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Background and Aims Chemoembolization is a standard treatment for hepatocellular carcinoma (HCC). Radioembolization with 90Y microspheres is a new, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC. Methods We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up timepoints. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multi-variate analyses were performed. Results Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P<.05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs. 36%, P=0.104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, P=0.046), median survival times were not statistically different (17.4 months vs 20.5 months, P=0.232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P=0.42). Conclusion Patients with HCC treated by chemoembolization or radioembolization with 90Y microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post-hoc analyses of sample size indicated that a randomized study with >1000 patients would be required to establish equivalence of survival times between patients given the different therapies.

Background and Aims Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. Methods From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were randomly assigned to groups that received Y90 therapy (n=24, 50% Child-Pugh A) or cTACE (n=21, 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention to treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and KM survival time. We performed inverse probability of censoring weighting and competing risk analyses. Results Patients in the Y90 radioembolization group had significant longer median TTP (>26 months) than patients in the cTACE group (6.8 months) (P=.0012) (hazard ratio=0.122; 95% CI, 0.027–0.557; P=.007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P=.031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group) (P<.001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P=.433). Median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3–NC) vs 18.6 months for the Y90 group (95% CI, 7.4–32.5) (P=.99). Conclusions In a phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce dropout from transplant waitlists. ClinicalTrials.gov no. NCT00956930

Chemoembolization and other ablative therapies are routinely utilized in downstaging from United Network for Organ Sharing (UNOS) T3 to T2, thus potentially making patients transplant candidates under the UNOS model for end-stage liver disease (MELD) upgrade for hepatocellular carcinoma (HCC). This study was undertaken to compare the downstaging efficacy of transarterial chemoembolization (TACE) versus transarterial radioembolization. Eighty-six patients were treated with either TACE (n = 43) or transarterial radioembolization with Yttrium-90 microspheres (TARE-Y90; n = 43). Median tumor size was similar (TACE: 5.7 cm, TARE-Y90: 5.6 cm). Partial response rates favored TARE-Y90 versus TACE (61% vs. 37%). Downstaging to UNOS T2 was achieved in 31% of TACE and 58% of TARE-Y90 patients. Time to progression according to UNOS criteria was similar for both groups (18.2 months for TACE vs. 33.3 months for TARE-Y90, p = 0.098). Event-free survival was significantly greater for TARE-Y90 than TACE (17.7 vs. 7.1 months, p = 0.0017). Overall survival favored TARE-Y90 compared to TACE (censored 35.7/18.7 months; p = 0.18; uncensored 41.6/19.2 months; p = 0.008). In conclusion, TARE-Y90 appears to outperform TACE for downstaging HCC from UNOS T3 to T2.

We present the correlation between radiologic and pathologic findings in HCC patients who underwent radioembolization with yttrium-90 ( 90 Y) microspheres prior to resection or transplantation. Thirty-five patients with a total of 38 lesions who underwent liver explantation after 90 Y radioembolization were studied. Imaging surrogates following treatment were evaluated; the explants were examined for assessment of necrosis by pathology. The correlation betwen radiologic and histologic findings of the treated lesions was analyzed. Twenty-three of 38 (61%) target lesions showed complete pathologic necrosis. All target lesions demonstrated some degree of histologic necrosis at explant. Complete histologic necrosis was seen in 89% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 100%, 78%, and 93% of the lesions that were shown to have complete response by European Association for the Study of the Liver (EASL) necrosis criteria, partial response by World Health Organizaton (WHO) criteria, or thin rim enhancement on posttreatment imaging, respectively. In contrast, complete pathologic necrosis was seen in only 52% and 38% of the lesions that showed partial response by EASL criteria and peripheral nodular enhancement, respectively. Conclusion: Post-radioembolization imaging findings of response by EASL and WHO criteria are predictive of the degree of pathologic necrosis. Rim enhancement was an imaging characteristic that correlated well with histologic necrosis.