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Prophylactic Cranial Irradiation in Operable Stage IIIA Non–Small-Cell Lung Cancer Treated With Neoadjuvant Chemoradiotherapy: Results From a German Multicenter Randomized Trial

Christoph Pöttgen, Wilfried Eberhardt, Andreas Grannass, Soenke Korfee, Georg Stüben, Helmut Teschler, Georgios Stamatis, Horst Wagner, Bernward Passlick, Volker Petersen, Volker Budach, Hans Wilhelm, Isabel Wanke, Herbert Hirche, Hans-Jochen Wilke, Martin Stuschke

From the Departments of Radiotherapy, Internal Medicine (Cancer Research), Neurology, and Diagnostic and Interventional Radiology; Institute for Biomathematics and Statistics, University of Duisburg-Essen; Department of Internal Medicine/Hematology/Oncology, Kliniken Essen-Mitte; Departments of Pulmonology and Thoracic Surgery, Ruhrlandklinik, Essen; Department of Pulmonology, Asklepios Klinik, Gauting; Department of Thoracic Surgery, University of Freiburg, Freiburg; Department of Internal Medicine (Med Klinik III), Technical University, Munich; and the Department of Radiotherapy, Charité Campus-Mitte, Berlin, Germany

Address reprint requests to: Christoph Pöttgen, MD, Department of Radiotherapy, University of Duisburg-Essen, Germany Hufelandstrasse 55, D-45122 Essen, Germany; e-mail: christoph.poettgen{at}uk-essen.de

Purpose: To investigate the role of prophylactic cranial irradiation (PCI) within a trimodality protocol (chemotherapy, chemoradiotherapy, surgery) for patients with operable stage IIIA non–small-cell lung cancer (NSCLC).

Patients and Methods: After mediastinoscopic staging, patients with operable stage IIIA NSCLC were enrolled to a German multicenter trial and randomly assigned to receive either primary resection followed by adjuvant thoracic radiation therapy (50 to 60 Gy; arm A) or preoperative chemotherapy (cisplatin/etoposide [PE]; three cycles) followed by concurrent chemoradiotherapy (PE plus 45 Gy; 1.5 Gy twice per day) and definitive surgery (arm B), respectively. Patients in arm B were scheduled to receive PCI (30 Gy; 2 Gy daily fractions).

Results: One hundred twelve patients were randomly assigned between November 1994 and July 2001. One hundred six patients were eligible (arm A: 51, arm B: 55), 90 males and 16 females, 50 with squamous cell, 16 with large cell, five with adenosquamous, and 35 with adenocarcenoma (median age, 57 years; range, 37 to 71 years). Forty-three patients received PCI as scheduled in arm B. Eleven long-term survivors (arm A: four; arm B: seven) underwent a comprehensive neuropsychological examination. PCI significantly reduced the probability of brain metastases as first site of failure (7.8% at 5 years v 34.7%; P = .02), the overall brain relapse rate was reduced comparably (9.1% at 5 years v 27.2%; P = .04). A slightly reduced neurocognitive performance in comparison with the age-matched normal population was found for patients in both treatment groups. No significant difference between patients who were treated with or without PCI could be noted.

Conclusion: PCI is effective in preventing brain metastases following this aggressive trimodality approach. Neurocognitive late effects are not significantly different between patients treated with or without PCI.

Supported by a grant from Deutsche Krebshilfe (project No. 70-2141).

Presented in part at the 23rd Annual Meeting of the European Society for Therapeutic Radiology and Oncology (ESTRO 23), Amsterdam, the Netherlands, October 25-28, 2004.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.