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Child's Nervous System : ChNS :... Apr 2022Pediatric pituitary adenomas (pPAs) are uncommon. Thus, their presentation and outcomes after treatment are less well-understood than those of pituitary adenomas in...
Pediatric pituitary adenomas are more aggressive, more likely to be hormone producing and are more difficult to cure than adult pituitary adenomas: case series and systematic literature review.
PURPOSE
Pediatric pituitary adenomas (pPAs) are uncommon. Thus, their presentation and outcomes after treatment are less well-understood than those of pituitary adenomas in adulthood (aPAs).
METHODS
A retrospective chart review was conducted for all patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) for pPA at NewYork-Presbyterian Hospital/Weill Cornell Medicine (NYP/WCM) from 2005-2020. Eleven patients were identified, and information pertaining to age, sex, adenoma characteristics, procedural details, and outcomes was reviewed. A systematic review of the literature was also performed to compare outcomes of EETS versus microscopic endonasal transsphenoidal surgery (METS) for pPA.
RESULTS
From 2005-2020, 11 patients underwent EETS for pPA at NYP/WCM. Mean age at operation was 14.9 ± 2.7 years, and 5 patients (45.5%) were male. 10 adenomas (90.9%) were hormone-producing. Of the functional adenomas, 8 (80.0%) were PRL-secreting and 2 (20.0%) were GH-secreting. Maximum adenoma diameter (MAD) ranged from 1.2-5.1 cm, with a median of 1.55 cm. Cavernous sinus invasion (CSI) occurred in 2 patients with macroprolactinoma. Gross total resection (GTR) was achieved in 10 (90.9%). Biochemical remission occurred in 5/10 (50.0%). Post-operative complications were documented in 8 cases (72.7%) and included diabetes insipidus, hypopituitarism, sinusitis, weight gain, cerebrospinal fluid leak, meningitis, and hydrocephalus. Systematic literature review of 105 microscopic and 175 endoscopic cases revealed high frequency of hormone-producing tumors (83.6%) and similar rates of GTR (82.4% vs 85.1%) and biochemical cure (75.8% vs 64.3%).
CONCLUSIONS
pPAs are more likely to be hormone producing and may be more aggressive and difficult to cure than aPAs. EETS is an effective treatment, although complication rates may be higher than in adult populations.
Topics: Adenoma; Adult; Child; Hormones; Humans; Male; Pituitary Neoplasms; Prolactinoma; Retrospective Studies; Treatment Outcome
PubMed: 35048170
DOI: 10.1007/s00381-022-05445-3 -
Neurosurgical Review Feb 2020Craniopharyngiomas (CPs) are rare, benign tumors derived from Rathke's pouch, known for their high recurrence rates and associated morbidity and mortality. Despite...
Craniopharyngiomas (CPs) are rare, benign tumors derived from Rathke's pouch, known for their high recurrence rates and associated morbidity and mortality. Despite significant investigation on risk factors for recurrence, a lack of consensus persists. Recent research suggests that specific histopathological and molecular characteristics are prognostic for disease progression. In this systematic review, we analyzed and consolidated key features of CPs that contribute to increased recurrence rates. This systematic review was performed in accordance with PRISMA guidelines. A search string was created with the keywords "craniopharyngioma," "histology," "histopathology," "molecular," and "recurrence." Literature was collected from 2006 to 2016 on the PubMed/Medline and Web of Science databases. The initial search resulted in 242 papers, examined with inclusion and exclusion criteria. The final review included a total of 37 studies, 36 primary studies covering a total of 1461 patients and 1 previous meta-analysis. Cystic lesions and whorl-like arrays were found to be associated with increased recurrence, while previously considered reactive gliosis and finger-shaped protrusions were not. The genetic elements found to be associated with increased risk of recurrence were Ki-67, Ep-CAM, PTTG-1, survivin, and certain RAR isotypes, as well as the glycoproteins osteonectin and chemokines CXCL12/CXCR4. The effects of VEGF, HIF-1α, and p53, despite extensive study, yielded conflicting results. Certain histopathological and molecular characteristics of CPs provide insight into their pathogenesis, likelihood of recurrence, and potential novel targets for therapy.
