This is a mono-center study to explore the efficacy and adverse reaction in hepatocellular carcinoma patients with decompensated cirrhosis treated by CyberKnife SBRT (CK-SBRT).
Primary outcome measures
- Overall survival rate: OS is defined starting from the date of CK-SBRT to the date of final follow-up or demise of patients.
- Progression-free survival: PFS is estimated starting from the date of CK-SBRT to the date of disease progression or demise of patients.
- Local control rate: LC is calculated starting from the date of CK-SBRT to progress (the lesion diameter is more than original tumor in contrast-enhanced CT or contrast enhanced MRI).
Secondary outcome measures
- Radiation-induced liver injury (RILD) rate:
RILD included classic RILD and non-classic RILD. Classic RILD manifests as symptoms of fatigue, hepatomegaly, and anicteric ascites, etc. Additionally, the serum alkaline phosphatase level in these patients increases to more than twice the normal level, but the serum transaminase and bilirubin levels remain normal[4, 5]. Non-classic RILD usually occurrs in patients with hepatitis and cirrhosis who are also with markedly elevated serum transaminases (>5 times the upper limit of normal) rather than elevated alkaline phosphatase or a decline in liver function (measured by a worsening of Child-Pugh score by 2 or more).
RILD was evaluated every three days during CK-SBRT, every month for initial three months and every three months thereafter until 8 months after CK-SBRT.
- To observe acute and late gastrointestinal toxicities following CK-SBRT.
The hepatocellular carcinoma patients were diagnosed by image examination and laboratory test or pathology.
- Primary HCC diagnosed by a surgeon and/or radiologist and oncologist;
- The diameter of lesion ≤5cm.
- Age of 30-80 years old.
- Unfeasible or refusing to undergo other treatments, such as resection, liver transplantation, etc.
- Residual normal liver volume ≥700 cc;
- With decompensated cirrhosis (Child-Pugh B or C classification);
- Without portal vein tumor thrombus;
- Eastern Cooperative Oncology Group (ECOG) score 0-1;
- Distances between tumor and normal organs (esophagus, stomach, duodenum, bowel) are more than 5 mm;
- Platelet count≥50 × 109/L, white blood count≥1.5 × 109/L;
- Patients infected with hepatitis B virus who are treated with adefovir or entecavir; patients infected with hepatitis C virus whose HCV DNA are negative.
- Eastern cooperative oncology group (ECOG) PS score 0 or 1.
- White blood count≥2*109/L, platelets count≥60*109/L.
- A life expectancy of ≥6 months.
- All participants understand the research subject and sign a written informed consent document.
- With previous therapies, such as resection, liver transplantation, radiofrequency ablation, transarterial chemoembolization, etc.
- The outline of lesion is not confirmed by image examination;
- With hepatic or any other abdomen radiotherapy history;
- With severe internal medicine diseases.
- Pregnant women.
- Participants who are in another trial while on study.
Radiation treatment planning
All participants are implanted with 3 to 4 fiducial markers one week prior to CT localization. The distance between markers and lesion is less than 6cm. Before CT localization, a vacuum-bag is used for fixing the body, the arms and the legs (both arms are along the body, and both hands are on thighs). The acquired parameters of CT images are as follows: tilted angel of 0°; slice thickness of 1 mm; voltage of 120 KV tube current of 400 mA; pixel size of 512 × 512. When the patients received simulation, they need hold their breath with smooth breathing. We adopt contrast-enhanced CT or contrast-enhanced MRI as an auxiliary image for fusion. The radiation oncologists contour gross tumor volume (GTV), planning target volume (PTV) and organs at risk. GTV is defined as the visible lesion based on image examination. PTV expands 3-5mm of GTV. The prescribed doses are 50-54Gy/5-6fx. All CK-SBRT plans are calculated by G4 CyberKnife MultiPlan (Version 4.0.2) and VSI CyberKnife MultiPlan (Version 4.6.1). The plans enclose PTV with 70–90% isodose line of maximum dose equated to the prescribed dose. Normal tissues tolerance doses comply with AAPM TG-101 report.
Evaluation and follow-up
The CK-SBRT plan is delivered every day including on weekend. During CK-SBRT, the adverse reaction is evaluated every day. Physical examination and laboratory test are assessed every three days. In case patients present nausea and/or vomiting, they will receive corresponding drug treatment. The treatment schedule will be delayed when patients with uncontrollable vomiting. Moreover, when Child-Pugh score is two points higher than treatment before, the treatment will be also suspended, even be terminated. After CK-SBRT, the patients are followed up, which includes physical examination, laboratory test and image examination. The follow up period defines as every month for initial three months, and every three months thereafter until 3 years. The trail is planned to begin on August 2020.
A quality assurance
Two radiation oncologists and two physicists form the CyberKnife QA group.
LC, OS and PFS are estimated using the Kaplan-Meier method. Uni-variable and multi-variable hazard ratios are calculated using the Cox proportion hazard model. P values<0.05 are considered statistically significant.