Stereotactic Radiosurgery (SRS) for Brain Metastasis

Recently, several large randomized studies have shown that in patients with limited brain
metastases, whole brain radiation can be safely deferred when treated with SRS and close
surveillance. In light of this, most of such patients are now treated with SRS alone without
WBRT. However, the SRS doses set by Radiation Therapy Oncology Group (RTOG) 90-05 continue to
be applied to patients without previous cranial irradiation.

The potential insufficiency of current SRS dose for long-term tumor control is of pressing
concern. The advances chemotherapy has led to an improvement in overall survival in many
patients with metastatic cancer, including malignancies often associated with brain
metastases, such as lung (40-50%) and breast (15%). As these patients survive longer, more
patients may develop brain metastases and the current dose of SRS may not be adequate to
control the brain metastases for the duration of their survival. In fact, there is evidence
that the control rate declines with time after SRS, and after 3 years, the local control rate
may be only about 60%. In the case of brain metastases from relatively radio-resistant
melanoma, the reported 12-months local control rates for SRS range from 52% to 75%. More
potent SRS doses could lead to improved long-term control of brain metastases.

Inclusion Criteria:

- Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ
cell cancer, or unknown primary tumor.

- Radiographic evidence by MRI of brain metastasis. (If patient is unable to tolerate
contrast, an MRI without contrast is acceptable)

- All brain metastases must be outside the brain stem (midbrain, pons and medulla).

- Patient must have 10 or less brain metastases.

- The maximum diameter of any lesion must be less than 4.0 cm.

- Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any
targeted agents are allowed provided that:

- Systemic therapy was administered > 7 days before SRS

- Radiation was not to the brain.

- Surgery to the brain was > 7 days prior to SRS and there remains at least one
additional brain metastasis that can be targeted with SRS

- Age ≥ 18 years.

- Eastern Cooperative Oncology Group (ECOG) Performance Score of 2 or better.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of protocol therapy.

- A female of child-bearing potential is any woman (regardless of sexual
orientation, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 12 consecutive months
(i.e., has had menses at any time in the preceding 12 consecutive months).

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

- Patients who have had chemotherapy, immunotherapy or any targeted therapy within 7
days prior to anticipated SRS treatment date or those planning for systemic therapy
within 7 days following the protocol treatment.

- Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.

- Patients with leptomeningeal metastasis.

- Patients with a contraindication to MRI such as implanted metal devices or foreign
bodies or severe claustrophobia.

- Patients with life expectancy < 3 months.

- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia.

- Psychiatric illness/social situations that would limit compliance with study
requirements.

- Patients must not be pregnant at the time of SRS treatment.