cellular atlas of endometrial-type epithelial cells, stromal cells and microenvironmental cell populations across tissue sites. Cellular and molecular signatures of endometrial-type epithelium and stroma differed across tissue types, suggesting a role for cellular restructuring and transcriptional reprogramming in the disease. Epithelium, stroma and proximal mesothelial cells of endometriomas showed dysregulation of pro-inflammatory pathways and upregulation of complement proteins. Somatic ARID1A mutation in epithelial cells was associated with upregulation of pro-angiogenic and pro-lymphangiogenic factors and remodeling of the endothelial cell compartment, with enrichment of lymphatic endothelial cells. Finally, signatures of ciliated epithelial cells were enriched in ovarian cancers, reinforcing epidemiologic associations between these two diseases.

Radioembolization in the Setting of Systemic Therapies.

90 Yttrium (Y90) radioembolization has been shown to improve outcomes for primary and metastatic liver cancers, but there is limited understanding of the optimal timing and safety of combining systemic therapies with Y90 treatment. Both therapeutic effects and toxicities could be synergistic depending on the timing and dosing of different coadministration paradigms. In particular, patients with liver-only or liver-dominant metastatic disease progression are often on systemic therapy when referred to interventional radiology for consideration of Y90 treatment. Interventional radiologists are frequently asked to offer insight into whether or not to hold systemic therapy, and for how long, prior to and following transarterial therapy. This study reviews the current evidence regarding the timing and safety of systemic therapy with Y90 treatment for hepatocellular carcinoma, metastatic colorectal carcinoma, intrahepatic cholangiocarcinoma, metastatic neuroendocrine tumors, and other hepatic metastases. A particular focus is placed on the timing, dosing, and toxicities of combined therapy.

Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment.

BACKGROUND: There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. METHODS: This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6-9 months) and late follow-up (9-16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. RESULTS: The overall portomesenteric thrombosis burden improved in eight (72%) TIPS patients, three (27%) anticoagulated patients, and two (10%) untreated patients at early follow-up (p = 0.001) and in seven (78%) TIPS patients, two (29%) anticoagulated patients, and three (17%) untreated patients in late follow-up (p = 0.007). No bleeding complications attributable to anticoagulation were observed. CONCLUSION: TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.

MRI-Derived Sarcopenia Associated with Increased Mortality Following Yttrium-90 Radioembolization of Hepatocellular Carcinoma.

PURPOSE: To evaluate the influence of sarcopenia on survival in patients with hepatocellular carcinoma (HCC) treated with 90Y radioembolization. MATERIALS AND METHODS: This single-center retrospective cohort study analyzed 82 consecutive patients (65 men and 17 women, mean age 65 years, range 31-83 years) with HCC treated with 90Y radioembolization between December 2013 and December 2017. Sarcopenia was assessed on pre-procedure MRI performed within 100 days prior to 90Y radioembolization by segmenting the paraspinal musculature at the level of the superior mesenteric artery origin and subtracting fat-intensity pixels to yield fat-free muscle area (FFMA). Sarcopenia was defined as FFMA ≤31.97 cm2 for men and ≤28.95 cm2 for women. Survival at 90 days, 180 days, 1 year, and 3 years following initial treatment was assessed using medical and public obituary records. RESULTS: Sarcopenia was identified in 30% (25/82) of patients. Death was reported for 49% (32/65) of males and 71% (8/17) of females (mean follow-up 19.6 months, range 21 days-58 months). Patients with sarcopenia were found to have increased mortality at 180 days (31.8% vs. 8.9%) and 1 year (68.2% vs. 21.2%). Sarcopenia was an independent predictor of mortality adjusted for BCLC stage and sub-analysis demonstrated that sarcopenia independently predicted increased mortality for patients with BCLC stage B disease. CONCLUSION: Sarcopenia was associated with increased 180-day and 1-year mortality in HCC patients undergoing 90Y radioembolization. Sarcopenia was an independent predictor of survival adjusted for BCLC stage with significant deviation in the survival curves of BCLC stage B patients with and without sarcopenia.

