Small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3 and TP53 mutations after distinct responses to tyrosine kinase inhibitors: A case report

Background: Although anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have improved the survival rates of lung cancer patients with ALK fusion mutations, their effectiveness varies significantly across different subtypes. We report a case of small intestine metastasis in a lung adenocarcinoma patient with co-occurring echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variant 3 (V3) and tumor protein 53 (TP53) mutations after distinct responses to ALK-TKIs.

Case presentation: A 45-year-old woman was diagnosed with stage IV lung adenocarcinoma with brain metastasis. Next-generation sequencing revealed EML4-ALK V3 and TP53 co-mutations. After the initial treatment with ensartinib, the patient experienced intracranial disease progression. Radiation therapy (RT) was then administered. Despite good response to RT for the intracranial disease, the primary tumor enlarged. Thus, the patient was treated with oral ensartinib concurrent with chemotherapy, with a partial response in both the primary tumor and intracranial metastases. However, after three cycles of treatment, the patient discontinued chemotherapy because of acute kidney injury. Subsequent thoracic RT resulted in a partial response of the primary tumor; however, new brain and bone metastases were detected, prompting a switch to lorlatinib. The patient developed symptoms of intestinal obstruction 14 months after the initial diagnosis. Surgical intervention revealed a poorly differentiated metastatic lung adenocarcinoma of the upper jejunum. Genetic testing confirmed EML4-ALK V3 and TP53 co-mutations and high expression of programmed cell death-ligand 1. Despite pembrolizumab treatment, the patient's condition deteriorated, and she passed away.

Conclusion: We reported a rare case of small intestinal metastasis in a lung adenocarcinoma patient with concurrent EML4-ALK V3/TP53 mutations after distinct responses to ALK-TKIs in different lesions. Our findings revealed heterogeneity in ALK mutations and responses to ALK-TKIs, necessitating the close monitoring of genetic subtypes and associated mutations for tailored treatment strategies. Maintaining a heightened awareness of potential intestinal metastasis and vigilance in monitoring intestinal symptoms and abdominal metastases are pivotal for managing advanced lung adenocarcinoma.