Introduction: The lack of a definitive imaging modality to distinguish post-treatment radiographic imaging changes (PTRIC), including pseudoprogression and radiation necrosis, from true tumor progression presents a major unmet clinical need in the management of GBM patients. At present there are no animal models of PTRIC
Methods: We developed a rodent model of PTRIC by intracranially implanting rats with either preirradiated (2-10 Gy) or nonirradiated glioma cells transfected with a constitutively active luciferase reporter. The rats were treated with or without temozolomide (TMZ) chemotherapy and rats implanted with nonirradiated cells were treated with focused tumor irradiation (2-10 Gy) to the implanted tumor cells and surrounding brain. Cell growth was monitored by bioluminescence imaging of the luciferase reporter and brain MRI measurement of tumor growth. Tumor histology was confirmed by light microscopy and immunohistochemistry.
Results: Animals implanted with irradiated cells did not produce PTRIC even when co-treated with TMZ. Rats considered to have tumor progression demonstrated steadily increasing luciferase activity coupled with increasing gadolinium-enhanced tumor volume and were found in animals receiving radiation doses less than 2Gy X3 without TMZ chemotherapy. Conversely, pseudoprogression was manifest by decreasing luciferase activity with increasing gadolinium volume over time found in tumors treated with 2Gy X3 and concurrent TMZ. Tumor histology was correlated with luciferase activity.
Conclusions: Our preliminary data suggests a potential model of pseudoprogression and/or radiation necrosis. This model needs to be further characterized with advanced imaging techniques including perfusion MR and multitracer PET imaging. We plan to use this model for future molecular and cellular studies to understand the cause and potential exploitation of these effects for better patient care.
Patient Care: Pseudoprogression is a major unmet clinical problem for patients with brain tumors. A model of pseudoprogression will allow for a better understanding of this perplexing problem
Learning Objectives: After this session, participants will be able to: 1: Discuss models of pseudo progression, 2. understand potential mechanism underlying imaging changes consistent with pseudo progression, 3. identify imaging modalities that might be useful in differentiating tumor progression from pseudo progression