Comparing Real World, Personalized, Multidisciplinary Tumor Board Recommendations with BCLC Algorithm: 321-Patient Analysis.

PURPOSE: To evaluate hepatocellular carcinoma (HCC) treatment allocation, deviation from BCLC first-treatment recommendation, and outcomes following multidisciplinary, individualized approach. METHODS: Treatment-naïve HCC discussed at multidisciplinary tumor board (MDT) between 2010 and 2013 were included to allow minimum 5 years of follow-up. MDT first-treatment recommendation (resection, transplant, ablation, transarterial radioembolization (Y90), transarterial chemoembolization, sorafenib, palliation) was documented, as were subsequent treatments. Overall survival (OS) analyses were performed on an intention-to-treat (ITT) basis, stratified by BCLC stage. RESULTS: Three hundred and twenty-one patients were treated in the 4-year period. Median age was 62 years, predominantly male (73%), hepatitis C (41%), and Y90 initial treatment (52%). There was a 76% rate of BCLC-discordant first-treatment. Median OS was not reached (57% alive at 10 years), 51.0 months, 25.4 months and 13.4 months for BCLC stages A, B, C and D, respectively. CONCLUSION: Deviation from BCLC guidelines was very common when individualized, MDT treatment recommendations were made. This approach yielded expected OS in BCLC A, and exceeded general guideline expectations for BCLC B, C and D. These results suggest that while guidelines are helpful, implementing a more personalized approach that incorporates center expertise, patient-specific characteristics, and the known multi-directional treatment allocation process, improves patient outcomes.

Safety and Effectiveness of Yttrium-90 Radioembolization around the Time of Immune Checkpoint Inhibitors for Unresectable Hepatic Metastases.

PURPOSE: To assess the safety and effectiveness of yttrium-90 radioembolization and checkpoint inhibitor immunotherapy within a short interval for the treatment of unresectable hepatic metastases. MATERIALS AND METHODS: This single-institution retrospective study included 22 patients (12 men; median age, 65 y ± 11) with unresectable hepatic metastases and preserved functional status (Eastern Cooperative Oncology Group performance status 0/1) who received immunotherapy and radioembolization within a 15-month period (median, 63.5 d; interquartile range, 19.7-178.2 d) from February 2013 to March 2018. Primary malignancies were uveal melanoma (12 of 22; 54.5%), soft tissue sarcoma (3; 13.6%), cutaneous melanoma (3; 14%), and others (4; 18.2%). Studies were reviewed to March 2019 to assess Common Terminology Criteria for Adverse Events grade 3/4 toxicities, disease progression, and death. RESULTS: There were no grade 4 toxicities within 6 mo of radioembolization. Grade 3 hepatobiliary toxicities occurred in 3 patients (13.6%) within 6 months, 2 from rapid disease progression and 1 from a biliary stricture. Two patients (9.1%) experienced clinical toxicities, including grade 4 colitis at 6 months and hepatic abscess at 3 months. Median overall survival (OS) from first radioembolization was 20 mo (95% confidence interval [CI], 12.5-27.5 mo), and median OS from first immunotherapy was 23 months (95% CI, 15.9-30.1 mo). Within the uveal melanoma subgroup, the median OS from first radioembolization was 17.0 months (95% CI, 14.2-19.8 mo). Median time to progression was 7.8 months (95% CI, 3.3-12.2 mo), and median progression-free survival was 7.8 mo (95% CI, 3.1-12.4 mo). CONCLUSIONS: Checkpoint immunotherapy around the time of radioembolization is safe, with a low incidence of toxicity independent of primary malignancy.

Yttrium-90 Radioembolization in the Office-Based Lab.

