Stereotactic Body Radiation Therapy (SBRT) Plus Immune Checkpoint Inhibitors (ICI) in Hepatocellular Carcinoma and Cholangiocarcinoma

Abstract

The combination of stereotactic body radiation therapy (SBRT) plus immune checkpoint inhibitors (ICI) must be explored to treat advanced primary liver tumors such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Limited retrospective reviews and case reports/series suggest this combination can be effective and safe in both cancer types. With ICIs moving into the first line (IMbrave 150, HIMALAYA, and TOPAZ-1) to manage these cancers, identifying a suitable population for this approach is challenging. Patients with macrovascular invasion (MVI)-positive HCC (especially if larger veins are involved) or recurrent HCCs post-locoregional therapies (such as transarterial radioembolization (TARE), transarterial chemoembolization (TACE), or ablation), as well as those ineligible for bevacizumab or tyrosine kinase inhibitors (TKIs), should be the focus of exploring this combination in HCC. Unresectable or oligometastatic CCA patients who cannot tolerate gemcitabine/cisplatin (GC) or those who progressed on GC without durvalumab and do not have targetable mutations could also be considered for this approach. In both HCC and CCA disease groups, SBRT plus ICI can be examined post-ICI as these two modalities act synergistically to enhance anti-tumor activity (based on pre-clinical studies). Large-scale randomized trials are needed to identify the subsets of primary liver cancers suitable for this approach and to clearly define its clinical benefit.

Transarterial chemoembolization combined with lenvatinib, programmed death-1 inhibitor, and iodine-125 seed brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis

“…Moreover, radiation therapy enhances antitumor T-cell response by stimulating effector phases, making it an excellent addition to PD-1 inhibitors 42 . Previous studies approved radiation plus PD-1 inhibitors therapy in HCC with PVTT 43,44 . Therefore, the combination therapy comprising lenvatinib, TACE, PD-1 inhibitor, and I 125 seed brachytherapy is expected to have a better therapeutic effect in the treatment of HCC, especially in patients with PVTT.…”

Combining Immune Checkpoint Inhibitors with Loco-Regional Treatments in Hepatocellular Carcinoma: Ready for Prime Time?

“…Retrospective reviews, case reports/series, and prospective data have looked at the association between SBRT and ICI in HCC specifically [ 60 , 61 ]. A prospective study analyzed safety of radiotherapy in patients with HCC followed by pembrolizumab and showed an acceptable toxicity [ 62 ].…”

The multikinase inhibitor axitinib in the treatment of advanced hepatocellular carcinoma: the current clinical applications and the molecular mechanisms

“…Mounting evidence demonstrated that the combination of immunotherapy (included the combination of different immunosuppressors) and radiotherapy/chemotherapy/ablation may significantly promote the therapeutic efficacy in patients with unresectable or metastatic HCC (50)(51)(52)(53). Combination therapy may have better antitumor properties than monotherapy.…”