Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis.

PURPOSE: 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. CONCLUSION: 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.

Fluorescein-guided resection of a left frontal pre-rolandic cerebral metastasis: how I do it.

BACKGROUND: Cerebral metastases (CM) are the most common intracranial tumors; several studies have underlined the fundamental role of neurosurgical lesion removal. METHOD: 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. CONCLUSION: 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.

The impact of preoperative MRI-based apparent diffusion coefficients on local recurrence and outcome in patients with cerebral metastases.

BACKGROUND: Surgery of single cerebral metastases is standard but frequently fails to achieve local tumour control. Reliable predictors for local tumour progression and overall survival are unknown. MRI-based apparent diffusion coefficients (ADC) correlate with tumour cellularity and invasion. The present study analysed a potential relation between the MRI based apparent diffusion coefficients local recurrence and outcome in patients with brain metastases. METHODS: A retrospective analysis was performed for patients with cerebral metastases and complete surgical resection evaluated by an early postoperative MRI < 72h. Minimal ADC and mean ADC were assessed in preoperative 1,5T-MRI scans by placing regions of interests in the tumour and the peritumoural tissue. RESULTS: Analysis of the relation between ADC values, local progression and outcome was performed in 86 patients with a mean age of 59 years (range 33-83 years). Primary site was NSCLC in 37.2% of all cases. Despite complete resection 33.7% of all patients suffered from local in-brain-progression. There were no significant differences in ADC values in groups based on histology. In the present cohort, the mean ADCmin and the mean ADCmean within the metastasis did not differ significantly between patients with and without a later local in-brain progression (634 × 10-6 vs. 661 × 10-6 mm2/s and 1324 × 10-6 vs. 1361 × 10-6 mm2/s; 1100 × 10-6 vs. 1054 × 10-6 mm2/s; each p > 0.05). Mean ADC values did not correlate significantly with PFS and OAS. CONCLUSION: In the present study analysed ADC values had no significant impact on local in brain progression and survival parameters.

Stereotactic radiosurgery and resection for treatment of multiple brain metastases: a systematic review and analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) has recently emerged as a minimally invasive alternative to resection for treating multiple brain metastases. Given the lack of consensus regarding the application of SRS versus resection for multiple brain metastases, the authors aimed to conduct a systematic literature review of all published work on the topic. METHODS: The PubMed, OVID, Cochrane, Web of Science, and Scopus databases were used to identify studies that examined clinical outcomes after resection or SRS was performed in patients with multiple brain metastases. Radiological studies, case series with fewer than 3 patients, pediatric studies, or national database studies were excluded. Data extracted included patient demographics and mean overall survival (OS). Weighted t-tests and ANOVA were performed. RESULTS: A total of 1300 abstracts were screened, 450 articles underwent full-text review, and 129 studies met inclusion criteria, encompassing 20,177 patients (18,852 treated with SRS and 1325 who underwent resection). The OS for the SRS group was 10.2 ± 6 months, and for the resection group it was 6.5 ± 3.8 months. A weighted ANOVA test comparing OS with covariates of age, sex, and publication year revealed that the treatment group (p = 0.045), age (p = 0.034), and publication year (0.0078) were all independently associated with OS (with SRS, younger age, and later publication year being associated with longer survival), whereas sex (p = 0.95) was not. CONCLUSIONS: For patients with multiple brain metastases, SRS and resection are effective treatments to prolong OS, with published data suggesting that SRS may have a trend toward lengthened survival outcomes. The authors encourage additional work examining outcomes of treatments for multiple brain metastases.

Fluorescein-guided resection of cerebral metastases is associated with greater tumor resection.