PURPOSE: To evaluate the feasibility and benefits of performing yttrium-90 radioembolization in an office-based lab (OBL) compared to a hospital setting. MATERIALS AND METHODS: A radioembolization program was established in March 2019 in an OBL that is managed by the radiology department of a tertiary care center. Mapping and treatment angiograms performed in the OBL from March 2019 through January 2020 were compared to mapping and treatment angiograms performed in the hospital during the same time period. RESULTS: One hundred seventy-six mapping and treatment angiograms were evaluated. There was no difference in the proportion of mapping versus treatment angiograms performed at each site, the proportion of lobar versus selective dose vial administrations, or the mean number of dose vials administered per treatment procedure. Procedure start delays were longer in the hospital than in the OBL (28.6 minutes vs 0.8 minutes; P < .0001), particularly for procedures that were not scheduled as the first case of the day (hospital later case delay, 38.8 minutes vs OBL later case delay, 0.5 minutes; P < .0001). Procedures performed in the hospital took longer on average than procedures performed in the OBL (2 hours, 1.8 minutes vs 1 hour, 44.4 minutes; P = .0004), particularly for procedures that were not scheduled as the first case of the day (hospital later case duration, 2 hours, 7.4 minutes vs OBL later case duration, 1 hour, 43 minutes; P = .0006). CONCLUSIONS: Establishing a radioembolization program within an OBL is feasible and might provide more efficient procedure scheduling than the hospital setting.

Comparative Analysis of Safety and Efficacy of Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma in Patients with and without Pre-Existing Transjugular Intrahepatic Portosystemic Shunts.

PURPOSE: To compare the safety and efficacy of transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients with and without transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: This single-institution study included a retrospective review of 50 patients who underwent transarterial chemoembolization for HCC between January 2010 and April 2017. Twenty-five patients had preexisting TIPS, and 25 patients were selected to control for age, sex, and target tumor size. Baseline median Model for End-Stage Liver Disease (MELD; 13 TIPS, 9 control; P < .001) and albumin-bilirubin (ALBI; 3 TIPS, 2 control; P < .001) differed between groups. Safety was assessed on the basis of Common Terminology Criteria for Adverse Events (CTCAE) and change in MELD and ALBI grade assessed between 3 and 6 months. Efficacy was assessed by tumor response and time to progression (TTP). RESULTS: There was 1 severe adverse event (CTCAE grade >2) in the TIPS group. There was no difference in the change in MELD or ALBI grade. Although there was no difference in tumor response (P = .19), more patients achieved a complete response in the control group (19/25, 76%) than in the TIPS group (13/25, 52%). There was no difference in TTP (P = .82). At 1 year, 2 patients in the control group and 3 patients in the TIPS group received a liver transplant. Seven patients died in the TIPS group. CONCLUSIONS: Transarterial chemoembolization is as safe and effective in patients with TIPS as in patients without TIPS, despite worse baseline liver function. Severe adverse events are rare and may be transient.

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS: The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS: Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

Radiation Segmentectomy: Potential Curative Therapy for Early Hepatocellular Carcinoma.

Purpose To report long-term outcomes of radiation segmentectomy (RS) for early hepatocellular carcinoma (HCC). The authors hypothesized that outcomes are comparable to curative treatments for patients with solitary HCC less than or equal to 5 cm and preserved liver function. Materials and Methods This retrospective study included 70 patients (median age, 71 years; range, 22-96 years) with solitary HCC less than or equal to 5 cm not amenable to percutaneous ablation who underwent RS (dose of >190 Gy) between 2003 and 2016. Patients who underwent subsequent curative liver transplantation were excluded to eliminate this confounding variable affecting survival. Radiologic response of time to progression and median overall survival were estimated by using the Kaplan-Meier method per the guidelines of the European Association for the Study of the Liver (EASL) and the World Health Organization (WHO). Results Seventy patients were treated with RS over 14 years. Sixty-three patients (90%) showed response by using EASL criteria, of which 41 (59%) showed complete response. Fifty patients (71%) achieved response by using WHO criteria, of which 11 (16%) achieved complete response. Response rates at 6 months were 86% and 49% by using EASL and WHO criteria, respectively. Median time to progression was 2.4 years (95% confidence interval: 2.1, 5.7), with 72% of patients having no target lesion progression at 5 years. Median overall survival was 6.7 years (95% confidence interval: 3.1, 6.7); survival probability at 1, 3, and 5 years was 98%, 66%, and 57%, respectively. Overall survival probability at 1, 3, and 5 years was 100%, 82%, and 75%, respectively, in patients with baseline tumor size less than or equal to 3 cm (n = 45) and was significantly longer than in patients with tumors greater than 3 cm (P = .026). Conclusion RS provides response rates, tumor control, and survival outcomes comparable to curative-intent treatments for selected patients with early-stage HCC who have preserved liver function. © RSNA, 2018 Online supplemental material is available for this article.

