Frequency of actionable molecular drivers in lung cancer patients with precocious brain metastases

Clin Neurol Neurosurg. 2021 Sep:208:106841. doi: 10.1016/j.clineuro.2021.106841. Epub 2021 Jul 24.

Abstract

Brain metastases frequently occur during the course of disease in patients suffering from lung cancer. Occasionally, neurological symptoms caused by brain metastases (BM) might represent the first sign of systemic tumor disease (so called precocious metastases), leading to the detection of the primary lung tumor. The biological basis of precocious BM is largely unknown, and treatment options are not well established for this subgroup of patients. Therefore, we retrospectively analyzed 33 patients (24 non-small cell lung cancer (NSCLC)), 9 small cell lung cancer (SCLC)) presenting with precocious BM focusing on molecular alterations potentially relevant for the tumor's biology and treatment. We found five FGFR1 amplifications (4 adenocarcinoma, 1 SCLC) among 31 analyzed patients (16.1%), eight MET amplifications among 30 analyzed tumors (7 NSCLC, 1 SCLC; 26.7%), three EGFR mutations within 33 patients (all adenocarcinomas, 9.1%), and five KRAS mutations among 32 patients (all adenocarcinomas; 15.6%). No ALK, ROS1 or RET gene rearrangements were detected. Our findings suggest that patients with precocious BM of lung cancer harbor EGFR mutations, MET amplifications or FGFR1 amplifications as potential targeted treatment options.

Keywords: FGFR1; MET; Metastasis; NSCLC; Precocious.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Retrospective Studies
  • Survival Rate

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)