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Simple Summary: The available treatment strategies for patients with brain metastases remain suboptimal, with current research focused on identifying therapies intended to improve patient outcomes while reducing the risk of treatment-related complications. Several studies have investigated the role of pre-operative neoadjuvant stereotactic radiotherapy, and have proposed it as a valid alternative to post-operative adjuvant stereotactic radiotherapy. The aim of our systematic review was to comprehensively analyze the current literature and ongoing clinical trials evaluating neoadjuvant stereotactic radiotherapy in patients with brain metastases, describing treatment protocols and related outcomes. Early evidence suggests that neoadjuvant stereotactic radiotherapy may offer rates of local control and overall survival comparable to those obtained with adjuvant postoperative SRS, but comparative studies are currently lacking. In addition, neoadjuvant stereotactic radiotherapy shows low rates of post-treatment radiation necrosis and leptomeningeal metastases. Ongoing clinical trials aim to evaluate long-term outcomes in large patient cohorts, with some focused on comparing neoadjuvant stereotactic radiotherapy to adjuvant stereotactic radiosurgery. Background: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9–57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7–60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1–10) post-NaSRT. Median follow-up was 19.2-months (range, 1–41.3). Actuarial post-treatment rates were 4% (95%CI: 2–6%) for symptomatic radiation necrosis, 15% (95%CI: 12–18%) and 47% (95%CI: 42–52%) for local and distant recurrences, 6% (95%CI: 3–8%) for leptomeningeal metastases, 81% (95%CI: 75–87%) and 59% (95%CI: 54–63%) for 1-year local tumor control and overall survival. Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Gliomas infiltrating the corpus callosum (G-I-CC) may carry significant tumor burden by causing severe neurocognitive and functional impairments. The role of surgical resection has been widely debated over the years, as it has been correlated with significant survival improvement but may also predispose the patient to major post-operative complication risks. The aim of our systematic review was to comprehensively analyze the current literature on G-I-CC, describing clinical presentations, management strategies, outcomes, and prognoses. We found that most G-I-CC are IDH-wildtype grade-4 glioblastomas involving the corpus callosum genu and with bilateral lobe infiltration. In patients with high-grade G-I-CC, surgical resection, especially gross-total, led to significantly longer survival when coupled with post-surgery radiation and temozolomide. Rates of symptom improvement and complications did not significantly differ in preservation versus resection of tumor-infiltrated corpus callosum. Overall, maximally safe resection should be considered in patients with G-I-CC, co-adjuvated with intraoperative neuromonitoring and cortical mapping to further reduce complication risks. Background: Gliomas infiltrating the corpus callosum (G-I-CC) majorly impact patient quality-of-life, but maximally safe tumor resection is challenging. We systematically reviewed the literature on G-I-CC. Methods: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with G-I-CC. Clinicopathological features, treatments, and outcomes were analyzed. Results: We included 52 studies comprising 683 patients. Most patients experienced headache (33%), cognitive decline (18.7%), and seizures (17.7%). Tumors mostly infiltrated the corpus callosum genu (44.2%) with bilateral extension (85.4%) into frontal (68.3%) or parietal (8.9%) lobes. Most G-I-CC were glioblastomas (84.5%) with IDH-wildtype (84.9%) and unmethylated MGMT promoter (53.5%). Resection (76.7%) was preferred over biopsy (23.3%), mostly gross-total (33.8%) and subtotal (32.5%). The tumor-infiltrated corpus callosum was resected in 57.8% of cases. Radiation was delivered in 65.8% of patients and temozolomide in 68.3%. Median follow-up was 12 months (range, 0.1–116). In total, 142 patients (31.8%) experienced post-surgical complications, including transient supplementary motor area syndrome (5.1%) and persistent motor deficits (4.3%) or abulia (2.5%). Post-treatment symptom improvement was reported in 42.9% of patients. No differences in rates of complications (p = 0.231) and symptom improvement (p = 0.375) were found in cases with resected versus preserved corpus callosum. Recurrences occurred in 40.9% of cases, with median progression-free survival of 9 months (0.1–72). Median overall survival was 10.7 months (range, 0.1–116), significantly