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Factors Affecting the Risk of Brain Metastases After Definitive Chemoradiation for Locally Advanced Non–Small-Cell Lung Carcinoma

From the Department of Radiation Oncology and the Division of Medical Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA.

Submitted July 31, 2000; accepted October 30, 2000. Address reprint requests to Theodore J. Robnett, MD, Department of Radiation Oncology, 2 Donner Bldg, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104; email: robnett{at}xrt.upenn.edu

PURPOSE: As therapy for locally advanced non–small-cell lung carcinoma (NSCLC) improves, brain metastases (BM) may become a greater problem. We analyzed 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 treated definitively with chemoradiation from June 1992 to June 1998 at the University of Pennsylvania were reviewed. Most patients (89%) received cisplatin, paclitaxel, or both. All had negative brain imaging before treatment. Posttreatment brain imaging was performed for suspicious symptoms. Incidence of BM was examined as a function of age, sex, histology, stage, performance status, weight loss, tumor location, surgery, radiation dose, initial radiation field, chemotherapy regimen, and chemotherapy timing.

RESULTS: Crude and 2-year actuarial rates of BM were 19% and 30%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (P < .04) versus stage II/IIIA. Histology alone was not significant (P < .12), although patients with IIIB nonsquamous tumors had an exceptionally high 2-year BM rate of 42% (P < .01 v all others). Examining treatment-related parameters, crude and 2-year actuarial risk of BM were 27% and 39%, respectively, in patients receiving chemotherapy before radiotherapy and 15% and 20%, respectively, when radiotherapy was not delayed (P < .05). On multivariate analysis, timing of chemotherapy (P < .01) and stage IIIA versus IIIB (P < .01) remained significant.

CONCLUSION: Patients with later stage, nonsquamous NSCLC, particularly those receiving induction chemotherapy, have sufficiently common BM rates to justify future trials including prophylactic cranial irradiation.

Presented in part at the Eighty-Second Annual Meeting of the American Radium Society, April 1-5, 2000, London, England, and in part at the Thirty-Sixth Annual Meeting of the American Society of Clinical Oncology, May 20-13, 2000, New Orleans, LA.

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