Control of intraocular metastases of non-small cell lung cancer with ALK rearrangement using ALK TKIS

Keywords

ocular metastasis - non-small cell lung carcinoma - EML4-ALK translocation - targeted therapy - choroidal metastasis

Introduction: Intraocular metastases from lung cancer are rare, with prevalence estimates ranging from less than 0.1% in symptomatic cases to 7.1% with systematic screening. Lung cancer, primarily non-small cell lung cancer (NSCLC), ranks as the second most common cause of ocular metastases, after breast cancer. ALK-rearranged NSCLC, which constitutes 2-7% of NSCLC cases, is particularly associated with brain metastases and affects younger, non-smoking patients. Despite its rarity, the prevalence and treatment responses of ocular metastases in ALK-rearranged NSCLC remain underexplored. This study reports three cases of ALK-rearranged NSCLC with ocular metastases treated with ALK TKIs. Case Summaries First Case: A 74-year-old female, initially treated with crizotinib, developed brain and ocular metastases. Transition to alectinib led to a durable response in both primary and metastatic sites. Second Case: A 55-year-old female presented with headaches and vision loss. Initially treated with crizotinib, she experienced ocular metastases and subsequent progression. Treatment with ceritinib and later lorlatinib resulted in significant improvement of visual acuity and disease control. Third Case: A 79-year-old male with advanced NSCLC and ocular involvement was initially treated with chemotherapy and lorlatinib. Lorlatinib proved effective, leading to a positive response in ocular and other metastatic sites.

Discussion: Ocular metastases are infrequent, often involving the choroid and presenting as unilateral and unifocal. Lung cancer is the second most frequent primary site of ocular metastases. Diagnostic differentiation between primary and metastatic ocular tumors is crucial, and imaging modalities play a significant role in this process. Advances in systemic treatments, particularly TKIs, have improved outcomes for patients with ocular metastases. ALK TKIs, like alectinib and lorlatinib, have shown efficacy in treating ocular metastases, with lorlatinib offering particularly promising results.

Conclusion: Ocular metastases, though rare, pose significant challenges in oncology. Advances in molecular testing and imaging are enhancing the differentiation of ocular neoplasms and metastases. For ALK-rearranged NSCLC, targeted therapies such as TKIs have improved patient outcomes, highlighting the importance of a multidisciplinary approach for effective management.

Corresponding author: Júlia Sousa Leal Franco (e-mail: [e-mail]).