Topics: Craniopharyngioma; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Predictive Value of Tests; Prognosis; Risk Assessment
PubMed: 29666970
DOI: 10.1007/s10143-018-0978-5 -
World Neurosurgery Aug 2022Atypical teratoid/rhabdoid tumor (ATRT) is a rare malignant neoplasm in the pediatric population. ATRT is characterized by rhabdoid cells combined with the loss of... (Review)
Review
The Impact of Surgical Resection and Adjuvant Therapy on Survival in Pediatric Patients with Atypical Teratoid/Rhabdoid Tumor: Systematic Review and Pooled Survival Analysis.
BACKGROUND
Atypical teratoid/rhabdoid tumor (ATRT) is a rare malignant neoplasm in the pediatric population. ATRT is characterized by rhabdoid cells combined with the loss of either the INI1 (integrase interactor 1) or BRG1 (Brahma-related gene-1) protein.
OBJECTIVE
To systematically review and analyze patient and tumor characteristics, prognosis, and impact of treatment on survival in pediatric patients with ATRT confirmed by alterations in INI1 or BRG1. This systematic review is the first to include only pediatric cases of ATRT confirmed with either INI1 or BRG1 alterations.
METHODS
MEDLINE was searched using the terms "atypical teratoid/rhabdoid tumor" AND "paediatric/pediatric." Cases were included if confirmed by loss of INI1 or BRG1. The extracted dataset was analyzed using descriptive statistics, log-rank test, and Kaplan-Meier survival analysis via SPSS.
RESULTS
A total of 38 articles were included in this study. The average age at diagnosis was 3 years. The most common locations reported are the supratentorial region and cerebral hemispheres. Ninety-three patients were reported to show evidence of dissemination. The average overall survival was 29 months. A significant difference in survival was noted between the tumor location groups, particularly worse outcomes for patients with spinal ATRT (P < 0.001). Extent of resection and adjuvant therapy were significant for survival (χ = 10.107, P = 0.018 and χ = 20.38, P < 0.0001, respectively).
CONCLUSIONS
ATRT of the central nervous system in pediatric populations is a rare neoplasm associated with a poor prognosis in most patients. Future studies should be directed to find a standardized treatment protocol.
Topics: Central Nervous System Neoplasms; Child; Humans; Neoplasms, Neuroepithelial; Rhabdoid Tumor; Survival Analysis; Teratoma
PubMed: 35470083
DOI: 10.1016/j.wneu.2022.04.073 -
Journal of Neuro-oncology Sep 2023Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic outcomes and seizure burden. A better understanding of factors that influence seizure outcomes in the surgical management of primary brain tumors of childhood can guide treatment approach thereby improving patient quality of life.
METHODS
We performed a systematic analysis using articles queried from PubMed, EMBASE, and Cochrane published from January 1990 to August 2022 to determine predictors of seizure outcomes in pediatric patients undergoing resection of primary brain tumors.
RESULTS
We identified 24 retrospective cohort studies, one prospective cohort study, and one mixed retrospective and prospective study for the systematic analysis. A total of 831 pediatric patients were available for analysis. 668 (80.4%) patients achieved seizure freedom after surgery. Complete tumor resection increased the likelihood of a seizure-free (Engel I) outcome compared to subtotal resection (OR 7.1, 95% CI 2.3-21.9). Rates of Engel I seizure outcomes did not significantly differ based on factors such as age at seizure onset, duration of epilepsy, gender, tumor laterality, or age at surgery, but trended towards significance for improved outcomes in temporal lobe tumors.
CONCLUSION
Primary brain tumors in the pediatric population are commonly associated with seizures. Resection of these lesions reduces seizure burden and is associated with high rates of seizure freedom. Complete resection, compared to subtotal resection, significantly increases the likelihood of seizure-free outcomes.
Topics: Child; Humans; Retrospective Studies; Prospective Studies; Quality of Life; Electroencephalography; Treatment Outcome; Seizures; Supratentorial Neoplasms; Brain Neoplasms
PubMed: 37707753
DOI: 10.1007/s11060-023-04446-9 -
Clinical Neurology and Neurosurgery Mar 2023Seizures present in 50-90 % of cases with low-grade brain tumors. Frontal lobe epilepsy is associated with dismal seizure outcomes compared to temporal lobe epilepsy.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Seizures present in 50-90 % of cases with low-grade brain tumors. Frontal lobe epilepsy is associated with dismal seizure outcomes compared to temporal lobe epilepsy. Our objective is to conduct a systematic review, report our case series, and perform a pooled analysis of clinical predictors of seizure outcomes in frontal lobe low-grade brain tumors.
