RESUMO
PURPOSE: We studied a pediatric group of patients with sellar-suprasellar tumors, aiming to develop a convolutional deep learning algorithm for radiological assistance to classify them into their respective cohort. METHODS: T1w and T2w preoperative magnetic resonance images of 226 Chilean patients were collected at the Institute of Neurosurgery Dr. Alfonso Asenjo (INCA), which were divided into three classes: healthy control (68 subjects), craniopharyngioma (58 subjects) and differential sellar/suprasellar tumors (100 subjects). RESULTS: The PPV among classes was 0.828±0.039, and the NPV was 0.919±0.063. Also explainable artificial intelligence (XAI) was used, finding that structures that are relevant during diagnosis and radiological evaluation highly influence the decision-making process of the machine. CONCLUSION: This is the first experience of this kind of study in our institution, and it led to promising results on the task of radiological diagnostic support based on explainable artificial intelligence (AI) and deep learning models.
Assuntos
Craniofaringioma , Aprendizado Profundo , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias , Humanos , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/diagnóstico , Craniofaringioma/cirurgia , Criança , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Adolescente , Pré-EscolarRESUMO
BACKGROUND: Managing residual and recurrent craniopharyngioma effectively is crucial for improving patient outcomes. This study evaluates the combined use of gamma knife and phosphorus-32 brachytherapy, offering insights into alternative, less invasive treatment strategies. METHODS: We conducted a retrospective analysis of 97 patients treated from 2010 to 2016 for residual and recurrent craniopharyngioma using gamma knife and phosphorus-32 brachytherapy. We classified these patients into three groups: superficial solid (Group A), simple cystic (Group B), and mixed cystic-solid (Group C). We assessed the treatment's effectiveness by the tumor control rates and evaluated safety by monitoring vision, endocrine function improvements, and complication rates. RESULTS: The treatment achieved complete and adequate control rates of 49.5% and 87.6%, respectively. We observed improvements in vision or visual fields in 55.1% of the patients. The morbidity rate was 15.5%. The study found no significant differences in tumor control rates among the various lesion types. CONCLUSION: The combination of gamma knife and phosphorus-32 brachytherapy presents a viable, minimally invasive alternative for treating residual and recurrent craniopharyngioma. It offers high tumor control and functional improvement rates, suggesting its potential as a preferred strategy in some instances.
Assuntos
Braquiterapia , Craniofaringioma , Recidiva Local de Neoplasia , Neoplasia Residual , Neoplasias Hipofisárias , Radiocirurgia , Humanos , Craniofaringioma/radioterapia , Braquiterapia/métodos , Estudos Retrospectivos , Feminino , Masculino , Neoplasias Hipofisárias/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Pessoa de Meia-Idade , Adolescente , Radiocirurgia/métodos , Criança , Adulto Jovem , Neoplasia Residual/radioterapia , Radioisótopos de Fósforo/uso terapêutico , Pré-Escolar , Idoso , Terapia Combinada , Resultado do TratamentoRESUMO
INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.
Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Radiocirurgia , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Humanos , Radiocirurgia/métodos , Radiocirurgia/efeitos adversos , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Fracionamento da Dose de RadiaçãoRESUMO
INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome. METHODS: Clinical and pathology data were collected from 35 patients with ACP (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multidimensional scaling. Statistical associations between clusters and clinical features were achieved using the Fisher test and global biological process interpretations were aided by Gene Ontology enrichment analyses. RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = .0006), hypomethylated in CpG island, non-CpG Island sites, and globally (P < .001), and associated with greater tumor size (24.1 vs 9.5 cm3, P = .04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell adhesion, cytoskeleton organization, and cytokine binding, and cell type-specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of patients with ACP were consistently revealed by unsupervised machine learning methods, with one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.
Assuntos
Craniofaringioma , Metilação de DNA , Epigênese Genética , Neoplasias Hipofisárias , beta Catenina , Humanos , Craniofaringioma/genética , Craniofaringioma/patologia , Masculino , Feminino , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Adolescente , Adulto , Criança , Pessoa de Meia-Idade , Adulto Jovem , beta Catenina/genética , beta Catenina/metabolismo , Pré-Escolar , Idoso , Mutação , Ilhas de CpG/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Objective: Quality of Life (QoL) has been a multifactorial concerning issue in oncology. We aimed to inspect the pre-operative QoL among patients with craniopharyngioma and to explore the potential correlations between parameters of QoL and clinical indices. Subjects and methods: We enrolled a total of 109 patients with craniopharyngioma. We utilized Short Form 36 (SF-36), Symptom Check List-90, Generalized Anxiety Disorder Questionnaire scale (GAD7), Patient Health Questionnaire Depression (PHQ9) and Pittsburgh Sleep Quality Index to prospectively evaluated their QoL. Parameters of QoL along with clinical indices were compared among sub-groups divided according to Puget classification. Correlation analyses and regression analyses were performed to detect influential determinants to self-reported wellness. Results: Patients presented impaired QoL compared with general population (p < 0.001), as assessed by SF-36. Correlation analyses indicated the detrimental influence resulting from central diabetes insipidus (CDI). Multivariate linear regression unveiled the adverse effect of CDI on Mental Component Summary (coefficient = -13.869, p= 0.007), GAD7 total score (coefficient = 2.072, p = 0.049) as well as PHQ9 total score (coefficient = 3.721, p = 0.001). Multivariate logistic regression verified CDI as a risk factor of developing depressive symptoms (OR = 6.160, p = 0.001). Conclusion: QoL of patients with craniopharyngioma was remarkably compromised before operation. CDI exerted detrimental influences on patients' QoL and it might serve as a marker for early identification of patients at risk of depression.
