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Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care.
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Inteligencia Artificial , Diagnóstico por Imagen/métodos , Neoplasias/diagnóstico por imagen , HumanosRESUMEN
An alternative to therapeutic targeting of oncogenes is to perform "synthetic lethality" screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of mutant KRAS-driven cancers and demonstrate the potential of RNAi screens for discovering functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers with "undruggable" genetic alterations.
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Neoplasias/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular , Humanos , Ratones , Mutación , Células 3T3 NIH , Neoplasias/genética , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras) , Interferencia de ARN , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismoRESUMEN
OBJECTIVE: This study describes an innovative optic nerve MRI protocol for better delineating optic nerve anatomy from neighboring pathology. METHODS: Twenty-two patients undergoing MRI examination of the optic nerve with the dedicated protocol were identified and included for analysis of imaging, surgical strategy, and outcomes. T2-weighted and fat-suppressed T1-weighted gadolinium-enhanced images were acquired perpendicular and parallel to the long axis of the optic nerve to achieve en face and in-line views along the course of the nerve. RESULTS: Dedicated optic nerve MRI sequences provided enhanced visualization of the nerve, CSF within the nerve sheath, and local pathology. Optic nerve sequences leveraged the "CSF ring" within the optic nerve sheath to create contrast between pathology and normal tissue, highlighting areas of compression. Tumor was readily tracked along the longitudinal axis of the nerve by images obtained parallel to the nerve. The findings augmented treatment planning. CONCLUSIONS: The authors present a dedicated optic nerve MRI protocol that is simple to use and affords improved cross-sectional and longitudinal visualization of the nerve, surrounding CSF, and pathology. This improved visualization enhances radiological evaluation and treatment planning for optic nerve lesions.
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Imagen por Resonancia Magnética , Nervio Óptico , Humanos , Estudios Transversales , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/cirugía , Imagen por Resonancia Magnética/métodosRESUMEN
Chordomas, arising from notochord remnants, are rare neoplasms with aggressive growth patterns despite their histologically low-grade nature. This review explores their embryological origins, molecular markers like brachyury, and genetic alterations driving pathogenesis. Diagnosis relies on advanced imaging and biopsy confirmation due to overlapping features with chondrosarcoma. The WHO classification distinguishes conventional, dedifferentiated, and poorly differentiated chordomas, each with distinct prognostic implications. Recent genomic analyses uncovered recurrent mutations in PI3K signaling pathways and chromatin remodeling genes, informing prognostic models. Surgery remains the cornerstone of treatment, though adjuvant radiation complements surgical resection. Although chordomas are generally considered refractory to medical therapy, emerging targeted molecular strategies show potential promise in ongoing trials. This review aims to provide a concise yet comprehensive overview of chordomas, guiding clinicians in diagnosis, treatment, and prognostication for improved patient outcomes.
