Clinical Investigation
Stereotactic Body Radiation Therapy in Recurrent Hepatocellular Carcinoma

This study was presented at the 70th Annual Meeting of the Japanese Cancer Association in Nagoya, Oct 3-5, 2011.
https://doi.org/10.1016/j.ijrobp.2011.11.058Get rights and content

Purpose

To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC).

Methods and Materials

This was a matched-pair study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4–5 fractions over 4–5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses.

Results

The median follow-up time was 14 months for all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size (≤4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable.

Conclusion

SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.

Introduction

Patients with hepatocellular carcinoma (HCC) have a poor prognosis, with a high recurrence rate. Intrahepatic recurrence rate is exceedingly high in both early and advanced disease after curative treatment. Liver transplantation and repeated hepatectomies are theoretically the best therapies for recurrent HCC. However, multiple practical obstacles exist, including the extreme shortage of organs, extrahepatic spread, multicentric tumors, and inadequate normal liver reserve, making these ideal options available only to selected patients. Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are also treatment options for recurrent disease, and both may lead to significant but only small survival benefits 1, 2, 3, 4. In general, overall prognosis is still dismal. It is worthwhile to explore new therapeutic strategies for recurrent HCC.

HCC is a radiosensitive tumor (5). However, radiotherapy has a limited role in treating this disease because of the poor radiation tolerance of normal liver and the difficulty in tumor localization caused by organ motion. Recent technological developments in radiation therapy, such as stereotactic body radiation therapy (SBRT) and imaged-guided radiotherapy, make it possible to deliver a substantial dose of radiation to the tumor and avoid radiosensitive normal liver in the vicinity. Preliminary results of SBRT in HCC have shown its safety and efficacy in primary disease control 6, 7, 8, 9, 10. Nevertheless, its effect on survival is seldom reported, and no studies of SBRT that focus on recurrent HCC, to our knowledge, have been published.

In this study, we analyzed the outcomes of 36 patients with recurrent HCC after SBRT using Cyberknife (Accuray Inc., Sunnyvale, CA) image-guided radiosurgery system. We examined its safety and efficacy for recurrent HCC patients and compared survival rate with that of a historical control group.

Section snippets

Patients

From January 2008 to December 2009, 36 patients with 42 lesions were enrolled in this study. The eligibility criteria were (1) patients who were previously diagnosed with HCC by cytohistology (19 patients) or noninvasive criteria (17 patients); that is, based on [a] a nodule of >2 cm together with the classic enhancement on one imaging technique or an alpha fetoprotein (AFP) of >200 ng/ml, or [b] a 1- to 2-cm nodule with typical features on two imaging studies [11]); (2) patients undergoing

Tumor response and local control

Follow-up CT scan or MRI was available for 35 patients (41 lesions). One patient developed brain metastasis 2 months after SBRT. He died before the first follow-up CT scan or MRI. Of the 41 evaluable lesions, the complete response (CR), partial response (PR), stable disease (SD), and PD rates were 22.0%, 36.6%, 39.0%, and 2.4%, respectively. Treatment responses of recurrent HCC and newly developed HCC after prior treatment to SBRT were not statistically different. Out-field intrahepatic

Discussion

Standard treatment of recurrent HCC has not yet been established. In this study, our preliminary results support the fact that SBRT could be a treatment option for patients who are unsuitable for surgery. There are some advantages for SBRT in treating recurrent HCC. First, in addition to high in-field local control, the survival rates in this study appear comparable to those seen with other treatment modalities. Our study resulted in 2-year OS of 64%, which is comparable to that of RFA 2, 12

Conclusions

In conclusion, our study supports that SBRT is feasible in treating recurrent unresectable HCC, resulting in 59% tumor response rate (CR + PR), 98% in-field disease control rate (CR + PR + SD), and an encouraging survival rate. The acute toxicities are usually mild and tolerable. However, out-field recurrence is still the main course of failure and further studies of combination of SBRT and systemic therapies may be reasonable.

References (20)

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    Citation Excerpt :

    According to the clinical guideline, SBRT is now widely applied as treatment in patients with HCC that are not suitable for surgery, TACE, or other loco-regional treatment [10,11]. The treatment failure pattern is mainly caused by intra-hepatic recurrence [12]. Theoretically, prophylactic normal liver irradiation could affect the risk of recurrence by eliminating the micro-metastasis.

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Conflict of interest: none.

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