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Neuroendocrinology 2020Craniopharyngioma (CP) is a rare embryonic malformation of the sellar/parasellar region with a low histological grade. Clinical manifestations are related to... (Review)
Review
Craniopharyngioma (CP) is a rare embryonic malformation of the sellar/parasellar region with a low histological grade. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. Recent insight into the molecular pathogenesis of CP opens new perspectives on targeted therapy in papillary CP harboring BRAF-V600E mutations. Further research to elucidate pathogenic mechanisms and hopefully prevent hypothalamic involvement of CP is warranted. If the tumor is favorably localized, the therapy of choice is complete resection, with care taken to preserve the optical and hypothalamic functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), the recommended therapy is a limited hypothalamus-sparing surgical strategy followed by local irradiation. Surgical treatment strategies should be based on a multidisciplinary approach involving experienced teams. Centralizing the treatment of CP in experienced "centers of excellence" and multicenter-based networks for reference assessments should be considered to assure a high standard of treatment quality. CP recurrence and progression are frequent. Irradiation has proven effective in reducing recurrences and progression. Proton beam therapy, available in a wider range in the near future, will help to avoid radio-oncological side effects. Anatomical involvement and/or surgical lesions of posterior hypothalamic areas can result in serious sequelae that compromise quality of life (QoL), such as hypothalamic obesity and psychopathological symptoms. Novel insights into neuropsychological sequelae after CP occurrence should be the basis for the development of therapeutic neuropsychological interventions. CP should be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' clinical and QoL consequences by experienced multidisciplinary teams.
Topics: Craniopharyngioma; Humans; Pituitary Neoplasms
PubMed: 31678973
DOI: 10.1159/000504512 -
American Family Physician Sep 2013Prolactinomas and nonfunctioning adenomas are the most common types of pituitary adenomas. Patients with pituitary adenomas may present initially with symptoms of... (Review)
Review
Prolactinomas and nonfunctioning adenomas are the most common types of pituitary adenomas. Patients with pituitary adenomas may present initially with symptoms of endocrine dysfunction such as infertility, decreased libido, and galactorrhea, or with neurologic symptoms such as headache and visual changes. The diagnosis may also be made following imaging done for an unrelated issue in an asymptomatic patient; this is termed a pituitary incidentaloma. Oversecretion of hormones from a dysfunctional pituitary gland may result in classic clinical syndromes, the most common of which are hyperprolactinemia (from oversecretion of prolactin), acromegaly (from excess growth hormone), and Cushing disease (from overproduction of adrenocorticotropic hormone). In the diagnostic approach to a suspected pituitary adenoma, it is important to evaluate complete pituitary function, because hypopituitarism is common. Therapy for pituitary adenomas depends on the specific type of tumor, and should be managed with a team approach to include endocrinology and neurosurgery when indicated. Dopamine agonists are the primary treatment for prolactinomas. Small nonfunctioning adenomas and prolactinomas in asymptomatic patients do not require immediate intervention and can be observed.
Topics: Adenoma; Hormones; Humans; Pituitary Neoplasms
PubMed: 24010395
DOI: No ID Found -
Brain Pathology (Zurich, Switzerland) Jul 2022Ependymal neoplasms occur at all ages and encompass multiple tumor types and subtypes that develop in the supratentorial compartment, the posterior fossa, or the spinal... (Review)
Review
Ependymal neoplasms occur at all ages and encompass multiple tumor types and subtypes that develop in the supratentorial compartment, the posterior fossa, or the spinal cord. Clinically, ependymomas represent a very heterogeneous group of tumors from rather benign subependymomas to very aggressive and often deadly childhood ependymomas of the posterior fossa. Newly identified biological markers and classification schemes, e. g. based on global DNA methylation profiling, have led to the definition of 10 types of ependymal tumors and an improved prediction of patients' outcome by applying the new classification system. While the exact genetic basis for several ependymoma types still remains unclear, the knowledge about ependymoma driving events has significantly increased within the last decade and contributed to a classification based on molecular characteristics and localization rather than histological features alone. Convincing evidence is now pointing towards gene fusions involving ZFTA or YAP1 causing the development of supratentorial ependymomas. Also, H3, EZHIP, or TERT mutations have been detected in a fraction of infratentorial ependymal tumors. Finally, MYCN amplifications have recently been identified in spinal ependymomas, in addition to the previously known mutations in NF2. This review summarizes how recent findings regarding biology, molecular tumor typing, and clinical outcome have impacted the classification of ependymomas as suggested by the updated 2021 WHO CNS tumor classification system. We focus on changes compared to the previous classification of 2016 and discuss how a formal grading could evolve in the future and guide clinicians to treat ependymoma patients.
