Transarterial Chemoembolization with Drug-Eluting Beads vs. Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Outcomes from a Multicenter Randomized Phase II Trial

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<h3>Purpose/Objective(s)</h3> Transarterial chemoembolization (TACE) is the most widely used local treatment option for patients with hepatocellular carcinoma (HCC) who are not eligible for surgery or ablation and whose disease is confined to the liver. However, local control after TACE is limited. Although stereotactic body radiation therapy (SBRT) has demonstrated high local tumor control, there have been no randomized comparisons of the two techniques. TACE delivered with drug eluting beads (TACE-DEB) was therefore compared with SBRT in a multicenter randomized trial. <h3>Materials/Methods</h3> Patients were potential candidates for the study if they were eligible for TACE but ineligible for surgery or ablation. They could also be recruited if they required treatment prior to liver transplantation. Other inclusion criteria were ECOG 0-1, cirrhosis Child Pugh A, and 1-3 tumors up to a cumulative diameter of ≤6cm. Exclusion criteria were macrovascular invasion, ascites, and untreated esophageal varices grade 3-4. A maximum of 4 TACE-DEB procedures and ablation after incomplete TACE were both allowed. SBRT was delivered in 6 fractions of 8-9Gy. Primary end point was time to progression (TTP). Secondary endpoints were local control (LC) (mRECIST); overall survival (OS); response rate (RR) (mRECIST); toxicity (CTCAE v4.03); and quality of life (QoL) (EORTC QLQ-C30, EORTC QLQ-HCC 18 and EuroQoL-5D). The calculated sample size was 100 patients. <h3>Results</h3> Between May 2015 and April 2020, 30 patients were randomized to the study. Due to slow accrual the trial was prematurely closed. Two patients in the SBRT arm were considered ineligible (low thrombocyte count, >3 tumors in the liver), leaving 16 patients in the TACE arm and 12 in the SBRT arm. One patient randomized for SBRT was subsequently treated with TACE (implanted fiducials used for SBRT tumor tracking not detectable on the Linac). Median follow-up was 28.1 months. In the intention-to-treat analyses, median TTP was 12 months for TACE and 19 months for SBRT (p=0.15). Median LC was 12 months for TACE and >40 months (not reached) for SBRT (p=0.056). Median OS was 36.8 months for TACE and 44.1 months for SBRT (p=0.36). Post-hoc analyses per protocol showed 100% for SBRT 1- and 2-year LC, and 54.4% and 43.6% for TACE (p=0.02). Both treatments resulted in RR>80%. Three episodes of possibly related toxicity grade ≥3 were observed after TACE. No episodes were observed after SBRT. QoL remained stable after both treatment arms. <h3>Conclusion</h3> SBRT showed higher local antitumoral activity than TACE-DEB in this small group of HCC patients, and no detrimental effects on TTP, OS, toxicity and QoL. But, to overcome poor accrual in randomized trials including SBRT, to validate our results, and to generate the evidence needed to include SBRT in HCC treatment guidelines, international cooperation is needed.