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Cancers
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Advances in the Management and Prognosis of Brain Metastases
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Advances in the Management and Prognosis of Brain Metastases

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 5965

Editors

Dr. Guixiang Liao

E-Mail Website
Guest Editor
Department of Radiation Oncology, Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University, the First Affiliated Hospital of Southern University of Science and Technology), Shenzhen 518020, China
Interests: brain metastases; non-small cell lung cancer; radiotherapy; chemotherapy
Dr. Muhammad Khan

E-Mail Website
Guest Editor
Department of Radiation Oncology, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou 510095, China
Interests: radiation oncology; brain tumors; brain metastases; tumor microenvironment; cancer therapy; immunotherapy; combination therapy

Special Issue Information

Dear Colleagues,

Brain metastases represent the most common intracranial malignancy, affecting 20–40% of adult cancer patients, with lung, breast, and melanoma accounting for the majority of cases. They carry a poor prognosis, with median survival of only 1–2 months without treatment.

Surgery benefits selected patients with solitary accessible lesions, extending median survival to 10–12 months. Radiotherapy remains a cornerstone: whole-brain radiotherapy achieves disease control but limited survival (3–6 months), whereas stereotactic radiosurgery offers local control rates of 70–90% for limited lesions. Advances in targeted therapy (e.g., EGFR, ALK, HER2 inhibitors) and immunotherapy (checkpoint inhibitors) have improved intracranial response rates (40–70%) and prolonged survival, particularly in lung cancer and melanoma.

Despite these advances, overall survival remains poor. Multidisciplinary care is critical to balancing tumor control, neurologic function, and quality of life. This Special Issue aims to expand our understanding of the latest advances in the management and prognosis of brain metastases, with a particular focus on multimodality approaches.

Dr. Guixiang Liao
Dr. Muhammad Khan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunotherapy
  • target therapy
  • stereotactic radiotherapy
  • prognosis
  • quality of life

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Published Papers (5 papers)

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Research

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12 pages, 827 KB  
Article
Prognostic Factors for Intracranial Progression in Her-2-Overexpressing Breast Cancer Patients with Brain Metastases as Primary Relapse Site—Real-Life Data
by Agnieszka Majewska, Tomasz Byrski and Michał Falco
Cancers 2026, 18(10), 1659; https://doi.org/10.3390/cancers18101659 - 20 May 2026
Viewed by 513
Abstract
Background: Her-2 positive breast cancer is characterised by a high risk of metastases to the central nervous system, which significantly affects prognosis. The aim of this study was to analyse risk factors and treatment outcomes for brain metastases diagnosed at the time of [...] Read more.
Background: Her-2 positive breast cancer is characterised by a high risk of metastases to the central nervous system, which significantly affects prognosis. The aim of this study was to analyse risk factors and treatment outcomes for brain metastases diagnosed at the time of first progression. Materials and Methods: A retrospective analysis was conducted on 1226 patients treated between 2010 and 2022. Distant metastases were diagnosed in 186 (15.7%) patients, including 48 (25.8%) with BM at the time of first progression. The impact of clinical factors and treatment on overall survival (OS) and intracranial progression-free survival (PFS) was analysed. Results: Patients with BM were significantly younger than other patients with distant metastases (mean 52.4 years vs. 61.1 years, p = 0.0001). The most significant prognostic factor for OS was the number of intracranial lesions (p = 0.0004). OS did not differ significantly depending on the use of local therapy (local therapy vs. whole-brain radiotherapy) or systemic therapy (observation vs. chemotherapy vs. anti-Her2 treatment). Conclusions: The number of brain metastases remains a key prognostic factor and should be taken into account in therapeutic decision-making, which highlights the importance of early identification of high-risk patients and the number of intracranial lesions in treatment selection. Full article
(This article belongs to the Special Issue Advances in the Management and Prognosis of Brain Metastases)
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Review

