Factors affecting the risk of brain metastases after definitive chemoradiation for locally advanced non-small-cell lung carcinoma

Purpose: As therapy for locally advanced nonsmall-cell lung carcinoma (NSCL C) improves, brain metastases (BM) may become a greater problem. We analyze d our chemoradiation experience for patients at highest risk for the brain as the first failure site. Methods: Records for 150 consecutive patients with stage II/III NSCLC treat ed definitively with chemoradiation from June 1992 to June 1998 at the Univ ersity of Pennsylvania were reviewed. Most patients (89%) received cisplati n, paclitaxel, or both. All herd negative brain imaging before treatment. P osttreatment brain imaging was performed for suspicious symptoms. Incidence of BM was examined as a function of age, sex, histology, stage, performanc e status, weight loss, tumor location, surgery, radiation dose, initial rad iation field, chemotherapy regimen, and chemotherapy timing. Results: Crude and 2-year actuarial rates of BM were 19% and 30%, respectiv ely. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (P < .04) versus stage II/IIIA. Histology alone was not signifi cant (P < .12), although patients with IIIB nonsquamous tumors had an excep tionally high 5-year BM rate of 42% (P < .01 v all others). Examining treat ment-related parameters, crude and 2-year actuarial risk of BMI were 27% an d 39%, respectively, in patients receiving chemotherapy before radiotherapy and 15% and 20%, respectively, when radiotherapy wets not delayed (P < .05 ). On multivariate analysis, timing of chemotherapy (P < .01) and stage III A versus IIIB (P < .01) remained significant. Conclusion: patients with later stage, nonsquamous NSCLC, particularly thos e receiving induction chemotherapy, have sufficiently common BM rates to ju stify future trials including prophylactic cranial irradiation. J Clin Onco l 19:1344-1349. (C) 2001 by American Society of Clinical Oncology.