Tyrosine Kinase Inhibitor Therapy for Brain Metastases in Non-Small-Cell Lung Cancer: A Primer for Radiologists

A 73-year-old woman with EGFR-mutated NSCLC, which was initially treated with erlotinib for 9 months with an initial partial response of the primary lung tumor. The patient’s primary lung tumor then progressed, and the patient developed brain metastases. Repeat genetic analysis showed that the patient’s tumor now had a T790M mutation, so she was started on osimertinib. Images captured before (A–C) and 6 weeks after starting treatment with osimertinib (D–F) demonstrate a partial response to therapy of the left temporal (A and D), left frontal (B and E), and right occipital (C and F) enhancing brain metastases (arrows).

A 58-year-old man who was originally diagnosed with EGFR wild-type and was negative for EML4/ALK adenocarcinoma of the lung. After 3 years of traditional chemotherapy, the patient developed brain metastases. At that time, a biopsy of the patient’s pericardial metastasis came back positive for EML4/ALK fusion. Note small metastatic lesions (arrows) at the time of diagnosis of the brain metastases in the pons (A) and medial right orbital gyrus (D). After starting crizotinib, several of the patient’s brain metastases, including the lesions in the pons (B) and right medial orbital gyrus (E), increased in size (arrows), and there was development of new lesions such as the lesion in the left cerebellar hemisphere on B (arrow). The patient was then switched to alectinib, which resulted in a partial response in the brain with decreased size of previously identified lesions (arrows) (C and F).

A 50-year-old woman with NSCLC with ROS1-CD74 (Cluster of Differentiation 74) fusion. The patient was initially started on crizotinib. The primary lung tumor was responsive to therapy, but there was progressive disease in the brain. Given the numerous brain metastases, the patient elected to undergo local therapy with whole-brain radiation. The pretherapy images (A and B) demonstrate multiple peripherally enhancing lesions with surrounding hyperintense FLAIR signal consistent with surrounding vasogenic edema (arrows in A and B). The posttherapy images (D and E) demonstrate a decrease in the size and surrounding edema of the brain metastases (arrows in D and E). The patient was also able to remain on crizotinib for systemic therapy, given the favorable response in the chest (arrows in C and F).

A 58-year-old man with EGFR-mutant NSCLC treated with erlotinib. Pretreatment images (A and C) show a solidly enhancing left frontal brain metastasis measuring 17 mm in diameter. Posttreatment images (B and D) demonstrate the implications of different measurement methods on the response to therapy. The measurement on B includes both the cystic and solid components of the lesion and demonstrates an increase of 25% of the lesion size, consistent with progressive disease. The measurement on D was performed according to the RANO criteria specifications, which only include the enhancing nodular component of the lesion, which has a perpendicular diameter of at least 5 mm. This method of measurement calculated a decrease of 31%, which is consistent with partial response to therapy. This patient continued to have a response to therapy and further decrease in the size of this lesion.