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15 pages, 860 KB  
Review
Surgical Management of Recurrent Brain Metastases: A Review
by James W. Sampson, Eric A. Goethe and Sherise D. Ferguson
Cancers 2026, 18(16), 2671; https://doi.org/10.3390/cancers18162671 - 18 Aug 2026
Viewed by 284
Abstract
As survival for cancer patients improves, the incidence of brain metastases has risen. This is likely due to improved systemic disease control, increased diligence in surveillance imaging in high-risk pathologies, improved neuro-imaging techniques and increased systemic screening for clinical trial enrollment. While there [...] Read more.
As survival for cancer patients improves, the incidence of brain metastases has risen. This is likely due to improved systemic disease control, increased diligence in surveillance imaging in high-risk pathologies, improved neuro-imaging techniques and increased systemic screening for clinical trial enrollment. While there are well-established treatments for brain metastases, many patients will experience recurrence after definitive treatment. The management of these recurrent lesions is not well established and often varies on a per-patient basis, owing to the clinical complexity and variety of these patients. Patients with recurrent brain metastases have surgical procedural options to achieve local tumor control, including laser interstitial thermal therapy (LITT) repeat open surgical resection with or without placement of intracavity brachytherapy. Repeat resection can offer rapid improvement in neurological symptoms, performance status, and potentially survival. LITT is less invasive than a standard craniotomy but offers a chance at directed local treatment while still obtaining tissue for diagnostic purposes and achieving acceptable survival outcomes. Further study is needed to determine the role of LITT for recurrent brain metastases, but it is a useful tool, particularly for patients with deep-seated lesions who may not tolerate a large surgery. Intracavitary brachytherapy allows for the immediate delivery of highly conformal radiation to the surgical bed with excellent local control and low rates of radiation necrosis, even in previously irradiated patients. The decision regarding which of the above to employ for recurrent brain metastases will vary on a case-by-case basis, and further studies are needed to standardize their use for this growing problem. Full article
(This article belongs to the Special Issue Advances in the Management and Prognosis of Brain Metastases)
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18 pages, 1592 KB  
Review
Leptomeningeal Metastasis in Non-Small-Cell Lung Cancer with Actionable Genomic Alterations: Pathogenesis, Diagnosis, and Emerging Therapeutic Strategies
by Sung-Won Lim, Bo Mi Ku and Myung-Ju Ahn
Cancers 2026, 18(13), 2169; https://doi.org/10.3390/cancers18132169 - 6 Jul 2026
Viewed by 1229
Abstract
Leptomeningeal metastasis (LM) is a severe and increasingly recognized complication of advanced non-small-cell lung cancer (NSCLC), particularly in patients with actionable genomic alterations. Although LM has historically been associated with poor outcomes, molecularly targeted systemic therapies with improved central nervous system (CNS) activity [...] Read more.
Leptomeningeal metastasis (LM) is a severe and increasingly recognized complication of advanced non-small-cell lung cancer (NSCLC), particularly in patients with actionable genomic alterations. Although LM has historically been associated with poor outcomes, molecularly targeted systemic therapies with improved central nervous system (CNS) activity are reshaping its therapeutic landscape. This review summarizes current concepts in the pathogenesis, diagnosis, and risk stratification of LM, focusing on systemic treatment strategies for NSCLC harboring actionable driver alterations. We highlight the rationale and emerging evidence for next-generation tyrosine kinase inhibitors targeting EGFR, ALK, and other oncogenic drivers, and discuss their role as the cornerstone of LM management. Intrathecal chemotherapy, immunotherapy, and radiotherapy are also reviewed within a risk-adapted treatment framework. An individualized approach integrating molecular profiling, neurological status, and disease distribution is essential to optimize outcomes. Prospective studies are needed to refine systemic treatment strategies and establish evidence-based algorithms for this high-risk population. Full article
(This article belongs to the Special Issue Advances in the Management and Prognosis of Brain Metastases)
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16 pages, 1979 KB  
Review
Triple-Negative Breast Cancer Brain Metastasis: A Comprehensive Review of Epidemiology, Molecular Pathobiology, and Therapeutic Frontiers
by Hongli Yang, Yang Zhao, Yue Wang, Xiaoyuan Ma, Jinmei Ling, Xianyi Zeng, Zihuang Li and Guixiang Liao
Cancers 2026, 18(7), 1179; https://doi.org/10.3390/cancers18071179 - 7 Apr 2026
Cited by 2 | Viewed by 2033
Abstract
Triple-negative breast cancer (TNBC) is associated with a high risk of brain metastases (BMs). Although systemic therapies have improved extracranial disease control, the central nervous system (CNS) remains less accessible to numerous agents. As a result, this limited drug penetration makes brain metastases [...] Read more.
Triple-negative breast cancer (TNBC) is associated with a high risk of brain metastases (BMs). Although systemic therapies have improved extracranial disease control, the central nervous system (CNS) remains less accessible to numerous agents. As a result, this limited drug penetration makes brain metastases (BMs) remain common in TNBC, which are a leading cause of serious symptoms. This review summarizes recent key advances in triple-negative breast cancer brain metastases (TNBC-BMs), including epidemiology, prognostic stratification, biological mechanisms of CNS tropism and treatment resistance, and evolving management strategies. We discuss potential mechanisms of brain colonization, including the FOXC1-CXCR4 axis, ST6GALNAC5-related interactions with the blood–brain barrier (BBB), and the bidirectional crosstalk between metastatic cells and the brain microenvironment, particularly astrocytes and microglia. Furthermore, we evaluate the evolving clinical management, emphasizing the transition from whole-brain radiotherapy (WBRT) toward more selective local approaches such as stereotactic radiotherapy (SRS) and hippocampal sparing techniques. Concurrently, we examine the integration of CNS active systemic therapy across specific molecular subsets. This review systematically distinguishes standard-of-care interventions from investigational strategies, ultimately underscoring critical evidence gaps within the TNBC-BM landscape. Full article
(This article belongs to the Special Issue Advances in the Management and Prognosis of Brain Metastases)
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Other

