The Preliminary Observation On Curative Effect Of γ-Knife Treatment On Small Hepatocellular Carcinoma(SHCC)

Objective: Hepatocellular carcinoma (HCC) is one of most common malignant tumors all over the world. About 1 million people died of such disease each year. In addition, HCC is one of 5 high incidence tumor, and it is the third biggest reason about tumor-related death. Small hepatocellular carcinorma (SHCC) is described as: Maximum diameter of individual nodules less than 3cm diameter or two nodules no more than 3cm. SHCC is also described as sub-clinical liver cancer or early HCC. As there is no obvious symptoms and signs, it is generally founded by physical examination.SHCC can be treated by many kinds of medical methods, and surgical resection is the most commonly used one. However, such treatment always stimulates the activity of transforming growth factor, and the proliferation of immune cells are inhibited meanwhile. As the result, the growth of residual tumor will be accelerated. A study reported that the SHCC-5-year relapse rate whom treated by surgery is up to 43.5%. Apart from this, the patients who suffer from SHCC always associate with chronic hepatitis, and cirrhosis, which greatly reduce the application of surgery.Liver transplantation is a not bad choice for the patient, but it is bounded by high expense and lack of liver resources. Now a days, with the development of minimally invasive technique and the deeply research on HCC radiotherapy, non-surgical methods are used to treat SHCC such as radiotherapy, hepatic arterial chemoembolization(TACE), Intra-tumoral injection of ethanol or acetic acid (PAI) and Radio frequency ablation (RFA). In recent years, a lot of studies show that radiotherapy have achieved almost the same effect with the surgery on HCC treatment.The whole bodyγ-knife with high accuracy is one of the Stereotactic radiotherapy. Because of the size of SHCC is very small, the iso-dose curve is high and CTV dose attenuation is very obvious, the dose distribution is similar to the Bragg peak. Not only we can make the three dimensional conformal radiotherapy (3DCRT), but the target dose also becomes higher from outside to the inside of the tumor, so there is a difference of dose between the normal tissue and tumor area. Hypofractionated radiation therapy can increases the single dose and the biological effects of radiation, reduces the hypoxia and quiescent cells'resistance to radiotherapy, so it is a better mode of treatment. Radiotherapy ofγ-knife significantly alleviates the liver damage and raises the local control rate, survival rate, and living quality because of the high dose radiation.γ-knife has been gradually applied the inoperable patients with SHCC. This study will treat the patients with SHCC byγ-knife, have periodic reviews and follow-ups, and evaluate the effect of treatment and complications.Methods: During Jan, 2005 to Oct.2007, 22 inoperable SHCC cases byγ-knife radiotherapy.1 Simulating patients with the CT simulator: mark the relative position on the surface of patients'body, simulation phantom, and the treatment table, which will reduce the positioning error. Scan mode: intravenous injection of contrast medium (OPTIRAY) 100ml to imaging, in order to scanning the portal vein and artery phases continuously.2 Transferring the simulated information to theγ-knife treatment planning system (TPS work station).3 Planning treatment plan: SGS-Ⅰstereotacticγray body treatment system, delineate radiotherapy target volume, make the treatment plan: PTV with 50-70% iso-dose curve included, (36-50)Gy/(8-12)F, (4-5)Gy/F, 5F/W, average radiation dose 43.5Gy4 Transferring the treatment plan to treatment control system. Begin to treat after the plan checking.5 Treating the patients with liver protectant and drugs enhance immune system during the treatment interval.6 Having periodic reviews and follow-ups: review time: 1st, 3rd, 6th, 9th month and 1st, 2nd, 3rd year after treatment, review items: patient symptoms, blood test, liver function, abdominal CT/MRI and AFP. Evaluate the recent treatment near-term efficacy using tumor evaluation standards of W.H.O. Evaluate the long-term efficacy with 3-year survival rate. The classification side effects and complications refer to RTOG.7 Analyzing cumulative survival rates with Kaplan-Meier rule.Results: Statistics (begin from the end of treatment):1 Follow-up time of 22 cases is between 3and 69 months (35.5 months on average) follow-up proportion is 100%.2 Near-term Efficacy: 3 months after treatment: CR (4 cases, 18.18%), PR (12 cases 54.55%), NC (4 cases 18.18%), PD (2 cases 9.09%).Total effective rate is 72.73 %( 16/22).3 Long-term Efficacy: up to oct.2007, 8 patients died. The median survival time is 40.0 months. 1-year, 2-year, 3-year survival rates are 81.20%, 68.7%, 62.4% respectively.4 Death reason: after 3, 2, 1 year after the radiotherapy, there are 3, 2, 1 patients death respectively. Reasons of death: gastrointestinal bleeding caused by portal hypertension (2/6); multiple metastases and multiple organ failures (2/6); intrahepatic multiple metastases and liver failure (1/6); lung metastases and hemoptysis (1/6).5 Side effects and complications of treatment: all patients were well tolerated, the side effects are slight and there is no serious radiation liver injury.Conclusion:1γ-knife radiotherapy has high efficacy and total survival rate, and it is a good technique for treatment.2 Treatment process is safe, feasible, low toxicity, radiation response can be tolerated.3γ-knife can be combined with other treatments, patients with advanced or recurrent HCC will benefit from that.4 More clinical trails are still needed, in order to have a regression analysis to explore the efficacy and impact factors. 5 Further studies will be needed to explore the target delineation, dose-effect relationship, and best dose division.