Risk factors and prognostic factors for pulmonary large cell neuroendocrine carcinoma with brain metastasis

Cancer Med. 2023 Feb;12(4):4087-4099. doi: 10.1002/cam4.5267. Epub 2022 Sep 20.


Background: As the studies regarding the brain metastasis (BM) of pulmonary large cell neuroendocrine carcinoma (LCNEC) are insufficient, the present research aims to describe the risk factors and prognostic factors that are related to cancer-specific survival (CSS) for LCNEC patients with BM.

Methods: The data of LCNEC patients between January 2010 and October 2018 were obtained from the SEER database. Binary logistic regression analyses were utilized to screen the possible risk factors related to BM. Prognostic factors for LCNEC patients with BM were indentified by Cox regression analyses. Moreover, a nomogram was established to predict the 6-, 12-, and 18-month CSS rates. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were utilized to assess the discrimination and reliability of the model. Clinical decision curves (DCAs) were used to evaluate the clinical benefits and utility of our model.

Results: Totally, 1875 patients were enrolled, with 294 (15.7%) of them having BM at diagnosis. Multivariate logistic regression analyses revealed that patients with age < 65 (odds ratio, OR = 1.564) and N2 staging (OR = 1.775) had a greater chance of developing BM. Age (≥ 65 vs. < 65: hazard ratio, HR = 1.409), T staging (T1 vs. T0: HR = 4.580; T2 vs. T0: HR = 6.008; T3 vs. T0: HR = 7.065; T4 vs. T0: HR = 6.821), N staging (N2 vs. N0: HR = 1.592; N3 vs. N0: HR = 1.654), liver metastasis (HR = 1.410), primary site surgery (HR = 0.581) and chemotherapy (HR = 0.452) were independent prognostic factors for LCNEC patients with BM. A nomogram prediction model was constructed by incorporating these factors. Using the C-index, calibration curves, ROC curves, and DCAs, we found that the clinical prediction model performed well.

Conclusion: We described the risk factors and prognostic factors that were associated with CSS for LCNEC patients with BM. The related nomogram was established and validated to help clinicians formulate more rational and effective treatment strategies.

Keywords: brain metastasis; large cell neuroendocrine carcinoma; nomogram; prognostic factors; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / therapy
  • Carcinoma, Neuroendocrine* / therapy
  • Dichloroacetic Acid
  • Humans
  • Lung Neoplasms* / therapy
  • Models, Statistical
  • Nomograms
  • Prognosis
  • Reproducibility of Results
  • Risk Factors
  • SEER Program


  • Dichloroacetic Acid