Central Nervous System Involvement and the Role of Prophylactic Cranial Irradiation in Small Cell Lung Cancer

Abstract

This paper studies the frequency and manifestations of central nervous system (CNS) involvement and assesses the role of prophylactic cranial irradiation in small cell lung cancer (SCLC). All patients with confirmed diagnosis, admitted to our department within the last 15 years, were included. Patients were staged as having limited or extensive disease. Irradiation (40Gy/20f) was offered to all complete responders immediately after polychemotherapy. There were 200 patients (176 men and 24 women, median age 58), 68 with limited and 132 with extensive disease. Twenty (10%) presented with CNS involvement, 14 (7%) developed it during chemotherapy and 47 (23.5%) during follow-up. In total, 81 (40.5%) developed CNS involvement, and in 57 (28.5%) it was the main manifestation. There was no relation to disease extent or type of response to therapy. The most frequent site of metastases was brain (33%), followed by leptomeninges (6%), spinal cord (1.5%), and pituitary (1.5%). Of 79 complete responders, 51 (65%) received prophylactic cranial irradiation (PCI) and 28 (35%) did not. Frequency of CNS involvement was not significantly different (49% and 39%, respectively). Actuarial probabilities of developing CNS involvement were also not different. Nevertheless, 91% of complete responders without PCI relapsed only to CNS involvement, versus 48% with prophylactic irradiation. Cranioprophylaxis administration was followed by an improvement in overall survival, which was highly significant in limited disease. The actuarial survival of complete responders at two and four years was 46% and 26% with cranioprophylaxis versus 18% and 9% without, respectively. CNS involvement in SCLC not only is a frequent complication, but also its frequency increases with lengthening survival. The necessity of routine use of brain CT scan during staging and follow-up is questioned in view of the present data. Administration of cranioprophylaxis did not reduce the frequency of CNS involvement in our series apparently because while it significantly delays CNS involvement, it does not abolish it. Nevertheless, survival of complete responders was prolonged with cranioprophylaxis and very significantly so in limited disease. This last finding, although clear cut, must await confirmation from randomized trials.