CHICAGO–Prophylactic cranial radiation reduced the risk of brain metastases by more than 50% in non-small cell lung cancer patients, researchers reported here at the American Society for Radiation Oncology.
However, the radiation treatment did not extend patients’ lives and significantly increased the risk of short- and long-term memory loss, the randomized controlled trial showed.
Quality of life did not differ between patients who received radiation and those who did not, said the lead researcher of the study presented as Abstract #2, Benjamin Movsas, MD, the Herndon Chair in Oncology Research and Chairman of Radiation Oncology at Henry Ford Health System in Detroit.
“This is the first randomized study to analyze neurocognitive and quality-of-life factors for non-small cell lung cancer patients who undergo prophylactic cranial irradiation,” Dr. Movsas said. “With better, more targeted treatments, more lung cancer patients are surviving longer and therefore are at increased risk of developing brain metastases. This study provides key information that will lead to a better understanding of the true risks versus benefits of this intervention.”
In the Radiation Treatment Oncology Group study, 340 eligible patients with Stage III non-small-cell lung cancer that had not progressed after initial treatment were randomized to prophylactic cranial irradiation (30 Gy administered in 2-Gy fractions) or to observation from September 2002 to August 2007.
The treatment involves external-beam radiation therapy to the entire brain to try to sterilize potential tumor cells that are so small that they cannot be seen on the most sensitive imaging tests, Dr. Movsas explained.
All patients underwent three neurocognitive assessments: the Mini-Mental Status Exam, Activities of Daily Living Scale, and the Hopkins Verbal Learning Test. Quality of life was assessed using two instruments developed by the European Organization for Research and Therapy in Cancer.
A total of 18% of patients who were not treated with prophylactic cranial irradiation later developed brain metastases. In contrast, only 8% of those who underwent the procedure developed brain metastases.
“It would require treating about five patients with radiation to prevent one brain cancer metastases,” Dr. Movsas said.
The groups had similar scores on both quality-of-life assessments and two of the three tools used to assess neurocognitive function. Patients in the prophylactic cranial irradiation arm demonstrated significant declines in short-term and long-term recall on the Hopkins Verbal Learning Test at one year compared with patients in the observation group.
Dr. Movsas said that patients and doctors would consider the prophylactic treatment a “slam dunk,” except that overall, patients undergoing the prophylactic radiation did not achieve any improvement in survival, and experienced persistent neurocognitive adverse outcomes.
“People did have memory problems such as being unable to recognize family or friends, and there were subtle deficits in memory and cognition that persisted for at least a year,” he said.
‘The Whole Picture’
“It's critical for studies to report on not only patient outcomes, such as local control and survival, but also on how the treatments affect the patients, including neurocognition and quality-of-life factors,” Dr. Movsas said. “We need the ‘whole picture’ in order to be able to accurately assess and discuss treatment options with our patients.”
ASTRO President Anthony L. Zietman, MD, the Jenot W. and William U. Shipley Professor of Radiation Oncology at Harvard Medical School, said of the study, “With small-cell lung cancer, we routinely give cranial radiation, as these patients are at a high risk of brain metastases, and they live longer. With non-small cell lung cancer, the picture is not so clear. This kind of study helps us to customize therapy. Cranial radiation does reduce brain metastases, but at a price. The physician has to weigh the pros and cons for each individual patient.”
The study was supported by grants from the National Cancer Institute.