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Low Radiation Dose effect of Tomotherapy for Hepatocellular Carcinoma
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Low Radiation Dose effect of Tomotherapy for Hepatocellular Carcinoma

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Tae Hyun Kim …

Tae Hyun Kim
Center for Liver Cancer, National Cancer Center

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  • 1. Tae Hyun Kim Center for Liver Cancer, National Cancer Center Low Radiation Dose effect of Tomotherapy for Hepatocellular Carcinoma
  • 2.  Surgery, local ablative treatments (i.e., radiofrequency ablation [RFA], percutaneous ethanol injection [PEI]), transarterial chemoembolization (TACE), and liver transplantation are well established treatment modalities for hepatocellular carcinoma (HCC)  In cases that these treatments are ineffective or unsuitable, radiotherapy (RT) with X-ray could be safe and effective alternative Seong J. Int J Radiat Oncol Biol Phys 2000;47:1331-1335 Kim TH et al. Am J Clin Oncol 2006;29:568-575  Tomotherapy - is capable of intensity modulation using helical beams as well as imaging guidance - Several previous studies for HCC patients with or without PVTT have showed promising results, i.e., better tumor response, better overall survival in responsive subgroup, and low Tomotherapy for Hepatocellular Carcnioma
  • 3. Plan Comparisons: IMRT vs. Tomotherapy Coplannar IMRT Non-coplannar IMRT Tomotherapy Hseih CH et al. Radiat Oncol 2010;5:40 Conformality of Target coverage Tomotherapy>Non-coplannar IMRT>Coplanner IMRT Low dose of radiation to liver Non-coplannar IMRT>Coplanner IMRT>Tomotherapy
  • 4. Low Radiation Dose Effect of Tomotherapy for Hepatocellular Carcinoma  A high dose of radiation can be delivered to the small volume of liver without influence in function.  In RT planning, irradiated volume of liver receiving low dose of radiation (≤ 10Gy) is less concerned than irradiated volume of liver receiving a high dose of radiation Q. Is low dose of radiation ( 10Gy), to liver negligible?≤ or Is low dose of radiation not related with RT induced hepatic toxicity? Lawrence TS et al. Int J Radiat Oncol Biol Phys 1992;23:781-788  The portion of un-irradiated liver has a very strong potential ability of regeneration and functional compensation  Radiation Tolerance Dose of Liver: depend on irradiated liver volume Irradiated liver volume Tolerance dose 100% 30 - 35Gy 70% 42Gy 50% 52Gy 20% 70Gy
  • 5. Radiation induced Hepatic Toxicity  Classic radiation induced liver disease (RILD) - Induced by veno-occlusive disease, severe congestion and fibrosis of the sinosoids in central portion of lobules with atrophy the inner portion of liver plates - Clinical manifestations: anicteric ascites, elevated alkaline phosphatase (ALP), and minimal or no increase bilirubin Lawrence TS et al. Int J Radiat Oncol Biol Phys 1995;31:1237-1248  Non-classic radiation induced hepatic toxicity (RIHT), mostly in HBV endemic areas - Induced by hepatocyte damage. - Clinical manifestations: elevated aminotransferase (ALT) and elevated bilirubin. Cheng JC et al. Int J Radiat Oncol Biol Phys 2002;54:156-625 Kim TH et al. Int J Radiat Oncol Biol Phys 2007;67:225-31  HBV reactivation and CHB exacerbation - Increase of >1x log10 IU/mL. - HBV reactivation, and 2 times baseline level of ALT.≥ Hoofnagel Hepatology 2009;49:s156-165 Q. Is non-classic RIHT related with HBV reactivation?
  • 6. Hepatitis reactivation and RT RT group RT group  Not all non-classic RILD was related with HBV reactivation, but some proportion of non-classic RILD might be related with HBV reactivation. Kim JH et al Int J Radait Oncol Biol Phys 2007;69:813-819 Q. Does radiotherapy induce the HBV reactivation? Control group
  • 7. Hepatitis reactivation and RT  HBV reactivation - can be spontaneous, but is most commonly triggered by cancer chemotherapy, immune suppression, or alteration of immune function. - Can lead to clinically apparent acute hepatitis, such as elevation of ALT and bilirubin. Q. What is cause of HBV reactivation by radiotherapy? (4Gy )  Non-cytotoxic low dose of radiation to liver can induce releasing of the inflammatory cytokines, including IL-6, from endothelial cells and subsequently can induce HBV reactivation Chou CH et al Clin Cancer Res 2007;13:851
  • 8. Low Radiation Dose Effect of Tomotherapy for Hepatocellular Carcinoma  A: Low dose of radiation is safe, but not negligible.  Especially in HBV endemic area, low dose of radiation might have a potential to induce the HBV reactivation and/or CHB exacerbation and thus we should be minimize the low dose of radiation and monitor the HBV DNA level carefully after RT Irradiated liver volume Tolerance dose 100% 30 - 35Gy 70% 42Gy 50% 52Gy 20% 70Gy Lawrence TS et al. Int J Radiat Oncol Biol Phys 1992;23:781-788 Q. Is low dose of radiation (less than 10Gy) to liver safe or negligible? or Is low dose of radiation not related with RT induced hepatic toxicity?
  • 9. Coplannar IMRT Non-coplannar IMRT Tomotherapy Hseih CH et al. Radiat Oncol 2010;5:40 Target coverage Tomotherapy>Non-coplannar IMRT>Coplanner IMRT Low dose of radiation to liver Non-coplannar IMRT>Coplanner IMRT>Tomotherapy Low Radiation Dose Effect of Tomotherapy for Hepatocellular Carcinoma  Is a risk of HBV reactivation and/or CHB exacerbation higher in Tomotherapy than IMRT or other RT modalities?  There are no comparison study until now, and thus further clinical studies should be warranted.
  • 10. Low Radiation Dose Effect of Tomotherapy for Hepatocellular Carcinoma  The most common and important obstacle to conducting the clinical trial regarding Tomotherapy for HCC patients and applying it in clinical practice. - National Insurance do not cover the Tomotherapy for HCC patients, and thus patients’ burden for Tomotherapy is high. - To apply Tomotherapy for HCC patients as a common clinical practice, the research support for clinical trial comparing Tomotherapy with other RT modalities should be needed