Page 52 - Read Online

Spieler et al. Hepatoma Res 2019;5:4 I http://dx.doi.org/10.20517/2394-5079.2018.77 Page 9 of 13

Figure 2. Hypofractionated radiation therapy increases tumor cell programmed death ligand 1 receptor expression

can act as an in-situ vaccine through tumor necrosis factor-α (TNF-α) and T-cell stimulation matured from
case reports describing an abscopal effect, where tumor regression was observed outside of the treatment
[62]
field following local irradiation . The clinical significance of the abscopal effect remains hypothetical with
limited supportive clinical data to date.

In HCC, preclinical models report positive results for combined radiation and checkpoint blockade.
Radiation upregulates programmed death ligand 1 (PD-L1) expression, and tumors treated with combination
radiation plus anti-PD-L1 inhibitors had significantly greater results than radiation or immunotherapy
[63]
alone .
[64]
Gustafson et al. in 2017 reviewed peripheral blood immunophenotypes in a series of patients with liver
cancer before and after the administration of SABR. A 50% drop in peripheral CD3+ T-cells was observed,
suggesting that T-cells were trafficking to tumor and lymph nodes both at the target site and possibly to
[64]
disease outside of the treatment field .
[63]
A recent clinical study by Kim et al. shows that PD-L1 expression is elevated following SABR treatment
of HCC, similar to effects identified in murine models. This phenomenon points to potential therapeutic
[63]
benefit from combination treatment with a PD-L1 checkpoint inhibitor such as atezolizumab . Phase I/II
clinical trials are underway evaluating SABR plus ipulimumab, a cytotoxic T-lymphocyte associated protein
[55]
4 (CTLA-4) inhibitor [Figure 2] .

In summary, the combination of immunotherapy with SABR to treat advanced HCC is a novel strategy with
promising potential.

SABR TOXICITY
Historically, the risk of hepatic decompensation due to RILD has discouraged the use of radiotherapy to treat
liver cancer. RILD triggers a fibrotic process leading to the obliteration of central venules and widespread