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Cordoma , Humanos , Cordoma/genética , Cordoma/terapia , Cordoma/patología , Cordoma/diagnóstico , Pronóstico , Biomarcadores de Tumor/genética , Mutación , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Manejo de la Enfermedad , Proteínas FetalesRESUMEN
INTRODUCTION: Surgical resection has long been the treatment of choice for meningiomas and is considered curative in many cases. Indeed, the extent of resection (EOR) remains a significant factor in determining disease recurrence and outcome optimization for patients undergoing surgery. Although the Simpson Grading Scale continues to be widely accepted as the measure of EOR and is used to predict symptomatic recurrence, its utility is under increasing scrutiny. The influence of surgery in the definitive management of meningioma is being re-appraised considering the rapid evolution of our understanding of the biology of meningioma. DISCUSSION: Although historically considered "benign" lesions, meningioma natural history can vary greatly, behaving with unexpectedly high recurrence rates and growth which do not always behave in accordance with their WHO grade. Histologically confirmed WHO grade 1 tumors may demonstrate unexpected recurrence, malignant transformation, and aggressive behavior, underscoring the molecular complexity and heterogeneity. CONCLUSION: As our understanding of the clinical predictive power of genomic and epigenomic factors matures, we here discuss the importance of surgical decision-making paradigms in the context of our rapidly evolving understanding of these molecular features.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/genética , Meningioma/cirugía , Meningioma/patología , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/patología , Procedimientos Neuroquirúrgicos , Estudios RetrospectivosRESUMEN
INTRODUCTION: Sparsely granulated somatotroph adenoma/tumor (SGST) is thought to be more clinically aggressive than densely granulated somatotroph adenoma/tumor (DGST). However, the literature is not entirely consistent as to the disparate demographic and behavioral features of these subtypes. In this study, we conducted a meta-analysis to further clarify the demographic, clinicopathological, prognostic, and molecular characteristics of SGST versus DGST. METHODS: We accessed two electronic databases to search for potential data. Pooled estimates of odds ratio (OR), mean difference (MD), and corresponding 95% confidence interval (CI) were calculated using the random-effect model. RESULTS: SGST was associated with younger patient age and lower male-to-female ratio (p < 0.001) compared to DGST. Clinically, SGST had larger tumor size and high rate of cavernous sinus and suprasellar extension (p < 0.001) than DGST. During postoperative follow-up, SGST was associated with a lower endocrinological remission rate (OR 0.60; 95% CI 0.40 to 0.90; p = 0.01) and a poorer response rate to SRL (OR 0.16; 95% CI 0.08-0.35; p < 0.001) in comparison to DGST. The prevalence of GSP mutations was significantly lower in SGST (OR 0.36; 95% CI 0.17 to 0.79; p = 0.01). CONCLUSION: SGST and DGST were demographically, clinicopathologically, and molecularly different from each other with the former associated with adverse treatment outcomes and poor response to medical therapy. There are still gaps in translational studies that could help us better understand the behavior of these tumors and identify potential targets in the treatment of sparsely granulated tumors.
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Adenoma , Adenoma Hipofisario Secretor de Hormona del Crecimiento , Neoplasias Hipofisarias , Masculino , Humanos , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Adenoma/cirugía , Pronóstico , Resultado del TratamientoRESUMEN
The management of clinically aggressive meningiomas remains challenging due to limited treatment options aside from surgical removal and radiotherapy. High recurrence rates and lack of effective systemic therapies contribute to the unfavorable prognosis of these patients. Accurate in vitro and in vivo models are critical for understanding meningioma pathogenesis and to identify and test novel therapeutics. In this chapter, we review cell models, genetically engineered mouse models, and xenograft mouse models, with special emphasis on the field of application. Finally, promising preclinical 3D models such as organotypic tumor slices and patient-derived tumor organoids are discussed.
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Neoplasias Meníngeas , Meningioma , Humanos , Animales , Ratones , Meningioma/genética , Meningioma/terapia , Agresión , Modelos Animales de Enfermedad , Organoides , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/terapiaRESUMEN
OBJECTIVE: The aim of this study was to report the authors' experience developing a Lean Six Sigma clinical care pathway (CCP) for endoscopic endonasal transsphenoidal operations. METHODS: Using Lean Six Sigma quality improvement principles-including the define, measure, analyze, improve, and control framework-the authors developed a CCP for endoscopic endonasal transsphenoidal operations, incorporating preoperative, intraoperative, and inpatient and outpatient postoperative phases of care. Efficacy and quality metrics were defined as postoperative length of stay (LOS), presentation to the emergency department (ED) or readmission within 30 days of discharge, and hospital charges. The study included all adult patients who underwent elective endoscopic endonasal resection for pituitary adenoma, Rathke's cleft cyst, craniopharyngioma, pituicytoma, or arachnoid cyst during the sampling period (April 1, 2018, to December 31, 2022). RESULTS: Two hundred twenty-eight patients met criteria and were included; 94 were treated before and 134 were treated after implementation of the CCP. Differences between groups in age, gender, race, BMI, American Society of Anesthesiologists classification, geographic distribution, preoperative serum sodium, tumor size, adenoma functional status, and prior surgery were not significant. The mean postoperative LOS significantly decreased from 4.5 to 1.7 days following CCP implementation (p < 0.0001); LOS variability also decreased, with the standard deviation declining from 3.1 to 1.5 days. The proportion of patients discharged on postoperative day (POD) 1 significantly increased from 0% to 61.9% (p < 0.0001). Fewer than one-quarter of the patients (23.4%) were discharged by POD 2 prior to the CCP, while 88.8% of were discharged by POD 2 after CCP implementation (p < 0.0001). Rates of 30-day ED presentations or readmissions were not significantly different (2.1% vs 6.0%, p = 0.20, and 7.5% vs 6.7%, p > 0.99, respectively). Mean per-patient hospital costs declined from $38,326 to $26,289 (p < 0.0001), with an associated change in cost variability from a standard deviation of $16,716 to $12,498. CONCLUSIONS: CCP implementation significantly improved LOS and costs of endoscopic endonasal resection, without adversely impacting postoperative ED presentations or readmissions.
