OBJECTIVE: Blood tests, such as those included in the validated LabBM score (laboratory parameters in patients with brain metastases) predict survival after treatment of brain metastases. The model incorporates five test results [serum lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin, platelets and hemoglobin]. However, many other abnormalities, albeit less well-studied, may be present in patients with metastatic cancer. Therefore, this study aimed to examine a broader range of blood tests.
METHODS: This retrospective analysis included 132 patients managed with primary whole-brain radiotherapy. Additional tests, such as liver enzymes, lymphopenia, hyponatremia, and others, were also conducted. Extracranial disease extent was also analyzed.
RESULTS: According to forward conditional Cox regression analyses, blood tests (albumin, hemoglobin, lymphopenia, hyponatremia) in conjunction with the number of organs affected by extracranial metastases (at least two, such as liver and bones) provided the best prognostic model. Based on these parameters, at least four prognostic strata can be assigned (median survival between 4.6 and <1 months, p=0.0001).
CONCLUSIONS: This initial pilot study in a limited number of patients suggests that numerous blood test results may contribute to further refinement of existing prognostic models, and provides justification for additional large-scale studies.

OBJECTIVE: Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm3) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score-matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions.
METHODS: Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched.
RESULTS: Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm3, p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38-6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38-3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04-1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02-0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02).
CONCLUSIONS: Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.

Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

OBJECTIVE: MicroRNAs (miRNAs) have been identified as key regulators in various cancer types, including brain tumors. This study aimed to investigate the differential expression of miRNA-17 in glial tumors, cerebral metastases, and normal glial tissues.
METHODS: A total of 42 patients were included in this cross-sectional study. Tissue samples were obtained from patients with glial tumors or cerebral metastases and from normal glial tissues. miRNA-17 expression levels were computed by using real-time polymerase chain reaction. Receiver operating characteristics analysis was used to determine the predictive potential of miRNA-17.
RESULTS: In this study, we demonstrated a statistically significant difference in miRNA-17 expression levels between glial tumors and the control group (p=0.001), with higher miRNA-17 expression observed in glial tumors. Similarly, there was statistically higher miRNA-17 expression in metastatic cases compared with the control group (p=0.007).
CONCLUSIONS: These findings suggest miRNA-17 might be a potential biomarker for differentiating glial tumors and cerebral metastases from normal glial tissue, although further research is necessary to validate these findings and investigate the potential role of miRNA-17 in the pathogenesis of these brain tumors.

OBJECTIVE: Brain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement.
METHODS: A pooled analysis was performed by searching on PubMed and using the keywords: \"brain metastases in adrenocortical carcinoma\", and \"leptomeningeal metastases in adrenocortical carcinoma\". Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected.
RESULTS: A total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children.
CONCLUSIONS: Brain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

Cerebral metastases (CM) are the most common intracranial tumors; several studies have underlined the fundamental role of neurosurgical lesion removal.
We describe the surgical resection of a left frontal single metastasis. We attempted to achieve a radical resection under the intraoperative guidance of fluorescein, with the aid of intraoperative neurological monitoring. This technique can be applied to each contrast enhancing, intra-axial, infiltrative lesion.
Fluorescein-guided surgery is a valuable tool in CM surgery to increase the rate of resection; further prospective evaluation of the role of fluorescein in this field is in planning, aiming to study the prognostic impact.

A modern approach for brain metastases includes whole-brain radiotherapy plus simultaneous boost (WBRT+SIB). We developed a survival score in 128 patients treated with WBRT+SIB. Three models, each including three prognostic groups, were created. Positive predictive values (PPVs) for death ≤6 and survival ≥6 months were calculated. On multivariate analyses, performance score (KPS) and the number of brain metastases were significantly associated with survival. On univariate analyses, age showed a strong trend, and extra-cerebral cranial metastases a trend. In Model 1 (KPS, number of lesions), compared groups had 6-month survival rates of 15%, 38% and 57%. In Model 2 (KPS, lesions, age), rates were 17%, 33% and 75%, and in Model 3 (KPS, lesions, age, extra-cerebral metastases), 14%, 34% and 78%. PPVs for death ≤6 and survival ≥6 months were 85% and 57% (Model 1), 83% and 75% (Model 2), and 86% and 78% (Model 3). Thus, all models were accurate in predicting death ≤ 6 months; poor-prognosis patients may not benefit from SIB. Models 2 and 3 were superior in predicting survival ≥ 6 months. Given that Model 3 requires more data (including extensive staging), Model 2 is considered favorable for many patients. If extra-cerebral metastases are already known or extensive staging has been performed, Model 3 can also be used.

