Responses to crizotinib and disease monitoring with circulating tumor cells in lung adenocarcinoma patient with MET exon 14 skipping mutation: A case report

Abstract

Rationale: Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation was a targetable alteration in nonsmall-cell lung cancer (NSCLC), and the MET inhibitor of crizotinib had the most efficacy among all the targeted drugs. Most of the cancer-related deaths are associated with metastasis. Circulating tumor cells (CTCs) have been a valuable biomarker in assessing metastasis. Recent experiences suggested that CTCs detection may help improve diagnosis and predict prognosis for patients with NSCLC. However, few literatures have reported the CTCs detection based on the (MET) exon 14 skipping, which are positive in NSCLC patients.

Patient concerns: The patient, a 69-year-old Chinese male, with a 50 years history of smoking. Because of the cough, the patient went to the hospital and found the upper right lung tumor and the right supraclavicular lymph node enlarged. He was worried that it was cancer.

Diagnoses: The patient was performed biopsy of the right clavicle lymph node metastasis on October 12 and sent the tissue specimen for pathological evaluation. Finally, the patient was diagnosed to be with a pT3N3Mx stage IIIC lung adenocarcinoma.

Interventions: The patient began to take orally crizotinib 250 mg twice a day for the medical therapy after lymph node biopsy. At the same time, the CTCs were detected to observe the prognosis of the patients.

Outcomes: Compared with the first CTCs result, the second test revealed a decrease in the amount of CTCs, while the mesenchymal CTCs have increased, indicating the possibility of distal metastasis.

Lessons: This is the first proof that CTCs can be quantitatively assayed by MET exon 14 skipping mutation, which demonstrates the clinical response to crizotinib. More cases should be reported and further evaluation for treatment options and prognosis evaluation is necessary.

Figure 1

Response to crizotinib treatment. (A) Chest CT scans before crizotinib treatment showing a space-occupying mass with multiple lymph node metastases. (B) Chest CT scans after 4 weeks of crizotinib treatment showing a 42.4% reduction of the lung tumor, meeting RECIST partial response criteria.

Figure 2

Diagram of MET c.3025–3028+5del mutation leading to exon 14 skipping.

Figure 3

The number of single CTCs. CTCs test on October 13, before crizotinib treatment revealed 10 CTCs in total including none mesenchymal CTCs. CTCs test on December 4, after crizotinib treatment revealed 8 CTCs in total including 6 mesenchymal CTCs.