Inaccurate tumor delineation due to limitations of conventional MR-based planning may contribute significantly to the dismal prognosis for gliomas. Conventional magnetic resonance imaging (MRI) currently represents the gold standard for guiding surgical debulking and radiation therapy (RT) with regions appearing abnormal on T2/FLAIR used to define the extent of tumor infiltration and regions of contrast enhancement on T1-weighted images defining regions of high tumor density. However, MRI enhancement can be inaccurate, as approximately 1/3 of non-enhancing tumors prove to be high-grade gliomas, and conversely some low-grade tumors and non-tumoral pathologies are known to enhance. While infiltrative disease is known to extend beyond areas of contrast enhancement, tumor delineation is difficult in this region due to the non-specific nature of T2 signal abnormalities which can also include gliosis and peri-tumoral edema. We hypothesize that the poor overall and progression-free survival are, in part, due to poor targeting with standard MR-based RT planning, which likely misses areas of aggressive tumor. These significant deficiencies highlight a critical need to utilize more accurate imaging-based techniques to guide surgical and RT target delineation of tumor boundaries and regions of aggressive disease. Radiolabeled amino acid tracer's shows promise for identifying aggressive disease and better differentiation between tumor and normal brain tissue. Our preliminary data suggest that 18F-DOPA PET imaging can delineate regions of high density tumor that extend beyond regions of T1 contrast enhancement and beyond T2/FLAIR abnormalities. Moreover, in non-contrast enhancing lesions seen on MRI, regions of high 18F-DOPA PET uptake correlated with highest grade of tumor. As improved survival in gliomas is associated with extent of resection, these data suggest that 18F-DOPA PET imaging may provide critical anatomic information about tumor extent not discernible on conventional MRI and could significantly improve the outcomes for patients with gliomas treated with surgery and/or radiation. Thus, this application will evaluate the impact of 18F-DOPA PET on neurosurgical targeting and RT through two clinical trials. PET thresholds for distinguishing high grade, low grade, and non-malignant portions of brain tissue will be derived from pathology correlations with stereotactically acquired specimens, and the impact of PET guidance on neurosurgical and radiotherapy planning will be evaluated through comparisons of MR vs. MR + PET treatment volumes as well as prospective evaluation of clinical outcomes in comparison with current practice. The utility of 18F-DOPA PET imaging also will be compared against state-of-the-art perfusion and diffusion tensor MRI. Ultimately, more accurate delineation of tumor extent through 18F-DOPA PET imaging may lead to increased survival associated with more complete surgical resections and more accurate targeting of radiation therapy.
Inaccurate tumor delineation due to limitations of conventional MR-based planning may contribute significantly to the dismal prognosis for gliomas. The focus of this application is to test whether 18F-DOPA PET imaging could be used to more accurately identify tumor boundaries and regions of the most aggressive disease for neurosurgical and radiotherapy planning. If successful, this approach would benefit surgical patients, as resection extent is associated with improved survival in both high and low grade gliomas, as well as RT patients through reduced local recurrences and improved progression free and overall survival.
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