Introduction: Melanoma continues to represent the most serious skin cancer worldwide. However, few attempts have been made to connect the body of research on advanced melanoma. In the present review, we report on strides made in the diagnosis and treatment of intracranial metastatic melanoma. Methods: Relevant Cochrane reviews and randomized-controlled trials published by November 2022 were systematically retrieved from the Cochrane Library, EMBASE, and PubMed databases (N = 27). Search and screening methods adhered to the 2020 revision of the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Results: Although the research surrounding the earlier detection of melanoma brain metastasis is scarce, several studies have highlighted specific markers associated with MBM. Such factors include elevated BRAFV600 mutant ctDNA, high LDH concentration, and high IGF-1R. The approach to treating MBM is moving away from surgery and toward nonsurgical management, namely, a combination of stereotactic radiosurgery (SRS) and immunotherapeutic agents. There is an abundance of emerging research seeking to identify and improve both novel and established treatment options and diagnostic approaches for MBM, however, more research is still needed to maximize the clinical efficacy, especially for new immunotherapeutics. Conclusions: Early detection is optimal for the efficacy of treatment and MBM prognosis. Current treatment utilizes chemotherapies and targeted therapies. Emerging approaches emphasize biomarkers and joint treatments. Further exploration toward preliminary identification, the timing of therapies, and methods to ameliorate adverse treatment effects are needed to advance MBM patient care.

OBJECTIVE: This study aimed at validation of a prognostic model, originally developed by Rades et al., in an age-restricted, particularly vulnerable subgroup of patients with brain metastases, because international variations in clinical practice and survival outcomes may impact on the performance of survival prediction tools.
METHODS: Retrospectively, data from a single institution were analyzed. The study included 50 patients managed with palliative whole-brain radiotherapy. The Rades et al. score was assigned and the resulting 3 prognostic strata compared.
RESULTS: The 3-month survival rates for the 3 strata were 0, 35, and 41%, respectively (p<0.001 pooled over all strata, log-rank test for Kaplan-Meier curves). However, the prognostic impact of extracranial metastases suggested by Rades et al., together with the performance status and number of brain metastases in their study of 94 patients, was absent. In contrast, cancer type (better survival for breast and melanoma) and lack of steroid treatment were significant in the present study.
CONCLUSIONS: The original Rades et al. score is a useful prognostic model in our validation database. However, additional factors, such as primary cancer type and need to prescribe corticosteroids, appear to play a role and might therefore be considered when performing future large-scale studies.

Amino acid PET is an established method to assist differential diagnosis of therapy-related changes versus recurrence in gliomas. However, its diagnostic value in brain metastases is yet to be determined. The goal of this study was to summarize evidence on the diagnostic utility of amino acid PET in recurrent brain metastases. Methods: The medical databases MEDLINE, EMBASE, and the Cochrane Library were screened for English-language studies with at least 10 patients who had undergone first-line treatment including radiotherapy and in whom a final diagnosis had been determined by histologic examination or imaging and clinical follow-up. Pooled estimates with 95% CIs were calculated. Heterogeneity was assessed using I2 statistics. Results: Following the above criteria, 12 studies with the tracers methyl-[11C]-methionine (n = 6), O-(2-[18F]fluoroethyl)-l-tyrosine (n = 3), methyl-[11C]-methionine and O-(2-[18F]fluoroethyl)-l-tyrosine (n = 1), and 6-[18F]fluoro-L-dopa (n = 2), with a total of 547 lesions in 397 patients, were included. Pooled sensitivity and specificity were 82% (95% CI, 76-86) and 84% (95% CI, 79-88), respectively. Pooled positive and negative predictive values were 84% (95% CI, 77-90) and 83% (95% CI, 77-88), respectively. Positive and negative likelihood ratios, and diagnostic odds ratio were 3.8 (95% CI 3.0-4.8), 0.3 (95% CI 0.2-0.3), and 16.7 (95% CI 10.8-25.9), respectively. Heterogeneity was overall low. Conclusion: The present meta-analysis indicates a good accuracy of amino acid PET in the differential diagnosis of recurrent brain metastases. In particular, specificity of 84% suggests that amino acid PET may reduce the number of invasive procedures and overtreatment in patients with treatment-related changes. This study provides class IIa evidence on the utility of amino acid PET in the differential diagnosis of recurrent brain metastases.