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Introduction: Locoregional treatment of liver metastases
Vol 29, No 2
April 2002
Introduction: Locoregional Treatment of Liver Metastases
D
ESPITE THE DEVELOPMENT of new systemic treatment strategies, the management of liver metastases still remains as a significant problem for oncologists. The ideal treatment for liver metastasis would produce local control of the liver metastases and prevent local or extrahepatic recurrence. This issue of Seminars in Oncology presents an update on various locoregional treatment modalities for liver metastases. The treatment approaches for local control of liver metastases are categorized into two subgroups: regional or local. Regional treatments utilize vessels feeding metastases in order to increase concentration of chemotherapeutic drugs or bioresponse modifiers. In contrast, local treatments of liver metastases are designed to directly deliver therapy to the tumor, for example, by placing a probe into tumor tissues to destroy the tumor cells via mechanical disruption. Resection of liver metastases and externalbeam radiation can be either local or regional. Surgical resection of liver metastases is still considered to be the standard locoregional treatment especially for metastatic colorectal carcinoma. Sasson and Sigurdson report on surgical treatment of liver metastases from colorectal carcinoma and emphasize that surgical removal of liver metastasis can provide a survival benefit to some patients. Despite its clear clinical benefit, surgical intervention is limited to only a small fraction of patients due to bilobal location of metastases and/or involvement of the major vessels. Based on the unique venous drainage of the gastrointestinal tract through the portal vein, the liver is the most common, and sometime only the site of distant metastases from colorectal carcinoma. Liver metastases also have a unique characteristic that their blood supply comes mainly from the hepatic artery. These considerations are the basis for hepatic arterial infusion (HAI) of chemotherapeutic drugs. Ensminger summarizes the rationales for HAI, and Dizon and Kemeny report on their clinical experience using this unique technique. For the treatment of chemotherapy-resistant tu-
Seminars in Oncology, Vol 29, No 2 (April), 2002: pp 105-106
mors or for treatment with chemotherapy drugs that have a low first-pass extraction rate, therapeutic efficacy of HAI is limited. To overcome this limitation, Weinreich and Alexander investigate isolated hepatic perfusion of liver metastases from colorectal carcinoma and melanoma. An alternative approach for chemotherapy-resistant tumors includes embolization of the hepatic artery. This technique provides localization of therapeutic agents in the tumor tissue as well as ischemic damage to the tumor cells. This approach would be most useful for hypervascular metastases such as melanoma, leiomyosarcoma, and islet cell tumors. Sullivan reports on his experience with chemoembolization, and Hebra and Thirlwell report on radioembolization of liver metastases. Direct delivery of treatment to liver metastases offers better local control. Based on the experience with primary hepatocellular carcinoma, various local treatments have been explored in patients with liver metastases. Parikh et al present their experience with radiofrequency ablation of hepatic metastases. Sotsky and Ravikumar report on cryotherapy in the treatment of liver metastases from the colorectal cancer, and Giovannini summarizes his experience with percutaneous alcohol ablation for liver metastasis. Current data suggest that radiofrequency ablation is the most effective in situ local treatment for liver metastases. It was long believed that the normal liver is sensitive to radiation and thus the usage of external-beam radiation therapy for liver tumors is limited. Malik and Mohiuddin report on the efficacy and safety of external-beam radiotherapy and suggest that it should be considered as one of the options for local management of liver metastases. Direct delivery of a gene to a liver metastasis is a new therapeutic approach reported by Havlik et
Copyright 2002, Elsevier Science (USA). All rights reserved. 0093-7754/02/2902-0015$35.00/0 doi:10.1053/sonc.2002.32592 105
106
al. Despite the promise of this approach, the clinical benefit of direct gene delivery to liver metastases is marginal and further improvements in technique are awaited. Finally, the most difficult challenge in the management of liver metastases is the prevention of subsequent local and systemic metastases. In this respect, Dizon and Kemeny report on successful prevention of local and systemic recurrence by combining HAI with systemic chemotherapy for colorectal carcinoma. Our group developed a new approach using immunoembolization of liver metastases with granulocyte-macrophage colony-stimulating factor to control local disease as well as extrahepatic metastases. The preliminary data on our experience is summarized in the chapter of locoregional immuno(bio)therapy for liver metastases.
