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Treatment of Inoperable Liver Cancers with Radioactive Microspheres
European Oncology Review, 2005:35-8
Universal Challenge in Oncology
All oncologists must deal with the frequent and frustrating occurrence of patients dying of liver-dominant disease. Exciting new advances in biologic, genetic and cytotoxic agents have produced important and significant prolongation of time to progression and survival for many solid tumours, particularly colorectal adenocarcinoma. However, nearly all patients with metastatic liver disease will die of that condition. In the US that is over 80,000 patients per year, and a similar number in Europe. Radiation therapy is a cornerstone of curative and palliative therapy in nearly all malignancies, but has not been applied with much success to hepatic disease due to the low tolerance of the organ to radiation compared with tumour. Although technology advances in radiation delivery have improved to some degree, use of hepatic radiation, the best opportunity to irradiate the tens of thousands of potential patients with hepatic tumours, may be via implantation internally with radioactive particles, i.e. 90Y-microspheres.
New Approach to an Established Idea
Brachytherapy – physically implanting tumours with radiation – has a long and established history of successful anti-tumour activity in many organs, with the most common use in prostate, uterine cervix and head and neck malignancies. The key principles of brachytherapy involve delivery of tumourcidal doses of radiation to the malignant tumour, but, due to rapid radiation dose fall-off, minimal adjacent normal tissues are damaged. Currently, a few specialised centres can place radiation sources manually into the liver percutaneously or via open laparotomy. A more easily and broadly applied technique is 90Y-microspheres, which use the unique vascular anatomy of the liver to preferentially implant hepatic tumours. It is established that the hepatic arterial system supplies 80% to 100% of the blood to liver tumours (primary and metastatic); however, the normal liver derives nearly all of its blood flow from the parallel portal system. In addition, metastatic tumours in particular form up to 200 times more vessels in plexus around tumours compared with the normal liver immediately nearby. This combination has led to the discovery that 90Y-microsphere release in the hepatic artery produces preferential accumulation of spheres in the tumours of at least 3:1 and up to 20:1 ratio compared with normal liver.
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- Gray B, et al., “Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer”, Ann. Oncol. (2001);12 (12): pp. 1,711–1,720.
- Kennedy A S, et al., “Liver brachytherapy for unresectable colorectal metastases: US results 2000-2004”, Proceedings of the 2005 Gastrointestinal Cancers Symposium, 2005: p. 155.
- Van Hazel G, et al., “Selective internal radiation therapy (SIRT) plus systemic chemotherapy with FOLFOX A phase I dose escalation study”, Proceedings of the 2005 Gastrointestinal Cancers Symposium, 2005: p. 216.
- Van Hazel G, et al., “Selective internal radiation therapy (SIRT) plus systemic chemotherapy with irinotecan. A phase I dose escalation study”, Proceedings of the 2005 Gastrointestinal Cancers Symposium, 2005: p. 137.