Radiotherapy Immediately After Surgery Postpones Relapse, but not Death, in Patients With Low-Grade GliomasKey Words
Brain cancer,
glioma, radiotherapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Patients treated with radiotherapy immediately following surgery for low-grade glioma (a form of brain cancer) lived about two years longer before relapse than patients treated with radiotherapy only after their disease had begun to progress. However, the early treatment didn’t help patients live longer overall and it remained unclear what effect it had on their mental function and quality of life.
Source
The Lancet, published online August 18, 2005, and in print on Sept. 17, 2005 (see the journal abstract).
Background
Gliomas belong to one group of several types of primary brain tumors that begin in the glial cells surrounding and supporting the brain’s nerve cells. Doctors typically remove the tumor surgically, but this won’t cure the patient. Subsequent radiotherapy may extend the patient’s life but may also affect how well the brain works.
Since patients with malignant (high-grade) glioma may have as little as a year to live, radiotherapy and/or chemotherapy is usually given right after surgery. However, patients can expect to live five years or longer with low-grade gliomas. Almost all low-grade glioma patients will eventually receive radiation to the brain, but the question is when.
Radiotherapy carries the risk of neurocognitive (mental function) changes and threatens the quality of life. Some doctors take a “wait-and-see” approach, holding off on radiotherapy until clinical signs indicate that the cancer is progressing. Others advise radiotherapy shortly after surgery for two reasons. First, there is evidence that newer radiotherapy techniques reduce the risk of brain impairment and second, it appears that radiation lengthens the time before the cancer progresses.
The study described here is one of the few prospective randomized clinical trials to show evidence in support of that second benefit. Interim results have been known since 1998, but the findings are now long-term.
The Study
This trial was designed to test an active versus a conservative treatment approach following surgery for low-grade glioma. Between March 1986 and September 1997, 311 patients from 24 centers across Europe were randomly assigned to one of two groups. The 154 patients in the early radiotherapy group received radiation to the brain immediately after their surgery; the 157 patients in the wait-and-see group received further treatment only after their disease had begun to progress.
All patients had about the same level of neurocognitive function at the start of the trial. Those getting early radiation received five daily doses of 1.8 Gy each week for six weeks, a total of 54 Gy. Both groups were regularly examined for tumor progression (relapse), and treated as clinically appropriate when it occurred.
In 1998, an interim analysis showed that after a median follow-up period of five years, 49 percent of all patients had relapsed; there was a small advantage for the early radiation group in progression-free survival, and no difference in overall survival between the groups among the 30 percent who had died. Long-term results are described below.
The study was led by M.J. van den Bent, M.D., Ph.D. from the Erasmus University Hospital in Rotterdam, Netherlands.
Results
At the five-year mark, 55 percent of the patients receiving early radiation were progression-free, compared to 35 percent of the wait-and-see group. After almost eight years (93 months) of follow-up, researchers found that patients in the early radiation group were living about two years longer before relapse: a median of 5.3 years compared to 3.4 years for the wait-and-see group, a 41 percent advantage.
However, there continued to be no significant difference in overall survival: 7.4 years for the early radiation group as compared to 7.2 years for the wait-and-see group. Reflecting the fact that overall survival was comparable, patients in the radiotherapy group (who went longer before relapse) survived for only one year after relapse, compared to 3.4 years for controls.
Six patients in the early radiation group had to stop treatment because of side effects, but otherwise, the authors describe the toxic effects as “modest in general.” The authors report that neurological signs and symptoms did not differ significantly between the two groups after one year, but did not publish that data. The trial included an optional quality of life study, but not enough centers participated for a meaningful analysis.
Limitations
The pivotal question with low-grade glioma patients, said Howard A. Fine, M.D., chief of the Neuro-Oncology Branch of the National Cancer Institute’s Center for Cancer Research, is whether the benefit of radiotherapy immediately following surgery is worth the risk of brain impairment. “Unfortunately this trial doesn’t answer that question.”
If patients were to lose 20 IQ points as a result of brain changes, he said, their quality of life would be significantly harmed, yet they may show none of the toxicity symptoms that were tracked in this study. Lead author M.J. van den Bent and colleagues acknowledge “that the time to neurological deterioration might be a more appropriate endpoint than survival in future studies.”
There are many more high-grade than low-grade gliomas. These results apply only to the tumor types included in the low-grade glioma group. What’s more, the various low-grade gliomas may each respond differently to therapy, said Fine, though the current study did not address this. “The low-grade oligodendrogliomas, for example, are more likely to be treated with chemotherapy following surgery, than are the low-grade astrocytomas.”
Comments
“This trial is one of the few prospective studies we have in low-grade gliomas,” said Fine, who explained that these results have been generally known – and used to guide clinical practice – for several years. Citing improved, modern radiotherapy techniques, van den Bent asserted “there is no evidence that irradiation . . . might worsen the condition of the patient . . . and [it] prolongs progression-free survival,” though he adds that a wait-and-see policy is reasonable for patients who have no evidence of clinical progression.
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