CHICAGO — Prophylactic brain irradiation significantly reduces the likelihood of brain metastases in patients with non–small cell lung cancer, but offers no survival advantage and produces temporary declines in memory.
The lack of survival benefit runs contrary to a 5% improvement in survival observed with prophylactic cranial irradiation (PCI) in small cell lung cancer, in which the rate of brain metastasis is higher and PCI use is fairly common.
Among the 340 patients in the current phase III study, PCI significantly decreased the incidence of central nervous system metastases at 1 year, from 18% with observation alone after definitive lung therapy to 7.7%.
However, disease-free survival was 56.4% with PCI and 51.2% with observation; the overall survival rate was 75.6% and 76.9%, respectively.
There was significantly greater deterioration in both immediate and delayed recall in the PCI arm, compared with the observation arm, Dr. Benjamin Movsas reported on behalf of the Radiation Therapy Oncology Group (RTOG) 0214 study investigators at the annual meeting of the American Society for Radiation Oncology.
Immediate recall on the Hopkins Verbal Learning Test deteriorated 45% in the PCI arm vs. 13% in the observation arm at 3 months, improving to 19% vs. 5% at 6 months and 26% vs. 7% at 12 months.
All patients had stage III non–small cell lung cancer, and had completed a combination of chest radiation, chemotherapy, and/or surgery without progression. PCI was administered for about 10 minutes on 5 consecutive days for 3 weeks, totaling 30 Gy of radiation in 2-Gy units.
Prior studies in small cell lung cancer evaluated neurocognitive function in relatively small numbers of patients, from which it was concluded that there was no clear evidence of neurocognitive impairment with PCI, said Dr. Movsas, chair of radiation oncology at the Henry Ford Health System in Detroit.
However, a more recent randomized “sister” study of PCI in small cell lung cancer that was presented at the same meeting showed a significant increase in neurocognitive decline at 1 year in the higher-dose PCI arm, compared with the lower-dose PCI arm, he said.
Dr. Minesh Mehta, who was invited to discuss the RTOG 0214 study, remarked that the memory data were most intriguing, particularly the suggestion of recovery over time. A recent study also showed a similar biphasic pattern of memory recovery in patients who were treated with whole-brain radiation therapy, implicating an “early responding” cell population (J. Clin. Oncol. 2007;25:1260-6).
These declines in memory were “subtle” and occurred early, but also appeared to recover over time. Notably, PCI's effect on memory did not translate into sustained lower quality of life at any of the time points evaluated, said Dr. Mehta, an oncology professor at the University of Wisconsin in Madison.
Both investigators suggested that the current findings support the use of neuroprotective strategies in radiation patients. That could potentially include agents such as donepezil (Aricept) or radiation-sparing techniques, including sparing the hippocampus, which is involved in memory and is the site of only about 3% of brain metastases, Dr. Movsas said in an interview. RTOG 0614 (a phase III study) is testing the ability of memantine (Namenda) to reduce cognitive dysfunction from whole-beam radiation therapy.
Dr. Mehta noted that target accrual for the current study was 1,058 patients, but that it was forced to close early because of low accrual, resulting in a 50% loss of data on memory outcomes. He went on to note that the study population represents just 0.1% of the more than 50,000 stage IIIA/B non–small cell lung cancer patients who are diagnosed annually. Possible reasons for the low accrual could be lack of interest or faith in PCI for non–small cell lung cancer, concern about its toxicity, or lack of access by radiation oncologists to patients after thoracic radiotherapy.
“It is a severe indictment of the whole field,” he said.
Disclosures: The study was supported by grants from RTOG and the National Cancer Institute. Dr. Movsas reported no disclosures.
The overall survival rate was 75.6% with PCI and 76.9% without PCI.
Source Dr. Movsas