IAEA initiatives in liver cancer

Full text: Hepatocellular carcinoma (HCC) is a malignant epithelial tumor arising from parenchymatous liver cells. It is one of the world's most common malignancies, causing almost one million deaths annually. About 315,000 new cases of HCC are reported per year which constitutes 5.6% of all cancers among males and 2.7% of all cancers among females. Control strategies to prevent occurrence of HCC are sub-optimal; this is evident by the rising incidence of HCC even in developed nations like the USA, where the prevalence of the disease is one of the lowest in the world. Currently, patients with HCC have an extremely poor prognosis with a five year survival rate of less than 5%. However, morbidity and mortality in such patients are not determined by the presence of HCC alone, but are also influenced by the activity of the underlying liver disease, as well as the functional status of the liver. The stage of the tumor (size, number, vascular invasion, extra hepatic spread) has been consistently documented to be an important determinant of the natural course of the disease. These factors are major variables that influence various therapeutic strategies directed against this tumor in recent times. Therefore, therapy in HCC needs to be optimized depending upon the above mentioned influences on the final outcome of the disease. Various forms of therapy such as surgical resection, orthotopic liver transplantation (OLT), percutaneous injection to induce coagulative necrosis of the tumor using agents like ethanol, acetic acid, hot saline, microwave and laser have been considered as radical treatment of HCC, aiming at curing the disease. The understanding of pathology, pathogenesis, natural course and risk factors of HCC during the last three decades has resulted in the development of multiple therapeutic approaches with promising yet varying results. Most patients with hepatoma from the developing countries at the time of their presentation to the doctor fall into the intermediate/inoperable category, and for these, radionuclide methods to deliver high radiation doses to tumor must be considered. Uncontrolled studies using radioisotopes like I-131, Y-90, Ho-166, Re-186 conjugated to monoclonal antibodies, lipiodol or chemical compounds have shown promising results. However due to lack of prospectively designed randomised trials, their efficacy is yet to be optimally evaluated. There has also been reports (from one study only) on the usefulness of radionuclide therapy as an adjuvant treatment following resection of 'curable' HCC. It has been shown that patients given a single administration of 1GBq. Of I-131 Lipiodol have significantly greater survival and less recurrence than those not treated. It is important that the results of this study be verified and confirmed by reproducing the results in another prospective trial. It may be noted that the disease is most prevalent in those communities with least resources for setting up clinical trials. Hence the role of the International Organizations like IAEA and WHO are extremely important in assisting them in setting up such trials and coordinating them. For nuclear medicine and the IAEA-WHO to develop a key role in the treatment of HCC, new methods must be evolved, tested and standardized in full random controlled trials. Currently the only commercially available radiopharmaceutical for the treatment of liver cancer, I-131 Lipiodol, has been found to be prohibitively expensive, and it is virtually not practical to use this radiopharmaceutical on a routine basis in the poor and developing countries of the world. In the year 2001 the IAEA started a new coordinated research in order to identify and test a new cost-effective radiopharmaceutical for the treatment of liver cancer. With the help of scientists for Korea, Singapore and USA it has been possible to label Rhenium 188 with Lipiodol which has shown excellent concentration in the HCC when administered trans-arterially. We have already concluded a Phase-1 study with a meticulously designed dosimetry protocol in order to deliver maximum tolerated dose to the patients. The study revealed that the right quantity of the radioconjugate can be delivered after 'scout' dose dosimetry studies have been done, to spare normal liver and lung from excess radiation dose. The phase-1 data showed that the treatment is safe with minimal side-effects, at a dose up to about 200 mCi of Re-188 lipiodol. The Phase-2 study is in progress. We have already observed good results. However the efficacy of the treatment has to be confirmed in a large number of patients. The multi-centre Phase-2 study is expected to be complete in 2005. (author)