It is known that partial volumes of liver can tolerate a tumoricidal dose of therapeutic radiation if sufficient normal liver is spared. However, the exact relationship between dose, volume of normal liver spared, and risk of complication has not been established. The development of 3D radiation treatment planning technology has allowed for a reduction in the volume of normal liver irradiated (more accurate targeting) and provided quantification of the volume of normal liver treated. A mathematical model to predict the normal tissue complication probability (NTCP) for an individual treatment plan has been developed as well. We have utilized 3D technology and an NTCP model to safely escalate the dose of focal hepatic radiation in prior and current phase I clinical trials conducted over the past 10 years. Local control and survival data are encouraging. However, the parameters of the model currently utilized are based on data with substantial uncertainties related to liver motion and patient setup.
In specific Aim 1, we plans to complete a phase one study to determine the maximum safe dose of radiation for focal liver malignancies, while accounting for positional uncertainties in the NTCP parameter definitions, allowing delivery of significantly higher doses of radiation than was possible using our earlier approach. Current planning techniques require the inclusion of a margin of normal liver for these uncertainties, to ensure adequate target coverage.
In Specific Aim 2, we hypothesize that reduction of liver motion together with investigation of patient setup will allow for treatment of smaller target volumes, which will subsequently permit an increase in the dose delivered without increasing the risk of RILD (radiation induced liver disease).
In Specific Aim 3 we will evaluate outcome of patients treated on a phase II trial, to determine if application of improved estimates of parameters for the NTCP model, and reduction in the volume of normal liver irradiated will allow safe delivery of higher radiation doses resulting in improved survival rates in patients with intrahepatic malignancies that warrant further study in a phase III setting.
| Cao, Yue; Alspaugh, Jonathan; Shen, Zhou et al. (2006) A practical approach for quantitative estimates of voxel-by-voxel liver perfusion using DCE imaging and a compartmental model. Med Phys 33:3057-62 |
| Dawson, Laura A; Ten Haken, Randall K (2005) Partial volume tolerance of the liver to radiation. Semin Radiat Oncol 15:279-83 |
| Ben-Josef, Edgar; Normolle, Daniel; Ensminger, William D et al. (2005) Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies. J Clin Oncol 23:8739-47 |
| Dawson, Laura A; Biersack, Matthew; Lockwood, Gina et al. (2005) Use of principal component analysis to evaluate the partial organ tolerance of normal tissues to radiation. Int J Radiat Oncol Biol Phys 62:829-37 |
| Thomas, Emma; Chapet, Olivier; Kessler, Marc L et al. (2005) Benefit of using biologic parameters (EUD and NTCP) in IMRT optimization for treatment of intrahepatic tumors. Int J Radiat Oncol Biol Phys 62:571-8 |
| Dawson, Laura A; Lawrence, Theodore S (2004) The role of radiotherapy in the treatment of liver metastases. Cancer J 10:139-44 |
| Rosu, Mihaela; Dawson, Laura A; Balter, James M et al. (2003) Alterations in normal liver doses due to organ motion. Int J Radiat Oncol Biol Phys 57:1472-9 |
| Dawson, Laura A; McGinn, Cornelius J; Lawrence, Theodore S (2003) Conformal chemoradiation for primary and metastatic liver malignancies. Semin Surg Oncol 21:249-55 |
| Dawson, Laura A; Normolle, Daniel; Balter, James M et al. (2002) Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53:810-21 |
| Balter, James M; Brock, Kristy K; Litzenberg, Dale W et al. (2002) Daily targeting of intrahepatic tumors for radiotherapy. Int J Radiat Oncol Biol Phys 52:266-71 |
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