BACKGROUND: Sodium fluorescein (fluorescein) crosses a disrupted blood-brain barrier similarly to gadolinium contrast in contrast-enhancing cerebral tumors. When exposed to light with 560 nm wavelength during surgery, fluorescein emits a yellow-green fluorescent light that can be visualized through an operating microscope equipped with an appropriate emission filter. The distribution of the fluorescence correlates with the contrast on a gadolinium contrast-enhanced MRI. OBJECTIVE: The objective of this single-center retrospective study was to investigate if the use of fluorescein would increase the extent of resection and to examine if fluorescein guided resection influences postoperative neurological status. METHODS: During the study period from August 2014 to August 2018, 117 patients were operated for cerebral metastases. Of these, 56 operations were guided by fluorescein and 61 by traditional white light. All patients had an early postoperative MRI within 72 h after surgery. RESULTS: The use of fluorescein increased the extent of resection in patients with cerebral metastases. The use of fluorescein was not associated with increased postoperative sequelae or neurological damage regardless of underlying primary cancer. CONCLUSION: Fluorescein is a helpful supplement in the neurosurgical treatment of cerebral metastases.

[Cytologic control of the resection margins of hemispheric gliomas and metastases]. / Tsitologicheskii kontrol' granits rezektsii polusharnykh gliom i metastazov.

INTRODUCTION: Postoperative MRI is the conventional method for assessing the radicalness of hemispherical tumors excision, but the method has limitations on sensitivity in the assessment of tumor infiltration of the peritumoral zone. The 'gold standard' for detecting tumor cells is the microscopic visualisation. AIM: To study the possibilities of a cytological study of the excision margins of glial and metastatic tumors for an objective assessment of the radical nature of the operation. MATERIAL AND METHODS: The study included 35 patients with intracerebral tumors who underwent open surgery at a university clinic of Volga Research Medical University in 2018-2019: 15 patients with metastasis, 13 patients with MRI-contrasting gliomas Grade III-IV and 7 patnents with non-MRI-contrasting gliomas Grade II-III. During the surgery, samples for cytological examination were taken from the following sites: from the tumor, from the nearest perifocal zone, and at a distance of 5-7 mm, along the border of the extended resection. 154 samples were examined: from 2 to 5 for each patient. RESULTS: The data on the radicalness of the operation, obtained by methods of cytological analysis of the resection margins and postoperative MRI, are not only consistent (p=0.001), but also complement each other, in particular, in some cases, tumor cells were found even in those areas where the tumor tissue was not detected with MRI. In cases of cerebral metastases excision, tumor cells in the nearest perifocal zone were found in 8 out of 28 samples (28.6%), at the extended resection margins - in 3 out of 29 (10.3%). In cases of resection of MRI-contrasting gliomas Grade III-IV, tumor cells in the nearest perifocal zone were found in 22 out of 32 samples (68.8%), at the extended resection margins - in 14 out of 20 (70%). In cases of excision of diffuse gliomas Grade II-III, tumor cells in the nearest perifocal zone were found in 10 out of 17 samples (58.9%), at the extended resection margins - in 4 out of 11 (36.4%). CONCLUSION: The first data obtained demonstrated sufficient informativeness of the cytologic examination of the peritumoral zone as an additional tool for assessing the radicalness of glioma and metastasis surgery. Cytologic analysis of the perifocal zone shows that the extension of the borders of the removal of Grade III-IV gliomas has no advantages, because tumor cells were found both in the nearest perifocal zone and at the extended resection margins with with approximately the same frequency.

Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection technique was first introduced for malignant glioma. However, the impact of the 5-ALA fluorescence behaviour of cerebral metastases is still unclear. Aim of this study was to determine the impact of PpIX-fluorescence on the local progression-free and overall survival. MATERIALS AND METHODS: A secondary analysis was performed and included an updated follow-up of 136 patients comprised in two previous studies. Additionally, 82 new patients were included. All patients underwent surgical resection of cerebral metastasis and intraoperative estimation of 5-ALA-induced fluorescence. The 5-ALA fluorescence behaviour of cerebral metastases was correlated with the rate of local recurrences, the local progression-free and overall survival. RESULTS: 218 patients suffering from cerebral metastatic spread fulfilled the inclusion criteria and were analysed: complete surgical resection could be achieved in 123/218 patients (56.4%). Dichotomised degree of surgical resection (complete vs. incomplete or questionable complete resection) was not related to dichotomized 5-ALA fluorescence of cerebral metastases (p = 0.66). 51 patients (23.4%) developed a local in-brain progression within or at the border of the resection cavity. Of these, 8 patients showed a PpIX-fluorescent metastasis. There was a trend towards a correlation between a higher local in-brain progression in PpIX-non-fluorescent metastases (p = 0.03). Median time to local in-brain progression was 4 ± 11 months. PpIX-fluorescent and PpIX-non-fluorescent metastases showed a significantly different progression-free survival (p = 0.01). PpIX-positive and -negative metastases showed a significantly different overall survival (20 and 14 months respectively; p = 0.006). CONCLUSION: The 5-ALA fluorescence behaviour was related to the local progression-free and the overall survival in the present retrospective series and might be considered a prognostic marker. Further studies are required to appreciate the oncological impact of the 5-ALA induced fluorescence behaviour of cerebral metastases.

