Researchers from MIT and the Beth Israel Deaconess Medical Center have begun clinical trials of a new type of brain cancer therapy. The experimental form of radiation therapy is called boron neutron capture therapy, or BNCT.
BNCT has shown promising results in the ongoing FDA-approved Phase I clinical trials. To date, 11 patients suffering from glioblastoma multiforme, a highly malignant form of brain tumor, or brain metastases from melanoma, a malignant form of skin cancer that can spread to other parts of the body including the brain, have been given BNCT. Five patients with metastatic melanoma have also been given BNCT in a Phase I trial.
"The promise of BNCT is the selective irradiation of tumor cells in a way that is not achievable using current forms of conventional radiation," said Dr. Paul M. Busse, one of the principal investigators of the BNCT project and director of the clinical aspects of the research. "So far, our expectations have been met with respect to the scientific goals of the clinical trials, and two patients with melanoma have had complete regression of this disease -- a very encouraging beginning." He is associate chairman of the Joint Center for Radiation Therapy and an assistant professor at Harvard Medical School.
The research team has been directed by MIT Professor of nuclear engineering Otto K. Harling and Dr. Robert G. Zamenhof, a radiological physicist at Beth Israel and associate professor of radiology at Harvard Medical School.
If BNCT proves successful in controlling highly malignant brain tumors and peripheral melanoma in the future, it could be applicable to many other types of cancer which are at present not easily controlled by conventional therapeutic techniques.
THE BNCT PROTOCOL
Patients are first infused intravenously with a special drug which is tagged with a nonradioactive isotope called boron-10. The boron-10-tagged drug concentrates preferentially in tumor cells, where it lies in wait. The patients are then exposed to a specially designed beam of "epithermal neutrons" at the MIT research reactor in Cambridge.
When the beam is turned on, it passes through a "collimator" in the ceiling of the medical irradiation room and then through the patient's scalp and skull into the brain. When the brain is exposed to the epithermal neutrons, the boron-10 atoms absorb, or capture, the neutrons that pass close by. Once they have captured a neutron, the boron-10 atoms become unstable and immediately release highly energetic subatomic particles called alpha particles, which travel only short distances.
The success of BNCT relies on both the ability of the boron-10 atoms in the tumor cells to capture neutrons and the alpha particles' brief, precise and hopefully deadly targeting of the tumor cells' nuclei -- the most critical structures within the tumor cells. Because of the alpha particles' very short range, researchers expect that if the particles start their flight inside a tumor cell, they will mostly damage the tumor cell and not the normal brain cells nearby.
Before a judgement can be made regarding the efficacy of BNCT for brain tumors, the Phase I study must be completed so the maximum possible safe level of radiation can be established. This is because in BNCT, as in conventional forms of radiotherapy, the best therapeutic results are obtained when the patient is irradiated at a dose which is close to the tolerance level for their healthy tissue. However, even at lower radiation doses that have so far been delivered, tumor responses have been observed.
An interdisciplinary team of scientists and engineers from Harvard and MIT and previously Tufts-New England Medical Center devoted years of intense research effort to develop this experimental therapy to the stage where these clinical trials could be initiated. All three principal investigators work closely together to coordinate the clinical trials as well as ongoing research in various aspects of neutron capture therapy.
A version of this article appeared in MIT Tech Talk on February 11, 1998.