Radiation Therapy for Hepatocellular Carcinoma

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Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, and its incidence is on the rise. The primary therapy is resection or liver transplant, but only a minority of patients present with resectable disease. Historically, radiotherapy has not played a significant role in the treatment of liver malignancies because of the low tolerance of the whole liver to radiation. With improvements in 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy, higher doses of radiation can be delivered to target lesions with low doses to the noninvolved liver; thus, experience in the use of radiation for the treatment of focal HCC has increased. At the same time, our understanding of the relationships between radiation dose and volume and the risk of classic radiation-induced liver disease and other toxicities more likely to occur in HCC patients has improved considerably. These developments have led to a body of evidence that now supports the careful use of radiotherapy for unresectable HCC. The rationale for studying radiotherapy in a randomized trial is strong.

Section snippets

Fractionated Conformal Radiotherapy

Historically, radiotherapy (RT) has been quite limited in the treatment of HCC. Without multiphase contrast computed tomography scans or magnetic resonance imaging, as described by Brock in this issue (see pages 247-255), tumor delineation was a challenge, and radiation volumes often included a significant portion of the liver. Because the whole liver has a low tolerance to radiation, patients were at risk for liver toxicity and also did not derive much benefit from low-dose radiation therapy.

Stereotactic Body Radiotherapy of HCC

Stereotactic body radiotherapy (SBRT) has also been applied to select patients with HCC. Figure 2 shows a typical SBRT HCC case. This technique was pioneered by Blomgren et al,25 who treated 20 liver tumors, including 8 HCCs, with an objective response in 70% and stable disease in 25%. Generally, dose per fraction and total dose range was between 4 and 15 and 24 and 54 Gy, respectively. In contrast to patients with metastatic disease to the liver who have relatively normal liver function and

Combined Therapies

Because of the risk for developing multifocal or regional disease outside the irradiated volume, elsewhere in the liver, and the risk of RILD with high doses of RT, it is intuitive to think about combining RT with other treatment modalities for both a local and regional effect. TACE has been combined with RT, usually at reduced doses because of concerns about increased toxicity, mostly by Asian investigators.38, 39, 40, 41, 42, 43 Two general approaches are used for this combination. First, RT

Conclusions

Over the past 20 years, a worldwide experience in treating HCC with RT has been developed. With today's highly conformal techniques, high doses can be delivered via conventional fractionation or SBRT with a low risk of toxicity in patients with intact liver function. Patients with compromised liver function should be treated more cautiously. Because of a high likelihood of progressive disease outside of the treated volumes, combination therapy with TACE or systemic agents should be further

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