A Pilot Study Evaluating Minimized Time to Beam Hypofractionated IMRT With PET-Assisted Target Definition in Patients With High Grade Gliomas

A Pilot Study Evaluating Minimized Time to Beam Hypofractionated IMRT with PET Assisted Target Definition in Patients with High Grade Gliomas

BACKGROUND INFORMATION Standard Treatment High grade gliomas (HGG) comprise the vast majority of primary brain tumors. With conventional treatment, tumor recurrence and subsequent patient death is expected in all but a small minority of patients. Conventional treatment consists of maximal surgical debulking followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy. Typically the radiation therapy is given in 2 Gy fractions to a total dose of 60 Gy to the planning target volume (PTV).

What is the Optimal PTV? Currently it is not know what target volume constitutes the optimal PTV for an individual patient with a HGG. With conventional MRI-based target definition, a common practice is to draw a gross tumour volume (GTV) to include the contrast enhancing lesion seen on T1C images. An additional uniform margin of approximately 1.5 cm is added to address clinically occult glioma cells and create the clinical target volume (CTV), plus an additional 0.5 cm to create the final PTV. This practice is based on pattern of recurrence studies. In these studies, 80-90% of the HGGs tended to recur within 2 cm of the original T1C enhancing lesion. The addition of a uniform 2 cm margin to the initial GTV dramatically increases the volume of apparently normal brain irradiated, and the volume of brain irradiated is a principal determinant of subsequent radiation toxicity. By using positron emission tomography (PET) imaging to better characterize which regions harbour glioma cells, we hope to be able to minimize the size of the uniform margins applied to the GTV, and thus produce a more optimized PTV for each patient.

PET Imaging For this pilot study we will be using novel PET agents including F19AZA and C11 Methionine to assist in the construction of a more patient optimized PTV. The volumes constructed based on MRI reflect the underlying anatomy or structure of the tumor. On the other hand the volumes constructed base on PET imaging reflect the underlying physiology and thus will be referred to as the biological target volume (BTV) to distinguish it from the MRI base GTV. The clinician will then use the complementary information provided by the GTV and BTV to construct a composite CTV, and this will be grown with a uniform 0.5 cm margin into the PTV. The PET imaging will be carried out under a separate research protocol submitted by nuclear medicine, and the patient will need to sign an informed consent for each agent used. At the investigators discretion, the patient will be given the choice to undergo imaging using the full complement of PET agents or a selected subset of these agents.

IMRT 3D conformal RT (3D CRT) is the standard treatment technique used to treat HGGs at many centres. With the advancement of IMRT techniques, clinicians are able to deliver more sophisticated RT plans. With these more sophisticated approaches clinicians should be able limit the volume of apparently uninvolved brain encompassed in the high dose treatment volume. In our recent protocol we gained experience using helical tomotherapy-base IMRT. In the current protocol, we plan to use Linac-based IMRT. One of the advantages of Linac-based IMRT over helical tomotherapy is that the plan may include non-coplanar beams. This additional degree of freedom is expected to result in better plan conformation. Also, Linac-based IMRT plans can be added to the conformal plan of phase I and thereby adjusted accordingly.