The impact of cerebral metastases growth pattern on neurosurgical treatment.

The surgical resection of cerebral metastases is one key element in a multimodal therapy of brain oligometastatic patients. Standard surgery alone is often not sufficient to achieve local control. Various reasons have been discussed including microscopic and macroscopic tumor rests after surgery and different growth patterns of cerebral metastases: In this review, we assessed the surgical standard technique and then analyzed the growth pattern of cerebral metastases and discussed its oncologic impact and new strategies in the surgical management of cerebral metastases. A major percentage of cerebral metastases are not sharply delimitated but show an irregular tumor-brain interface or even an infiltrative growth pattern. Different patterns of adjacent brain invasions have been described and may correlate with the prognosis of patients with cerebral metastasis. Even metastases of the same histological subtype and the same origin show a heterogeneous brain invasion pattern. Future therapeutic strategies might have to take this heterogeneity into account. An infiltrative growth pattern of cerebral metastases might be one reason for their extraordinary high local recurrence rate and might have an influence on the individual overall survival. An intraoperative detection of residual tumor and development of more radical surgical techniques is therefore an important neurooncological challenge and might result in better tumor control. Supramarginal resection of cerebral metastases is a promising approach.

Diagnostic impact of integrated 18F-FDG PET/MRI in cerebral staging of patients with non-small cell lung cancer.

Background Integrated positron emission tomography/magnetic resonance imaging (PET/MRI) systems are increasingly being available and used for staging examinations. Brain metastases (BM) are frequent in patients with non-small cell lung cancer (NSCLC) and decisive for treatment strategy. Purpose To assess the diagnostic value of integrated 18F-2-fluoro-2-deoxy-D glucose (18F-FDG) PET/MRI in initial staging in patients with NSCLC for BM in comparison to MRI alone. Material and Methods Eighty-three patients were prospectively enrolled for an integrated 18F-FDG PET/MRI examination. The 3 T MRI protocol included a fluid-attenuated inversion-recovery sequence (FLAIR) and a contrast-enhanced three-dimensional magnetization prepared rapid acquisition GRE sequence (MPRAGE). Two neuroradiologists evaluated the datasets in consensus regarding: (i) present lesions; (ii) size of lesions; and (iii) number of lesions detected in MRI alone, compared to the PET component when reading the 18F-FDG PET/MRI. Results Based on MRI alone, BM were detected in 15 out of the 83 patients, comprising a total of 39 metastases. Based on PET alone, six patients out of the 83 patients were rated positive for metastatic disease, revealing a total of 15 metastases. PET detected no additional BM. The size of the BM correlated positively with sensitivity of detection in PET. Conclusion The sensitivity of PET in detection of BM depends on their size. 18F-FDG PET/MRI does not lead to an improvement in diagnostic accuracy in cerebral staging of NSCLC patients, as MRI alone remains the gold standard.

Fluorescein sodium-guided resection of cerebral metastases-an update.

BACKGROUND: Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identification of tumor tissue. In 2012, we started evaluating fluorescein (FL) with the dedicated microscope filter in cerebral metastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients. METHODS: Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25-85 years); 5 mg/kg bodyweight of FL was intravenously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events. RESULTS: Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL staining. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course. CONCLUSIONS: FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

