Clinical research on alternating hyperfraction radiotherapy for massive hepatocellular carcinoma

Abstract

The delivery of high tumoricidal doses of radiation with low rates of toxicity is of particular significance for massive hepatocellular carcinoma (HCC) radiotherapy. In order to observe the efficacy and adverse reactions of alternating hyperfraction radiotherapy treatment of massive HCC, seventy-two cases of massive HCC were randomly divided into two groups, group A and group B. The liver lesions of group A were divided into sublesions and treated with alternating hyperfraction radiotherapy [intensity modulated radiotherapy (IMRT)]. The interval between radiotherapy to the sublesions was a minimum of six hours. The average radiotherapy dose to the sublesions was 2 Gy/fraction, once a day, five times per week, treating the gross tumor volume with a total dose of 40-50 Gy, and the clinical target volume with a total dose of 30-40 Gy. By contrast, the lesions of group B were not divided into sublesions for the IMRT treatment, but were treated with an otherwise identical protocol, by 2 Gy/fraction, once a day, five times per week, and with the same total dose. Patients were followed up with regular blood tests, liver function tests, measurements of serum α-fetoprotein levels and contrast-enhanced magnetic resonance imaging (MRI) of the liver. Treatment responses were assessed every 3 months by MRI. The results revealed that the overall response rates of the two groups were 82.9 and 81.3%, respectively (P=0.864). The alternating hyperfraction radiotherapy protocol resulted in enhanced survival (P=0.002). The median survival time of the two groups was 9.7 and 6.5 months, respectively. The overall 6-month, 1-year, 2-year and 3-year survival rates of the two groups were 62.9 and 59.4% (P=0.770), 48.6 and 21.9% (P=0.040), 17.1 and 0.0% (P=0.025) and 2.9 and 0.0% (P=1.000), respectively. The I-II degree of abnormal liver function and radiation-induced liver disease of group B was higher than that of group A (P=0.021 and 0.046, respectively). In addition, the incidence rate of radiation-induced liver injury of group A was lower than that of group B. Therefore, treatment of massive HCC with alternating hyperfraction radiotherapy improved the quality of life and prolonged the overall survival time, compared with conventional IMRT, suggesting that it was an effective radiation pattern.

Keywords: alternating hyperfraction radiotherapy; massive hepatocellular carcinoma; radiation-induced liver disease.

Figure 1.

Survival times of patients in group A are longer than those of group B. Kaplan-Meier curves of survival durations of patients with massive HCC following alternating hyperfraction radiotherapy (group A) and regular IMRT (group B). Survival durations were significantly longer in patients receiving alternating hyperfraction radiotherapy (median survival, 9.7 months) than those receiving regular IMRT radiotherapy (median survival, 6.5 months; P=0.002). IMRT, intensity modulated radiotherapy.