Topics: Brain Neoplasms; Child; Ependymoma; Humans; Infratentorial Neoplasms; Supratentorial Neoplasms; World Health Organization
PubMed: 35307892
DOI: 10.1111/bpa.13068 -
Journal of Clinical Oncology : Official... Apr 2019The Children's Oncology Group trial ACNS0121 estimated event-free survival (EFS) and overall survival for children with intracranial ependymoma treated with surgery,... (Clinical Trial)
Clinical Trial
Conformal Radiation Therapy for Pediatric Ependymoma, Chemotherapy for Incompletely Resected Ependymoma, and Observation for Completely Resected, Supratentorial Ependymoma.
PURPOSE
The Children's Oncology Group trial ACNS0121 estimated event-free survival (EFS) and overall survival for children with intracranial ependymoma treated with surgery, radiation therapy, and-selectively-with chemotherapy. Treatment was administered according to tumor location, histologic grade, and extent of resection. The impacts of histologic grade, focal copy number gain on chromosome 1q, and DNA methylation profiles were studied for those undergoing surgery and immediate postoperative conformal radiation therapy (CRT).
METHODS
ACNS0121 included 356 newly diagnosed patients (ages 1 to 21 years). Patients with classic supratentorial ependymoma were observed after gross total resection (GTR). Those undergoing subtotal resection received chemotherapy, second surgery, and CRT. The remaining patients received immediate postoperative CRT after near-total resection or GTR. CRT was administered with a 1.0-cm clinical target volume margin. The cumulative total dose was 59.4 Gy, except for patients who underwent GTR and were younger than age 18 months (who received 54 Gy). Patients were enrolled between October 2003 and September 2007 and were observed for 5 years. Supratentorial tumors were evaluated for fusion; infratentorial tumors, for chromosome 1q gain. Classification of posterior fossa groups A and B was made by methylation profiles.
RESULTS
The 5-year EFS rates were 61.4% (95% CI, 34.5% to 89.6%), 37.2% (95% CI, 24.8% to 49.6%), and 68.5% (95% CI, 62.8% to 74.2%) for observation, subtotal resection, and near-total resection/GTR groups given immediate postoperative CRT, respectively. The 5-year EFS rates differed significantly by tumor grade ( = .0044) but not by age, location, fusion status, or posterior fossa A/posterior fossa B grouping. EFS was higher for patients with infratentorial tumors without 1q gain than with 1q gain (82.8% [95% CI, 74.4% to 91.2%] 47.4% [95% CI, 26.0% to 68.8%]; = .0013).
CONCLUSION
The EFS for patients with ependymoma younger than 3 years of age who received immediate postoperative CRT and for older patients is similar. Irradiation should remain the mainstay of care for most subtypes.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Child; Child, Preschool; Cytoreduction Surgical Procedures; Ependymoma; Female; Humans; Infant; Male; Progression-Free Survival; Radiotherapy, Conformal; Supratentorial Neoplasms; Transcription Factor RelA; Treatment Outcome; Young Adult
PubMed: 30811284
DOI: 10.1200/JCO.18.01765 -
Journal of Clinical Oncology : Official... Mar 2023Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging....
PURPOSE
Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging. Furthermore, CNSL diagnosis often remains unconfirmed because of contraindications for invasive stereotactic biopsies. Therefore, improved biomarkers are needed to better stratify patients into risk groups, predict treatment response, and noninvasively identify CNSL.
