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Earlier care relied mainly on surgery and radiation because systemic therapies were assumed to have limited central nervous system (CNS) activity. Over the last two decades, targeted agents with improved CNS penetration have expanded options and may help defer local treatments and toxicities. Key barriers persist: inconsistent trial inclusion of BrM patients and variability in measuring radiographic responses and CNS-specific endpoints, complicating comparisons. Systemic therapy integration with surgery and radiation requires nuanced, multidisciplinary decisions tailored to individuals. This review summarizes the current systemic treatment landscape for BrM in NSCLC while emphasizing the need to broaden inclusion and conduct prospective studies that deliberately enroll patients with active and untreated BrM, using rigorous intracranial outcome assessment to improve survival and quality of life.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/an-updated-review-on-systemic-therapy-for-brain-metastases-in-non-small-cell-lung-cancer/448533/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/an-updated-review-on-systemic-therapy-for-brain-metastases-in-non-small-cell-lung-cancer/448533.png","ImageObject",300,407,{"name":92,"@type":93},"Jacob","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why has systemic therapy for brain metastases in NSCLC evolved in recent years?","Question",{"text":112,"@type":113},"Systemic therapy options expanded as newer targeted treatments developed improved CNS penetration, enabling more CNS activity and potentially reducing reliance on local therapies such as surgery or radiation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What limits comparisons of treatment outcomes across clinical trials for BrM in NSCLC?",{"text":117,"@type":113},"Trials often lack consistent inclusion of BrM patients and vary in how radiographic responses are measured and which standardized CNS-specific endpoints are used, making results difficult to compare.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the goal of the review regarding future studies?",{"text":121,"@type":113},"The review calls for broader inclusion of BrM patients and well-designed prospective studies that include patients with active and untreated BrM and rigorously assess intracranial outcomes.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},448533,1790884335,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},962084931830,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","An updated review on systemic therapy for brain metastases in non-small cell lung cancer  \nShreya Louis1^, John Paul Aboubechara2^, Keshav Saigal3, Toni Cao1,4^, Seema Nagpal1,4^  \n1Department of Neurology, Stanford Health Care, Palo Alto, CA, USA; 2Department of Neurology, University of California Davis Medical Center, Davis, CA, USA; 3Stanford University, Palo Alto, CA, USA; 4Division of Neuro-Oncology, Stanford Cancer Center, Stanford, CA, USA Contributions: (I) Conception and design: S Nagpal, T Cao, S Louis, JP Aboubechara; (II) Administrative support: T Cao, S Nagpal; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI)  \nManuscript writing: All authors; (VII) Final approval of manuscript: All authors.  \nCorrespondence to: Seema Nagpal, MD. Department of Neurology, Stanford Cancer Center, 875 Blake Wilbur Drive CC2221, Stanford, CA 94305, USA; Division of Neuro-Oncology, Stanford Cancer Center, Stanford, CA, USA. Email: [snagpal@stanford.edu](snagpal@stanford.edu).  \nAbstract: Brain metastases (BrM) are a frequent and devastating complication of non-small cell lung cancer (NSCLC), affecting up to 40% of patients during their disease course. Historically, treatment relied primarily on surgery and radiation, as systemic therapies were thought to have limited activity in the central nervous system (CNS). However, over the past two decades, the development of more targeted therapies has transformed the treatment landscape. Many of these newer agents have improved CNS penetration, which may offer patients the possibility of deferring or reducing the need for local therapies and their associated toxicities. Despite these advances, many challenges remain. There is still a lack of consistent inclusion of BrM patients in clinical trials, and when they are included, there are inconsistencies in measuring radiographic responses as well as in standardized CNS-specific endpoints, making it difficult to compare outcomes across therapies. As treatment options expand, the integration of systemic therapies with surgery and radiation requires nuanced, multidisciplinary decision-making tailored to individual patients. In this review, we aim to summarize the current treatment landscape of pertinent therapies for BrM in NSCLC patients while highlighting the need for broadening inclusion of these patients and creating well-designed prospective studies that intentionally include patients with active and untreated BrM alongside rigorously assess intracranial outcomes. Such efforts will be critical to developing treatment plans in order to ultimately  \nimprove survival and quality of life for NSCLC patients with BrM.  \nKeywords: Brain metastases (BrM); non-small cell lung cancer (NSCLC); tyrosine kinase inhibitors (TKIs);  \nimmune-checkpoint inhibitors (ICIs); antibody-drug conjugates (ADCs)  \nSubmitted Jul 03, 2025. Accepted for publication Nov 11, 2025. Published online Dec 25, 2025.  \ndoi: 10.21037/tcr-2025-1434  \nView this article at: [https://dx.doi.org/10.21037/tcr-2025-1434](https://dx.doi.org/10.21037/tcr-2025-1434)  \nIntroduction  \nBrain metastases (BrM) are common, found in 15–20% of non-small cell lung cancer (NSCLC) patients at initial diagnosis and 30–40% later in the disease course (1,2) .  \nHistorically, treatment strategies for BrM included surgery and radiation therapy (RT), with limited utilization of systemic chemotherapies, which were thought to be too large or hydrophilic to cross the blood-brain barrier. Stereotactic radiosurgery (SRS), the mainstay of current  \n^ ORCID: Shreya Louis, 0000-0001-5752-6271; John Paul Aboubechara, 0000-0002-9363-5704; Toni Cao, 0000-0003-1539-8536; Seema Nagpal, 0000-0002-0289-2319.  \n© AME Publishing Company. Transl Cancer Res 2025;14(12):9053-9062 | [https://dx.doi.org/10.21037/tcr-2025-1434](https://dx.doi.org/10.21037/tcr-2025-1434)  \n9054 Louis et al. Updated review brain mets NSCLC","cbCaipylCIOVAkq4","https://ap.wps.com/l/cbCaipylCIOVAkq4","pdf",220119,"English","# Introduction\n# EGFR-TKIs\n# Systemic therapies and CNS-active targeted agents","[{\"question\":\"Why has systemic therapy for brain metastases in NSCLC evolved in recent years?\",\"answer\":\"Systemic therapy options expanded as newer targeted treatments developed improved CNS penetration, enabling more CNS activity and potentially reducing reliance on local therapies such as surgery or radiation.\"},{\"question\":\"What limits comparisons of treatment outcomes across clinical trials for BrM in NSCLC?\",\"answer\":\"Trials often lack consistent inclusion of BrM patients and vary in how radiographic responses are measured and which standardized CNS-specific endpoints are used, making results difficult to compare.\"},{\"question\":\"What is the goal of the review regarding future studies?\",\"answer\":\"The review calls for broader inclusion of BrM patients and well-designed prospective studies that include patients with active and untreated BrM and rigorously assess intracranial outcomes.\"}]","An updated review on systemic therapy for brain metastases in non-small cell lung cancer | PDF",1790727651,25]