Prophylactic Cranial Irradiation for Patients with Small-Cell Lung Cancer in Complete Remission

Reviewers: Li Liu, MD
Source: The New England Journal of Medicine, Volume 341, No 7 (August):476-484, 1999

Background

The brain is one of the most common sites for metastasis in small-cell lung cancer. Of patients who achieve a complete remission after chemotherapy +/- thoracic irradiation, in the absence of cranial irradiation, the probability of brain metastasis can be as high as 50% in 2-year survivors. Brain metastases are sometimes the only site of clinical relapse in complete responders and are often clinically devastating. Prophylactic cranial irradiation (PCI) significantly reduces the incidence of brain metastases. However, whether PCI improves overall survival remains debatable. This is a report of a meta-analysis on 7 randomized trials in an attempt to answer this question.

Methods

Only the trials that enrolled patients with histologically confirmed small-cell lung cancer in complete remission who were randomly assigned to receive PCI or no PCI, were included. Primary end point was overall survival, and analysis was on an intent to treat basis.

Results

A total of 17 trials were identified. Among them 7 (including 1 unpublished trial) were eligible for analysis with a total of 987 patients. PCI dose was generally 24-40Gy in various fractionations. Twenty-five patients received 8Gy/1 fraction. The median follow up was 5.9 years (range from 3.5 to 18.5 years).

• PCI resulted in a significant survival benefit as compared with the control group, with a pooled relative risk of 0.84 (p=0.01), corresponding to a 5.4% increase in the rate of survival at 3 years (15.3% in the control group vs. 20.7% in the treatment group).
• PCI also significantly increased brain metastasis-free survival and disease-free survival (p<0.0001 for both). There was a significant trend (p=0.01) toward decreased risk of brain metastases with earlier PCI.

Discussion

PCI not only significantly reduced the risk of brain metastasis among patients with small-cell lung cancer in complete remission, but also improved overall and disease-free survival. Partial or non-responders may not derive the equivalent benefit from PCI as compared with complete responders. The optimal dose and timing of PCI remain unclear at this point and should be studied in future trials.