PATIENTS AND METHODS
We explored the value of circulating tumor DNA (ctDNA) for early outcome prediction, measurable residual disease monitoring, and surgery-free CNSL identification by applying ultrasensitive targeted next-generation sequencing to a total of 306 tumor, plasma, and CSF specimens from 136 patients with brain cancers, including 92 patients with CNSL.
RESULTS
Before therapy, ctDNA was detectable in 78% of plasma and 100% of CSF samples. Patients with positive ctDNA in pretreatment plasma had significantly shorter progression-free survival (PFS, < .0001, log-rank test) and overall survival (OS, = .0001, log-rank test). In multivariate analyses including established clinical and radiographic risk factors, pretreatment plasma ctDNA concentrations were independently prognostic of clinical outcomes (PFS HR, 1.4; 95% CI, 1.0 to 1.9; = .03; OS HR, 1.6; 95% CI, 1.1 to 2.2; = .006). Moreover, measurable residual disease detection by plasma ctDNA monitoring during treatment identified patients with particularly poor prognosis following curative-intent immunochemotherapy (PFS, = .0002; OS, = .004, log-rank test). Finally, we developed a proof-of-principle machine learning approach for biopsy-free CNSL identification from ctDNA, showing sensitivities of 59% (CSF) and 25% (plasma) with high positive predictive value.
CONCLUSION
We demonstrate robust and ultrasensitive detection of ctDNA at various disease milestones in CNSL. Our findings highlight the role of ctDNA as a noninvasive biomarker and its potential value for personalized risk stratification and treatment guidance in patients with CNSL.
UNLABELLED
[Media: see text].
Topics: Humans; Circulating Tumor DNA; Prognosis; Lymphoma, Non-Hodgkin; Supratentorial Neoplasms; Risk Assessment; Brain; Biomarkers, Tumor; Mutation
PubMed: 36542815
DOI: 10.1200/JCO.22.00826 -
Journal of Clinical Oncology : Official... Sep 2012A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine,... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG).
PATIENTS AND METHODS
Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests.
RESULTS
In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02).
CONCLUSION
PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chi-Square Distribution; Disease-Free Survival; Glioma; Humans; Kaplan-Meier Estimate; Lomustine; Middle Aged; Multivariate Analysis; Neoplasm Grading; Procarbazine; Proportional Hazards Models; Risk Assessment; Risk Factors; Supratentorial Neoplasms; Time Factors; Treatment Outcome; Vincristine; Young Adult
PubMed: 22851558
DOI: 10.1200/JCO.2011.35.8598 -
Endocrinology and Metabolism Clinics of... Mar 2015Pituitary tumors are commonly encountered intracranial neoplasms that are invariably benign. Classic oncogene mutations are not encountered in these tumors, and... (Review)
Review
Pituitary tumors are commonly encountered intracranial neoplasms that are invariably benign. Classic oncogene mutations are not encountered in these tumors, and disrupted cell cycle control and growth factor signaling likely contribute to pathogenesis and natural history. They have unique clinical features that are determined by the secreted hormone gene product.
