Role of External Beam Radiotherapy in Hepatocellular Carcinoma

With advancements in technology, including improved image guidance and dose escalation with partial-liver treatments, high LC rates with relatively low toxicity have been achieved with various EBRT modalities. As systemic therapies improve, locoregional therapies, such as EBRT, will become more relevant. Multiple clinical trials utilizing EBRT alone or in combination with other treatment modalities, which include systemic or local therapies, are under way.(96) In regard to the future role of EBRT in HCC management, accurate tumor localization and visualization techniques may allow for further dose escalation and better outcomes. Magnetic resonance (MR)-based strategies, such as gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRIs, can offer more precise EBRT targeting and assessment of treatment accuracy.97 MR linear accelerators (MR-linacs), which couple an magnetic resonance imaging (MRI) scanner and linear accelerator, can track and visualize tumors in real time. Because MRIs can better delineate HCCs compared with planning CT-based images, MR-linacs, with realtime tracking, can allow for tighter tumor margins, lower OAR doses, and dose escalation. In a recent multi-institutional study, MR-guided liver SBRT was performed using a median delivered dose of 5000 cGy in 5 fractions. With a median follow-up of 21.2 months, the freedom from local progression was 100% for HCC. No grade 4 or greater gastrointestinal toxicities were observed.(98-100) SBRT, especially MR-based SBRT, may help expand the role of radiotherapy in HCC treatment. Neoadjuvant therapy has been used to downstage disease and to evaluate treatment response prior to resection for other solid malignancies. For HCC, transarterial radioembolization, and TACE, systemic therapy have been suggested as possible neoadjuvant approaches.(101) In a recent randomized, multicenter study involving patients with resectable HCC and PVTT, neoadjuvant radiotherapy involving 3DCRT of 1800 cGy in 6 fractions resulted in a significantly improved 2-year OS of 27% versus 9% in hepatectomy alone.(102) As for the safety of preoperative EBRT, Hasan and colleagues103 showed that preoperative EBRT (median of 4000 cGy in 5 fractions) resulted in 39% complete response with no increase in postoperative mortality or length of stay after transplant. Neoadjuvant EBRT presents another potential indication for EBRT in the management of HCC. Due to the increased evidence of efficacy and safety of EBRT for HCC, treatment algorithms have started to incorporate EBRT.47,(104-106) There remain many guidelines that continue to ignore EBRT as a treatment modality of HCC. Given the variability of recommendations from different guidelines, a multidisciplinary team involving hepatology, surgical oncology, medical oncology, and radiation oncology ideally should convene to make the appropriate treatment recommendations for each HCC patient.