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.

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.

BACKGROUND AND OBJECTIVES: Male breast cancer (MBC) is very rare, and previous reports of brain metastases (BM) from MBC are limited. To date, the genetic characteristics of MBC with BM have not been explored. In addition, there is only a single case report documenting the use of stereotactic radiosurgery (SRS) for MBC BM. The aim of this study was to summarize genetic alterations associated with BM in patients with MBC and evaluate the safety and efficacy of SRS in this population. METHODS: Four male patients with a total of 20 MBC BMs treated with SRS were retrospectively reviewed. We defined treatment response as complete response, partial response, stable disease, and local progression (LP), per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate cumulative incidence rate of LP. RESULTS: The median overall survival was 16.3 months (95% confidence interval: 1.4-31.3 months). The mean age at treatment was 59 years (IQR: 56-60.5 years). Three patients had estrogen receptor–positive lesions, whereas one patient had triple-negative disease. Three patients had notable pathogenic alterations (including in AURKA, BRCA1, BRCA2, CCND1, CHEK2, ERBB2, FLT3, RAF1, and SPINK1). The median lesion size was 5.7 mm (IQR: 3.9-8.6 mm). The median delivered dose was 23 Gy (IQR: 22-24 Gy). Follow-up imaging at 3 months showed a reduction in median lesion size (3.3 mm). The percentage of lesions which were classified as complete response:partial response:stable disease:LP was 0%:45%:55%:0%, respectively. Cumulative 6-month and 12-month local control rates were 100% and 100%, respectively. Only one lesion demonstrated LP at the last follow-up (15 months). CONCLUSION: This is the first report of genetic profiling of MBC with BM and excellent SRS outcomes. The receptor status and genetic alterations across our patients with MBC BM suggest heterogeneity in disease. Larger studies are needed to further explore MBC BM characteristics and treatment outcomes.

Interpreting pain improvements after interventions in clinical settings is challenging because placebo effects can influence patient-reported outcomes. In clinical practice, pain intensity reductions of 30% or greater are commonly considered indicative of meaningful analgesic benefit. However, the likelihood of achieving such reductions after placebo interventions is not known. We conducted a comprehensive meta-analysis to quantify pain intensity changes reported after placebo interventions in clinical trials of facial pain (FP). We systematically searched for randomized controlled trials (RCTs) and uncontrolled case series of FP treatments that included placebo or sham arms. The primary outcome was percentage change in pain intensity. The primary analysis focused on RCTs, with pooled effect sizes estimated using random-effects meta-analysis. Data from 115 studies (n = 3,208) were analyzed, including 71 RCTs (n = 2,128) and 44 uncontrolled case series (n = 1,080). Sham interventions yielded an average pain reduction of 29.73% (95% CI 24.09%-35.36%), with a prediction interval (−14.51% to 73.96%) among RCTs. Placebo responses varied by diagnosis ( P < 0.001), with larger effects in temporomandibular disorders and classical trigeminal neuralgia. Cumulative probability analyses showed that ≥50% pain relief occurred in ∼25% of placebo-treated patients, whereas ≥75% improvement was reported in ∼2.5%. In FP, placebo interventions often produce mild to moderate relief but rarely yield dramatic improvements of ≥75%. These results can guide the interpretation of reported pain relief in clinical settings and inform clinical trial design in chronic pain conditions, suggesting that ≥75% pain intensity reductions after analgesic interventions are unlikely to be primarily driven by placebo effects.