title: Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment: risk factors analysis.
abstract: BACKGROUND
  Brain metastases (BM) are frequent sites of initial failure in patients with locally advanced nonsmall cell lung cancer (LAD-NSCLC) undergoing multimodality treatments (MMT). New treatment and follow-up strategies are needed to reduce the risk of BM and to diagnose them early enough for effective treatment.
  
  
  METHODS
  The incidence rate of BM as the first site of recurrence in 112 patients with LAD-NSCLC treated with the same MMT protocol was calculated. The influence of patient, disease, and treatment-related factors on the incidence of BM and on the time-to-brain recurrence (TBR) was analyzed.
  
  
  RESULTS
  BM as the first site of failure was observed in 25 cases (22% of the study population and 29% of all recurrences). In 18 of those cases, the brain was the exclusive site of recurrence. Median TBR was 9 months. The 2-year actuarial incidence of BM was 29%. Central nervous system (CNS) recurrence was more common in patients younger than 60 years (P = 0.006) and in whom bulky (> or = 2 cm) mediastinal lymph nodes were present (P = 0.02). TBR was influenced by age (P = 0.004) and by bulky lymph node disease (P = 0.003). Multivariate analysis confirmed the prognostic role of age, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance.
  
  
  CONCLUSIONS
  Our study confirmed a high rate of BM in patients with LAD-NSCLC submitted to MMT. Most of these CNS recurrences were isolated and occurred within 2 years of initial diagnosis. Age younger than 60 years was associated with an increased risk of BM and reduced TBR, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. Although our data require further validation in future studies, our results suggest that additional trials on prophylactic cranial irradiation and on intensive radiologic follow-up should focus on these high-risk populations.
authors.affiliation: Department of Radiochemotherapy, IRCCS San Raffaele, Via Olgettina 60, 02132 Milan, Italy. ceresoli.giovanni@hsr.it
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Chiesa
authors.forename: Angelo
authors.initials: A
authors.lastname: Carretta
authors.forename: Stefano
authors.initials: S
authors.lastname: Schipani
authors.forename: Paolo
authors.initials: P
authors.lastname: Passoni
authors.forename: Angelo
authors.initials: A
authors.lastname: Bolognesi
authors.forename: Piero
authors.initials: P
authors.lastname: Zannini
authors.forename: Eugenio
authors.initials: E
authors.lastname: Villa
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016019:Survival Analysis