METHODS
Searches of five electronic databases from January 1990 to June 2022 were reviewed following PRISMA guidelines. Individual patient data was extracted from 22 articles that fit the inclusion criteria. A single-surgeon case series from our institution was also retrospectively reviewed and analyzed through a pooled cohort of 127 surgically treated patients with frontal lobe low-grade brain tumors.
RESULTS
The mean age at surgery was 30.8 years, with 50.4 % of patients diagnosed as oligodendrogliomas. The majority of patients (81.1 %) were seizure-free after surgery (Engel I). On the multivariate analysis, gross total resection (GTR) (OR = 8.77, 95 % CI: 1.99-47.91, p = 0.006) and awake resection (OR = 9.94, 95 % CI: 1.93-87.81, p = 0.015) were associated with seizure-free outcome. A Kaplan-Meier curve showed that the probability of seizure freedom fell to 92.6 % at 3 months, and to 85.5 % at 27.3 months after surgery.
CONCLUSION
Epilepsy from tumor origin demands a balance between oncological management and epilepsy cure. Our pooled analysis suggests that GTR and awake resections are positive predictive factors for an Engel I at more than 6 months follow-up. To validate these findings, a longer-term follow-up and larger cohorts are needed.
Topics: Humans; Adult; Treatment Outcome; Retrospective Studies; Epilepsy, Frontal Lobe; Epilepsy, Temporal Lobe; Frontal Lobe; Supratentorial Neoplasms; Electroencephalography
PubMed: 36709666
DOI: 10.1016/j.clineuro.2023.107600 -
World Neurosurgery Oct 2021Prolactin-secreting tumors respond well to medical management, with a few patients requiring surgery. We conducted a systematic review and meta-analysis to study the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Prolactin-secreting tumors respond well to medical management, with a few patients requiring surgery. We conducted a systematic review and meta-analysis to study the determinants of surgical remission in these tumors.
METHODS
We searched PubMed to identify eligible studies reporting postoperative remission in patients treated with transsphenoidal surgery for prolactinoma. Primary outcomes included postoperative remission, follow-up remission, and recurrence. Postoperative and follow-up remission were defined as normoprolactinemia at <1 year and >1 year after operation, respectively. Recurrence was defined as hyperprolactinemia after initial normalization of prolactin levels. Odds ratios (ORs) were calculated, stratified by radiologic size, tumor extension, and tumor invasion, and analyzed using a random-effects model meta-analysis.
RESULTS
Thirty-five studies were included. Macroadenomas were associated with lower rates of postoperative remission (OR, 0.20; 95% confidence interval [CI], 0.16-0.24) and lower rates of remission at follow-up (OR, 0.11; 95% CI, 0.053-0.22). Postoperative remission was less likely in tumors with extrasellar or suprasellar extension (OR, 0.16; 95% CI, 0.06-0.43) and tumors with cavernous sinus invasion (OR, 0.03; 95% CI, 0.01-0.13). Female gender and absence of preoperative dopamine agonist treatment were also associated with higher remission rates. Across the included studies, there was considerable heterogeneity in each primary outcome (postoperative remission, I = 94%; follow-up remission, I = 86%; recurrence, I = 68%).
CONCLUSIONS
Transsphenoidal surgery for prolactinomas may be particularly effective in small, noninvasive, treatment-naive tumors and may provide a viable first-line alternative to dopamine agonist therapy in such patients.
Topics: Humans; Neurosurgical Procedures; Pituitary Neoplasms; Prolactinoma; Remission Induction; Treatment Outcome
PubMed: 34325023
DOI: 10.1016/j.wneu.2021.07.035 -
Neuroendocrinology 2023Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement...
INTRODUCTION
Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence.
METHODS
A systematic review and cohort studys were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT >1 year after diagnosis.
RESULTS
Evidence of 18 included studies, reporting on 6,603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression, or recurrent disease. One study evaluated timing of GHRT and progression/recurrence-free survival and found no increased risk with earlier initiation. One study reported a higher than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0-17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence-free survival, or secondary tumors.
CONCLUSION
Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients.
Topics: Humans; Cohort Studies; Craniopharyngioma; Human Growth Hormone; Neoplasm Recurrence, Local; Hormone Replacement Therapy; Pituitary Neoplasms; Growth Hormone
PubMed: 37231961
DOI: 10.1159/000531226 -
International Journal of Radiation... Jun 2024Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue... (Review)
Review
PURPOSE
Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.