longer in low-grade tumors (p = 0.013) and after resection (p < 0.001), especially gross-total (p = 0.041) in patients with high-grade tumors. Conclusions: G-I-CC show clinicopathological patterns comparable to other more frequent gliomas. Maximally safe resection significantly improves survival with low rates of persistent complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Spine giant cell tumors (SGCTs) are intermediate malignant bone tumors, sometimes aggressive and responsible for debilitating axial pain and sensorimotor impairments. Non-surgical therapies, including denosumab, radiotherapy, and selective arterial embolization (SAE), have shown promising results in the treatment of patients with inoperable SGCTs. In this systematic review, we aimed to comprehensively analyze the current literature on denosumab, radiotherapy, and SAE for inoperable SGCTs, comparing treatment outcomes and complications using a random-effect model meta-analysis. We found that all three treatments were equally effective in providing symptom improvement and radiological tumor response, also showing low and comparable rates of treatment-related complications. Patients treated with denosumab showed lower rates of local recurrences and distant metastases. Background: Surgical resection remains the preferred treatment in spine giant cell tumors (SGCTs), but it is not always feasible. Conservative strategies have been studied for inoperable cases. We systematically reviewed the literature on inoperable SGCTs treated with denosumab, radiotherapy or selective arterial embolization (SAE). Methods: PubMed, Scopus, Web-of-Science, Ovid-EMBASE, and Cochrane were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to include studies of inoperable SGCTs treated with denosumab, radiotherapy or SAE. Treatment outcomes were analyzed and compared with a random-effect model meta-analysis. Results: Among the 17 studies included, 128 patients received denosumab, 59 radiotherapy, and 43 SAE. No significant differences in baseline patient characteristics were found between the three groups. All strategies were equally effective in providing symptom improvement (p = 0.187, I2 = 0%) and reduction in tumor volume (p = 0.738, I2 = 56.8%). Rates of treatment-related complications were low (denosumab: 12.5%; radiotherapy: 8.5%; SAE: 18.6%) and comparable (p = 0.311, I2 = 0%). Patients receiving denosumab had significantly lower rates of local tumor recurrence (10.9%) and distant metastases (0%) compared to patients receiving radiotherapy (30.5%; 8.5%) or SAE (35.6%; 7%) (p = 0.003, I2 = 32%; p = 0.002, I2 = 47%). Denosumab was also correlated with significantly higher overall survival rates at 18 months (99.2%) and 24 months (99.2%) compared to radiotherapy (91.5%; 89.6%) and SAE (92.5%; 89.4%) (p = 0.019, I2 = 8%; p = 0.004, I2 = 23%). Mortality was higher in patients receiving SAE (20.9%) or radiotherapy (13.6%) compared to denosumab (0.8%) (p < 0.001), but deaths mostly occurred for unrelated diseases. Conclusions: Denosumab, radiotherapy, and SAE are safe and effective for inoperable SGCTs. Clinical and radiological outcomes are mostly comparable, but denosumab may provide superior tumor control. [ABSTRACT FROM AUTHOR]

Simple Summary: Orbital metastases may significantly worsen the functional status of oncological patients, leading to debilitating visual impairments. Surgical resection, orbital exenteration, and complementary therapies may result in heterogeneous clinical outcomes. In this systematic review, we aimed to comprehensively analyze the current literature on orbital metastases, describing clinical and imaging features, available management, and treatment outcomes. We found that most orbital metastases occur at later stages after primary tumors, frequently showing diffuse location within the orbit and rarely invading intracranial structures. Biopsy-only techniques were more frequently preferred in view of the less invasive approaches, but surgical resection and orbital radiotherapy were related to improved clinical outcomes. Although patients with primary breast cancer and patients undergoing resection showed superior prognoses, overall survival rates were generally poor, suggesting the need to better understand orbital metastases' microenvironments for devising optimal systemic treatment strategies. Background: Orbital metastases often lead to severe functional impairment. The role of resection, orbital exenteration, and complementary treatments is still debated. We systematically reviewed the literature on orbital metastases. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon PRISMA guidelines to identify studies on orbital metastases. Clinical characteristics, management strategies, and survival were analyzed. Results: We included 262 studies comprising 873 patients. Median age was 59 years. The most frequent primary tumors were breast (36.3%), melanoma (10.1%), and prostate (8.5%) cancers, with median time interval of 12 months (range, 0–420). The most common symptoms were proptosis (52.3%) and relative-afferent-pupillary-defect (38.7%). Most metastases showed a diffuse location within the orbit (19%), with preferential infiltration of orbital soft tissues (40.2%). In 47 cases (5.4%), tumors extended intracranially. Incisional biopsy (63.7%) was preferred over fine-needle aspiration (10.2%), with partial resection (16.6%) preferred over complete (9.5%). Orbital exenteration was pursued in 26 patients (3%). A total of 305 patients (39.4%) received chemotherapy, and 506 (58%) received orbital radiotherapy. Post-treatment symptom improvement was significantly superior after resection (p = 0.005) and orbital radiotherapy (p = 0.032). Mean follow-up was 14.3 months, and median overall survival was 6 months. Fifteen cases (1.7%) demonstrated recurrence with median local control of six months. Overall survival was statistically increased in patients with breast cancer (p < 0.001) and in patients undergoing resection (p = 0.024) but was not correlated with orbital location (p = 0.174), intracranial extension (p = 0.073), biopsy approach (p = 0.344), extent-of-resection (p = 0.429), or orbital exenteration (p = 0.153). Conclusions: Orbital metastases severely impair patient quality of life. Surgical resection safely provides symptom and survival benefit compared to biopsy, while orbital radiotherapy significantly improves symptoms compared to not receiving radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognostic expectancies of patients affected by glioblastoma have remained almost unchanged during the last thirty years. Along with specific oncological research and surgical technical alternatives, corollary disciplines are requested to provide their contributions to improve patient management and outcomes. Technological improvements in radiology have led to the development of radiomics, a new discipline able to detect tumoral phenotypical features through the extraction and analysis of a large amount of data. Intuitively, the early foreseeing of glioma features may constitute a tremendous contribution to the management of patients. The present manuscript analyzes the pertinent literature regarding the current role of radiomics and its potentialities. Background: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, marks a step forward the future diagnostic approach to these neoplasms. Alongside this, radiomics has experienced rapid evolution over the last several years, allowing us to correlate tumor imaging heterogeneity with a wide range of tumor molecular and subcellular features. Radiomics is a translational field focused on decoding conventional imaging data to extrapolate the molecular and prognostic features of tumors such as gliomas. We herein analyze the state-of-the-art of radiomics applied to glioblastoma, with the goal to estimate its current clinical impact and potential perspectives in relation to well-rounded patient management, including the end-of-life stage. Methods: A literature review was performed on the PubMed, MEDLINE and Scopus databases using the following search items: "radiomics and glioma", "radiomics and glioblastoma", "radiomics and glioma and IDH", "radiomics and glioma and TERT promoter", "radiomics and glioma and EGFR", "radiomics and glioma and chromosome". Results: A total of 719 articles were screened. Further quantitative and qualitative analysis allowed us to finally include 11 papers. This analysis shows that radiomics is rapidly evolving towards a reliable tool. Conclusions: Further studies are necessary to adjust radiomics' potential to the newest molecular requirements pointed out by the 2021 WHO classification of CNS tumors. At a glance, its application in the clinical routine could be beneficial to achieve a timely diagnosis, especially for those patients not eligible for surgery and/or adjuvant therapies but still deserving palliative and supportive care. [ABSTRACT FROM AUTHOR]

