Page 53 - Read Online

Page 10 of 13 Spieler et al. Hepatoma Res 2019;5:4 I http://dx.doi.org/10.20517/2394-5079.2018.77

venous congestion. Signs and symptoms can present in classical or non-classical patterns, developing
between 2 weeks to 8 months after treatment. Outcomes vary from full recovery with supportive care to rare
cases of liver failure and death.

Improvements in normal tissue complications probabilities (NTCP) modeling and awareness of the liver’s
parallel physiology provide the rationale for partial-liver irradiation to minimize the risk of RILD. A phase
I trial of SABR in the treatment of liver metastases used partial hepatectomy outcome data to set volume
[65]
3
parameters for normal tissue sparing . The trial reported no cases of RILD when 700 cm of uninvolved
liver tissue were protected from doses exceeding 15 Gy in 3 fractions. Since then, NTCP modeling has
established mean liver dose constraints reducing the risk of RILD to less than 5% in selected patients with
[66]
CP-A hepatic function .

In CP-A patients, prospective studies show a range of grade 3 or higher toxicities in 11%-30% of patients,
almost all gastro-intestinal related [Table 1]. The highest number is from the PMH trial, in which patients
had a greater than typical disease burden (average tumor size > 7 cm, 55% with PVTT, 12% with metastatic
[41]
disease, all patients deemed untreatable by RFA, TACE or surgery) . Patients most commonly complain
of increased fatigue and poor appetite, usually resolving by 3 weeks after completion of their radiation
course. Non-RILD toxicities, such as gradual liver decompensation, moderately elevated liver enzymes or
virus reactivation can also occur. For patients with advanced cirrhosis, tissue-sparing volumetrics and dose
constraints may require reduction of the total dose prescribed.

It is difficult to distinguish RILD from progressive liver disease, which can be multi-focal and out of the
radiotherapy treatment field. For CP-B patients it may be reasonable to offer SABR when patients have no
other option, though it must be done with caution. Non-critical use in inexperienced hands may result in
toxicity. In 2015, a phase I/II trial reported 38% grade 3 or higher toxicities for CP-B HCC patients treated
[52]
with SABR . Ablative dose escalation should be applied carefully among CP-B patients as RILD rates
increase in this population and limited safety data exists. SABR is not recommended for patients with
CP-C disease. Proper commissioning of all equipment involved in SABR treatment, comprehensive quality
assurance programs and specialized training for all staff involved in planning and delivery are essential
[67]
safeguards .

CONCLUSION
SABR is a minimally-invasive treatment option for patients with non-metastatic HCC who are not candidate
for resection or liver transplant. Published series show that this treatment approach is associated with
excellent tumor control and can be done safely when NTCP guidelines are applied.

In addition, SABR may have some immunomodulation effects. Many ongoing clinical trials are looking
at innovative ways to combine hypofractionated radiation therapy with immunotherapy to potentiate the
systemic treatment response.

DECLARATIONS
Acknowledgments
The authors would like to thank Dr. John Chetley Ford for his help in the preparation of the SART video.

Authors’ contributions
Writing of initial manuscript: Spieler B
Mentor, manuscript revision: Portelance L
Mentor, manuscript revision, table design: Mellon EA, Jones PD, Venkat S, Giap H
Manuscript revision with edition of the section on SABR, systemic treatment and immunotherapy: Feun L