Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Metastases in the brain are a common hallmark of advanced stages of the disease, contributing to a dismal prognosis. Lung cancer can be broadly classified as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). NSCLC represents the most predominant histology subtype of lung cancer, accounting for the majority of lung cancer cases. Recent advances in molecular genetics, coupled with innovations in small molecule drug discovery strategies, have facilitated both the molecular classification and precision targeting of NSCLC based on oncogenic driver mutations. Furthermore, these precision-based strategies have demonstrable efficacy across the blood–brain barrier, leading to positive outcomes in patients with brain metastases. This review provides an overview of the clinical features of lung cancer brain metastases, as well as the molecular mechanisms that drive NSCLC oncogenesis. We also explore how precision medicine-based strategies can be leveraged to improve NSCLC brain metastases.

Ponatinib is a third‐generation BCR:ABL1 tyrosine kinase inhibitor used in selected patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL), particularly those with T315I mutations, or disease resistant, or those intolerant to prior tyrosine kinase inhibitors. Although effective, ponatinib has been associated with arterial occlusive events. We report a 63‐year‐old man with Ph+ ALL who, while receving ponatinib, developed a myocardial infarction requiring quadruple coronary artery bypass grafting, followed by symptomatic intracranial arterial stenosis necessitating superficial temporal artery to middle cerebral artery bypass. Despite multiple cardiovascular risk factors, the chronology of progressive coronary and cerebral vascular disease raised suspicion for ponatinib‐associated vasculopathy, although causality cannot be established. To our knowledge, this is the first reported case of sequential coronary and cerebral surgical revascularization occurring during ponatinib therapy. This case highlights the importance of careful cardiovascular surveillance, multidisciplinary management, and individualized risk‐benefit assessment in patients treated with ponatinib.

"CLO24-085: Precision Medicine Drivers in Non–Small Cell Lung Cancer Brain Metastases" published on 05 Apr 2024 by National Comprehensive Cancer Network.

Chronic lymphocytic leukemia is a hematologic malignancy characterized by overproduction of monoclonal B cells. Most people diagnosed with CLL do not immediately undergo treatment due to treatment guidelines. There are few cases of paraneoplastic syndrome associated CLL. This case is unique in that it is a paraneoplastic KLHL 11 antibody associated CLL. The patient is a 68-year-old female who originally presented to the hospital with abdominal pain and upon further imaging was found have retroperitoneal lymphadenopathy. After further studies including flow cytometry, she was diagnosed with CLL. She failed trials of Pembrolizumab, ibrutinib, and Obinutuzumab due to side effects. The patient then started experiencing excessive fatigue, bilateral temporal headache, nausea, vomiting, vertigo, tremor of bilateral upper extremities, and head bobbing. Her brain imaging was negative for acute abnormalities. Lumbar puncture was positive for CLL cells and the paraneoplastic panel came back positive with KLHL 11 antibodies. The patient’s symptoms continued to persist and her tremor and dysmetria continued to worsen. Due to the positive paraneoplastic panel, the patient was started on intravenous immunoglobulin but did not experience improvement. She was then trialed on intravenous methylprednisolone and still experienced no relief. She then underwent plasma exchange. Finally, she was given rituximab infusions with slight improvement. Her imaging remained negative for signs of leptomeningeal enhancement. Given the patient’s symptoms, negative brain imaging, and positive paraneoplastic panel, it was determined that the patient developed an irreversible paraneoplastic syndrome related to her CLL versus possible leptomeningeal disease. There are a few cases of paraneoplastic syndrome associated CLL involving paraneoplastic phemphigus, hypercalcemia, and nephrotic syndrome. This case is unique in that her symptoms presented with an ataxic syndrome with positive KLHL11 antibodies. It is important to be aware that some cases of CLL can present with unique paraneoplastic syndromes.