METHODS AND MATERIALS
A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies.
RESULTS
Treated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD2; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD2 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46).
CONCLUSIONS
Existing reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD2 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.
Topics: Humans; Re-Irradiation; Necrosis; Child; Neoplasm Recurrence, Local; Central Nervous System Neoplasms; Adolescent; Brain; Brain Stem; Ependymoma; Young Adult; Child, Preschool; Medulloblastoma; Radiation Injuries
PubMed: 38300187
DOI: 10.1016/j.ijrobp.2023.12.043 -
Endocrine Practice : Official Journal... Sep 2021Delayed hyponatremia is the primary cause of readmission after transsphenoidal surgery, with a reported incidence of 9% to 30.7%. Studies have failed to identify... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Delayed hyponatremia is the primary cause of readmission after transsphenoidal surgery, with a reported incidence of 9% to 30.7%. Studies have failed to identify consistent predictive factors for postoperative hyponatremia; thus, it is difficult to determine patients that are at a high risk. Fluid restriction is one approach for the prevention of hyponatremia. We have performed a meta-analysis and systematic review of the literature to evaluate the impact of fluid restriction on hyponatremia and hospital readmissions.
METHODS
Ovid EMBASE, PubMed, Scopus, and Cochrane were searched from inception to May 2021, using the Population, Intervention, Comparison, Outcome, and Study question format: Do patients who underwent transsphenoidal surgery and followed a postoperative fluid restriction regimen differ in terms of hyponatremia and readmission rates? Studies that implemented fluid restriction and reported hyponatremia and/or readmission rates were included for analysis. Data were pooled by meta-analysis and analyzed using fixed effect and random effect models.
RESULTS
A total of 143 manuscripts representing 103 unique studies were identified, with 5 studies included for analysis, yielding a pooled cohort of 1586 patients: 594 on fluid restriction protocols and 992 control patients. Fluid restriction protocols ranged from 1.0 to 2.5 L and varied in the length time between postoperative days 1 to 15. Patients on fluid restriction had a decreased risk of hyponatremia (risk ratio: 0.34; 95% CI, 0.21-0.57; P < .00001) and readmission due to hyponatremia (risk ratio: 0.24; 95% CI, 0.09-0.63; P = .0038).
CONCLUSION
Postoperative fluid restriction after transsphenoidal surgery represents an effective method for the prevention of hyponatremia and hospital readmission and has the potential to decrease health care costs.
Topics: Humans; Hyponatremia; Patient Readmission; Pituitary Neoplasms; Postoperative Complications; Retrospective Studies
PubMed: 34265453
DOI: 10.1016/j.eprac.2021.07.003 -
Endocrine-related Cancer May 2022Once temozolomide has failed, there is no recommended treatment option for pituitary carcinomas and aggressive pituitary tumors. Immune-checkpoint inhibitors (ICIs)...
Once temozolomide has failed, there is no recommended treatment option for pituitary carcinomas and aggressive pituitary tumors. Immune-checkpoint inhibitors (ICIs) represent the most recent therapeutic avenue, having raised hope with the publication of the first successful case in 2018. Here, we present an overview of immunotherapy in pituitary carcinomas and aggressive pituitary tumors, starting with the rationale for using ICIs and the implications of tumor-infiltrating lymphocytes in anterior pituitary tumors, followed by a systematic review of all published cases, analyzing both treatment response and potential predictors of response and finishing with research and clinical perspectives. Seven corticotroph and four lactotroph tumors have been so far treated with ICIs. Corticotroph tumors showed radiological partial response in 57% of cases, followed by stable disease in 29% of cases, which was accompanied by biochemical partial or complete response in 83% of cases. Half of lactotroph tumors showed radiological complete or partial response, accompanied by biochemical complete response in 33% of the cases. In the case of a dissociate response, continuation of immunotherapy combined with local treatment represents a good option. At this time, a high tumor mutational burden appears to be the most promising predictive marker of response. MMR deficiency does not guarantee a response. Negative PD-L1 staining should not preclude ICIs administration. Therefore, ICIs are a promising option after temozolomide failure. This review highlights key clinical aspects that can already be implemented into practice and also discusses tumor biology concepts and perspectives expected to improve immunotherapy outcomes.
Topics: Carcinoma; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Pituitary Neoplasms; Temozolomide
PubMed: 35521777
DOI: 10.1530/ERC-22-0037