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Page 2 of 10 Shimizuguchi et al. Hepatoma Res 2020;6:66 I http://dx.doi.org/10.20517/2394-5079.2020.51

Keywords: Hepatocellular carcinoma, stereotactic body radiation therapy, vulnerable patients

INTRODUCTION
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world and the
[1,2]
fourth most common cause of cancer death in Japan . Treatment of HCC consists of surgical resection,
[3,4]
radiofrequency ablation, transarterial chemoembolization, and use of systemic anticancer agents .
Moreover, the use of stereotactic body radiation therapy (SBRT), a nonsurgical local treatment, has rapidly
increased in the past decade owing to its ability to deliver a precise radiation dose with modern radiation
[5]
oncology devices and techniques . Referring to the eligibility criteria for prospective liver SBRT trials, the
ideal candidate for the treatment is considered to: (1) be in fair general condition; (2) have adequate liver
function [Child-Pugh (CP) score 5 to 6]; and (3) a tumor size, number, and location that are amenable to
dose constraints for organs at risk (OAR) in treatment planning . However, patients with liver tumors
[6-8]
who are referred to SBRT are usually unsuitable for surgery or other local therapies due to comorbidity
and impaired liver function. In addition, in daily practice, a considerable proportion of tumors are unfit
for typical SBRT planning due to the radiation therapy planning dose constraint. Both physical factors and
tumor factors affect the decision of treatment choice. The more patient factors that do not meet clinical
trial criteria, the higher tendency to select non-localized treatment or conservative options instead of liver
SBRT in clinical practice. To the best of our knowledge, no study has directly tested the impact of those
composite adverse factors in liver SBRT. Therefore, this study aimed to evaluate the efficacy and feasibility
of liver SBRT for cases with originally defined adverse factors.

METHODS
Patient data
We planned a retrospective study of patients with liver tumors who were treated by liver SBRT at the
Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital between 2014 and 2019.
The institutional patient database was used to screen patients. The eligibility criteria were as follows: (1)
diagnosis of primary liver malignancy; (2) first liver SBRT (subsequent SBRT episodes were excluded); and
(3) definitive treatment (not palliative intent). Patient characteristics, laboratory testing, imaging findings,
and SBRT parameters were extracted from the medical records, and the comorbidities of the patients were
[9]
evaluated by the Charlson comorbidity index . This study was approved by the Institutional Review Board
of Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital (#2450).

Treatment procedure
To visualize the liver tumor position, a fiducial marker (Visicoil, RadioMed LLC, California, USA; length:
10 mm, diameter: 0.75 mm) was implanted next to the target by the hand of a hepatologist 2 weeks
prior the treatment. Subsequently, a 4-dimensional computed tomography (CT) image with contrast-
enhancement was obtained for treatment planning. Treatments were conducted using a Vero 4DRT system
(Mitsubishi Heavy Industry, Tokyo, Japan), which equips the tracking system.

Gross tumor volume was defined in the planning CT scan with the guide of contrast-enhanced magnetic
resonance imaging image fusion. The clinical target volume (CTV) was obtained by adding a 4-mm margin
to the gross tumor volume within the liver volume, while the planning target volume (PTV) was generated
by adding a margin to the CTV for uncertainness of setup and tracking (usually a 5-6 mm margin to the
CTV).

A total of 40 Gy in 5 fractions over two weeks was prescribed to the 70% isodose fitting to the PTV. The
modified prescription was allowed to achieve dose constraints: A reduced prescription dose (down to 32 Gy)