Kypho-Intra Operative Radiation Therapy (IORT) for Localized Spine Metastasis, Phase I/II Study

Approximately 20% of patients with spine metastasis present with unstable lesions, which
represent a common therapeutic dilemma in patients with advanced stage cancer and limited
survival time. Management necessitates spinal stabilization surgery such as laminectomy,
vertebroplasty, or kyphoplasty for mechanical back pain control and irradiation for the
underlying malignant process. Because of the limited survival time of patients with
metastatic cancer, novel, more convenient treatment concepts to shorten the overall treatment
time or hospitalization are desirable. We developed a novel approach to combine kyphoplasty,
a minimally invasive procedure, with a single dose of intraoperative radio- therapy (IORT)
for the treatment of spinal cord metastases.

Patients treated with Kypho-IORT will receive a prescribed dose of 8 Gy in 1 fraction from
The Intrabeam® Photon Radiosurgery System source. The target volume includes only the tumor.
The technique of the operation and the delivery of radiotherapy has been described and
published previously. TARGiT Academy training and requisite test cases have been completed
prior to enrolling subjects on this study. The balloon kyphoplasty, which is an advancement
of the vertebroplasty, is a treatment option for fractured vertebral bodies which utilizes
bone cement to provide needed support.

Outcome measures will include complete or partial pain relief or a stable response at the
index site requiring no increase in narcotic pain medication. Therefore, patients with
complete or partial pain relief will be considered responders. Patients with complete or
partial pain relief at the index site but a progressive response at the secondary site(s)
will be considered non-responders.

Quality of Life Measurements. It is hypothesized that quality of life (QOL) will improve
after Kypho-IORT due to rapid and durable pain control after spine treatment. In the current
study, we will measure the QOL [EORTC QLQ-C30 (version 3)], the Brief Pain Inventory (BPI),
ambulation , and steroid and narcotic use pre- and post-procedure at 1-week, 3-month,
6-month, 9-month, 1-year, and 2-year intervals. The involved spine will be imaged at 3-month
intervals up to one year, and at 2 years post-procedure.

All the evidence to date supports the description of the Intrabeam as delivering an accurate
and reliable dose. Physicists on site will be responsible for verifying the miniature x-ray
source is operational prior to use and setting up the parameters within the control console
software for treatment delivery. During the procedure, the control console monitors the
system for safe and accurate dose delivery.

Inclusion Criteria:

- Karnofsky Index ≥ 60.

- History/physical examination within 4 weeks prior to procedure.

- Imaging of the involved spine within 8 weeks prior to procedure to determine the
extent of the spine involvement.

- Numerical Rating Pain Scale within 4 week prior to procedure (score must be ≥ 5 for at
least one of the planned sites for spinal IORT.

- Neurological examination within 4 week prior to procedure to rule out rapid neurologic
decline.

- Spine Instability Neoplastic Score (SINS score) = ≤12.

- Negative serum pregnancy test within 4 weeks prior to procedure for women of
childbearing potential.

- Women of childbearing potential and male participants who are sexually active must
agree to use a medically effective means of birth control.

- The patient must have localized spine metastasis from the T5 to L5 levels by a
screening imaging study [bone scan, PET, CT, or MRI] (a solitary spine metastasis; two
separate spine levels; or up to 3 separate sites are permitted). Each of the separate
sites have a maximal involvement of ONE vertebral body. Patients can have other
visceral metastasis.

- Patients must provide study specific informed consent prior to study entry.

Exclusion Criteria:

- Spine instability due to a compression fracture; SINS score >12.

- Frank spinal cord compression or displacement or epidural compression within 3 mm of
the spinal cord

- Patients with rapid neurologic decline

- Bony retropulsion causing neurologic abnormality

- Patients allergic to contrast dye used in MRIs or CT scans or who cannot be
premedicated for the use of contrast dye