A case report of exceptional clinical response to chemoradiotherapy and tyrosine kinase inhibitors in a patient with EML4-ALK fusion variant 1 non-small cell lung cancer

Abstract

Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion occurs in approximately 5% of non-small cell lung cancer (NSCLC) cases. Variants 1 and 3a/b are the most common EML4-ALK variants. Emerging evidence indicates that patients with variant 1 and those with variant 3a/b exhibit differential therapeutic responses. However, the National Comprehensive Cancer Network guidelines have not included the EML4-ALK fusion subtype in treatment decision-making to date. Herein, we report the case of a non-smoking 36-year-old female patient who was diagnosed with right lung adenocarcinoma in 2005 (cT1N3M0, IIIB) and received definitive chemoradiotherapy. The patient achieved a partial response, and her disease remained under control for 8 years. However, in May 2013, the patient was diagnosed with brain metastasis and underwent subsequent surgical resection, followed by postoperative brain radiotherapy and chemotherapy. Postoperative pathology confirmed ALK gene rearrangement, and next-generation sequencing performed in 2020 identified the EML4-ALK variant as variant 1. After progression-free survival lasting 4 years, new metastatic lesions were found in the patient's right lung, and she was administered crizotinib for 20 months. Due to a suspicious recurrence in the intracranial surgical margin area, as well as an unbearable gastrointestinal reaction to crizotinib, alectinib was later adopted. At the 7-month follow-up, positron emission tomography/computed tomography revealed a clinical complete response. This case of an NSCLC patient with EML4-ALK fusion variant 1 who exhibited an exceptional response to chemoradiotherapy and ALK inhibitors might broaden horizons in efforts to reveal the molecular mechanism of radiosensitivity in ALK-positive NSCLC and provide reference for further research regarding the optimal radiotherapy delivery dose and tyrosine kinase inhibitor selection.