Cerebrospinal fluid (CSF) is a promising source of molecular biomarkers in the detection and monitoring of brain malignancies. Unlike peripheral blood, where biomarker detection is hindered by the blood-brain barrier and the complex nature of biofluids, CSF offers a more direct and enriched source of tumor-derived markers, including circulating tumor DNA (ctDNA), microRNA (miRNA), proteins, and extracellular vesicles (EVs). These biomarkers, originating from brain tumor cells, are often more concentrated in CSF than in peripheral blood due to the proximity of CSF to the central nervous system (CNS). The presence of ctDNA in CSF is notably higher than in plasma, making CSF an advantageous medium for liquid biopsy in brain tumor patients. Traditional liquid biopsy approaches relying on peripheral venous blood samples often face challenges in detecting low concentrations of tumor-derived biomarkers. The direct contact of CSF with the CNS minimizes background noise, potentially enhancing the accuracy and sensitivity of diagnostic assays. Despite the barriers posed by the blood-brain barrier and other physiological factors that limit biomarker levels in the systemic circulation, CSF's unique position within the CNS allows for more effective biomarker collection. While peripheral blood remains the standard medium for liquid biopsy in oncology, the proximity of CSF to brain tumors suggests it may offer superior diagnostic capabilities. Emerging evidence from non-CNS malignancies indicates that collecting biofluids closer to the tumor site can significantly improve biomarker detection. Although this approach has been well-documented in other solid tumors, its application to CNS malignancies remains underexplored. This study hypothesizes that targeted blood sampling from CNS tumor-draining veins could similarly enhance biomarker detection, thereby increasing the sensitivity and efficacy of liquid biopsy techniques in diagnosing and monitoring brain malignancies.

Brain metastases (BM), which most commonly originate from lung, breast, or skin cancers, remain a major clinical challenge, with standard treatments such as stereotactic radiosurgery (SRS), surgical resection, and whole-brain radiation therapy (WBRT). The prognosis for patients with BM remains poor, with a median overall survival (OS) of just 10–16 months. Although recent advances in systemic therapies, including small molecule inhibitors, monoclonal antibodies, chemotherapeutics, and gene therapies, have demonstrated success in other malignancies, their effectiveness in central nervous system (CNS) cancers is significantly limited by poor blood–brain barrier (BBB) permeability and subtherapeutic drug concentrations in the brain. Nanoparticle-based drug delivery systems have emerged as a promising strategy to overcome these limitations by enhancing CNS drug penetration and selectively targeting metastatic brain tumor cells while minimizing off-target effects. This review summarizes recent preclinical and clinical developments in nanoparticle-based therapies for BM. It is evident from these studies that NPs can carry with them a range of therapeutics, including chemotherapy, immunotherapy, small molecule inhibitors, gene therapies, radiosensitizers, and modulators of tumor microenvironment to the BM. Moreover, preclinical studies have shown encouraging efficacy in murine models, highlighting the potential of these platforms to improve therapeutic outcomes. However, clinical translation remains limited, with few ongoing trials. To close this translational gap, future work must address clinical challenges such as trial design, regulatory hurdles, and variability in BBB permeability while developing personalized nanoparticle-based therapies tailored to individual tumor characteristics.

The diagnosis of brain tumors typically relies on magnetic resonance imaging (MRI), computed tomography (CT), and invasive procedures like biopsies or surgical resection for confirmation and genetic profiling. However, these methods have limitations, especially in distinguishing treatment effects like pseudo-progression from actual tumor progression, and repeated biopsies pose risks. Liquid biopsy (LB) offers a non-invasive alternative, detecting tumor-derived biomarkers in blood and cerebrospinal fluid (CSF). Despite its potential, the low concentration of brain tumor biomarkers in blood due to the blood-brain barrier (BBB), limits the clinical utility of LB. MRI-guided focused ultrasound (MRgFUS) combined with microbubbles provides a novel solution by temporarily disrupting the BBB, facilitating the passage of therapeutic agents, and enabling tumor biomarker detection. This technique, termed “sonobiopsy,” enables non-invasive biomarker collection for liquid biopsy, potentially improving brain tumor diagnosis and monitoring.

Background: Hepatoblastoma (HB) is the most prevalent pediatric liver malignancy, typically affecting children under 5 years of age. Although advances in multimodal therapy, including surgical resection and chemotherapy, have significantly improved survival rates, distant metastases, particularly to the lungs and the brain, remain a critical prognostic challenge. Brain metastases (BMs) from HB are exceedingly rare, with only a limited number of cases reported in the literature, and the management of these lesions is challenging. Stereotactic radiosurgery (SRS) is an increasingly popular treatment option for BM due to its ability to deliver high doses of radiation to the target volume with minimal exposure to surrounding normal tissues. In this paper, we present a rare case of HB with brain metastasis that was treated with SRS for the 1 ^st time. Case Description: The case was a 4-year-old male with a history of stage IV HB who was diagnosed with a single BM. Post-treatment magnetic resonance images following SRS revealed a reduction in lesion size on 6 ^th -month follow-up imaging and then a stable lesion on further follow-up imaging. The case highlights the potential efficacy of SRS as a treatment option for BM from HB and supports its usage in the management of this complex condition. The progression-free survival was 17 months, and the overall survival was 84 months. Conclusion: SRS may represent a safe and effective treatment modality for HB BM, particularly in patients who are not suitable candidates for surgical resection or systemic therapy. Larger studies with extended follow-up are necessary to more accurately assess the long-term safety, efficacy, and clinical utility of SRS in the management of HB-related BM.