Role of prophylactic cranial irradiation in prevention of central nervous system metastases in small cell lung cancer. Potential benefit restricted to patients with complete response

The records of 332 patients with small cell lung cancer treated on National Cancer Institute protocols between 1970 and 1980 were reviewed to evaluate the association of prophylactic cranial irradiation with the development of central nervous system metastases and survival. Stage of disease, involvement of liver, bone marrow, and bone, and the degree of response to systemic therapy were prognostic features significantly associated with the development of central nervous system metastases. Prophylactic cranial irradiation had no influence on leptomeningeal, spinal, or epidural metastases, but a significant reduction In intracerebral metastases was observed. There was also a statistically significant improvement in overall survival in patients who received prophylactic cranial irradiation (p < 0.005), with actuarial two-year survival of 18 to 20 percent in patients who received prophylactic cranial irradiation and 5 percent in patients who did not receive prophylactic cranial irradiation. Among patients who achieved a complete response to systemic combination chemotherapy, with or without chest irradiation, fewer central nervous system metastases developed in those who received prophylactic cranial irradiation, (25 percent versus 52 percent at two years) and they survived longer (38 percent versus 16 percent at two years) than patients who did not receive prophylactic cranial irradiation, although neither difference was significant after adjustment for prognostic features. Central nervous system metastases were the first and only site of relapse from complete remission in 17 percent of patients with a complete response who did not receive prophylactic cranial irradiation, whereas no patient who received prophylactic cranial irradiation had a relapse solely in the central nervous system. These findings emphasize the need for a prospective study in which patients with a complete response randomly receive or do not receive prophylactic cranial irradiation after stratification for prognostic features, in patients who did not achieve a complete response to systemic therapy, there was no significant association between prophylactic cranial irradiation and the development of central nervous system metastases. The short survival of these patients and the high rate of central nervous system relapse over time (to nearly 100 percent for two-year survivors) argue against the use of prophylactic cranial irradiation in this subset of patients.