A Phase I/II Study of Reirradiation for Recurrent Pediatric Brain and Spinal Cord Tumors and Primary Glioblastoma Multiforme Using the Photon Radiosurgery System

Central nervous system tumors account for approximately 20% of all childhood neoplasms. The treatment modalities used in the primary management of brain tumors are surgery, radiation therapy and chemotherapy. In recent years, considerable progress has been made in each of these therapeutic approaches. In spite of these advancements local tumor recurrence continues to be an important reason for treatment failure in these children. The local tumor recurrence rate varies according to the primary tumor type, treatment technique and tumor-stage at initial presentation. After conventional treatment, the local tumor recurrence rate ranges from 10% - 40% in tumors like medulloblastoma, craniopharyngioma, ependymoma and low-grade gliomas . However in aggressive tumors like glioblastoma multiforme the tumor recurrence rate in spite of the best modern treatments remains at 80-100%.

Radiation therapy has always played a key role in the management of adult and pediatric brain tumors. There has been considerable interest in treating brain tumors using stereotactic radiosurgery (SRS) using the Gamma knife or Linear accelerator and stereotactic radiotherapy (SRT). The goal of stereotactic treatment is to deliver a high dose of radiation with high geometric precision to a discrete tumor located in the brain. This is accomplished by the use of rigid immobilization skull frames and CT / MRI information for treatment planning and tumor targeting. Presently there are several therapeutic options available for children with recurrent brain tumors. Reirradiation has been employed in recurrent gliomas, medulloblastomas and ependymomas with stereotactic radiosurgery stereotactic radiation and brachytherapy . Following reirradiation, tumor control rates of 50-70% have been obtained. The radiosurgery doses used in children with radiation recurrent tumors have ranged from 10-24 Gy. The reirradiation has been generally well tolerated with retreatment complications like transient edema, cranial neuropathy or radiation necrosis observed in 10-15% of children. The results with high dose chemotherapy and bone marrow / stem cell transplantation in children with recurrent malignant gliomas, medulloblastoma and ependymoma have been disappointing with significant morbidity and mortality. Intraoperative radiation has also been utilized for the treatment of primary and recurrent brain tumors. In a report from Japan, 17 patients including two children with radiation recurrent malignant brain tumors were treated with intraoperative radiation to doses of 20 - 40 Gy. Intraoperative radiation was delivered using special applicators and electron beams. The radiation was delivered after tumor resection and doses of 23 - 40 Gy were delivered to depths of 0.5-1.5 cm. The median survival for patients with malignant gliomas and other tumors (ependymoma, oligodendroglioma) was 12 months and 51 months respectively. The two children with ependymoma were cured and are currently alive at 134 and 88 months after intraoperative radiation. Three patients developed symptomatic brain necrosis, two of them had relief of symptoms with surgery and one patient died. Three patients also developed postoperative meningitis. In another report from University of Nebraska Medical Center, 49 patients with glioblastoma multiforme were treated with interstitial Cobalt 60 high dose-rate irradiation to a dose of 20 Gy to the tumor with a 1-cm margin. The patients with no prior radiation therapy (Group I) received an additional 40 Gy of external irradiation. Nineteen of these patients (Group II) had been previously irradiated, and they received only interstitial irradiation. The Cobalt 60 probe was guided into the tumor using CT scans and a stereotactic frame. This treatment was well tolerated, one patient had a dural leak and another had a subdural hematoma. There were no cases of meningitis or radiation necrosis. The median survival for Group I and Group II patients were 7 months and 6 months respectively.

The photon radiosurgery system (PRS) is an intraoperative irradiation device that is capable of delivering high radiation doses to brain tumors. This system has recently been approved for clinical use by the Food and Drug Administration (FDA).

Photon Radiosurgery System (PRS)

The Photon Radiosurgery System (PRS) incorporates a miniature, 40 KeV x-ray source capable of delivering a prescribed radiation dose directly to a target volume. The PRS consists in part of an electron beam-activated x-ray source with a sealed vacuum tube that is 10 cm long and 3.2 mm in outer diameter that is designed for insertion into the body. This vacuum tube incorporates an electron beam target on the inside surface of its tip. When an accelerated electron beam is generated and sent down the tube to strike the target, Bremsstrahlung and line x-rays are emitted from the tip of the tube in a nearly isotropic pattern.