Randomized Trial Comparing Radiosurgery With vs Without Whole Brain Radiotherapy

Before treatment starts, patients will have a complete history (including details of previous
chemotherapy, radiotherapy, and surgery for systemic disease). Patients will have a complete
neuropsychological exam and will have their Karnofsky Performance Score (KPS) figured out.
Seven cognitive function tests and a quality of life (QOL) questionnaire will be given to the
patients as well. It will take about 40 minutes to complete the QOL questionnaire.

Patients in this study will be randomly picked (as in the toss of a coin) to be in one of two
treatment groups. Patients in one group will receive immediate whole brain radiation therapy.
Patients in the other group will hold off on radiation and just be closely observed. There is
an equal chance of being in either group.

All patients will receive radiosurgery treatment to the known metastases (1-3 lesions) at the
beginning. All participants will be followed with serial diagnostic and functional MRI.
Experimental functional imaging will be used to evaluate short-term memory and picture
recognition as well as blood flow within the brain.

Formal neuropsychological testing will also be performed at each follow-up interval. Patients
must come back at 4 months for neuropsychological testing. Patients will be seen for
follow-up with neuropsychological evaluation, as well as diagnostic/function MRI at 1 , 2 , 4
, 6 , 9 , 12 , 15 , and 18 months and then every six months from then on. Each visit will
require about 40 minutes of time.

Cost information related to protocol treatment and subsequent therapies will be tracked and
collected for cost analysis between the two treatment groups.

Patients who did not receive whole brain radiation and develop recurrent disease shall
receive treatment based on the number of lesions. If there are greater than 2 lesions, whole
brain radiation will be given. If there are 1-2 lesions, patients will be randomly assigned
to a local treatment (surgery or radiosurgery) or whole brain radiation therapy. Further
recurrences in patients having not yet received whole brain radiation will be given this
treatment at the time of recurrence.

The expected length of the study is 3.8 years with 6 months follow-up following the end of
the study. Thus, the length of participation can range from 6 months for patients enrolling
at the end of the study to over 4 years for patients enrolling at the beginning.

This is an investigational study. A total of 152 patients will take part in the study. All
will be enrolled at MD Anderson.

Inclusion Criteria:

1)age 18 and older at time of registration. 2) recursive partitioning class (RPA) I or II.
3) 1 to 3 newly diagnosed brain metastases 4) must be eligible to have all lesions treated
by SRS as determined by the radiation oncologist on the basis of location and size. 5)MRI
with contrast must be performed with 1 month of registration. 6)Signed informed consent
form approved by the IRB agreeing to randomization .

Exclusion Criteria:

1) prior WBRT 2) prior resection of brain metastasis, SRS or Gamma knife. 3) > 3 brain
metastases present on MRI 4) lymphoma, small cell lung cancer, leukemia, germ cell tumors.
5) leptomeningeal disease. 6) unknown primary.7) RPA Class III (i.e. KPS < 70) 8)
pregnancy.

Post-entry exclusion: No post-entry exclusions will be allowed after registration has
occurred. All randomized patients will be included in the analysis and those lost to
follow-up will be assigned the least favorable outcome (recurrence, death).