TAKAMI SATO
This issue of Seminars in Oncology is the first comprehensive review of locoregional management of liver metastases. Since the number of patients in each study is relatively small and direct comparisons have not been done, randomized clinical trials need to be conducted to determine the optimal approach for the management of a specific type of liver metastasis. Furthermore, combination of local, regional, and systemic treatment would also need to be explored to improve the final outcome of patients with liver metastasis. Takami Sato, MD Jefferson Medical College of Thomas Jefferson University Philadelphia, PA Guest Editor
April 2002
Introduction: Locoregional Treatment of Liver Metastases
D
ESPITE THE DEVELOPMENT of new systemic treatment strategies, the management of liver metastases still remains as a significant problem for oncologists. The ideal treatment for liver metastasis would produce local control of the liver metastases and prevent local or extrahepatic recurrence. This issue of Seminars in Oncology presents an update on various locoregional treatment modalities for liver metastases. The treatment approaches for local control of liver metastases are categorized into two subgroups: regional or local. Regional treatments utilize vessels feeding metastases in order to increase concentration of chemotherapeutic drugs or bioresponse modifiers. In contrast, local treatments of liver metastases are designed to directly deliver therapy to the tumor, for example, by placing a probe into tumor tissues to destroy the tumor cells via mechanical disruption. Resection of liver metastases and externalbeam radiation can be either local or regional. Surgical resection of liver metastases is still considered to be the standard locoregional treatment especially for metastatic colorectal carcinoma. Sasson and Sigurdson report on surgical treatment of liver metastases from colorectal carcinoma and emphasize that surgical removal of liver metastasis can provide a survival benefit to some patients. Despite its clear clinical benefit, surgical intervention is limited to only a small fraction of patients due to bilobal location of metastases and/or involvement of the major vessels. Based on the unique venous drainage of the gastrointestinal tract through the portal vein, the liver is the most common, and sometime only the site of distant metastases from colorectal carcinoma. Liver metastases also have a unique characteristic that their blood supply comes mainly from the hepatic artery. These considerations are the basis for hepatic arterial infusion (HAI) of chemotherapeutic drugs. Ensminger summarizes the rationales for HAI, and Dizon and Kemeny report on their clinical experience using this unique technique. For the treatment of chemotherapy-resistant tu-
Seminars in Oncology, Vol 29, No 2 (April), 2002: pp 105-106
mors or for treatment with chemotherapy drugs that have a low first-pass extraction rate, therapeutic efficacy of HAI is limited. To overcome this limitation, Weinreich and Alexander investigate isolated hepatic perfusion of liver metastases from colorectal carcinoma and melanoma. An alternative approach for chemotherapy-resistant tumors includes embolization of the hepatic artery. This technique provides localization of therapeutic agents in the tumor tissue as well as ischemic damage to the tumor cells. This approach would be most useful for hypervascular metastases such as melanoma, leiomyosarcoma, and islet cell tumors. Sullivan reports on his experience with chemoembolization, and Hebra and Thirlwell report on radioembolization of liver metastases. Direct delivery of treatment to liver metastases offers better local control. Based on the experience with primary hepatocellular carcinoma, various local treatments have been explored in patients with liver metastases. Parikh et al present their experience with radiofrequency ablation of hepatic metastases. Sotsky and Ravikumar report on cryotherapy in the treatment of liver metastases from the colorectal cancer, and Giovannini summarizes his experience with percutaneous alcohol ablation for liver metastasis. Current data suggest that radiofrequency ablation is the most effective in situ local treatment for liver metastases. It was long believed that the normal liver is sensitive to radiation and thus the usage of external-beam radiation therapy for liver tumors is limited. Malik and Mohiuddin report on the efficacy and safety of external-beam radiotherapy and suggest that it should be considered as one of the options for local management of liver metastases. Direct delivery of a gene to a liver metastasis is a new therapeutic approach reported by Havlik et
Copyright 2002, Elsevier Science (USA). All rights reserved. 0093-7754/02/2902-0015$35.00/0 doi:10.1053/sonc.2002.32592 105
106
al. Despite the promise of this approach, the clinical benefit of direct gene delivery to liver metastases is marginal and further improvements in technique are awaited. Finally, the most difficult challenge in the management of liver metastases is the prevention of subsequent local and systemic metastases. In this respect, Dizon and Kemeny report on successful prevention of local and systemic recurrence by combining HAI with systemic chemotherapy for colorectal carcinoma. Our group developed a new approach using immunoembolization of liver metastases with granulocyte-macrophage colony-stimulating factor to control local disease as well as extrahepatic metastases. The preliminary data on our experience is summarized in the chapter of locoregional immuno(bio)therapy for liver metastases.
TAKAMI SATO
This issue of Seminars in Oncology is the first comprehensive review of locoregional management of liver metastases. Since the number of patients in each study is relatively small and direct comparisons have not been done, randomized clinical trials need to be conducted to determine the optimal approach for the management of a specific type of liver metastasis. Furthermore, combination of local, regional, and systemic treatment would also need to be explored to improve the final outcome of patients with liver metastasis. Takami Sato, MD Jefferson Medical College of Thomas Jefferson University Philadelphia, PA Guest Editor