Prophylactic cranial irradiation in locally advanced non-small-cell lung cancer after multimodality treatment:: Long-term follow-up and investigations of late neuropsychologic effects

Purpose: Relapse pattern and late toxicities in longterm survivors were analyzed after the introduction of prophylactic cranial irradiation (PCI) into a phase II trial on trimodality treatment of locally advanced (LAD) non-small-cell lung cancer (NSCLC). Patients and Methods: Seventy-five patients with stage IIIA(N2)/111B NSCLC were treated with induction chemotherapy preoperative radiochemotherapy, and surgery. PCI was routinely offered during the second period of study accrual. Patients were given a total radiation dose of 30 Gy (2 Gy per daily fraction) over a 3-week period starting 1 day after the last chemotherapy cycle. Results: Introduction of PCI reduced the rate of brain metastases as first site of relapse from 30% to 8% at 4 years (P = .005) and that of overall brain relapse from 54% to 13% (P < .0001). The effect of PCI was also observed in the good-prognosis subgroup of 47 patients who had a partial response or complete response to induction chemotherapy, with a reduction of brain relapse as first failure from 23% to 0% at 4 years (P = .01). Neurapsychologic testing revealed impairments in attention and visual memory in long-term survivors who received PCI as well as in those who did no, receive PCI. T2-weighted magnetic resonance imaging revealed white matter abnormalities of higher grades in patients who received PCI than in those who did not. Conclusion: PCI at a moderate dose reduced brain metastases in LAD-NSCLC to a clinically significant extent, comparable to that in limited-disease small-cell lung cancer. Late toxicity to normal brain was acceptable. This study supports the use of PCI within intense protocols for LAD-NSCLC, particularly in patients with favorable prognostic factors. (C) 1999 by American Society of Clinical Oncology.