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Purpose: External beam radiation therapy (EBRT) is a safe and emerging bridging liver-directed therapy (LDT) to liver transplant (LT) for patients with hepatocellular carcinoma (HCC). The prevalence and clinical characteristics of patients receiving EBRT as an LDT for LT have not been evaluated. Our aim was to describe the utilization of EBRT in patients with HCC evaluated for LT in the United States., Methods and Materials: We analyzed United Network for Organ Sharing data from October 2013 to June 2020 and identified patients with HCC who applied for model for end-stage liver disease (MELD) exceptions for LT wait list prioritization. The primary outcome was the period prevalence of EBRT. We examined associations between clinical variables and EBRT and fit survival models with EBRT as a time-varying predictor., Results: We identified 18,543 patients with HCC with MELD exception applications. EBRT was used in 658 patients (3.5%) either alone (1.2%) or combined with other LDT (2.3%). Transarterial chemoembolization was the most used LDT (59.3%), followed by thermal ablation (27.9%) and radioembolization (15.2%). EBRT prevalence rose by an average of 12.2% per year (P = .001). Use of EBRT differed by geographic region, ranging from 2% to 8% (P < .001). EBRT and no EBRT groups had similar initial MELD score, portal vein thrombosis, tumor diameter, number of tumors, bilirubin, and α-fetoprotein (P > .05). Median time-to-transplant from wait list registration for EBRT versus no EBRT groups was 10 months (95% confidence interval, 9.4-10.9) versus 11.9 months (95% confidence interval, 11.7-12.2; P < .001). Evaluated as a time-varying predictor, EBRT increased the risk of LT by 30% (sub-hazard ratio, 1.30; P < .001), while the effect of EBRT on the risk of wait list removal due to clinical deterioration or death (sub-hazard ratio, 1.07; P = .489) was nonsignificant., Conclusions: In the United States, EBRT is rarely used compared with other LDTs and exhibits geographic variation. Low EBRT utilization highlights a gap in the treatment armamentarium for HCC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

BACKGROUND. Transarterial chemoembolization (TACE) has synergistic properties when combined with ablative therapies for hepatocellular carcinoma (HCC). OBJECTIVE. The purpose of our study was to compare outcomes for inoperable HCC between TACE with percutaneous thermal ablation (TACE-TA) and TACE with stereotactic body radiotherapy (TACE-SBRT) using propensity score-weighted cohorts. METHODS. This retrospective study included 190 patients with a single inoperable HCC treated from 2007 to 2018 by either TACE-SBRT ( n = 90) or TACE-TA ( n = 100). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS) and hepatotoxicity (defined as Child-Pugh score elevation of ≥ 2 within 2-6 months after treatment). Fine-Gray competing risk models with propensity score weighting and transplant as the competing risk factor were used to model OS and PFS. RESULTS. The median follow-up time was 48.2 months. Both OS and PFS were significantly higher for TACE-TA (77% and 76%, respectively, at 2 years) than TACE-SBRT (49% and 50%, respectively, at 2 years) in the propensity score-weighted multivariate model (OS: subdistribution hazard ratio [sHR] = 2.70, p < .001; PFS: sHR = 1.71, p = .02). Treatment-related hepatotoxicity occurred in 9% of patients who underwent TACE-TA versus 27% of those who underwent TACE-SBRT ( p = .01). For the subset of patients with Barcelona Clinic Liver Cancer A HCC and Child-Pugh A cirrhosis (TACE-SBRT, n = 36 patients; TACE-TA, n = 55 patients), OS ( p = .11) and PFS ( p = .19) were not significantly different between the two treatment modalities. CONCLUSION. Compared with TACE-SBRT, TACE-TA showed superior OS and PFS, possibly from its lesser hepatotoxicity. The two strategies did not differ in OS and PFS for patients with the earliest-stage HCC and preserved liver function. CLINICAL IMPACT. Across all patients, TACE-TA may be superior to TACE-SBRT for inoperable HCC.

Background: Determination of the comparative efficacy of one therapy over another for hepatocellular carcinoma (HCC) can be challenging. Application of a recognized value framework to published studies could objectively compare the potential benefit across available therapies., Materials and Methods: An umbrella review of phase III trials for HCC therapies was performed. ASCO Value Framework Net Health Benefit Score version 2 (ASCO-NHB v2) scores, the primary analysis, and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 scores, the secondary analysis, were computed using selected drug registration trials. Both scores were compared between drugs that were Food and Drug Administration (FDA)-approved by 2020 and those that were not., Results: Of the 22 studies identified, nine were FDA-approved and 13 were not. Across 22 trials, the median overall survival (OS) was 9.2 months (range, 1.9-16.4 months), with a median gain of 0.35 month (range, 2.3-3.3 months). HCC therapies that were FDA-approved showed longer OS (median 10.7 v 7.9 months, P < .01) and higher ASCO NHB scores (+18.4 v -5.7 scores, P < .01). The median gain in OS was 2.2 months in the approved treatments compared with -0.3 months in the unapproved group, with no difference in progression-free survival between the two groups., Conclusion: The nine FDA-approved therapies for HCC have higher mean NHB score than those that were not FDA-approved. The application of ASCO-NHB v2 and other proposed value frameworks could examine data of future therapies for HCC through a patient-oriented approach., Competing Interests: Emerson Y. ChenOther Relationship: Horizon CME, Taiho Pharmaceutical Vinay PrasadConsulting or Advisory Role: UnitedHealthcareSpeakers' Bureau: EvicoreResearch Funding: Arnold VenturesPatents, Royalties, Other Intellectual Property: I receive Royalties from my book Ending Medical Reversal, I am a paid writer for Medscape, I received an advance for a book entitled: Malignant Johns Hopkins Press, I make a podcast called Plenary Session and we have backers on Patreon, these are individuals who contribute for us to make the podcast, I receive royalties from my book Malignant Charles D. LopezConsulting or Advisory Role: Boston Scientific, Celgene, Boston Biomedical, Pfizer, Exelixis, Astellas PharmaResearch Funding: Taiho PharmaceuticalTravel, Accommodations, Expenses: RenovoRx Adel KardoshConsulting or Advisory Role: ExelixisNo other potential conflicts of interest were reported.

