SBIR-STTR Award

Chordomas and chondrosarcomas of the spine commonly extend into the spinal canal and impinge on the dura and cord. During resection, the lesion is peeled from the dura, resulting in positive margins. With current external beam radiation therapy, the tumor bed can be effectively treated. However, because the distance between the dura and cord surface is only 2 to 2.5 mm, dose to the dura must be limited to a suboptimal level. To increase the dose to the dura without over-irradiating the cord, it is proposed to intraoperatively deliver a supplemental dose using a radioactive beta-emitting plaque. With this plaque, dose to the cord surface would be only 10 percent of the dose to the dura and the dose to the mid portion of the cord would be substantially less. The additional dose delivered will markedly increase the probability of tumor control. The specific aim of this program is to develop a novel beta-emitting brachytherapy plaque for intraoperative irradiation of the dura. Two different beta-emitting radionuclides will be tested and their dosimetry will be evaluated for clinical utility. The results of this evaluation will lead to an optimum design of this plaque, which will be bench-tested in preparation for clinical trial.

Tumors of the thoracic and lumbar spine commonly extend into the vertebral canal and impinge on the dura, often infiltrating its superficial layers. This infiltration of sarcoma cells into the dura surface is a major cause of failure of aggressive surgery to obtain cure of these patients. With external beam radiation therapy, the majority of the tumor bed can be treated to effective dose levels. However, because of the close proximity of the cord, the dose to the dura must be limited to well below the desired treatment range. Therefore, to increase the dose to the dural surface without over-irradiating the cord, it is proposed to intraoperatively deliver a supplemental dose using a specially made beta-emitting radioactive device. The additional dose delivered will, at very small risk and potentially great advantage to the patient, markedly increase the probability of tumor control. During Phase I of this program, a "proof of principle" device was developed. On the basis of the successful results of the Phase I program, physicians at the Massachusetts General Hospital have clinically employed the "proof of principle" device to successfully treat seven appropriate patients with vertebral or paravertebral tumors, and assess patient tolerance and outcome under an IRB approved protocol. Radiation oncologists who have employed the existing plaque design have identified a number of features that would result in improved dose delivery. The specific aim of this program is to further develop this brachytherapy device beyond the "proof of principle" developed during the Phase I program. A customizable geometry plaque will be developed to improve the conformity of the dose distribution to the treatment target. This will include differential loading to improve dose drop-off, an improved method of incorporating anatomical features into the plaque configuration, and methods for manufacturing completed plaques before activation to facilitate achieving more complex geometries and reducing the radiation hazard. The resultant plaque and its dosimetry will be evaluated for clinical utility through a human trial. The results of this evaluation will lead to an optimum design of this device, in preparation for clinical use.

Thesaurus Terms:
beta radiation, biomedical equipment development, chordoma, human therapy evaluation, neoplasm /cancer radionuclide therapy, osteosarcoma, radionuclide implant, therapy design /development radiation therapy dosage, spinal cord injury, therapy adverse effect, vertebrae clinical research, human subject, medical implant science, patient oriented research, statistics /biometry