healthmedicinet

Patients and treatment protocol

Between September 2005 and September 2008, a total of 11 patients who were diagnosed
with advanced HCC with IVC and RA tumor thrombus were treated by a combination of
TACE and EBRT. The retrospective analysis of the data was approved by Chinese PLA
General Hospital investigational review board.

Pre-treatment evaluation consisted of a complete history and physical examination,
blood cell count, liver and renal panels, AFP value, computed tomography (CT) scan
of the chest, tri-phase CT scan or dynamic magnetic resonance imaging (MRI) of the
liver, and total body bone scan. Fluorodeoxyglucose positron emission tomography (PET)
or PET/CT scans were optional.

Treatments were performed when no contraindications were identified. The treatment
protocol started with 2–3 sessions of TACE (interval: 1 month), depending on the intrahepatic
tumor burden. Two weeks after TACE, EBRT was conducted to target the IVC and RA tumor
thrombus. Patients were followed up every 3 months to check whether new tumor lesions
in the liver had developed. When lesions were detected, TACE was performed again to
control intrahepatic lesions.

Treatment

All TACE procedures were performed using digital subtraction angiography (DSA) guidance.
After a routine preoperative preparation, TACE was performed under sterile conditions,
with the patient under local anesthesia. The right femoral artery was cannulated using
a 4 F vascular sheath (Radifocus Introducer II; Terumo Corp., Japan) by Seldinger’s
technique. Selective angiography of the celiac artery, superior mesenteric artery
and inferior phrenic artery was performed using a 4 F hepatic artery catheter (HE,
Terumo Corp., Japan) inserted through the vascular sheath. Maximum catheter selectivity
of the hepatic artery and inferior phrenic artery was achieved using a microcatheter
(Progreat, Terumo Corp., Japan), with administration from the afferent branch to the
tumor lesion. Drug dosages per procedure varied, ranging from 6–20 mL for lipiodol
(Guerbet Corp., France), 30–50 mg of doxorubicin (Pfizer Pharmaceuticals Ltd, USA),
100–150 mg oxilaplatin (Sanofi Pharmaceuticals Co., Ltd, France), and 8–12 mg mitomycin
(Zhejiang Hisun Pharmaceutical Co. Ltd, China), depending on the size of the tumor
lesion and laboratory results. Lipiodol-chemotherapeutic agents were administered
until stasis, minimizing reflux into non-target vessels. Injection was continued until
near stasis was observed in the artery directly feeding the tumor (i.e., the contrast
column should clear within 2–5 heartbeats). Gelatin sponge or polyvinyl alcohol particles
(PVA, 500–700 ?m, COOK Corp., USA) was injected as supplement when necessary.

Three days after the procedure, patients were administered polyenephosphatidylcholine
(465 mg, iv, qd, Chengdu Tiantaishan Pharmaceutical Co., China) and glutathione (1,800 mg,
iv, qd, LaboratorioFarmaceutico C.T.S.R.L, Italy) to normalize liver function, as
well as pain killers and an anti-emetic. On the 3rd day after the completion of TACE,
the patients were assessed for adverse effects by undergoing a physical examination
and laboratory testing consisting of blood cell count, as well as liver and renal
panels. The patients were discharged from the hospital when the laboratory results
were determined to be within normal range.

EBRT was initiated after the intrahepatic lesions were controlled by TACE. EBRT was
initiated 2 weeks after the last session of TACE. All patients underwent three-dimensional
conformal radiotherapy (3D-CRT). For radiotherapy planning, the patients underwent
contrast-enhanced CT scans in a supine position, with both arms raised above the head.
Simulation CT data was transferred to a radiation treatment planning system (Pinnacle,
The Philips Medical System, Netherland). The clinical target volume (CTV) included
IVC and RA tumor thrombus without primary intrahepatic disease and was defined as
the radiographically abnormal areas and noted on the planning CT images from the diagnostic
enhanced CT and/or MRI. The 4D-CT and respiratory gating techniques were not used
in the present study. Considering setup error and target motion, PTV was determined
as the CTV plus 5 mm for the anterior, posterior, medial, and lateral margins, and
10 mm for the superior and inferior margins. Organs at risk (OARs) included the liver,
heart, duodenum, spinal cord, and kidneys. Dose constraints for OARs were defined
as follows: the mean dose and V35 (Vn, the percentage of volume receiving more than
n Gy) of the liver were maintained at??30 Gy and 50 %, respectively. The mean dose
and V50 of the heart were maintained at??40 Gy and 50 %, respectively. The V50 and
V45 of the duodenum were maintained at??2 % and 25 %, respectively. The maximum dose
was maintained??45 Gy for the spinal cord. The mean dose for each kidney was maintained??23 Gy.
3D-CRT was delivered by using a linear accelerator with 10-MV X-rays, 3–5 beams. A
daily fraction of 2 Gy was administered at five fractions per week to deliver a total
dose of 60 Gy.

Evaluation

Acute and late toxicities from treatments were graded according to NCI-CTCAE version
4.0 9]. Responses were defined using the mRECIST criteria 10] based on an enhanced CT of the thorax and MRI of the liver.

Data analyses

SPSS for Windows, version 16.0; SPSS Inc., Chicago, Ill, USA) was used for data analysis.
The duration of OS was calculated from the diagnosis of HCC until death or until the
date of the last follow-up visit for patients still alive.