Clinical investigations
Liver
A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus

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Purpose

To evaluate the potential role of external beam radiation therapy (EBRT) in the treatment of patients with hepatocellular carcinoma (HCC) who have portal vein (PV) and/or inferior vena cava (IVC) tumor thrombi.

Methods and materials

One hundred fifty-eight patients with HCC who had PV and/or IVC tumor thrombus were reviewed and analyzed by Kaplan-Meier and Cox regression analysis. Forty-four patients with HCC who received local limited EBRT (in addition to other treatment modalities) were classified as the EBRT group. The total radiation dose was 36–60 Gy (median, 50 Gy) and was focused on the tumor thrombi. One hundred fourteen patients with HCC who did not receive EBRT were selected from hospitalized patients with HCC who had PV and/or IVC thrombi during the same period; these were classified as the non-EBRT group, and their intrahepatic tumors were treated with transarterial chemoembolization or resection, on the basis of the patients' status. Parameters observed included survival rates and the tumor thrombus response to EBRT as seen on CT scan or MRI.

Results

Of the 44 patients who received EBRT, 15 (34.1%) showed complete disappearance of tumor thrombi, 5 (11.4%) were in partial remission, 23 (52.3%) were stable in their tumor thrombi, and 1 (2.3%) showed disease progression at the end of the study period. The median survival was 8 months, and the 1-year survival rate was 34.8% in the EBRT group. In the non-EBRT group, the median survival and 1-year survival rates were 4 months and 11.4%, respectively. In stepwise multivariate analysis, EBRT showed a strongly protective value (relative risk = 0.324, p < 0.001). Survival was not related to intrahepatic tumor status in the non-EBRT patients. However, in the EBRT group, poorer prognosis was significantly related to intrahepatic multifocal or diffusion lesions, and the most common reason for death was liver failure caused by uncontrolled intrahepatic disease.

Conclusion

Although EBRT is palliative in intent, it is preferred for prolonging survival in the treatment of tumor thrombi.

Introduction

The incidence of portal vein (PV) and/or inferior vena cava (IVC) tumor thrombi is higher in patients with hepatocellular carcinoma (HCC); it has been reported in as many as 44–84% of these patients in autopsy data (1). It has also been estimated, from clinical data, that the incidence of HCC thrombosis ranges between 34% and 50% (2, 3). Most of these patients have a poorer prognosis (4); their duration of survival is only 2.4–2.7 months without treatment (4, 5, 6, 7). If patients with PV or IVC thrombi receive systemic chemotherapy, the median survival time is 3.9–9.2 months (7, 8). Transarterial chemoembolization (TACE) has also been attempted in patients with major PV invasion, and the median survival time in these patients is between 10 months and 1 year (9, 10). The mean survival is likely longer in patients with PV tumor thrombosis who are treated with hepatectomy and preoperative TACE (11). However, both TACE and surgical resection are not indicated for HCC with PV trunk occlusion by tumor thrombi because of a lack of efficacy and possible complications. There is no choice but external beam radiation therapy (EBRT) in such cases. Some studies have reported survival of 7–12 months in patients with PV thrombus who receive EBRT (12, 13), but the number of cases was smaller, and there was no control group. In the present study, we report the preliminary results for 44 patients with HCC who had PV and/or IVC thrombi and who received EBRT, alone or in combination with additional therapy (TACE or removal of primary tumors), and compared them with 114 patients with HCC who had PV and/or IVC tumor thrombi treated without EBRT.

Section snippets

Patients

We conducted a retrospective chart review of 158 patients with HCC who had PV and/or IVC/atrium tumor thrombi diagnosed and treated at the Zhongshan Hospital, Fudan University (Shanghai, China), from January 1998 to August 2003. During this period, 1926 patients with HCC were hospitalized at the Liver Cancer Institute, Zhongshan Hospital, including 158 patients with tumor thrombi in PV and/or IVC. The proportion of HCC with tumor thrombi is as low as 8.2% in our data, whereas the incidence of

Distributions of tumor thrombus

In the 158 patients with HCC who had PV and/or IVC/atrium tumor thrombosis examined in the present study, the distribution of thrombi was 34.8% (55 of 158) in the PV branches, 44.3% (70 of 158) in the PV trunk, and 20.9% (33 of 158) in the IVC/atrium.

Overall survival analysis and prognostic factors

The Kaplan-Meier survival curves in Fig. 2 show that patients with similar AFP status, intrahepatic tumor type, and thrombus location had virtually identical survival rates, but survival decreased as the stage increased but increased for the

Discussion

Historically, the use of radiation was largely limited to unresectable advanced primary liver cancer treated during the pre-CT era, and this led to the conclusion that primary liver cancers are radioresistant. There is, however, no evidence that primary liver cancers have an inherent radioresistance; rather, the doses of radiation administered have generally been limited by the need to avoid damage to the surrounding structures. Over the past decade, we have used CT scans to design radiation

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