In the battle against malignant brain tumors, dual implantation of radioactive seeds and chemotherapy wafers following surgery showed promising results in a study led by specialists at the Neuroscience Institute at the University of Cincinnati (UC) and University Hospital.
The study, published in the February issue of the Journal of Neurosurgery, revealed that patients treated with simultaneous implantation of radioactive seeds and chemotherapy wafers following removal of glioblastoma multiforme (GBM) experienced longer survival compared with patients who had implantation of seeds or wafers alone.
The study was the first ever to explore the combination treatment in patients suffering from recurrent GBM. The early phase trial involved 34 patients, all of whom underwent the same treatment. No patients received a placebo. The study's purpose was to assess the safety and effectiveness of the highly localized, combination therapy.
The median survival was 69 weeks, and nearly a quarter (eight) of the study's patients survived two years. In comparison, patients with recurrent GBM who undergo conventional treatment (chemotherapy) have a median survival of approximately 26 weeks.
"Treatment of recurrent GBM presents a major challenge to neurosurgeons and neuro-oncologists," said investigator Ronald Warnick, MD, chairman of the Mayfield Clinic and professor of neurosurgery at UC. "Glioblastoma is an aggressive, highly malignant tumor with unclear boundaries. Because of its diffuse nature, surgeons are unable to remove it completely, and it regrows in the majority of patients. Our aim is to find a way to keep the infiltrating glioblastoma cells from growing into adjacent, healthy tissue."
Because most GBM tumors recur within two centimeters of the initial tumor margin, Warnick and his team have focused their efforts on highly localized treatment.
Previously they studied the implantation of permanent, low-activity iodine-125 seeds following the surgical removal of the tumor. The seeds, housed in a titanium casing filled with iodine-125 (a radioisotope of iodine) are the size of grains of rice. The seeds are left in the brain cavity permanently, and radiation is delivered for six months.
Other institutions have studied implantation of chemotherapy wafers, which are the size of a nickel. The wafers contain BCNU (carmustine), a standard form of chemotherapy. The wafers are placed along the surface of the brain following removal of the tumor.
Combining radiation seeds and chemotherapy wafers was a logical next step, Warnick said. The combination of seeds and wafers "appears to provide longer survival" compared with studies of seeds and wafers alone, he said, and "disease progression also seems to be further delayed."
Warnick cautioned that the effectiveness of the combination therapy is not definitive, because the study did not include a control group.
In the most notable downside to the dual therapy, brain tissue death developed in nearly 25 percent of patients and appeared to be higher than in treatment with seeds or wafers alone. The tissue death was treated successfully with surgery or hyperbaric oxygen therapy, however, and did not affect survival.
Future studies will involve using a combination of seeds and wafers to treat patients newly diagnosed with GBM, Warnick said.
In addition to Warnick, study co-investigators included John Breneman, MD, a radiation oncologist with the Neuroscience Institute and a professor of radiology at UC; Robert Albright, MD, a neuro-oncologist who practices in Cincinnati and Northern Kentucky, and Borimir Darakchiev, MD, a former resident in the UC's neurosurgery department.
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