Small-cell cancer of the lung generally has a poor prognosis; the median duration of survival is 12 to 20 months. The five-year survival rate in patients who initially respond to chemotherapy and radiation is about 20 percent. About 10 percent of patients have brain metastasis at the time of diagnosis, and 50 percent have brain metastasis if still alive in two years. The brain is suspected to be a “sanctuary” for subclinical metastases in patients with small-cell lung cancer, a notion that prompted researchers to study cranial irradiation as a way of preventing clinically evident disease. Studies in the past 20 years have sought to find out if such treatment improved the prognosis in patients with small-cell lung cancer. Aupérin and other members of the Prophylactic Cranial Irradiation Overview Collaborative Group performed a meta-analysis to see if prophylactic cranial irradiation produced a survival benefit.
Clinical trials were included that involved patients with small-cell lung cancer who were in complete remission after induction chemotherapy and had no evidence of brain metastasis. The patients had been randomized to receive prophylactic cranial irradiation or no cranial irradiation (control group). Published and unpublished trials were considered. Additional data obtained were patient sex, age, initial stage of disease, performance status at time of randomization, details of induction therapy and information on recurrence of disease, including local and regional metastasis. The primary end point of the study was overall survival, defined as time from randomization until death from any cause. Secondary outcomes were disease-free survival and cumulative incidence of brain metastasis, as well as other metastases.
Seven trials were included in the meta-analysis. Data were reviewed on 987 patients: 526 who had received prophylactic irradiation and 461 control subjects. The median age was 59 years, and about 76 percent were men. The amount of time from induction to randomization was variable, although most of the patients received radiation treatments within six months of receiving chemotherapy.
After three years, 846 patients in the seven studies had died. A total of 20.7 percent of the treated patients was still alive, compared with 15.3 percent of patients in the control group. These results correspond to an absolute increase in survival of 5.4 percent and a mean reduction in the risk of death of 16 ± 6 percent. Regarding secondary end points, prophylactic cranial irradiation resulted in an absolute decrease in brain metastasis of 25.3 percent (33.3 percent in treated patients versus 58.6 percent in control patients). This corresponds to a 54 ± 7 percent relative reduction in the risk of brain metastasis. Higher doses of radiation produced a greater decrease in brain metastasis but did not affect overall survival.
The authors conclude from this meta-analysis that prophylactic cranial irradiation produces a survival benefit in patients with small-cell carcinoma of the lung. It also improves overall and disease-free survival. They believe it should become part of standard therapy for patients whose disease is in remission after induction chemotherapy.