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Adenoma , Craneofaringioma , Neoplasias Hipofisarias , Adulto , Humanos , Mejoramiento de la Calidad , Neoplasias Hipofisarias/cirugía , Hipófisis/patología , Nariz/cirugía , Endoscopía , Adenoma/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: H3G34-mutant diffuse hemispheric glioma (DHG) is recognized as a new, distinct entity in the latest World Health Organization classification for central nervous system tumors and is associated with a particularly aggressive course. The authors performed a systematic review and pooled analysis to investigate the frequency of genetic events in these tumors and to determine whether these events were associated with survival trends. METHODS: Two electronic databases were accessed to search for relevant data. Included criteria were studies that had individual patient data on H3.3 G34-mutant gliomas. To analyze the impact of genetic events on overall survival, Kaplan-Meier analysis and Cox regression models were used, and corresponding hazard ratios and 95% confidence intervals were computed. RESULTS: In total, 20 studies with 257 H3G34-mutant DHGs were included for integrated analyses. The H3 glycine-to-valine (H3G34V) mutation showed a significantly worse prognosis than the glycine-to-arginine (H3G34R) mutation (median overall survival, 9.9 vs 14.8 months; hazard ratio, 3.040; 95% confidence interval, 1.208-7.651; P = .018), and this result remained statistically significant in the multivariate Cox regression model. Among H3G34 DHGs, TP53 mutation was the most common genetic alteration (94.9%), followed by ATRX alterations (87.5%), MGMT methylation (79.5%), and PDGFRA alterations (33.2%). The presence of PDGFRA amplification or EGFR amplification conferred poor survival. After adjusting for age and sex, these alterations were still independent indicators for adverse outcomes. CONCLUSIONS: The authors highlight the important role of molecular stratification of H3G34 DHGs, which may help refine our understanding of the natural history of this group of malignant tumors.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Genotipo , Glioma/patología , Glicina/genética , Humanos , PronósticoRESUMEN
INTRODUCTION: Gliosarcomas are extremely rare malignant brain tumors, which can be classified as primary gliosarcoma (PGS) if the tumors arise de novo or secondary gliosarcoma (SGS) in patients who had previously been treated for glioblastoma. Given their rarity, it is unclear if PGS is clinically and genetically different from SGS. This meta-analysis aimed to investigate the clinicopathological features, prognostic survivals, and molecular profiles of these rare tumors. METHODS: We searched PubMed and Web of Science for relevant studies. Odds ratio (OR), hazard ratio (HR), and their 95% confidence intervals (CI) were pooled using the random-effect model. RESULTS: We included eight studies with 239 PGS and 79 SGS for meta-analyses. Compared to PGS, SGS occurred at a younger age and had lower rates of gross total resection and radiation therapy. Bevacizumab was more commonly administered in SGS. SGS patients had a significantly worse PFS (HR 0.60; 95% CI 0.40-0.89) and OS (HR 0.46; 95% CI 0.31-0.68) in comparison to PGS. The incidences of EGFR mutation, IDH mutation, and MGMT methylation were not statistically different between PGS and SGS. CONCLUSION: Our results demonstrated that PGS and SGS had distinct clinicopathological profiles and prognoses but shared similar genetic profiles. This study facilitates our understanding of how these two malignant brain tumors behave clinically, but future studies will be required to elucidate the genetic pathways of PGS and SGS.
