INDIVIDUALIZED DOSE ESCALATION IN VOLUME-EFFECT ORGANS

$394,638P01FY2007CANIH

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

The long-term goal of this proposal is to increase intrahepatic and lung tumor dose and intrahepatic tumor[unreadable] resectability by optimizing dose distributions within the tumor and individualizing assessment of normal[unreadable] tissue toxicity though innovative normal tissue imaging. This goal will be carried out through two specific[unreadable] aims. Aim 1 is to optimize the use of radiation therapy in the treatment of intrahepatic cancer. We will[unreadable] escalate high dose non-uniform radiation with the goal of increasing both local control and resectability.[unreadable] During treatment we will measure global changes in hepatic function using indocyanine green extraction,[unreadable] and regional changes in blood flow using dynamic contrast-enhanced CT scanning to assess early liver injury.[unreadable] These data will permit us to develop a model in which early changes in liver function can be correlated with[unreadable] liver toxicity after treatment. We also propose to use this model to develop a new protocol in which we reoptimize[unreadable] planning during the course of treatment to minimize normal liver injury. Aim 2 is to optimize the[unreadable] use of radiation therapy in the treatment of Stage III unresectable lung cancer. We will assess the optimal[unreadable] timing of chemotherapy and escalated radiation in a randomized phase II trial. During treatment we will[unreadable] measure changes in FDG-PET, to assess early tumor response, and full ventilation-perfusion SPECT[unreadable] scanning and pulmonary function tests to assess early lung injury. These data will permit us to develop a[unreadable] model in which early changes in FDG-PET imaging and lung function can be correlated with tumor response[unreadable] and lung toxicity, respectively, after treatment. We also propose to use this model to develop a new protocol[unreadable] in which we re-optimize planning during the course of treatment to maximize tumor control and to minimize[unreadable] normal tissue injury. We anticipate that these studies will increase the local control and resectability of[unreadable] intrahepatic cancers and the local control of lung tumors while individualizing and, thus, minimizing the risk[unreadable] of normal tissue injury.

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