Objective: To evaluate yttrium-90 (Y90) radioembolization outcomes across Child-Pugh scores in patients with advanced hepatocellular carcinoma (HCC)., Materials and Methods: From April 2005 to December 2018, 106 consecutive patients with BCLC Stage C HCC who underwent Y90 radioembolization were retrospectively analyzed. Exclusion criteria included additional malignancy (n = 7), death unrelated to liver disease (n = 2), metastases (n = 2), or lack of follow-up data (n = 4). Ninety-one patients were analyzed. Overall survival (OS) was calculated using the Kaplan-Meier method and compared between groups with the log-rank test. Cox regression modeling was used to evaluate the prognostic factors for survival., Results: Mean age was 63 years and 85.7% were male. HCV infection was the most common etiology of liver disease (58.2%). Sixty-four (70.3%) patients were Child-Pugh A, 19 (20.9%) patients were B7, and eight (8.8%) patients were B8-9. Median OS after radioembolization was 20.2 [95% confidence interval (CI) 13.0-27.4], 6.0 (95% CI 4.4-7.6), and 5.5 (95% CI 2.5-8.5) months for Child-Pugh A, B7, and B8/9 groups, respectively (P < 0.001 for B7 vs. A; P = 0.537 for B7 vs. B8/9). The multivariable Cox regression analysis showed that Eastern Cooperative Oncology Group (ECOG) score (P < 0.001), Child-Pugh class (P = 0.005), tumor morphology pattern (P = 0.012), and Y90 delivery location (P = 0.020) were significant independent predictors of overall survival., Conclusions: Outcomes from Y90 for BCLC C HCC for Child-Pugh B7 patients were equivalent to B8/9 patients and significantly worse compared to Child-Pugh A patients. Although further research is warranted, these results suggest continued cautious patient selection for radioembolization in advanced HCC.

Radiation therapy (RT) is an effective treatment modality for hepatocellular carcinoma (HCC), but globally, it is underutilized. In Russia, practice patterns with regard to liver-directed radiation are unknown. Under the auspices of Russian Society of Clinical Oncology (RUSSCO), our team conducted an IRB-approved contouring workshop for Russian radiation oncologists. Pre- and post-workshop surveys were analyzed to determine baseline clinical experience and patterns of care for liver-directed RT among Russian providers. The effect of the contouring workshop on participants' knowledge was tested using mixed effects model. Forty pre-workshop and 24 post-workshop questionnaires were analyzable with a 100% response rate. Sixty percent of respondents had never evaluated a patient with HCC and only 8% (3 out of 40) reported treating an HCC patient with liver-directed RT. Nonetheless, 73% of respondents were comfortable offering liver-directed RT prior to the workshop. After the workshop, 85% of respondents felt comfortable treating a patient with HCC with liver-directed RT and 50% were comfortable recommending stereotactic body radiation therapy (SBRT). Measures of knowledge pertaining to evaluation of HCC patients and selection for appropriate liver-directed therapies were dramatically improved after the workshop. Liver-directed RT is not commonly used in Russia in the management of patients with HCC, and few centers are equipped for motion management. Our contouring workshop resulted in dramatically improved understanding of the evaluation and management of HCC patients. We recommend starting with a more protracted fractionated RT and building experience through attendance of additional educational activities, participation in multidisciplinary liver tumor boards, and prospective analysis of treatment toxicity and outcomes.

Purpose: To report the toxicities and outcomes for stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy (AHRT) in patients with Child-Pugh (CP) class A, B, or C and albumin-bilirubin (ALBI) score 1, 2, or 3 hepatocellular carcinoma., Methods and Materials: We retrospectively reviewed the data from 146 patients with hepatocellular carcinoma who had undergone SBRT (50 Gy in 5 fractions) or AHRT (45 Gy in 18 fractions). The primary endpoint was liver toxicity, defined as an increase in the CP score of ≥2 within 6 months of radiation therapy. The secondary endpoints of ALBI change, overall survival, and local control were also calculated., Results: The median follow-up was 23 months (range 1-59). Most received SBRT (72%), and 28% received AHRT. Of all 146 patients, 45 (31%) had a CP score elevation of ≥2 within 6 months of radiation therapy (RT) (27 patients [28%] with baseline CP-A/B7 and 18 [35%] with baseline CP-B8/B9/C cirrhosis; P = .45). On multivariate analysis, neither baseline CP nor ALBI score was predictive of toxicity. No patient with a decline in liver functionality of CP ≥2 within 6 months of RT returned to baseline at later time points. Eleven grade 4 toxicities were observed. The mean change in the raw ALBI score at ∼6 months was similar for all baseline ALBI groups. Twenty-two patients underwent orthotopic liver transplantation after RT, 13 of whom had baseline CP-B8/B9/C liver functionality. For all patients, the 1- and 2-year treated-lesion local control was greater for SBRT than for AHRT (2-year 94% vs 65%, P < .0001)., Conclusions: The tolerability of SBRT or AHRT as measured by a CP score decline of ≥2 within 6 months of RT was similar across baseline liver functionality groups. Compared with AHRT, SBRT was associated with superior local control. Because the true tolerability of limited-volume RT for patients with CP-B or CP-C cirrhosis is unknown, prospective trials validating its safety and efficacy are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)