Brain metastasis as exclusion criteria in extensive-stage small cell lung cancer trials: a trend over decades

Aim: To investigate the frequencies and trends of brain metastases (BMs) as exclusion criteria in extensive-stage small cell lung cancer (ES-SCLC) trials. Methods: We conducted a comprehensive search to identify prospective clinical trials in patients with ES-SCLC. PubMed searches were conducted with the key words "small cell lung cancer"and "extensive". The online archives of 20 oncology journals were also searched. Recent review articles in ES-SCLC were also investigated for additional articles. Eligible studies must have enrolled primarily ES-SCLC and been published in English. Studies involving brain/chest radiation and brain metastasis-specific trials were excluded. Studies were categorized into allowed/ undefined, conditional, or complete exclusion of BM. Results: In total, 491 published studies were identified by PubMed (240), journal websites (198), and review articles (53). Early publication year (1970-1999) and first-line/maintenance setting were associated with higher incidence of complete exclusion of cases with BMs (P < 0.0001 and 0.0233, respectively). Incidence of complete exclusion was 27% in the 1990s, and then decreased to 12% in the 2000s and 8% in the 2010s. Conclusion: A significant number of ES-SCLC trials continues to exclude patients with BM. Future studies need to ease eligibility regarding BM according to ASCO/Friends recommendations.