Simple Summary: Located in the lateral facial region, the infratemporal fossa (ITF) is the primary site for tumors of various etiologies and comprise 0.5% of all head and neck cancers. Due to the anatomical relationship of ITF tumors with different cranial nerves and neurovascular structures, clinical presentations vary among patients. Our study aims to review the literature on the various tumors that present in this region, their reported treatment strategies, and patient outcomes. We found that trigeminal schwannomas and meningiomas are the most common tumors. In terms of management, nost patients had transcranial surgery, and three-quarters had a gross-total resection. Background: Infratemporal fossa (ITF) tumors represent various pathologies and are seldom described in the literature, reflecting their rarity. Here we review the literature on tumors invading ITF and describe patient characteristics, treatment strategies, and clinical outcomes. Methods: Relevant articles were retrieved from PubMed, Scopus, and Cochrane. A systematic review and meta-analysis were conducted on the clinical presentation, treatment protocols, and clinical outcomes. Result: A total of 27 articles containing 106 patients with ITF tumors (median tumor size: 24.3 cm3 [interquartile range, 15.2–42 cm3]) were included (median age: 46 years [interquartile range, 32–55 years]; 59.4% were males]). Of the confirmed tumor pathology data, schwannomas (n = 24; 26.1%) and meningiomas (n = 13; 14.1%) were the most common tumors. Facial hypoesthesia (n = 22; 18.5%), auricular/preauricular pain (n = 20; 16.8%), and headaches (n = 11; 9.2%) were the most common presenting symptoms. Of patients who had surgical resection (n = 97; 95.1%), 70 (73.7%) had transcranial surgery (TCS) and 25 (26.3%) had endoscopic endonasal surgery (EES). Among available details on the extent of resection (n = 84), gross-total resection (GTR) was achieved in 62 (73.8%), and 5 (6.0%) had biopsy only. Thirty-five (33.0%) patients had postoperative complications. Among cases with available data on reconstruction techniques (n = 8), four (50%) had adipofascial antero-lateral thigh flap, three (37.5%) had latissimus dorsi free flap, and one (12.5%) had antero-lateral thigh flap. Fourteen (13.2%) patients had adjuvant chemotherapy, and sixteen (15.1%) had adjuvant radiotherapy. During a median follow-up time of 28 months (IQR, 12.25–45.75 months), 15 (14.2%) patients had recurrences, and 18 (17.0%) patients died. The median overall survival (OS) time was 36 months (95% confidence interval: 29–41 months), and the 5-year progression-free survival (PFS) rate was 61%. Conclusion: Various tumor types with different biological characteristics invade the ITF. The present study describes patient demographics, clinical presentation, management, and outcomes. Depending on the tumor type and patient condition, patient-tailored management is recommended to optimize treatment outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Meningioma is still the most common adult tumor of the CNS, most of which are slow-growing, benign tumors and could even be accidentally diagnosed; nonetheless, they sometimes show more aggressive behavior with higher recurrence rates and relatively reduced overall survival. Assuming this, in recent years, scientific research has been accelerated, looking for new insights and applications that could improve preoperative investigation, tailor surgical planning, and strongly impact meningioma patients' prognosis. Many fields have been developed, and the detection of brain invasion has firmly gained its potential role, leading to the revised version of WHO for CNS tumors in 2016 as a further criterion for defining atypia. Further studies are still ongoing to assess a widely accepted application of BI evaluation in intracranial meningioma management. Several recent studies are providing increasing insights into reliable markers to improve the diagnostic and prognostic assessment of meningioma patients. The evidence of brain invasion (BI) signs and its associated variables has been focused on, and currently, scientific research is investing in the study of key aspects, different methods, and approaches to recognize and evaluate BI. This paradigm shift may have significant repercussions for the diagnostic, prognostic, and therapeutic approach to higher-grade meningioma, as long as the evidence of BI may influence patients' prognosis and inclusion in clinical trials and indirectly impact adjuvant therapy. We intended to review the current knowledge about the impact of BI in meningioma in the most updated literature and explore the most recent implications on both clinical practice and trials and future directions. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a complete overview of characteristics, preoperative applications, and potential implications of BI in meningiomas. Nineteen articles were included in the present paper and analyzed according to specific research areas. The detection of brain invasion could represent a crucial factor in meningioma patients' management, and research is flourishing and promising. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment represents the essential basis for characterizing oncological cells and supporting their growth. Along with genomic sequencing, the study of the tumor microenvironment represents a big step forward in oncological research and in the customization of treatments. Compared to gliomas, for which research has discovered greater results, the correlation between the microenvironment and tumor phenotype, and consequent prognostic implications, are still incompletely understood for intracranial meningioma. Recently, studies about the immunogenetic landscape of meningiomas have been promoted, and it is now clear that understanding the multifactorial pathogenesis of meningioma and its correlation with other specific signs (i.e., PTBE) could lead to the development of new targeted therapies, and significantly affect meningioma patients' prognosis. The role of immunotherapy is gaining ever-increasing interest in the neuro-oncological field, and this is also expanding to the management of intracranial meningioma. Meningiomas are still the most common primary adult tumor of the CNS, and even though surgery and/or radiotherapy still represent cornerstones of their treatment, recent findings strongly support the potential role of specific immune infiltrate cells, their features and genomics, for the application of personalized treatments and prognostic implications. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a descriptive and complete overview about the characteristics, role and potential implications of immunology in meningioma tumors. Seventy articles were included and analyzed in the present paper. The meningioma microenvironment reveals complex immune tumor-immune cells interactions that may definitely influence tumor progression, as well as offering unexpected opportunities for treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: [68Ga]Ga-DOTA-SSTR PET imaging has recently been introduced in the management of patients with brain tumors, mostly meningiomas and pituitary adenomas or carcinomas. The current literature demonstrated the superior diagnostic accuracy of this imaging modality, especially for lesions difficult to be detected or characterized on conventional imaging protocols, such as skull base or transosseous meningiomas. [68Ga]Ga-DOTA-SSTR PET tracers also seem to provide superior volume contouring for radiotherapy planning and may also be used to evaluate the tumor's overexpression of somatostatin receptors for devising patient-tailored peptide receptor radionuclide therapy. In this review, we comprehensively analyzed the current literature discussing the implementation of [68Ga]Ga-DOTA-SSTR PET imaging in brain tumors, further presenting ongoing clinical trials and suggesting potential future applications. Background: The development of [68Ga]Ga-DOTA-SSTR PET tracers has garnered interest in neuro-oncology, to increase accuracy in diagnostic, radiation planning, and neurotheranostics protocols. We systematically reviewed the literature on the current uses of [68Ga]Ga-DOTA-SSTR PET in brain tumors. Methods: PubMed, Scopus, Web of Science, and Cochrane were searched in accordance with the PRISMA guidelines to include published studies and ongoing trials utilizing [68Ga]Ga-DOTA-SSTR PET in patients with brain tumors. Results: We included 63 published studies comprising 1030 patients with 1277 lesions, and 4 ongoing trials. [68Ga]Ga-DOTA-SSTR PET was mostly used for diagnostic purposes (62.5%), followed by treatment planning (32.7%), and neurotheranostics (4.8%). Most lesions were meningiomas (93.6%), followed by pituitary adenomas (2.8%), and the DOTATOC tracer (53.2%) was used more frequently than DOTATATE (39.1%) and DOTANOC (5.7%), except for diagnostic purposes (DOTATATE 51.1%). [68Ga]Ga-DOTA-SSTR PET studies were mostly required to confirm the diagnosis of meningiomas (owing to their high SSTR2 expression and tracer uptake) or evaluate their extent of bone invasion, and improve volume contouring for better radiotherapy planning. Some studies reported the uncommon occurrence of SSTR2-positive brain pathology challenging the diagnostic accuracy of [68Ga]Ga-DOTA-SSTR PET for meningiomas. Pre-treatment assessment of tracer uptake rates has been used to confirm patient eligibility (high somatostatin receptor-2 expression) for peptide receptor radionuclide therapy (PRRT) (i.e., neurotheranostics) for recurrent meningiomas and pituitary carcinomas. Conclusion: [68Ga]Ga-DOTA-SSTR PET studies may revolutionize the routine neuro-oncology practice, especially in meningiomas, by improving diagnostic accuracy, delineation of radiotherapy targets, and patient eligibility for radionuclide therapies. [ABSTRACT FROM AUTHOR]