Combined Modality Stereotactic Body Radiotherapy vs. Salvage Stereotactic Body Radiotherapy in the Management of Patients with Hepatocellular Carcinoma

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<h3>Purpose/Objective(s)</h3> The management of hepatocellular carcinoma (HCC) is complex and requires careful consideration of the patient's tumor characteristics and underlying liver function. Local therapies including stereotactic body radiation therapy (SBRT), trans-arterial chemoembolization, trans-arterial radioembolization, trans-arterial embolization, and microwave ablation have been shown to be safe and effective. Limited data exist characterizing the outcomes of combined modality therapy (CMT), defined as thermal ablative or transarterial liver directed therapy followed by consolidative SBRT. We hypothesized that upfront CMT would result in better outcomes compared to local therapy followed by SBRT for local salvage. <h3>Materials/Methods</h3> Patients with HCC who were treated with SBRT were prospectively enrolled into an institutional database from 2012-2021. Patients treated with upfront CMT or local therapy followed by salvage SBRT were identified. Overall survival (OS) and local control (LC) were evaluated using the Kaplan-Meier method. Local control was evaluated using both radiographic and pathologic data when available. <h3>Results</h3> 67 patients with a total of 77 tumors were included in our analysis with a median follow up of 31.8 months. Median tumor size was 3.3 cm. Median dose delivered was 45 Gy in a median of 5 fractions. 27 (40%) patients received CMT and 40 (60%) patients received salvage SBRT. The groups were comparable in terms of baseline characteristics including age, Child Pugh score, Milan eligibility, and radiation dose. There was a significantly greater proportion of CMT patients who were listed for transplant (60% 16/27 versus 30% 12/40 in the salvage SBRT group, <i>p</i> = .01). The estimated 1-year LC rate were similar between the two cohorts with 100% LC in the CMT group and 94.3% LC in the salvage SBRT group (<i>p</i> =0.62). OS was also similar between cohorts with an estimated 1-year OS of 92.59% in the CMT group and 89.5% in the salvage SBRT group (<i>p</i> =0.3). Radiographic response rates between the CMT and salvage SBRT cohorts were comparable with a radiographic complete response (rCR) of 73% (19/26) in the CMT group and 67% (29/43) in the salvage SBRT group. Of the tumors that were pathologically analyzed either at explant or autopsy, pathologic complete response rates (pCR) were similar with 50% (7/14) of CMT patients and 67% (8/12) of salvage SBRT patients achieving a pCR. Toxicity rates were low with only 3 patients (11.1%) in the CMT cohort and 3 patients (7.5%) in the salvage SBRT cohort who had grade 3+ adverse events. Regardless of treatment type, 56% had stable or improved CPT scores by 6 months post SBRT. <h3>Conclusion</h3> Both upfront CMT and salvage SBRT following local failure provide excellent local control, are associated with similar overall survival, and have acceptable rates of toxicity. Further studies are needed to evaluate the role of CMT with SBRT in patients with HCC to avoid over treatment and maximize cost efficiency.