center of the tumor and its borders are computed. An entry point is identified 
and marked on the skull with a radiopaque marker. In cases in which the tumor 
is better defined by MRI scanning a MRI scan with an MRI compatible Leksell 
frame is used. 
b. Virus injection. After localizing the entry point the patient is returned to the 
surgery suite, and if necessary, anesthesia is induced. The patient is positioned 
for surgery and the Leksell frame is held with a Mayfield adapter. The scalp is 
scrubbed for 10 minutes with Betadine and painted with Betadine paint. An one 
inch incision is made in the scalp and a bur hole made at the entry point. The 
dura is coagulated with bipolar cautery. Bur hole ultrasound is used to confirm 
the localization of the lesion. The dura is opened and the surface of the cortex 
is coagulated and incised at a point on a crown of a gyrus. 
The virus is injected at a single site within the tumor using a fine, blunt-tipped 
needle with a side opening and a syringe that is capable of dispensing microliter 
quantities of the virus solution. After virus injection and withdrawal of the needle 
a piece of Gelfoam is placed over the dural leaflets. The bur hole is covered 
with a silicone bur hole cover. The galea is closed with interrupted inverted Vicryl 
and the skin with staples. 
B. Volume and amount of virus injected. 
Factors such as tumor size, location, and the preoperative neurological condition 
of the patient will determine the injectable volume which will be no more than 1 ml. 
The total amount of adenovirus will be no more than 1.5 x 10 9 particles. This trial will 
begin by testing the toxicity of a low dose of virus in 5 patients, observing them for 1 
month and, if no significant toxicity is observed, increasing the test dose in another 5 
patients and observing them for 1 month. Initially, 5 patients will be entered into the 
study and treated with a single injection of 1 x 10 8 particles of virus into a single site 
within the tumor. These patients will be observed for at least one month to detect 
toxicity. The External Clinical Advisory Committee will be asked to review the patients' 
records and advise, based upon Common Toxicity Criteria (Appendix D) whether an 
additional 5 patients should be treated with an escalated dose of virus. A progress 
report will be submitted to the Baylor Affiliates Review Board for Human Subject 
Research (ARB) for approval to continue. If a decision is made to increase the test 
dose and approval is given by the ARB another 5 patients will be treated with 5 x 10 8 
virus particles, observed for 1 month, and their records reviewed by the External 
Clinical Advisory Committee. If no significant toxicity is observed another 5 patients 
will receive 1.5 x 10 9 virus particles and will be observed. 
The sample size of five patients per dose of virus was based on standard 
statistical theory. It is designed to assure that there is a 95% probability that we would 
observe one patient with a toxic event out of a sample of five if the true rate of toxicity 
for the whole patient population is 45% or higher. 
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Recombinant DNA Research, Volume 20 
