Endoscopic Transnasal Management of Meningoceles and Encephaloceles in Children: A Systematic Review.

OBJECTIVE: To review surgical techniques used in the endoscopic transnasal repair of pediatric basal meningoencephaloceles and compare perioperative outcomes in children <2 and ≥2 years old. DATA SOURCES: MEDLINE, EMBASE, and CENTRAL. REVIEW METHODS: Data sources were searched from inception to August 22, 2022, using search terms relevant to endoscopic transnasal meningoencephalocele repair in children. Reviews and Meta-analyses were excluded. Primary outcomes were the incidence of intraoperative and postoperative complications, including cerebrospinal fluid leak, recurrence, and reintervention. Quality assessments were performed using Newcastle-Ottawa Scale, ROBIN-I, and NIH. RESULTS: Overall, 217 patients across 61 studies were identified. The median age at surgery was 4 years (0-18 years). Fifty percent were female; 31% were <2 years. Most defects were meningoencephaloceles (56%), located transethmoidal (80%), and of congenital origin (83%). Seventy-five percent of repairs were multilayered. Children ≥2 years underwent multilayer repairs more frequently than those <2 years (P = 0.004). Children <2 years more frequently experienced postoperative cerebrospinal fluid leaks (P = 0.02), meningoencephalocele recurrence (P < 0.0001), and surgical reintervention (P = 0.005). Following multilayer repair, children <2 years were more likely to experience recurrence (P = 0.0001) and reintervention (P = 0.006). CONCLUSION: Younger children with basal meningoencephaloceles appear to be at greater risk of postoperative complications following endoscopic endonasal repair, although the quality of available evidence is weakened by incomplete reporting. In the absence of preoperative cerebrospinal fluid leak or meningitis, it may be preferable to delay surgery as access is more conducive to successful repair in older children.

Re-examining prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis.

Background: Patients with small cell lung cancer (SCLC) are at high risk for brain metastases. Prophylactic cranial irradiation (PCI) is recommended in this population to reduce the incidence of brain metastases and prolong survival. We aimed to assesses the efficacy of PCI in this population in the era of routine brain imaging. To our knowledge, this is the first systematic review and meta-analysis to examine the use among patients who were radiographically confirmed not to have brain metastases after completion of first-line therapy. Methods: In this systematic review and meta-analysis, cohort studies and controlled trials reporting on the use of PCI for patients SCLC were identified in EMBASE, MEDLINE, CENTRAL, and grey literature sources. The literature search was conducted on November 12, 2023. Summary data were extracted. Random-effects meta-analyses pooled hazard ratios (HR) for the primary outcome of overall survival between PCI and no intervention groups. This study is registered with the Open Science Framework, DOI:10.17605/OSF.IO/BC359, and PROSPERO, CRD42021249466. Findings: Of 4318 identified records, 223 were eligible for inclusion. 109 reported on overall survival in formats amenable to meta-analysis; PCI was associated with longer survival in all patients with SCLC (HR 0.59; 95% CI, 0.55-0.63; p < 0.001; n = 56,770 patients), patients with limited stage disease (HR 0.60; 95% CI, 0.55-0.65; p < 0.001; n = 78 studies; n = 27,137 patients), and patients with extensive stage disease (HR 0.59; 95% CI, 0.51-0.70; p < 0.001; n = 28 studies; n = 26,467 patients). Between-study heterogeneity was significant when pooled amongst all studies (I2 = 73.6%; 95% CI 68.4%-77.9%). Subgroup analysis did not reveal sources of heterogeneity. In a subgroup analysis on studies that used magnetic resonance imaging to exclude presence of brain metastases at restaging among all patients, overall survival did not differ significantly between patients who did or did not receive PCI (HR 0.74; 95% CI, 0.52-1.05; p = 0.08; n = 9 studies; n = 1384 patients). Interpretation: Our findings suggested that administration of PCI is associated with a survival benefit, but not when considering studies that radiographically confirmed absence of brain metastases, suggesting that the survival benefit conferred by PCI might be therapeutic rather than prophylactic. Funding: No funding.

Association of Brain Metastases With Survival in Patients With Limited or Stable Extracranial Disease: A Systematic Review and Meta-analysis.

