Use of the functional imaging modalities, f MRI r CBV and PET FDG, alters radiation therapy 3-D treatment planning in patients with malignant gliomas

Background: Malignant gliomas present one of the most difficult challenges to definitive radiation therapy, not only with respect to local control, but also with respect to clinical functional status. While tumor target volume definitions for malignant gliomas are often based on CT and conventional MRI, the functional imaging modalities, echo planar r CBV (regional cerebral blood volume mapping) and 18F-fluorodeoxyglucose PET, are more sensitive modalities for the detection of neovascularization, perhaps one of the earliest signs of glial tumor initiation and progression. Methods: In order to address the clinical utility of functional imaging in radiation therapy 3-D treatment planning, we compared tumor target volume definitions and overall dosimetry in patients either undergoing co-registration of conventional Gadolinium-enhanced MRI, or co-registration of functional imaging modalities, prior to radiation therapy 3-D treatment planning. Fourteen patients were planned using 3-D radiation therapy treatment planning, either with or without inclusion of data on functional imaging. All patients received proton beam, as well as megavoltage x-ray radiation therapy, with the ratio of photon:proton optimized to the individual clinical case at hand. Both PET FDG and f MRI scans were obtained postoperatively pre-radiation, during radiation therapy, one month following completion of radiation therapy, and at three month follow-up intervals. Dose volume histograms were constructed in order to assess dose optimization, not only with respect to tumor, but also with respect to normal tissue tolerance (e.g., motor strip, dominant speech area, brainstem, optic nerves). Results: In 5 of 14 cases, functional imaging modalities, as compared with conventional MRI and CT, contributed additional information that was useful in radiation therapy treatment planning. In general, both fMRI rCBV and PET FDG uptake decreased during the course of radiation therapy. In 1 patient, however, fMRI rCBV increased, in an area outside of the highest dose target volume, during radiation therapy, resulting in a modification of radiation therapy treatment planning to include the high rCBV region. The patient experienced an unexpectedly short progression-free survival with evidence of recurrence on conventional scans, months after the region was recognized on functional scans. Conclusions: The functional imaging modalities, fMRI and PET FDG, render additional information of use in radiation therapy treatment planning of patients with malignant gliomas. More accurate tumor target volume determinations is one mechanism of increasing local control in malignant gliomas. The potential prognostic significance of elevated rCBV during radiation therapy warrants study on a larger prospective basis. The co-registration technique allows for the inclusion of regions of relatively high functional imaging parameters in the high dose target volume, while sparing functionally silent regions. In so doing, it allows for radiation dose escalations within the constraints of clinical tolerance