Assuntos
Craniofaringioma , Diabetes Insípido Neurogênico , Neoplasias Hipofisárias , Humanos , Qualidade de Vida , Craniofaringioma/complicações , Craniofaringioma/cirurgia , Fatores de Risco , Inquéritos e Questionários , Neoplasias Hipofisárias/complicaçõesRESUMO
Adamantinomatous craniopharyngioma (ACP) is a rare sellar region tumor seen in 0.5-2 cases per million persons each year,1 presenting a bimodal distribution that peaks at 5-15 years in children and 45-60 years in adults.2 Arising from embryonic remnants of the Rathke pouch epithelium, ACPs are associated with calcifications in 90% of cases and grow cranially toward the floor of the diencephalon.1 Craniopharyngiomas are benign but locally aggressive tumors, with microsurgery being the best chance of cure.3 The natural history is to compress the optic apparatus and hypothalamic-pituitary axis as they expand, with a propensity to encase the carotids. Endoscopic transbasal approaches have gained wide acceptance in the management of these tumors.4-6 However, open microsurgical approaches via pterional and orbitozygomatic craniotomies afford wider visualization of different corridors that help mitigate the surgical risks.7-9 The orbitozygomatic craniotomy allows lesions that extend above the optic chiasm to be safely approached from an inferior-to-superior corridor.9 The wide exposure of the basal arachnoid cisterns allows protection of the lenticulostriate perforators during resection.8-11 We demonstrate a step-by-step orbitozygomatic approach with dissection of the sylvian, carotid, carotid-oculomotor, chiasmatic, and lamina terminalis cisterns that allowed safe resection of a third ventricular ACP. The patient was a male in his 70s, who presented with progressive headaches and visual impairment. Magnetic resonance imaging showed a multicystic suprasellar lesion extending through the third ventricle. The surgery was performed with no complication (Video 1). Postoperative vision stabilized, and magnetic resonance imaging showed complete resection.
Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Neoplasias da Base do Crânio , Adulto , Criança , Humanos , Masculino , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Craniofaringioma/patologia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Craniotomia/métodos , Neoplasias da Base do Crânio/cirurgia , MicrocirurgiaRESUMO
Research from the last 20 years has provided important insights into the molecular pathogenesis of craniopharyngiomas (CPs). Besides the well-known clinical and histological differences between the subtypes of CPs, adamantinomatous (ACP) and papillary (PCP) craniopharyngiomas, other molecular differences have been identified, further elucidating pathways related to the origin and development of such tumors. The present minireview assesses current knowledge on embryogenesis and the genetic, epigenetic, transcriptomic, and signaling pathways involved in the ACP and PCP subtypes, revealing the similarities and differences in their profiles. ACP and PCP subtypes can be identified by the presence of mutations in CTNNB1 and BRAF genes, with prevalence around 60% and 90%, respectively. Therefore, ß-catenin accumulates in the nucleus-cytoplasm of cell clusters in ACPs and, in PCPs, cell immunostaining with specific antibody against the V600E-mutated protein can be seen. Distinct patterns of DNA methylation further differentiate ACPs and PCPs. In addition, research on genetic and epigenetic changes and tumor microenvironment specificities have further clarified the development and progression of the disease. No relevant transcriptional differences in ACPs have emerged between children and adults. In conclusion, ACPs and PCPs present diverse genetic signatures and each subtype is associated with specific signaling pathways. A better understanding of the pathways related to the growth of such tumors is paramount for the development of novel targeted therapeutic agents.
Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Adulto , Criança , Humanos , Craniofaringioma/genética , Craniofaringioma/metabolismo , Craniofaringioma/patologia , Neoplasias Hipofisárias/genética , Mutação/genética , Microambiente TumoralRESUMO
Objectives: To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Design: Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions. Methods: Clinicopathological features were retrieved from the patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths. Results: Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1 mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; P = 0.04) and a trend to recurrent disease (76% vs 24%; P = 0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597vs 0.607, IQR: 0.445-0.778; P = 0.04), but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomeres and CTNNB1-mutated aCPs. Conclusions: CTNNB1: mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres, demonstrating a relationship between the Wnt/ß-catenin pathway and telomere biology in the pathogenesis of aCPs.