Importance: Intracranial metastatic disease (IMD) is a severe complication of cancer with profound prognostic implications. Patients with IMD in the setting of limited or stable extracranial disease (IMD-SE) may represent a unique and understudied subset of patients with IMD with superior prognosis. Objective: To evaluate overall survival (OS), progression-free survival (PFS), and intracranial PFS (iPFS) in patients with IMD-SE secondary to any primary cancer. Data Sources: Records were identified from MEDLINE, EMBASE, CENTRAL, and gray literature sources from inception to June 21, 2021. Study Selection: Studies in English reporting OS, PFS, or iPFS in patients with IMD-SE (defined as IMD and ≤2 extracranial metastatic sites) and no prior second-line chemotherapy or brain-directed therapy were selected. Data Extraction and Synthesis: Author, year of publication, type of study, type of primary cancer, and outcome measures were extracted. Random-effects meta-analyses were performed to estimate effect sizes, and subgroup meta-analysis and metaregression were conducted to measure between-study differences in February 2022. Main Outcomes and Measures: The primary end point was OS described as hazard ratios (HRs) and medians for comparative and single-group studies, respectively. Secondary end points were PFS and iPFS. Results: Overall, 68 studies (5325 patients) were included. IMD-SE was associated with longer OS (HR, 0.52; 95% CI, 0.39-0.70) and iPFS (HR, 0.63; 95% CI, 0.52-0.76) compared with IMD in the setting of progressive extracranial disease. The weighted median OS estimate for patients with IMD-SE was 17.9 months (95% CI, 16.4-22.0 months), and for patients with IMD-PE it was 8.0 months (95% CI, 7.2-12.8 months). Pooled median OS for all patients with IMD-SE was 20.9 months (95% CI, 16.35-25.98 months); for the subgroup with breast cancer it was 20.2 months (95% CI, 10.43-38.20 months), and for non-small cell lung cancer it was 27.5 months (95% CI, 18.27-49.66 months). Between-study heterogeneity for OS and iPFS were moderate (I2 = 56.5%) and low (I2 = 0%), respectively. Conclusions and Relevance: In this systematic review and meta-analysis of patients with IMD-SE, limited systemic disease was associated with improved OS and iPFS. Future prospective trials should aim to collect granular information on the extent of extracranial disease to identify drivers of mortality and optimal treatment strategies in patients with brain metastases.

Erythroblastic oncogene B-2 status and intracranial metastatic disease in patients with gastrointestinal cancer: a systematic review.

PURPOSE: The incidence of intracranial metastatic disease (IMD) in patients with gastrointestinal (GI) cancers is rising. Expression of the erythroblastic oncogene B-2 (ERBB2) is associated with an in increased risk of IMD in patients with breast cancer. The implications of ERBB2 expression for IMD risk in patients with GI cancers is less clear. The objective of this systematic review was to determine the incidence of IMD and OS in patients with ERBB2+ gastrointestinal cancers. METHODS: A literature search of MEDLINE, EMBASE, CENTRAL, and grey literature sources was conducted from date of database inception to July 2021. Included studies reported outcomes on patients with IMD secondary to ERBB2 GI cancers. RESULTS: Fourteen cohort studies met inclusion criteria, of which thirteen were retrospective. Eleven studies reported on gastric, esophageal, or gastroesophageal junction cancers. Three studies directly compared incidence of IMD based on ERBB2 status and among these, ERBB2+ patients had a higher incidence of IMD. One study indicated that ERBB2+ patients had significantly longer OS from the times of primary cancer (P = .015) and IMD diagnosis (P = .01), compared with patients with ERBB2- disease. CONCLUSIONS: In this systematic review, patients with ERBB2+ GI cancer were more likely to develop IMD. Future study is required on the prognostic and predictive value of ERBB2 status in patients with GI cancers.