A systematic review to assess the management of patients with cerebral metastases secondary to colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) rarely metastasizes to the brain. The incidence of cerebral metastases (CM) is estimated between 1 and 3%. Given the improved survival from advanced CRC as a result of surgical and oncological advances, it is anticipated that the incidence of patients with CM from CRC will rise over the next few years. The aim of this article was to systematically review the treatment options and outcome of patients with CM from CRC. METHODS: PubMed and Medline databases were examined using the search words or MESH headings "colorectal" "cancer/carcinoma/adenocarcinoma", "cerebral"/"brain" and "metastases/metastasis". RESULTS: CM from CRC are diagnosed on average 28.3 months after the primary tumour. The median survival time following diagnosis is 5.3 months. Surgery (with or without associated radiotherapy), stereotactic radiosurgery, whole brain radiotherapy and best supportive care result in median survival of 10.3, 6.4, 4.4 and 1.8 months, respectively. On average, the 1-year overall survival rate for patients with CM from CRC regardless of the treatment modality is estimated to be around 24%. CONCLUSIONS: The prognosis of patients with CM from CRC is dismal. Surgery may increase survival, but the additional benefit of perioperative radiotherapy cannot be ascertained due to paucity of data. Further studies are required to identify the role of the different oncological and surgical therapies and identify those patients likely to benefit most. Identification of patients who are at higher risk of developing brain metastases may be another important area for future research.

Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA-N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.

BACKGROUND: This study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy. PATIENTS AND METHODS: In this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life. RESULTS: This trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46-0.98; P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14-0.57; P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56-1.16; P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild. CONCLUSION: In patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.

Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling.

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.

Preoperative stereotactic radiosurgery for cerebral metastases: safe, effective, and decreases steroid dependency.

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.

Unraveling the Impact of miRNA-17 in Glial Tumors and Cerebral Metastases: A Step Towards Enhanced Diagnosis and Prognosis.

BACKGROUND/AIM: 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. MATERIALS AND 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). CONCLUSION: 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.

Comprehensive Analysis of Blood Test Results Predicting Prognosis in Patients Undergoing Whole-brain Radiotherapy for Brain Metastases.

BACKGROUND/AIM: 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. PATIENTS AND 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). CONCLUSION: 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.

Intraventricular Cerebral Metastases: A Comprehensive Systematic Review.

BACKGROUND/AIM: Intraventricular cerebral metastases (IVCM) are a rare but clinically significant subset of brain metastases. This systematic review aimed to provide a comprehensive analysis of IVCM by synthesizing current literature on epidemiology, clinical presentation, imaging features, pathophysiology, and treatment options. MATERIALS AND METHODS: A systematic literature search was conducted, identifying 11 relevant studies encompassing 11 studies encompassing 842 IVCM cases. Data regarding primary tumor origins, patient demographics, presenting symptoms, treatment modalities, and survival outcomes were analyzed. RESULTS: IVCM cases displayed a diverse range of primary tumor origins, with the kidney (27.4%), thyroid (21.6%), lung (19.8%), colon (11.7%), melanoma (8.4%), and breast ductal carcinoma (7.9%) being common sources. Patients presented with a wide spectrum of symptoms, including headaches (42.3%), nausea (31.5%), altered mental status (25.7%), neurological deficits (18.2%), and others. Treatment approaches varied, encompassing surgical resection (41.2%), radiation therapy (32.5%), chemotherapy (15.3%), and immunotherapy (7.9%). Overall survival was generally limited, with a mean duration of approximately 10.3 months (±8.7 months). The time to recurrence after treatment exhibited considerable variability. CONCLUSION: IVCM represents a challenging and underexplored metastatic disease. This systematic review underscores the need for further research to enhance our understanding of IVCM's pathophysiology and develop tailored diagnostic and treatment approaches. Such efforts are crucial to improving outcomes and the overall quality of life for patients facing this complex condition. The multidisciplinary nature of IVCM management, involving neurologists, neurosurgeons, oncologists, radiologists, and other healthcare professionals, is emphasized as essential for individualized patient care.

Utility of Amino Acid PET in the Differential Diagnosis of Recurrent Brain Metastases and Treatment-Related Changes: A Meta-analysis.

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.

Melanoma Brain Metastases: A Systematic Review of Opportunities for Earlier Detection, Diagnosis, and Treatment.

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.

Prognostic Factors and Independent Validation of a Risk Stratification Model in Octogenarian Patients Irradiated for Brain Metastases.

BACKGROUND/AIM: 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. PATIENTS AND 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. CONCLUSION: 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.