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Neoplasias Encefálicas , Glioblastoma , Gliosarcoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Glioblastoma/patología , Gliosarcoma/genética , Gliosarcoma/patología , Gliosarcoma/terapia , Humanos , Mutación , PronósticoRESUMEN
INTRODUCTION: Diffuse midline gliomas (DMGs) are infiltrative midline gliomas harboring H3K27M mutations and are generally associated with poor outcomes. H3K27M mutations include mutations in HIST1H3B/C (H3.1), HIST2H3B/D (H3.2), or H3F3A (H3.3) genes. It is still unclear whether these mutations each portend a universally poor prognosis, or if there are any factors which modulate outcome. The main objective of this study was to study overall survival (OS) of H3.1 versus H3.3 K27M-mutant DMGs in pediatric and adult patients. METHODS: PubMed and Web of Science were searched, and we included studies if they have individual patient data of DMGs with available H3K27M genotype. Kaplan-Meier analysis and Cox regression models were used to analyze the survival of H3.1 and H3.3 mutations in each subgroup. RESULTS: We included 26 studies with 102 and 529 H3.1 and H3.3-mutant DMGs, respectively. The H3.1 mutation was more commonly seen in younger age. In pediatric population, H3.3 mutation conferred a shorter survival (median OS of 10.1 vs 14.2 months; p < 0.001) in comparison to H3.1-positive patients, which was further confirmed in the multivariate Cox analysis. Conversely, H3.3 was associated with a prolonged survival in adult patients as compared with H3.1 mutation (median OS of 14.4 vs 1.7 months; p = 0.019). CONCLUSION: We demonstrated that the prognosis of H3.1 and H3.3 K27M mutation in DMG patients is modulated by patient age. Routine H3K27M mutation genotyping in newly diagnosed DMGs may further stratify patients with these difficult tumors.
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Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Niño , Glioma/patología , Histonas/genética , Humanos , Mutación , PronósticoRESUMEN
INTRODUCTION: Esthesioneuroblastoma (ENB) is an uncommon primary sinonasal tumor which can extend intracranially. Exactly how to classify them pathologically still remains discrepant; the Hyams grading system, for example, has not been universally adopted. This individual patient data (IPD) meta-analysis aimed to investigate the prognostic implication of each Hyams grade on patient outcomes. METHODS: We accessed two electronic databases including PubMed and Web of Science. Raw patient data from potential articles were extracted. To examine the associations of various clinicopathological factors with the Hyams grades, we utilized Chi-square, t-test, and Mann-Whitney, as appropriate. Log-rank test and Cox regression analysis were used to elucidate the impact of the Hyams grades on recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS) of ENB patients. RESULTS: We included 33 studies with 492 ENB patients. We found significant associations of Kadish stages, Dulguerov stages, rates of recurrence, metastasis, and patient mortality with Hyams grade. Log-rank tests and Cox regression models demonstrated significant differences in RFS and OS of Hyams grade I - II, grade III, and grade IV patients. There was no statistical difference in RFS and OS of Hyams grade I and II. Radiotherapy was only effective in grade III - IV ENBs and chemotherapy showed no benefits to patients. CONCLUSION: We verify that the Hyams grading system appears to be a reliable prognostic indicator to assess ENB patient outcomes. Consolidating the Hyams grading system into a three-tier system based on similar clinical outcomes of grades I and II may simplify this classification schema.
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Estesioneuroblastoma Olfatorio , Cavidad Nasal , Neoplasias Nasales , Estesioneuroblastoma Olfatorio/patología , Estesioneuroblastoma Olfatorio/terapia , Humanos , Cavidad Nasal/patología , Estadificación de Neoplasias , Neoplasias Nasales/patología , Neoplasias Nasales/terapia , Pronóstico , Estudios RetrospectivosRESUMEN
INTRODUCTION: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients. METHODS: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS). RESULT: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR 1.446; 95% CI 1.143-1.829) whereas ACVR1 (HR 0.712; 95% CI 0.518-0.976) and FGFR1 mutations (HR 0.408; 95% CI 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR 0.620; 95% CI 0.386-0.996). Adjusted for age, gender, and tumor location, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors. CONCLUSIONS: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. This may aid neuro-oncologists in appropriate risk stratification.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/genética , Glioma/genética , Histonas/genética , Humanos , Mutación , PronósticoRESUMEN
INTRODUCTION: Meningioma is the most common primary brain tumor. Most meningiomas are benign; however, a subset of these tumors can be aggressive, presenting with early or multiple tumor recurrences that are refractory to neurosurgical resection and radiotherapy. There is no standard systemic therapy for these patients, and post-surgical management of these patients is usually complicated due to lack of accurate prediction for tumor progression. METHODS: In this review, we summarise the crucial immunosuppressive role of checkpoint regulators, including PD-1 and PD-L1 interacting in the tumor microenvironment, which has led to efforts aimed at targeting this axis. RESULTS: Since their discovery, checkpoint inhibitors have significantly improved the outcome in many types of cancers. Currently, targeted therapy for PD-1 and PD-L1 proteins are being tested in several ongoing clinical trials for brain tumors such as glioblastoma. More recently, there have been some reports implicating increased PD-L1 expression in high-grade (WHO grades II and III) meningiomas. Several clinical trials are underway to assess the efficacy of checkpoint inhibitors in the therapeutic management of patients with aggressive meningiomas. Here, we review the immune suppressive microenvironment in meningiomas, and then focus on clinical and pathological characterization and tumor heterogeneity with respect to PD-L1 expression as well as challenges associated with the assessment of PD-L1 expression in meningioma. CONCLUSION: We conclude with a brief review of ongoing clinical trials using checkpoint inhibitors for the treatment of high-grade and refractory meningiomas.
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Antígeno B7-H1/genética , Neoplasias Encefálicas/genética , Genes cdc/genética , Meningioma/genética , Animales , Antígeno B7-H1/biosíntesis , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Humanos , Inmunohistoquímica , Meningioma/patología , Meningioma/terapiaRESUMEN
INTRODUCTION: Spindle cell oncocytoma (SCO) is an extremely rare sellar neoplasm. No observational studies have been reported so far to investigate the prognostic factors of this tumor entity. This systematic review aimed to elucidate the risk factors for tumor recurrence/progression of SCO. METHODS: We searched for relevant articles in PubMed and Web of Science. Studies providing individual patient data with follow-up information of SCO cases were included. Pearson's Chi square and Fisher's exact test were used for categorical variables while t test or Mann-Whitney tests were applied for continuous variables, if applicable. We used the Cox regression model to assess the effects of suspected variables on progression-free survival (PFS). RESULTS: A total of 38 case reports and case series comprising of 67 SCOs were included for final analyses. Recurrent/progressive tumors were noted in 38.8% of cases. Among the clinicopathological factors, only the extent of surgery was a significant risk factor for tumor recurrence/progression. SCO patients with a subtotal resection had a significantly higher risk for tumor relapse in comparison with complete removal (HR 7.51; 95% CI 1.75-32.31; p = 0.007). CONCLUSION: Our study demonstrated the characteristic clinicopathological features of SCOs with a high recurrence/progression rate and outlined the predictor for tumor relapse. Failure to achieve gross total resection is the only risk factor for tumor recurrence/progression.
