Phase I feasibility trial of stereotactic body radiation therapy for primary hepatocellular carcinoma.
ABSTRACT Hepatocellular carcinoma (HCC) is increasing in incidence and the majority of patients are not candidates for radical therapies. Therefore, interest in minimally invasive therapies in growing.
A Phase I dose escalation trial was conducted at Indiana University to determine the feasibility and toxicity of stereotactic body radiation therapy (SBRT) for primary HCC. Eligible patients had Child-Turcotte-Pugh's Class (CTP) A or B, were not candidates for resection, had 1-3 lesions and cumulative tumour diameter less than or equal to 6 cm. Dose escalation started at 36 Gy in 3 fractions (12 Gy/fraction) with a subsequent planned escalation of 2 Gy/ fraction/level. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater toxicity.
Seventeen patients with 25 lesions were enrolled. Dose was escalated to 48 Gy (16 Gy/fraction) in CTP-A patients without DLT. Two patients with CPC-B disease developed grade 3 hepatic toxicity at the 42-Gy (14 Gy/fraction) level. The protocol was amended for subsequent CTP-B patients to receive a regimen of 5 fractions starting at 40 Gy (8 Gy/fraction) with one patient experiencing progressive liver failure. Four additional patients were enrolled (one died of unrelated causes after an incomplete SBRT course) without DLT. The only factor related to more than one grade 3 or greater liver toxicity or death within 6 months was the CTP score (p=0.03). Six patients underwent a liver transplant. Ten patients are alive without progression with a median FU of 24 months (10-42 months), with local control/stabilisation of the disease of 100%. One and two-year Kaplan-Meier estimates for overall survival are 75% and 60%, respectively.
SBRT is a non-invasive feasible and well tolerated therapy in adequately selected patients with HCC. The preliminary local control and survival are encouraging. A confirmatory Phase II trial is currently open to accrual.
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ABSTRACT: The role of radiotherapy in practice is mainly palliative. According to the Practice Guidelines for Management of Hepatocellular Carcinoma (2009) developed by the Korean Liver Cancer Study Group and the National Cancer Center, Korea, radiotherapy can be applied for 1) refractoriness to trans-catheter hepatic arterial chemo-embolization, 2) portal vein tumor thrombosis, and 3) palliative therapy to reduce the symptoms caused by hepatocellular carcinoma. Radiotherapy is one of the most rapidly developing fields of medical research. Recent advances in intensity-modulated radiotherapy, image-guided radiotherapy, and respiratory-gated radiotherapy technologies have enabled more accurate and precise radiation delivery for the treatment of hepatocellular carcinoma. Proton therapy is also emerging as a candidate therapy for ablative measures for patients ineligible for other curative local therapies. Due to recent advances in radiotherapy technologies, radiotherapy for hepatocellular carcinoma has been evolving into stereotactic ablative radiotherapy, which delivers an ablative dose of radiation in 1 to 4 sessions. Clinical series have confirmed that it is safe in Child-Pugh A patients and local control is sustained. The possibility for performing phase 3 randomized clinical trials involving the radiotherapy modality has increased with those advances. Not merely palliative, the role of radiotherapy in the treatment of hepatocellular carcinoma will be expanded to potentially curative therapy in patients who are ineligible for other curative local therapies.Journal of the Korean Medical Association 01/2013; 56(11):983. DOI:10.5124/jkma.2013.56.11.983 · 0.18 Impact Factor
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ABSTRACT: Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.12/2014; 11(4):217-36. DOI:10.7497/j.issn.2095-3941.2014.04.001
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ABSTRACT: Many patients with hepatocellular carcinoma (HCC) present with advanced disease, not amenable to curative therapies such as surgery, transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization (TACE) and radiation therapy. Especially TACE, delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy, has given favorable results on local control and survival. Radiotherapy, as a therapeutic modality of internal radiation therapy with radioisotopes, has also achieved efficacious tumor control in advanced disease. On the contrary, the role of external beam radiotherapy for HCC has been limited in the past, due to the low tolerance of surrounding normal liver parenchyma. However, technological innovations in the field of radiotherapy treatment planning and delivery, have provided the means of delivering radical doses to the tumor, while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy, evaluated for efficacy and safety for HCC, report encouraging results. In this review, we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment.