Combined Radiation Seed, Chemotherapy Wafer Implants Show Potential for Treating Brain Tumors

In the fight against malignant brain tumors, dual implantation of radioactive seeds and chemotherapy wafers following surgery showed promising results in a recent study.

The study, published in the February 2008 issue of the Journal of Neurosurgery, revealed that patients treated with simultaneous implantation of radioactive seeds and chemotherapy wafers following removal of a glioblastoma multiforme (GBM) tumor experienced longer survival compared with patients who had implantation of seeds or wafers alone. The study, led by specialists from the Neuroscience Institute at the University of Cincinnati (UC; OH, USA) and University Hospital, was the first ever to explore the combination treatment in patients suffering from recurrent GBM. The early phase trial involved 34 patients, all of who underwent the same treatment. No patients received a placebo.

The study's purpose was to evaluate the safety and effectiveness of the highly localized, combination therapy. The median survival was 69 weeks, and nearly one-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 neurooncologists,” said investigator Ronald Warnick, M.D., 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 2 cm of the initial tumor margin, Dr. 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, according to Dr. Warnick. The combination of seeds and wafers "appears to provide longer survival” compared with studies of seeds and wafers alone, and "disease progression also seems to be further delayed.”

Dr. 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 disadvantage of the dual therapy, brain tissue death developed in nearly 25% of patients and appeared to be higher than in treatment with seeds or wafers alone. Tissue death was treated successfully with surgery or hyperbaric oxygen therapy, and did not affect survival.

Future research will involve using a combination of seeds and wafers to treat patients newly diagnosed with GBM, according to Dr. Warnick.


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Neuroscience Institute at the University of Cincinnati