Clinical and molecular features of disseminated pediatric low-grade glioma and glioneuronal tumors: a systematic review and survival analysis

Abstract

Background Disseminated pediatric low-grade gliomas and glioneuronal tumors (dpLGG/GNTs) are associated with a poorer prognosis than non-disseminated pLGG/GNTs. To date there is no comprehensive report characterizing the genome profile of dpLGG/GNTs and their relative survival. This systematic review aims to identify the pattern of genetic alterations and long-term outcomes described for dpLGG/GNT. Methods A systematic review of the literature was performed to identify relevant articles. A quality and risk of bias assessment of articles was done using the GRADE framework and ROBINS-I tool, respectively. Results Fifty studies published from 1994 to 2020 were included in this review with 366 cases reported. There was sporadic reporting of genetic alterations. The most common molecular alterations observed among subjects were 1p deletion (75%) and BRAF-KIAA1549 fusion (55%). BRAF p.V600E mutation was found in 7% of subjects. A higher proportion of subjects demonstrated primary dissemination compared to secondary dissemination (65% vs 25%). First-line chemotherapy consisted of an alkylation-based regimen and vinca alkaloids. Surgical intervention ranged from biopsy alone (59%) to surgical resection (41%) and CSF diversion (28%). Overall, 73% of cases were alive at last follow-up. Survival did not vary by tumor type or timing of dissemination. All studies reviewed either ranked low or moderate for both quality and risk of bias assessments. Conclusion Chromosome 1p deletion and BRAF-KIAA1549 fusion were the most common alterations identified in dpLGG/GNT cases reviewed. The relative molecular heterogeneity between DLGG and DLGNT however deserves further exploration and ultimately correlation with their biologic behavior to better understand the pathogenesis of dpLGG/GNT.

Diffuse Leptomeningeal Glioneuronal Tumour

“…Two clusters of methylation patterns were discovered in one study, showing 1p deletion either accompanied by 19q deletion or 1q gain [7]. Some evidence exists linking 1p deletion and DL-GNT suggesting a role in favouring dissemination [7].…”

“…Genetically, DL-GNT is often associated with genetic alteration, with 1p deletions in 75% of subjects, BRAF-KIAA fusion in around 55% and BRAF p.V600E substitution mutations in 7% [ 7 ]. Two clusters of methylation patterns were discovered in one study, showing 1p deletion either accompanied by 19q deletion or 1q gain [ 7 ]. Some evidence exists linking 1p deletion and DL-GNT suggesting a role in favouring dissemination [ 7 ].…”

“…Two clusters of methylation patterns were discovered in one study, showing 1p deletion either accompanied by 19q deletion or 1q gain [ 7 ]. Some evidence exists linking 1p deletion and DL-GNT suggesting a role in favouring dissemination [ 7 ]. In our case, a KIAA1549-BRAF was found which, although also associated with pilocytic astrocytomas, is known to be found in DL-GNTs [ 8 ].…”

Resilience of Patients With Brain Tumor While Awaiting Surgery

“…23 The median waiting time from diagnosis until the date of preadmission for the operation (18 days) was shorter in our study than the median of an LMIC study (50 days). 3 However, our study collected the data from 1 advanced tertiary hospital in the metropolitan area so the waiting time may be shorter than those in other settings in rural areas.…”

“…Thailand is categorized as a low-and middleincome country (LMIC); the median surgery waiting time in LMICs was 50 days, which tends to be longer than that in high-income countries. 3 Brain tumor diagnosis may cause uncertainty in newly diagnosed patients before entering the treatment process because of disease prognosis, tumor-related symptoms, treatment plan, and emotional states. 4 For instance, while awaiting brain tumor surgery, patients may develop uncertainty related to disease prognosis, specifically for patients who experience postponing surgery and prolong waiting time for surgery, 5 resulting in inducing depressive symptoms, having physical disability, and reducing quality of life.…”