Page 158 - Read Online

Sullivan et al. Hepatoma Res 2018;4:68 I http://dx.doi.org/10.20517/2394-5079.2018.95 Page 5 of 10

significantly longer following TARE, but significant OS benefit was not achieved. Larger multi-center
experience will be necessary to better inform us of the clinical value of this approach.

Radiation therapy: photons and protons
Radiation is another modality available in the loco-regional treatment of HCC for patients who are not
surgical candidates and in whom catheter-based approaches are not preferred or have failed prior TACE.
Bilobar multifocal tumors and proximity to hollow viscus can pose technical challenges to external beam
radiotherapy, as with patient with poor liver reserve (e.g., ≥ B9) or fluctuating ascites. Historically, the use of
external beam radiation therapy (EBRT) was limited by radiation induced liver disease (RILD). The advances
in modern technique known as stereotactic body radiation therapy (SBRT) allows for the delivery of more
precise radiation to the lesion of interest while sparing normal liver and other structures. Several phase I
and II studies of photon SBRT have found favorable local control rates of 78%-96% and OS of 58%-94% at 1
year with acceptable toxicity (8%-39% grade 3 or greater, RILD 4%-7%) [47-52] . While SBRT relies on photons to
deliver radiation dose, charged particles such as protons have emerged as an alternative technique to deliver
radiation. The advantage of proton beam therapy is the ability to control the energy along its beam path,
thus minimizing the exit dose. This allows for precise delivery of the radiation dose to the lesion and sparing
greater liver parenchyma. Phase I/II studies using proton therapy found 2 to 3 year OS of 50%-63% with 0%-6%
grade 3 or greater toxicities [53-56] . No RCT has been performed directly comparing photon SBRT and proton
beam therapy, but both modalities appear safe and effective in the treatment of HCC. The enormous cost
of installing a proton center limits its widespread use. Nonetheless, modern techniques in external beam
radiotherapy has emerged as an effective alternative for the local control of HCC in patients who are not
suitable to undergo resection or ablation.

COMPARISON OF MODALITIES FOR LOCO-REGIONAL TREATMENT OF HCC
Resection vs. ablation
For patients who are stage BCLC 0 and A, resection and ablation are recommended as treatment
modalities. Several prospective RCTs have attempted to evaluate which of the two modalities, if any, is
superior. An early study from China investigated percutaneous ablation vs. open surgical resection and
found statistically equivalent OS of 68% and 64% respectively, as well as statistically equivalent DFS rates
[57]
of 46% and 52% respectively . Greater morbidity and the only death reported in the study occurred
in the surgical group. A second RCT from China, in contrast, found that 5-year OS was higher in the
open resection group compared to the percutaneous RFA group (75% vs. 55%, respectively) with lower
[58]
recurrence rates of resection compared to the RFA group (42% and 63%, respectively) . However, the
open resection group had a greater rate of adverse events than the RFA group. A third study again from
China comparing percutaneous RFA with open hepatectomy did not find a difference in 3 year OS
between RFA and resection (67% vs. 75%, respectively), with no difference in the recurrence rate at 3 years
[59]
(38% vs. 50% for resection and RFA, respectively) but a higher complication rate in the resection group .
A more recent study from Hong Kong which included long term follow-up to 10 years, showed statistically
similar OS of 48% in the open resection group and 42% for the RFA group. Recurrence-free survival was
[60]
29% in the resection group and 18% in the RFA group, which did not meet statistical significance . In this
study, the postoperative complication rate did not differ between the two although RFA did have shorter
length of stay. Taking all prospective RCTs into account, it appears that the survival and recurrence rates
are similar between RFA and resection, especially for smaller tumors (i.e., ≤ 3 cm) with the added benefit
of fewer complications with ablation. However, no trial has evaluated the outcome of ablation against
those of laparoscopic or robotic hepatectomy, which is expected to have lower morbidity compared to
open resection. Other factors include methods of ablation such that higher local recurrence has been
reported following percutaneous ablation compared with laparoscopic or open procedure. Collectively, for
HCCs ≤ 3 cm, clinical outcomes are comparable between ablation and resection, thus selection between
the two modalities lies with providers’ experience and patients’ preference. Our institutional bias is to