Stereotactic radiosurgery versus whole brain radiotherapy in patients with intracranial metastatic disease and small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Patients with small-cell lung cancer (SCLC) are at high risk for intracranial metastatic disease (IMD). Although stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as first-line treatment for IMD in most solid cancers, WBRT remains first-line treatment for IMD in patients with SCLC. We aimed to evaluate the efficacy of SRS in comparison with WBRT and assess treatment outcomes following SRS. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, CENTRAL, and grey literature sources for controlled trials and cohort studies published in English reporting on SRS for IMD treatment in patients with SCLC from inception to March 23, 2022. Studies were excluded that did not report on SRS for IMD secondary to SCLC. Summary data were extracted. The primary outcome was overall survival, presented as pooled hazard ratios (HR) through random-effects meta-analysis for studies comparing SRS with WBRT with or without SRS boost, and as medians for single-arm SRS studies. This study is registered with the Open Science Framework, DOI 10.17605/OSF.IO/8M4HC, and PROSPERO, CRD42021258197. FINDINGS: Of 3823 identified records, 31 were eligible for inclusion; seven were included in the meta-analysis. Overall survival following SRS was longer than following WBRT with or without SRS boost (HR 0·85; 95% CI 0·75-0·97; n=7 studies; n=18 130 patients), or WBRT alone (0·77; 0·72-0·83; n=7 studies; n=16 961 patients), but not WBRT plus SRS boost (1·17, 0·78-1·75; n=4 studies; n=1167 patients). Using single-arm studies, pooled median overall survival from SRS was 8·99 months (95% CI 7·86-10·16; n=14 studies; n=1682 patients). Between-study heterogeneity was considerable when pooled among all comparative studies (I2=71·9%). INTERPRETATION: These results suggest survival outcomes are equitable following treatment with SRS compared with WBRT in patients with SCLC and IMD. Future prospective studies should focus on tumour burden and differences in local and distant intracranial progression between WBRT-treated and SRS-treated patients with SCLC. FUNDING: None.

Intracranial Metastatic Disease: Present Challenges, Future Opportunities.

Intracranial metastatic disease (IMD) is a prevalent complication of cancer that significantly limits patient survival and quality of life. Over the past half-century, our understanding of the epidemiology and pathogenesis of IMD has improved and enabled the development of surveillance and treatment algorithms based on prognostic factors and tumor biomolecular characteristics. In addition to advances in surgical resection and radiation therapy, the treatment of IMD has evolved to include monoclonal antibodies and small molecule antagonists of tumor-promoting proteins or endogenous immune checkpoint inhibitors. Moreover, improvements in the sensitivity and specificity of imaging as well as the development of new serological assays to detect brain metastases promise to revolutionize IMD diagnosis. In this review, we will explore current treatment principles in patients with IMD, including the emerging role of targeted and immunotherapy in select primary cancers, and discuss potential areas for further investigation.

Evaluation of novel glomerular filtration rate estimation equations in adolescents and young adults with type 1 diabetes.

AIMS: Individuals with type 1 diabetes (T1D) are at an increased risk of chronic kidney disease making estimation of glomerular filtration rate (eGFR) an important component of diabetes care. Which eGFR equation is most appropriate to use in patients with T1D during the transition to adult care is unclear. We, therefore, sought to evaluate the performance of five eGFR equations in adolescents and young adults with T1D. METHODS: Measured iohexol-based glomerular filtration rate was compared to the Chronic Kidney Disease and Epidemiology Collaboration (CKD-EPI) eGFR, Chronic Kidney Disease in Children (CKiD) eGFR, and three recently developed age-adjusted versions of these in 53 patients with T1D and preserved GFR using bias, precision, and accuracy. RESULTS: The best performance was found in the sex-dependent CKiD equation (bias: -0.8, accuracy: 11.8 ml/min/1.73 m2). Bias and accuracy (26.4 and 26.8 ml/min/1.73 m2) were worst in the CKD-EPI equation. Age-dependent adjustment improved performance for this equation (bias: 5.3, accuracy: 13.4 ml/min/1.73 m2), but not for the CKiD equation (bias: 15.5, accuracy: 18.8 ml/min/1.73 m2). CONCLUSION: Age-adjustment improved performance for the CKD-EPI equation, but not for the CKiD equation. The sex-adjusted CKiD equation performed best out of all equations.

Clinical Biomarkers for Early Identification of Patients with Intracranial Metastatic Disease.

Nearly 30% of patients with cancer will develop intracranial metastatic disease (IMD), and more than half of these patients will die within a few months following their diagnosis. In light of the profound effect of IMD on survival and quality of life, there is significant interest in identifying biomarkers that could facilitate the early detection of IMD or identify patients with cancer who are at high IMD risk. In this review, we will highlight early efforts to identify biomarkers of IMD and consider avenues for future investigation.