UPTON, NY - Medical researchers at the U.S. Department of Energy's Brookhaven National Laboratory (BNL) have begun the next phase in their clinical trial of an experimental radiation therapy for brain tumors. The first patient was treated on May 29, the second on June 10, and the third on June 18.
The new phase is BNL's third round of treating patients with a radiation treatment called boron neutron capture therapy, or BNCT. It is being performed under a protocol sanctioned by the U.S. Food and Drug Administration (FDA), using a higher tumor radiation dose than had been used before.
Thirty brain tumor patients from all over the nation have come to BNL to be treated with BNCT since September 1994. All have had an especially lethal form of brain cancer known as glioblastoma multiforme, which strikes about 7,000 Americans each year and kills its victims in an average of less than a year despite conventional radiation treatments and chemotherapy.
Results from the first round of 15 BNCT patients showed that the treatment allowed many of the patients to enjoy a better quality of life in their remaining months than they would have had with the daily sessions of conventional treatment that glioblastoma patients normally undergo. On average, the patients survived just over a year. Two are still alive, one with no signs of tumor recurrence. The trial also confirmed that the initial radiation dose could be delivered safely, the main aim of the first round.
The researchers say it is too early to assess results from the second round that began in May 1996, in which an increased dose of radiation was used. Eleven of the 15 patients treated are still alive.
Now, in the third round of their trial, the researchers have increased the dose of the tumor-seeking compound that helps enhance the tumor-killing effect of radiation while sparing healthy brain tissue. Besides the Brookhaven team, physicians from the University Medical Center at Stony Brook and the Beth Israel Medical Center are also involved.
BNCT takes advantage of carefully aimed neutron radiation from BNL's Brookhaven Medical Research Reactor, a small reactor that operates at a thermal power level of 3 megawatts, about 1,000 times less than a commercial power reactor.
BNCT: A Tumor-Selective Radiation Therapy
Many cancer patients, including most glioblastoma patients, routinely receive radiation therapy as part of their treatment. But while the radiation beam can be aimed at a tumor's location, it cannot help but affect nearby non-cancerous cells as well.
BNCT aims to give tumor tissue a higher dose of radiation than healthy tissue through the use of an injected compound containing the element boron and the amino acid phenylalanine. Because cells use phenylalanine to build proteins, the boron is carried piggyback to the more rapidly growing cells: cancer cells. As a result, much more boron collects in cancerous cells than in non-cancerous ones.
BNCT is given in a single session lasting about an hour. When the patient's tumor is exposed to neutron radiation from the reactor, the boron inside the cells "captures" passing neutrons. The resulting interaction causes a fission reaction inside the tumor cells, enhancing the radiation's effect on tumor tissue while sparing healthy tissue.
The Origins of BNCT
Today's BNCT trials trace their roots to studies conducted in the late 1950s at BNL and the Massachusetts Institute of Technology (MIT), which has a small reactor similar to Brookhaven's Medical Research Reactor. At that time, patients were given BNCT at the Brookhaven Graphite Research Reactor and the MIT facility.
But the trials in the 1950s failed to produce satisfactory results. The lack of clinical success drove the researchers back to the laboratory bench, to develop better ways of delivering both the boron and the neutrons. Years of study, mainly at BNL, finally perfected the use of the boronphenylalanine used in today's trials. Meanwhile, physicists and engineers have improved the neutron-delivery system at BNL's medical reactor.
BNCT On Other Fronts
In 1996, physicians at MIT received FDA permission to begin treating glioblastoma patients. Earlier BNCT studies at MIT had focused on melanoma, another disease that often stymies even the most aggressive therapies. Other institutions in the U.S., Europe and Japan are also employing or exploring the usefulness of the therapy.
Brookhaven scientists are now engaged in laboratory studies to explore the potential of BNCT for other cancers, including lung cancer and leukemia. Theoretically, BNCT could work on any cancer in which tumor cells are growing and dividing rapidly enough that they take up the boron-phenylalanine faster than non-cancerous cells.
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Patients, their families and physicians can obtain more information about
the clinical trial by calling BNL's BNCT Office at (516) 344-3684.