Elevation of tumor mutation burden in ROS1-fusion lung adenocarcinoma resistant to crizotinib: A case report

Medicine (Baltimore). 2018 Dec;97(52):e13797. doi: 10.1097/MD.0000000000013797.

Abstract

Rationale: Although most of non-small cell lung cancer (NSCLC) patients with ROS1-fusions respond to crizotinb, acquired resistance eventually develop. The next-generations of ROS1 inhibitors have made some achievements, but the effects of immunotherapy have not been explored.

Patient concerns: A 44-year-old Chinese women presented with cough and dyspnea with a history of advanced lung adenocarcinoma.

Diagnosis: A PET/CT scan revealed primary tumors in bilateral lung lobes and multiple metastases in lymph nodes and bones. And ultrasound-guided left cervical lymph node biopsy revealed the pathological diagnosis was poor differentiated lung adenocarcinoma.

Interventions: The patients was started to be treated with 4 cycles of pemetrexed, carboplatin and bevacizumab, followed by one cycle of docetaxel, cisplatin and bevacizumab. As the ROS1-fusion was found by next generation sequencing, the patient received crizotinib treatment about 3 months.

Outcomes: After 5 cycles of chemotherapy, CT scans revealed increased size of bilateral lobe nodules indicative of progressive disease (PD). Then the patient received treatment of crizotinib and his progression-free survival reached 3 months. Due to uncontrollable disease progression, the patient expired.

Lessons: The genetic profile of NSCLC patients might be altered in various therapeutic processes. Thus, repeated genetic testing might be important at each progression. Moreover, immunotherapy might be a powerful weapon to overcome the resistance to Tyrosine kinase inhibitors (TKIs) in future.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib / therapeutic use*
  • Drug Resistance, Neoplasm / genetics*
  • Fatal Outcome
  • Female
  • Gene Fusion / drug effects
  • Gene Fusion / genetics
  • Humans
  • Mutation / drug effects
  • Mutation / genetics
  • Progression-Free Survival
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / drug effects
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / genetics*
  • Treatment Failure
  • Tumor Burden

Substances

  • Proto-Oncogene Proteins
  • Crizotinib
  • Protein-Tyrosine Kinases
  • ROS1 protein, human