Improving Outcome in Malignant Pleural Mesothelioma (MPM) Using Pulsed-Protracted External Beam Radiation (PERT) and Intrapleural Delivery of Stem Cells.

摘要

Malignant Pleural Mesothelioma (MPM) survival remains poor despite multidisciplinary treatment involving aggressive surgery, chemotherapy and adjuvant radiotherapy (RT). The large RT treatment volume, and concerns about the proximity of radiosensitive normal structures, restricts the tumoricidal dose of radiotherapy that can be delivered. These concerns limit the effectiveness of adjuvant RT. To overcome this limitation, an entirely novel radiation treatment schedule in combination with post-RT delivery of bone marrow-derived stem cells was examined to improve tumor control and facilitate normal tissue proliferation. A rat model of MPM was used. The RT regime consisted of 10 pulses of low-dose RT (0.2 Gy) using a 3 minute inter-pulse interval (PERT) to a daily dose of 2 Gy. The inclusion of post-RT stem cell therapy is to repopulate normal tissues in the RT field. RT tumor response was assessed by microPET/CT (Positron emission tomography/computed tomography) imaging. In vitro cell survival data was used to demonstrate PERT was not inferior to standard RT (2 Gy single continuous treatments). In vivo, The surgical procedure has been established and tumor model has been established and tumor volume determined by in situ with F18-FDG. Unexpected technological problems with respect to the microPET scanner have slowed the imaging aspect of the project. However, to date, we have demonstrated that RT is effective at reducing MPM tumor growth in vivo; and this is associated with recruitment of hematological stem cells. Studies are currently on-going to determine if PERT is superior to standard RT in MPM.