Updates in the Management of Paraneoplastic Syndrome.

Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors. While recognizing specific syndromes can aid early cancer detection, overutilization of paraneoplastic assays in the absence of a classic syndrome can precipitate overdiagnosis and overtreatment. PNS involve autoantibodies targeting intracellular or extracellular antigens, with variable immunotherapy responses based on antigen type. Diagnosing PNS is challenging, requiring exclusion of other differential diagnoses. New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence. Patients with cell surface antibodies respond better to immunotherapies compared to those with intracellular antigen targets. Understanding PNS syndromes, serological markers, and oncological features guides management, which facilitates initiation of immunosuppression for PNS alongside treatment of the underlying neoplasm, thereby improving neurologic and oncologic outcomes. Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins. Second-line immunosuppressants like rituximab or cyclophosphamide may be necessary if initial treatments fail. Specific therapies vary based on antibody target. Here, we summarize the current approach to the investigation, diagnosis, and treatment of patients with suspected PNS.

A Review of the Molecular Determinants of Therapeutic Response in Non-Small Cell Lung Cancer Brain Metastases.

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.