Philadelphia- A trial involving two types of rare, malignant but treatable brain tumors shows that missing portions of two chromosomes can predict which patients will likely do better with therapy. The results, says senior author Walter J. Curran Jr., M.D., professor and chair of radiation oncology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, represents a paradigm shift in treating such tumors, known as gliomas.
Reporting last week in the Journal of Clinical Oncology, Dr. Curran and a team of American and Canadian researchers, in conjunction with the Philadelphia-based Radiation Therapy Oncology Group (RTOG), a federally-supported clinical trials organization, found that among 289 patients with either anaplastic oligodendroglioma or anaplastic oligoastrocytoma receiving either a combination of three chemotherapy drugs with radiation or radiation alone, those whose tumors had deletions in chromosome locations 1p and 19q tended to live nearly two and a half times longer than those patients without the missing chromosome portions. The "median survival time" of patients with the deletions was greater than seven years, meaning that one-half lived at least that long. For those with tumors lacking such deletions, one-half lived at least 2.8 years.
"Leukemias used to be the only cancers where chromosomal deletions were part of the treatment decision-making process," says Dr. Curran, who is also clinical director of the Kimmel Cancer Center at Jefferson. "Now, testing for such deletions in tumors should become mandatory for at least these types of gliomas."
In the study, 147 patients received the chemotherapy and radiation, while 142 were given only radiation. These rare, malignant tumors can be effectively treated, though seldom "cured" with surgery and radiation. One controversy, explains Dr. Curran, was whether or not adding chemotherapy early in the treatment will help individuals live longer. Most thought that chemotherapy would be beneficial.
However, the researchers found little difference in survival after three years between the two groups. While the group who received chemotherapy and radiation lived nearly a year longer without evidence of the cancer growing, nearly two-thirds of those patients experienced significant toxic side effects from the treatment.
Dr. Curran explains that there was some indirect evidence that showed that individuals with these types of tumors who had chromosomal deletions fared better. When the scientists compared the patients who had deletions and those who did not, they found stunning results.
"While finding unexpectedly that adding chemotherapy didn't help survival, equally important was the fact that we confirmed in a multicenter trial that the 1p and/or 19q deletion was highly predictive and prognostic of patient outcome, whether the patient received radiation and chemotherapy or radiation alone," Dr. Curran says. "Whether the patient had one or both deletions, the survival is much better."
In the same journal issue, a European team showed nearly identical results in a similar trial. Both trials showed such deletions were predictive of survival, Dr. Curran says.
"These two studies together have shifted the way we think of anaplastic or grade three gliomas," he says. "Up until now we've categorized them based on histologic appearance. We are now categorizing them according to chromosomal deletion status."
"That's actually more predictive than what they look like under the microscope," Dr. Curran says. "Those who have no chromosomal deletions have outcomes not all that different than the grade four glioblastomas, a much more deadly brain tumor. Those with both deletions are a totally different group of patients."
"Testing for chromosomal deletions should be a mandatory part now of the management of these patients based on these two trials."
"There has been a shift in clinical trial design in the last year," he says. "Now in patients with gliomas, we are going to apply this to future study design and probably treatment recommendations based on chromosomal deletions. I think more and more centers will begin to use such diagnostic genetics."
Journal
Journal of Clinical Oncology