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15 pages, 2411 KB  
Systematic Review
Prophylactic Cranial Irradiation in MRI-Staged Limited-Stage Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Survival and Neurocognitive Outcomes
by Shaoli Li, Xin Zheng, Yinnan Meng, Gang Chen, Caining Zhao, Sijin Zhong, Huixia Li, Rui Bai, Ying Dong and Feng-Ming (Spring) Kong
Cancers 2026, 18(12), 1970; https://doi.org/10.3390/cancers18121970 - 17 Jun 2026
Viewed by 814
Abstract
Background: The necessity of prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) is increasingly debated in the era of high-resolution magnetic resonance imaging (MRI). This meta-analysis evaluated the survival and neurocognitive effects of PCI in LS-SCLC patients confirmed negative for brain [...] Read more.
Background: The necessity of prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) is increasingly debated in the era of high-resolution magnetic resonance imaging (MRI). This meta-analysis evaluated the survival and neurocognitive effects of PCI in LS-SCLC patients confirmed negative for brain metastases (BM) by pre-PCI MRI. Methods: Following PRISMA guidelines, a systematic search of PubMed, Embase, and Cochrane Library was conducted through 23 September 2025. Pooled hazard ratios (HRs) and risk ratios (RRs) were calculated to assess overall survival (OS), progression-free survival (PFS), brain metastasis-free survival (BMFS), and BM rate. Results: Eleven studies involving 1894 patients were synthesized. PCI conferred a significant survival advantage, reducing the risk of death by 31% (HR = 0.69, 95% CI: 0.61–0.78), which translated to an absolute OS improvement of 8.5% at 2 years and 6.5% at 5 years. Substantial improvements were also observed in PFS (HR = 0.71, 95% CI: 0.60–0.84) and BMFS (HR = 0.53, 95% CI: 0.32–0.88), alongside a 36% reduction in BM rate (RR = 0.64, 95% CI: 0.53–0.77). Notably, PCI maintained its OS benefit even when compared directly against active MRI surveillance. While neurocognitive adverse events were reported, evidence suggests that these effects are predominantly transient and domain-specific, without a sustained decrease in global quality of life. Conclusions: In the MRI-staging era, PCI remains a significant therapeutic option for LS-SCLC. It offers a favorable risk–benefit profile by significantly enhancing survival while maintaining manageable neurocognitive safety. Full article
(This article belongs to the Special Issue Advances in the Management and Prognosis of Brain Metastases)
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