Sequencing microsphere selective internal radiotherapy after external beam radiotherapy for hepatocellular carcinoma: proof of concept of a synergistic combination.

Objectives: This study aims to explore the synergistic effects of combining Stereotactic Body Radiation Therapy (SBRT) and Selective Internal Radiation Therapy (SIRT) in that specific sequence for treating hepatocellular carcinoma (HCC), particularly in patients at high risk of radiation-induced liver disease (RILD).

Methods: We analyzed a case of a patient with HCC who was treated with SBRT at our institution. A virtual 90Y dose distribution was added using our in-house -BLINDED FOR REVIEW- model to keep a minimum dose to the healthy liver tissue. BED and EUD metrics were calculated to harmonize the dose distributions of SBRT and SIRT.

Results: Our radiation biology-based models suggest that the combination of SBRT and SIRT could maintain effective tumor control while reducing the dose to normal liver tissue. Specifically, an SBRT plan of 10 Gy x 3 fractions combined with SIRT yielded comparable tumor control probability to an SBRT-only plan of 10 Gy x 5 fractions.

Conclusion: The combination of SBRT and SIRT is a promising treatment strategy for HCC patients at high risk of RILD. While the LQ model and associated formalisms provide a useful starting point, further studies are needed to account for factors beyond these models. Nonetheless, the potential for significant dose reduction to normal tissue suggests that this combination therapy could offer substantial clinical benefits.

Advances in knowledge: This article presents a proposal to combine SBRT and SIRT, in this specific order, for HCC, discussing its advantages. A framework for future research into optimizing combination therapy for HCC is provided, utilizing a novel HCC vascular model to simulate 90Y doses.