Perceptions of Quality in Interventional Oncology.

PURPOSE: To inductively characterize perceptions of quality in interventional oncology (IO) based on values and experiences of patients and referring providers. MATERIALS AND METHODS: Brief ethnographic interviews were completed with referring providers and patients before and after a variety of liver-directed procedures about their experiences, concerns, and perceptions of IO services at a single institution. Constructivist grounded theory was used to systematically analyze interview transcripts for themes until thematic saturation was achieved. All transcripts were analyzed by a reviewer with 3-years of experience performing such analyses, and 50% were randomly selected to be coded by 2 additional blinded reviewers. Interreviewer agreement was assessed via Cohen κ. RESULTS: Interviews with 22 patients (mean age, 65 y ± 13; 9 women) and 12 providers (mean age, 54 y ± 9; 6 women) were required to reach and confirm thematic saturation. Interreviewer agreement for interview themes was excellent (κ = 0.78; P < .001). Perceptions of high-quality IO care relied on interventional radiologists being responsive, friendly, and open; engaging in multidisciplinary collaboration; having thoughtful, dedicated support staff; and facilitating well-coordinated care after procedures and follow-up more than technical expertise and periprocedural comfort. Patient and provider perceptions of quality differed, but disjointed care after procedures was the most common critique among both groups. CONCLUSIONS: An inductive qualitative approach effectively characterized specific aspects of perceptions of high-quality IO care among patients and referring providers.

Radioembolization for hepatocellular carcinoma: Statistical confirmation of improved survival in responders by landmark analyses.

Does imaging response predict survival in hepatocellular carcinoma (HCC)? We studied the ability of posttherapeutic imaging response to predict overall survival. Over 14 years, 948 patients with HCC were treated with radioembolization. Patients with baseline metastases, vascular invasion, multifocal disease, Child-Pugh > B7, and transplanted/resected were excluded. This created our homogeneous study cohort of 134 patients with Child-Pugh ≤ B7 and solitary HCC. Response (using European Association for Study of the Liver [EASL] and Response Evaluation Criteria in Solid Tumors 1.1 [RECIST 1.1] criteria) was associated with survival using Landmark and risk-of-death methodologies after reviewing 960 scans. In a subanalysis, survival times of responders were compared to those of patients with stable disease (SD) and progressive disease (PD). Uni/multivariate survival analyses were performed at each Landmark. At the 3-month Landmark, responders survived longer than nonresponders by EASL (hazard ratio [HR], 0.46; confidence interval [CI], 0.26-0.82; P = 0.002) but not RECIST 1.1 criteria (HR, 0.70; CI, 0.37-1.32; P = 0.32). At the 6-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.32; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.50; CI, 0.29-0.87; P = 0.021). At the 12-month Landmark, responders survived longer than nonresponders by EASL (HR, 0.34; CI, 0.15-0.77; P < 0.001) and RECIST 1.1 criteria (HR, 0.52; CI 0.27-0.98; P = 0.049). At 6 months, risk of death was lower for responders by EASL (P < 0.001) and RECIST 1.1 (P = 0.0445). In subanalyses, responders lived longer than patients with SD or PD. EASL response was a significant predictor of survival at 3-, 6-, and 12-month Landmarks on uni/multivariate analyses. CONCLUSION: Response to radioembolization in patients with solitary HCC can prognosticate improved survival. EASL necrosis criteria outperformed RECIST 1.1 size criteria in predicting survival. The therapeutic objective of radioembolization should be radiologic response and not solely to prevent progression. (Hepatology 2018;67:873-883).