Topics: Animals; Humans; Pituitary Neoplasms
PubMed: 25732636
DOI: 10.1016/j.ecl.2014.11.004 -
Neuroendocrinology 2020Jakob Erdheim (1874-1937) first described craniopharyn-giomas (CPs) as "hypophyseal duct tumours" and postulated the existence of two tumour types based on their... (Review)
Review
Jakob Erdheim (1874-1937) first described craniopharyn-giomas (CPs) as "hypophyseal duct tumours" and postulated the existence of two tumour types based on their histological features: (1) an aggressive type showing similarities to adamantinomas (tumours of the jaw) and (2) a more benign form characterised by the presence of papillary structures. More than a century later, these initial observations have been confirmed; based on their distinct genetic, epigenetic, and histological features, the WHO classifies CPs into two types: adamantinomatous CPs (ACPs) and papillary CPs (PCPs). Considerable knowledge has been generated on the biology of CPs in the last 20 years. Mutations in CTNNB1 (encoding β-catenin) are prevalent in ACP, whilst PCPs frequently harbour mutations in BRAF (p.BRAF-V600E). The consequence of these mutations is the activation of either the WNT/β-catenin (ACP) or the MAPK/ERK (PCP) pathway. Murine models support a critical role for these mutations in tumour formation and have provided important insights into tumour pathogenesis, mostly in ACP. A critical role for cellular senescence has been uncovered in murine models of ACP with relevance to human tumours. Several gene profiling studies of human and murine ACP tumours have identified potential targetable pathways, and novel therapeutic agents are being used in clinical and pre-clinical research, in some cases with excellent results. In this review, we will present the accumulated knowledge on the biological features of these tumours and summarise how these advances are being translated into potential novel treatments.
Topics: Animals; Craniopharyngioma; Humans; Pituitary Neoplasms
PubMed: 32126562
DOI: 10.1159/000506904 -
Neuroendocrinology 2020The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon... (Review)
Review
The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon cancers, and rarely from other solid and hematologic malignancies. Almost every cancer has been reported as a source of pituitary metastasis. Pituitary metastasis can involve both the anterior and posterior lobes, but the neuro-hypophysis is mainly involved. Clinical manifestations include diabetes insipidus, hypopituitarism, headache, visual disturbances, ophthalmoplegia, and also compression of adjacent structures by aggressive tumor masses. Metastatic spread to the pituitary from a distant primary malignancy is commonly associated with metastases to other tissues and poor prognosis, unless efficient systemic targeted medical treatment is available for the primary cancer (melanoma, lymphoma).
Topics: Humans; Pituitary Neoplasms
PubMed: 32101869
DOI: 10.1159/000506810 -
Journal of Neurosurgery Jun 2016OBJECT Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of... (Meta-Analysis)
Meta-Analysis Review
OBJECT Meningioma is the most common benign intracranial tumor, and patients with supratentorial meningioma frequently suffer from seizures. The rates and predictors of seizures in patients with meningioma have been significantly under-studied, even in comparison with other brain tumor types. Improved strategies for the prediction, treatment, and prevention of seizures in patients with meningioma is an important goal, because tumor-related epilepsy significantly impacts patient quality of life. METHODS The authors performed a systematic review of PubMed for manuscripts published between January 1980 and September 2014, examining rates of pre- and postoperative seizures in supratentorial meningioma, and evaluating potential predictors of seizures with separate meta-analyses. RESULTS The authors identified 39 observational case series for inclusion in the study, but no controlled trials. Preoperative seizures were observed in 29.2% of 4709 patients with supratentorial meningioma, and were significantly predicted by male sex (OR 1.74, 95% CI 1.30-2.34); an absence of headache (OR 1.77, 95% CI 1.04-3.25); peritumoral edema (OR 7.48, 95% CI 6.13-9.47); and non-skull base location (OR 1.77, 95% CI 1.04-3.25). After surgery, seizure freedom was achieved in 69.3% of 703 patients with preoperative epilepsy, and was more than twice as likely in those without peritumoral edema, although an insufficient number of studies were available for formal meta-analysis of this association. Of 1085 individuals without preoperative epilepsy who underwent resection, new postoperative seizures were seen in 12.3% of patients. No difference in the rate of new postoperative seizures was observed with or without perioperative prophylactic anticonvulsants. CONCLUSIONS Seizures are common in supratentorial meningioma, particularly in tumors associated with brain edema, and seizure freedom is a critical treatment goal. Favorable seizure control can be achieved with resection, but evidence does not support routine use of prophylactic anticonvulsants in patients without seizures. Limitations associated with systematic review and meta-analysis should be considered when interpreting these results.
Topics: Humans; Meningioma; Seizures; Supratentorial Neoplasms
PubMed: 26636386
DOI: 10.3171/2015.4.JNS142742