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Title: Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Curative therapy is not an option for most patients, often because of underlying liver disease. Experience in radiation therapy (RT) for HCC is rapidly increasing. Conformal RT can deliver tumoricidal doses to focal HCC with low rates of toxicity and sustained local control in HCC unsuitable for other locoregional treatments. Stereotactic body RT and particle therapy have been used with long-term control in early HCC or as a bridge to liver transplant. RT has also been effective in treating HCC with portal venous thrombosis. Patients with impaired liver function and extensive disease are at increased risk of toxicity and recurrence. More research on how to combine RT with other standard and novel therapies is warranted. Randomized trials are also needed before RT will be generally accepted as a treatment option for HCC. This review discusses the current state of the literature and opportunities for future research.

Authors:
 [1];  [1]
  1. Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada)
Publication Date:
OSTI Identifier:
22267850
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 87; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; HEPATOMAS; LIVER; RADIATION DOSES; RADIOTHERAPY; THROMBOSIS; TOXICITY

Citation Formats

Klein, Jonathan, and Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca. Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities. United States: N. p., 2013. Web. doi:10.1016/J.IJROBP.2012.08.043.
Klein, Jonathan, & Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca. Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities. United States. doi:10.1016/J.IJROBP.2012.08.043.
Klein, Jonathan, and Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca. Sun . "Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities". United States. doi:10.1016/J.IJROBP.2012.08.043.
@article{osti_22267850,
title = {Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities},
author = {Klein, Jonathan and Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca},
abstractNote = {Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Curative therapy is not an option for most patients, often because of underlying liver disease. Experience in radiation therapy (RT) for HCC is rapidly increasing. Conformal RT can deliver tumoricidal doses to focal HCC with low rates of toxicity and sustained local control in HCC unsuitable for other locoregional treatments. Stereotactic body RT and particle therapy have been used with long-term control in early HCC or as a bridge to liver transplant. RT has also been effective in treating HCC with portal venous thrombosis. Patients with impaired liver function and extensive disease are at increased risk of toxicity and recurrence. More research on how to combine RT with other standard and novel therapies is warranted. Randomized trials are also needed before RT will be generally accepted as a treatment option for HCC. This review discusses the current state of the literature and opportunities for future research.},
doi = {10.1016/J.IJROBP.2012.08.043},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 87,
place = {United States},
year = {Sun Sep 01 00:00:00 EDT 2013},
month = {Sun Sep 01 00:00:00 EDT 2013}
}
  • Purpose: To determine the maximum tolerated dose (MTD) of three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with transcatheter arterial chemoembolization for locally advanced hepatocellular carcinoma. Methods and Materials: Patients were assigned to two subgroups based on tumor diameter: Group 1 had tumors <10 cm; Group II had tumors {>=}10 cm. Escalation was achieved by increments of 4.0 Gy for each cohort in both groups. Dose-limiting toxicity (DLT) was defined as a grade of {>=}3 acute liver or gastrointestinal toxicity or any grade 5 acute toxicity in other organs at risk or radiation-induced liver disease. The dose escalation wouldmore » be terminated when {>=}2 of 8 patients in a cohort experienced DLT. Results: From April 2005 to May 2008, 40 patients were enrolled. In Group I, 11 patients had grade {<=}2 acute treatment-related toxicities, and no patient experienced DLT; and in Group II, 10 patients had grade {<=}2 acute toxicity, and 1 patient in the group receiving 52 Gy developed radiation-induced liver disease. MTD was 62 Gy for Group I and 52 Gy for Group II. In-field progression-free and local progression-free rates were 100% and 69% at 1 year, and 93% and 44% at 2 years, respectively. Distant metastasis rates were 6% at 1 year and 15% at 2 years. Overall survival rates for 1-year and 2-years were 72% and 62%, respectively. Conclusions: The irradiation dose was safely escalated in hepatocellular carcinoma patients by using 3DCRT/IMRT with an active breathing coordinator. MTD was 62 Gy and 52 Gy for patients with tumor diameters of <10 cm and {>=}10 cm, respectively.« less
  • We review the evidence for optimal surgical management and adjuvant therapy for patients with stages I and II non-small cell lung cancer (NSCLC) along with factors associated with increased risks of recurrence. Based on the current evidence, we recommend optimal use of mediastinal lymph node dissection, adjuvant chemotherapy, and post-operative radiation therapy, and make suggestions for areas to explore in future prospective randomized clinical trials.
  • Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local diseasemore » control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment of HCC.« less
  • Background. Chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, or whether embolization (TAE) alone gives the same survival advantage, is not known. Purpose. To evaluate whether specific patient characteristics and/or radiological transarterial techniques result in better outcomes. Method. A PubMed search was carried out for cohort and randomized trials (n = 175) testing transarterial therapies; meta-analysis was performed where appropriate. Results. Anticancer drugs were used as sole agent in 75% of cases (double 15% and triple 6%): doxorubicin (36%), cisplatin (31%), epirubicin (12%), mitoxantrone (8%), mitomycin (8%), and SMANCS (5%). Embolizing agents used were:more » gelatin sponge particles (71%), polyvinyl alcohol (PVA) particles (8%), degradable starch microspheres (DSM) (4%), and embospheres (4%). Sessions per patient were 2.5 {+-} 1.5 (interval: 2 months). Objective response was 40 {+-} 20%; survival rates at 1, 2, 3, and 5 years were: 62 {+-} 20%, 42 {+-} 17%, 30 {+-} 15%, and 19 {+-} 16%, respectively, and survival time was 18 {+-} 9.5 months. The post-TACE complications were: acute liver failure, 7.5% (range 0-49%); acute renal failure, 1.8% (0-13%); encephalopathy, 1.8% (0-16%); ascites, 8.3% (0-52%); upper gastrointestinal bleeding; 3% (0-22%); and hepatic or splenic abscess, 1.3% (0-2.5%). Treatment-related mortality was 2.4% (0-9.5%), mainly due to acute liver failure. Our meta-analysis of nine randomized controlled trials (RCTs) confirmed that TACE improves survival; but a meta-analysis of TACE versus TAE alone (3 RCTs, 412 patients) demonstrated no survival difference. Conclusions. No chemotherapeutic agent appears better than any other. There is no evidence for benefit with lipiodol. Gelatin sponge is the most used embolic agent, but PVA particles may be better. TAE appears as effective as TACE. New strategies to reduce the risk of post-TACE complications are required.« less
  • Purpose: To evaluate the safety and effectiveness of proton beam therapy for hepatocellular carcinoma (HCC) located adjacent to the alimentary tract. Patients and Methods: Forty-seven patients (median age, 69 years; range, 43-82 years) who had HCC located within 2 cm of the alimentary tract underwent proton beam therapy. Liver damage according to the Child-Pugh classification was Class A in 35 patients, Class B in 9, and Class C in 3. Treatment protocols of the early 16 patients and the late 31 patients were 72.6 GyE in 22 fractions and 77 GyE in 35 fractions, respectively. Results: During the median follow-upmore » period of 23 months, 24 patients died; the remaining 23 patients were alive until September 2008. The median overall survival was 33.9 months (95% confidence interval [CI], 10.8-57.0 months). Actuarial overall and local progression-free survival rates at 3 years were 50.0% and 88.1%, respectively. Grade 2 and 3 alimentary tract hemorrhage was observed in 3 (6.4%) and 1 (2.1%) patients, respectively. Conclusions: Our proton beam therapy strategy for HCC located adjacent to the alimentary tract seems to be effective but should be performed with caution.« less