Institutional decision to adopt Y90 as primary treatment for hepatocellular carcinoma informed by a 1,000-patient 15-year experience.

Yttrium-90 transarterial radioembolization (TARE) is a locoregional therapy (LRT) for hepatocellular carcinoma (HCC). In this study, we present overall survival (OS) outcomes in a 1,000-patient cohort acquired over a 15-year period. Between December 1, 2003 and March 31, 2017, 1,000 patients with HCC were treated with TARE as part of a prospective cohort study. A comprehensive review of toxicity and survival outcomes was performed. Outcomes were stratified by baseline Child-Pugh (CP) class, United Network for Organ Sharing (UNOS), and Barcelona Clinic Liver Cancer (BCLC) staging systems. Albumin and bilirubin laboratory toxicities were compared to baseline. OS outcomes were reported using censoring and intention-to-treat methodologies. All treatments were outpatient, with a median one treatment per patient. Five hundred six (51%) were CP A, 450 (45%) CP B, and 44 (4%) CP C. Two hundred sixty-three (26%) patients were BCLC A, 152 (15%) B, 541 (54%) C, and 44 (4%) D. Three hundred sixty-eight (37%) were UNOS T1/T2, 169 (17%) T3, 147 (15%) T4a, 223 (22%) T4b, and 93 (9%) N/M. In CP A patients, censored OS for BCLC A was 47.3 (confidence interval [CI], 39.5-80.3) months, BCLC B 25.0 (CI, 17.3-30.5) months, and BCLC C 15.0 (CI, 13.8-17.7) months. In CP B patients, censored OS for BCLC A was 27 (CI, 21-30.2) months, BCLC B 15.0 (CI, 12.3-19.0) months, and BCLC C 8.0 (CI, 6.8-9.5) months. Forty-nine (5%) and 110 (11%) patients developed grade 3/4 albumin and bilirubin toxicities, respectively. CONCLUSION: Based on our experience with 1,000 patients over 15 years, we have made a decision to adopt TARE as the first-line transarterial LRT for patients with HCC. Our decision was informed by prospective data and incrementally reported demonstrating outcomes stratified by BCLC, applied as either neoadjuvant or definitive treatment. (Hepatology 2017).

Immuno-oncology and Its Opportunities for Interventional Radiologists: Immune Checkpoint Inhibition and Potential Synergies with Interventional Oncology Procedures.

Immunotherapy, specifically the use of immune checkpoint inhibitors, offers a new approach to fighting cancer. Although the results of treatment with immune checkpoint inhibition alone have been remarkable for certain cancers, these results are not universal. Preclinical and early clinical studies indicate the potential for synergistic effects when immune checkpoint inhibition is combined with immunogenic local therapies such as ablation and embolization. This review offers an overview of immunology as it relates to immune checkpoint inhibition and the possibilities for synergy when combined with interventional radiology treatments.

Comparative study of post-transplant outcomes in hepatocellular carcinoma patients treated with chemoembolization or radioembolization.

PURPOSE: To analyze long-term outcomes in patients bridged/downstaged to orthotopic liver transplantation (OLT) by transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y90) for hepatocellular carcinoma (HCC). METHODS: 172 HCC patients who underwent OLT after being treated with transarterial liver-directed therapies (LDTs) (Y90: 93; TACE: 79) were identified. Pre-LDT and pre-OLT clinical/imaging/laboratory characteristics including United Network for Organ Sharing (UNOS) staging and alpha-fetoprotein values (AFP) were tabulated. Post-OLT HCC recurrence was assessed by imaging follow-up per standard of care. Recurrence-free (RFS) and overall survival (OS) were calculated. Uni/multivariate and sub-stratification analyses were performed. RESULTS: Time-to-OLT was longer in the Y90 group (Y90: 6.5 months; TACE: 4.8 months; p=0.02). With a median post-OLT follow-up of 26.1 months (IQR: 11.1-49.7), tumor recurrence was found in 6/79 (8%) TACE and 8/93 (9%) Y90 patients. Time-to-recurrence was 26.6 (CI: 7.0-49.5) and 15.9 months (CI: 7.8-46.8) for TACE and Y90, respectively (p=0.48). RFS (Y90: 79 months; TACE: 77 months; p=0.84) and OS (Y90: 57% alive at 100 months; TACE: 84.2 months; p=0.57) were similar. 54/155 patients (Y90: 29; TACE: 25) were downstaged to UNOS T2 or less. RFS hazard ratios for patients downstaged to ≤T2 versus those that were not were 0.6 (CI: 0.33-1.1) and 1.7 (CI: 0.9-3.1) respectively (p=0.13). 17/155 patients (Y90: 8; TACE: 9) that were >T2 were downstaged to UNOS T2 or less (within transplant criteria). Distribution (unilobar/bilobar), AFP, and pre-transplant UNOS stage affected RFS on univariate analyses. CONCLUSION: Despite longer time-to-OLT for Y90 patients, post-OLT outcomes were similar between patients bridged or downstaged by TACE or Y90. A trend towards improved RFS for downstaged patients was identified.

Indicators of Lung Shunt Fraction Determined by Technetium-99 m Macroaggregated Albumin in Patients with Hepatocellular Carcinoma.

PURPOSE: To determine the correlation of pre-procedural and imaging characteristics with lung shunt fraction (LSF) measured by technetium-99 m macroaggregated albumin (99mTc-MAA) scan in patients with hepatocellular carcinoma. METHODS: A retrospective study was conducted of 428 subjects with hepatocellular carcinoma from 2004 to 2011 assessed for lung shunting by 99mTc-MAA scan. Baseline characteristics included age, gender, ethnicity, tumor burden, maximum dimension, number of lesions, presence of extrahepatic metastases, macrovascular (hepatic and portal vein) invasion, ascites on imaging, laboratory values, and alpha-fetoprotein (AFP). Univariate and multivariate logistic regression analysis was performed. Receiver operating characteristic curves were used to obtain sensitivity (SN), specificity (SP), and positive likelihood ratios (LR+) of characteristics for low LSF (LSF <10%) and high LSF (LSF >20%). RESULTS: Statistically significant (p < 0.05) independent indicators of low LSF included bilirubin <1.45 mg/dL (SN = 49.5%, SP = 69.1%, LR+ = 1.60), maximum tumor size <7.15 cm (SN = 66.0%, SP = 75.9%, LR+ = 2.74), AFP ≤200 ng/mL (SN = 64.6%, SP = 65.0%, LR+ = 1.85), and absent macrovascular invasion (SN = 73.9%, SP = 64.9%, LR+ = 2.11). Independent indicators of high LSF included albumin <2.65 g/dL (SN = 64.3%, SP = 64.1%, LR+ = 1.79) and macrovascular invasion (SN = 74.4%, SP = 67.4%, LR+ = 2.28). A combined risk factor model was constructed. If there is no macrovascular invasion: [Formula: see text]. With macrovascular invasion, [Formula: see text] (R 2 = 0.257). Since these factors all have LR+ between 2 and 5, they only reflect slight increase in LSF predictivity. CONCLUSION: Serum AFP, albumin, bilirubin, and portal/hepatic vein invasion on cross-sectional imaging are statistically significant but weak clinical indicators of LSF, as shown by low SN, SP, and LR+ for clinically relevant cutoff LSF values. Thus, these factors cannot be relied upon in clinical practice.