Tumor Resection and Gliadel® Wafers, Followed by Temodar® With Standard Radiation or GammaKnife® for New GBM
Tumor Resection and Gliadel® Wafers, Followed by Temodar® With Standard Radiation or GammaKnife® for New GBM
A glioblastoma (GBM) is the most common malignant primary brain tumor, yet it is not easy to
 control. Recent studies show that survival improves for patients who get aggressive surgery
 to remove a tumor before starting radiation (RT) and chemotherapy (chemo) treatment. Surgery,
 RT and chemo are part of regular cancer care for GBM. RT is usually done in daily doses 5
 days a week over about 6 weeks. Beams of radiation are aimed at the tumor site plus some of
 the normal brain tissue around the tumor area. GammaKnife® (GK) radiosurgery also delivers
 radiation but in a larger dose over one day. GK sends beams to a precise target (tumor
 location) and very little normal brain tissue that is nearby. This study will compare GK
 treatment to the usual RT treatment after surgery, and with chemo.

 We want to know:

 -  How well each treatment keeps the tumor from growing back.

 -  What the effects (good and bad) of the treatments are.

 -  How you rate your quality of life.

 -  How the treatment affects your ability to think, understand, reason, and remember.

 -  How you rate your ability to think, understand, reason, and remember.

 -  If using a certain type of MRI scan can show the difference between new tumor growth and
 changes caused by treatment.

 -  If certain features found in tumor cells can help doctors predict how tumors will
 respond to treatment.
The primary purpose of this study is to determine if single fraction GK radiosurgical
 treatment to the resection bed can achieve equivalent local control and survival for patients
 with GBM after GTR, Gliadel® implant and temozolomide therapy compared to patients receiving
 standard postoperative RT with temozolomide, but offer improved quality of life and preserve
 cognitive function.

 In Phase I, it is proposed that 20 patients with newly diagnosed glioblastoma multiforme
 (GBM) undergo gross total resection (GTR) with Gliadel® (carmustine) wafer implantation to
 the resection cavity at that time will be eligible for study. These patients will then
 receive Gamma Knife® (GK) radiosurgery to the resection cavity margin within 4 weeks
 following surgical resection and within 24 hours of starting temozolomide (Temodar®)
 induction therapy. Temozolomide (Temodar®) maintenance therapy would be administered for 12
 months.

 In Phase II, it is proposed that 60 patients with newly diagnosed glioblastoma multiforme
 (GBM) undergo gross total resection (GTR) with Gliadel® (carmustine) wafer implantation to
 the resection cavity at the time of initial resection will be eligible for study. These
 patients will then be randomized to either standard fractionated conformal radiation therapy
 (RT) or Gamma Knife® (GK) radiosurgery to the resection cavity margin. Fractionated RT would
 be administered with concurrent temozolomide Gamma knife® radiosurgery to the resection
 cavity margin will be administered within 24 hours of starting temozolomide induction
 therapy. Both the GK and RT will be administered within 4 weeks following surgical resection.
 Temozolomide (Temodar®) maintenance therapy would be administered to all patients in both
 arms of the study for 12 months.

 It is believed that all patients will benefit from enrollment in the study regardless of the
 treatment arm to which they are randomized. All patients will be receiving focally aggressive
 surgical resection with Gliadel® implant in addition to temozolomide for prevention of both
 focal and distant recurrence.

 Patients who are randomized to receive GK radiosurgical treatment to the resection bed margin
 may benefit from increased local control based on a prior non-randomized study. However these
 patients will be treated in a non-standard fashion and may be subjected to a higher incidence
 of focal radiation necrosis or a higher incidence of failure beyond the resection margin
 compared to standard patients.

 The GK treated patients however, will be spared the standard 6 weeks of RT postoperatively.
 It is hypothesized that those receiving GK will therefore have an improved quality of life
 with respect to having less fatigue, lack of hair loss and a decreased incidence of delayed
 cognitive decline associated with standard RT.
Inclusion Criteria:

 -  single enhancing lesion of the brain with MRI appearance consistent with GBM

 -  Must be appropriate for Gliadel® wafer implant

 -  Pathologic confirmation of GBM

 -  no gross residual tumor found on the immediate postoperative MRI scan

 -  Volumetric measurements of the resection cavity margin being < 50 cc

 -  Karnofsky performance status (KPS) 80% or better

 -  Must be able to undergo MRI imaging with gadolinium

 -  Willingness to have follow up visits at Barrow Neurological Institute(BNI)

 Exclusion Criteria:

 -  multi-focal tumors

 -  tumors which extend across the corpus callosum,

 -  residual nodular disease

 -  Tumors, with a contraindication to Gliadel® implant, such as an anticipated extensive
 ventricular opening resulting from complete resection.

 -  Tumor measuring greater than 50cc in volume (on post-operative scan) Volume < 50 cc if
 volume if a significant volume of eloquent tissue is included in the proposed
 treatment volume

 -  Unable to undergo MRI with gadolinium

 -  History of cancer within 2 years of GBM diagnosis (basal and squamous cell skin
 cancers are allowed)

 -  Patient is not willing to follow up at BNI