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Adenoma Oxifílico , Neoplasias Hipofisarias , Adenoma Oxifílico/cirugía , Humanos , Recurrencia Local de Neoplasia , Hipófisis , Neoplasias Hipofisarias/cirugía , Factores de RiesgoRESUMEN
PURPOSE: Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities. METHODS: 72 pituitary tumors were evaluated for expression of the immune regulatory markers programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and tumor necrosis factor receptor superfamily member 4 (OX40) by immunohistochemistry (IHC). Lymphocyte infiltration, macrophage infiltration, and angiogenesis were analyzed using IHC. Expression of pituitary tumor initiating cell marker CD15 and mismatch repair proteins MutS protein homolog 2 (MSH2) and MutS protein homolog 6 (MSH6) was also assessed. RESULTS: Pituitary tumors were infiltrated by macrophages and T cells, and they expressed varying levels of PD-L1, PD-L2, VISTA, LAG3, and OX40. Functional tumors and tumors with high expression of tumor stem cell markers had higher immune cell infiltration and greater expression of immunosuppressive checkpoint regulators. Increased PD-L1 and LAG3 and reduced VISTA were observed in primary tumors compared to recurrent tumors. CONCLUSION: Immune cell infiltration and checkpoint regulator expression vary depending on functional status and presence of pituitary tumor initiating cells. Functional tumors may have a particularly immunosuppressive microenvironment. Further studies of immune checkpoint blockade of pituitary tumors, particularly functional tumors, are warranted, though combination therapy may be required.
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Antígeno B7-H1 , Neoplasias Hipofisarias , Humanos , Inmunohistoquímica , Proteínas MutS , Recurrencia Local de Neoplasia , Neoplasias Hipofisarias/genética , Microambiente TumoralRESUMEN
BACKGROUND: There are controversial results concerning the prognostic implication of TERT promoter mutation in glioma patients concerning MGMT status. In this meta-analysis, we investigated whether there are any interactions of these two genetic markers on the overall survival (OS) of glioma patients. METHODS: Electronic databases including PubMed and Web of Science were searched for relevant studies. Hazard ratio (HR) and its 95% confidence interval (CI) for OS adjusted for selected covariates were calculated from the individual patient data (IPD), Kaplan-Meier curve (KMC), or directly obtained from the included studies. RESULTS: A total of nine studies comprising 2819 glioma patients were included for meta-analysis. Our results showed that TERT promoter mutation was associated with a superior outcome in MGMT-methylated gliomas (HR = 0.73; 95% CI = 0.55-0.98; p-value = 0.04), whereas this mutation was associated with poorer survival in gliomas without MGMT methylation (HR = 1.86; 95% CI = 1.54-2.26; p-value < 0.001). TERT-mutated glioblastoma (GBM) patients with MGMT methylation benefited from temozolomide (TMZ) treatment (HR = 0.33; 95% CI = 0.23-0.47; p-value < 0.001). MGMT methylation was not related with any improvement in OS in TERT-wild type GBMs (HR = 0.80; 95% CI = 0.56-1.15; p-value = 0.23). CONCLUSIONS: The prognostic value of TERT promoter mutation may be modulated by MGMT methylation status. Not all MGMT-methylated GBM patients may benefit from TMZ; it is possible that only TERT-mutated GBM with MGMT methylation, in particular, may respond.
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Neoplasias Encefálicas/genética , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioma/genética , Telomerasa/genética , Proteínas Supresoras de Tumor/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Femenino , Glioma/metabolismo , Glioma/mortalidad , Humanos , Masculino , Mutación , Pronóstico , Análisis de Supervivencia , Telomerasa/metabolismo , Proteínas Supresoras de Tumor/metabolismoRESUMEN
PURPOSE: To evaluate surgical resection with brachytherapy placement as a salvage treatment in patients with recurrent high-grade meningioma who exhausted prior external beam treatment options. METHODS: Single-center retrospective review of our institutional experience of brachytherapy implantation from 2012 to 2018. The primary outcome of the study was progression free survival (PFS). Secondary outcomes included overall survival (OS) and complications. A matched cohort of patients not treated with brachytherapy over the same time period was evaluated as a control group. All patients had received prior radiation treatment and underwent planned gross total resection (GTR) surgery. RESULTS: A total of 27 cases were evaluated. Compared with prior treatment, brachytherapy implantation demonstrated a statistically significant improvement in tumor control [HR 0.316 (0.101 - 0.991), p = 0.034]. PFS-6 and PFS-12 were 92.3% and 84.6%, respectively. Compared with the matched control cohort, brachytherapy treatment demonstrated improved PFS [HR 0.310 (0.103 - 0.933), p = 0.030]. Overall survival was not statistically significantly different between groups [HR 0.381 (0.073 - 1.982), p = 0.227]. Overall postoperative complications were comparable between groups, although there was a higher incidence of radiation necrosis in the brachytherapy cohort. CONCLUSION: Brachytherapy with planned GTR improved PFS in recurrent high-grade meningioma patients who exhausted prior external beam radiation treatment options. Future improvement of brachytherapy dose delivery methods and techniques may continue to prolong control rates and improve outcomes for this challenging group of patients.
