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Page 8 of 10 Reyngold et al. Hepatoma Res 2018;4:49 I http://dx.doi.org/10.20517/2394-5079.2018.84

based hypofractionated ablative treatments will most certainly become more frequently used in the future.

In summary, while patients with relatively small, isolated tumors with well-compensated cirrhosis represent
ideal candidates for ablative dose escalation, this approach may also be used for select candidates with larger
tumors or Child-Pugh class B/C liver disease.

CONCLUSIONS
Radiation therapy is an important local modality for large unresectable HCC. Small tumors can be treated
with straight forward approaches that may not require respiratory motion management or soft tissue image
guidance. However, large liver tumors are among the most challenging cases to treat with radiation because
of the sensitivity of the liver parenchyma, the presence of underlying liver disease, the proximity of the duo-
denum, colon, stomach, and main bile ducts. Respiratory motion and interfraction motion of the surround-
ing bowel complicate sparing these organs. These challenges can be overcome by adhering to the following
principles which apply to both photon and proton beam therapy. In general, proton therapy spares liver pa-
renchyma better and IMRT spares GI luminal structures better.
(1) Evaluation and optimization of liver function prior to RT. Child-Pugh Class A and B7 are most appropri-
ate candidates for ablative RT.
(2) Selection of fractionation scheme that allows the delivery of ablative radiation doses of 100 Gy BED (80
Gy EQD2) while sparing sensitive normal structures. For most large central tumors, this requires the use of
15-25 fractions with an SBRT technique in order to stay within the tolerance of the OARs.
(3) Respiratory motion management. Breath hold or gating is preferred for large tumors because it minimiz-
es the liver volume that is treated, help to spare the GI tract, and minimizes motion artifact on cone beam
images.
(4) Use of soft tissue image guidance. When tumors are located near the GI tract, soft tissue guidance is most
important. CBCT allows for verification of the position of the GI tract as well the liver shape.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed data analysis and inter-
pretation: all authors
Performed data acquisition, as well as provided administrative, technical, and material support: all authors

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.