Neoadjuvant Radiosurgery for Resectable Brain Metastases: Phase I/II Study

PRIMARY OBJECTIVES:

I. To determine the safety (risk of acute and long-term toxicities) of neoadjuvant
radiosurgery at escalating doses followed by surgical resection of brain metastases. (Phase
I)

II. To determine the local control of brain metastases treated with neoadjuvant radiosurgery
followed by surgical resection. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the rate of distant brain failure when brain metastases are managed with
neoadjuvant radiosurgery followed by surgical resection.

II. To estimate the rate of salvage surgery, whole brain radiation therapy (WBRT), or
stereotactic radiosurgery (SRS) for patients treated with neoadjuvant radiosurgery followed
by surgical resection.

III. To determine the rate of radiation necrosis/steroid dependency. IV. To determine the
radiobiologic impact of neoadjuvant radiosurgery for resected brain metastases.

OUTLINE: This is a phase I, dose-escalation study of radiosurgery followed by a phase II
study.

Patients undergo radiosurgery on day 0. Within 2 weeks, patients undergo surgical resection.

After completion of study treatment, patients are followed up at 1, 3, 6, 9, and 12 months.

Inclusion Criteria:

- Have a prior histologic diagnosis of cancer other than small cell lung cancer,
lymphoma, and germ cell histologies

- Magnetic resonance imaging (MRI) evidence of 1-4 brain metastases, with at least one
lesion > 20 mm and ≤ 50 mm in maximal diameter and determined to be appropriate for
SRS and gross total resection; all other brain metastases are appropriate for SRS

- Patient can have prior SRS to lesions other than the one planned for neoadjuvant SRS
and resection

- Patient must have a Karnofsky performance score of ≥ 70

Exclusion Criteria:

- Patient deemed medically unfit to undergo surgical resection of brain metastasis

- Prior whole brain radiotherapy

- Patient with contraindication for imaging with MRI

- Inability to participate in study activities due to physical or mental limitations

- Inability or unwillingness to return for all the required follow-up visits

- At the time of planning, unable to deliver 10 Gray (Gy) or less to optic nerve/chiasm

- Tumor located in the brainstem

- Imaging or cytologic evidence of leptomeningeal disease