Asunto(s)
Braquiterapia/mortalidad , Neoplasias Meníngeas/mortalidad , Meningioma/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Neurocirugia/métodos , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirugía , Meningioma/patología , Meningioma/radioterapia , Meningioma/cirugía , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Surgical outcomes and healthcare utilization have been shown to vary based on patient insurance status. We analyzed whether patients' insurance affects case urgency for and readmission after craniotomy for meningioma resection, using benign meningioma as a model system to minimize confounding from the disease-related characteristics of other neurosurgical pathologies. METHODS: We analyzed 90-day readmission for patients who underwent resection of a benign meningioma in the Nationwide Readmission Database from 2014-2015. RESULTS: A total of 9783 meningioma patients with private insurance (46%), Medicare (39%), Medicaid (10%), self-pay (2%), or another scheme (3%) were analyzed. 72% of all cases were elective; with 78% of cases in privately insured patients being elective compared to 71% of Medicare (p > 0.05), 59% of Medicaid patients (OR 2.3, p < 0.001), and 49% of self-pay patients (OR 3.4, p < 0.001). Medicare (OR 1.5, p = 0.002) and Medicaid (OR 1.4, p = 0.035) were both associated with higher likelihood of 90-day readmission compared to private insurance. In comparison, 30-day analyses did not unveil this discrepancy between Medicaid and privately insured, highlighting the merit for longer-term outcomes analyses in value-based care. Patients readmitted within 30 days versus those with later readmissions possessed different characteristics. CONCLUSIONS: Compared to patients with private insurance coverage, Medicaid and self-pay patients were significantly more likely to undergo non-elective resection of benign meningioma. Medicaid and Medicare insurance were associated with a higher likelihood of 90-day readmission; only Medicare was significant at 30 days. Both 30 and 90-day outcomes merit consideration given differences in readmitted populations.
Asunto(s)
Craneotomía/economía , Hospitales/estadística & datos numéricos , Cobertura del Seguro , Seguro de Salud , Meningioma/economía , Readmisión del Paciente/economía , Readmisión del Paciente/estadística & datos numéricos , Anciano , Craneotomía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Medicaid , Neoplasias Meníngeas/economía , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Meningioma/patología , Meningioma/cirugía , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Estados UnidosRESUMEN
Endoscopic endonasal skull base surgery has emerged as the treatment modality of choice for a range of skull base lesions, particularly pituitary adenomas. However, navigation and manipulation of the nasal corridor and paranasal sinuses requires that surgeons are aware of effective techniques to maximize patient outcomes and avoid sinonasal morbidity postoperatively. This paper is a narrative review aimed to provide an updated and consolidated report on the perioperative management of the nasal corridor and paranasal sinuses in the setting of endoscopic skull base surgery for pituitary disease. Anatomic variants and common surgical techniques are discussed. Post-operative complications are evaluated in detail. Understanding the structural implications of the endonasal approach to the sphenoid is crucial to optimization of the surgical outcomes. We propose guidelines for perioperative management of endoscopic endonasal skull base surgery for pituitary diseases. Standardized treatment algorithms can improve patient satisfaction, and increase the comparability and the quality of reported information across research studies.