Case report
An 81-year-old man was referred to our hospital for the treatment of
liver cancer. He had chronic liver
disease due to significant alcoholic consumption. Enhanced computed
tomography (CT) showed a liver tumor with marginal enhancement in the
arterial phase at 28 mm in diameter in the right hepatic lobe (Figure
1a).
He underwent right hepatic lobectomy, and the tumor was completely
resected. A gross examination showed a firm, solid yellowish white to
tan-gray mass (Figure 1b). A histological examination revealed
components of both HCC and cholangiocarcinoma. Hematoxylin-eosin
staining showed a trabecular-sinusoidal growth pattern, morphologically
consistent with HCC (Figure 1c and 1d), and glandular formations
pattern, supportive of cholangiocarcinoma (Figure 1c and 1e).
Immunohistochemical staining showed that the HCC regions were positive
for Hepa-para-1 (Figure 1f), and the cholangiocarcinoma regions were
negative for heap-para-1 (Figure 1f), positive for CK 19 (Figure 1g),
and positive for CD 56 (Figure 1h). The patient was therefore
pathologically diagnosed with CHC.
Both the HCC and cholangiocarcinoma regions were negative for PD-L1
(Figure 1i and 1j). The microsatellite instability status was also
negative. The surrounding liver tissue had steatosis with macrovesicular
and fibrosis, suggesting alcoholic liver disease.
He underwent adjuvant chemotherapy with TS-1 at 80 mg/day, but CT showed
multiple lymph node metastases at 13 months after surgical treatment. He
received systemic chemotherapy with
gemcitabine and cisplatin
(GEM/CDDP), but we had to discontinue the GEM/CDDP therapy due to a
severe rash. Because lenvatinib was recommended for first-line HCC
treatment at that time, we administered lenvatinib at 8 mg/day for 4
months. However, we ultimately had to discontinue lenvatinib treatment
due to grade 3 decreased appetite. Because Atez/Bev became available in
Japan after the end of the lenvatinib treatment, we decided to
administer combination therapy with Atez/Bev, following institutional
review broad approval and the acquisition of written informed consent
from the patient.
The laboratory findings before Atez/Bev treatment are shown in Table 1.
The platelet count and hepatobiliary enzyme values were within the
normal limits. Both hepatitis B surface antigen and hepatitis C virus
antibody were negative. The serum levels of alpha-fetoprotein (AFP),
des-gamma-carboxy prothrombin (DCP),
carcinoembryonic antigen (CEA),
and carbohydrate antigen 19-9 (CA19-9) were also within the normal
ranges. Regarding the liver function, the Child-Pugh classification was
grade A (5 points), and the albumin-bilirubin (ALBI) score was
calculated to be -2.92, resulting in an assignment of ALBI grade 1.
Enhanced CT showed enlarged systemic lymph nodes
around the abdominal aorta, behind
the inferior vena cava, and at the anterior cervical region, suggestive
of multiple lymph node metastases (Figure 2).
We started treatment at 1200 mg atezolizumab and 15 mg/kg of body weight
bevacizumab every 3 weeks. CT after two cycles of therapy showed mild
shrinkage of enlarged lymph nodes and the response rate per RECIST was
determined to be stable disease (SD) (Figure 3). Due to the presence of
ascites, we interrupted bevacizumab and continued atezolizumab
monotherapy at the third, fourth, and fifth cycles. CT after five cycles
showed a lasting tumor response. We resumed bevacizumab treatment
combined with atezolizumab at the sixth and seventh cycles owing to the
improvement of edema by diuretics. We deemed him to have stable diseases
on CT after seven cycles of treatment. We continued atezolizumab
monotherapy at the eighth and ninth cycles due to bevacizumab-related
adverse events, such as fatigue, decreased appetite, and proteinuria.
After 10 cycles of treatment, CT showed the regrowth of enlarged lymph
nodes and the response rate per RECIST was determined to the progressive
disease (PD). Therefore, Atez/Bev treatment was discontinued, and the
patient ultimately achieved a 7.5-month progression-free survival (PFS).
At 28 months after the initial hepatic treatment (15 months after
initiation of systemic therapy), the patient was still alive. The
overall clinical course is shown in Figure 4.