Treatment Of Low-grade Gliomas Research Articles

Stereotactic Iodine-125 Brachytherapy for Low-Grade Glioma Treatment: A Monte Carlo study

Background: Stereotactic brachytherapy is an appropriate method that has been used for brain tumors and metastases treatment for more than 40 years for many patients in the world. Also, iodine-125 brachytherapy has been utilized in brain tumors for interstitial brachytherapy treatment since 1979. Even though the physical and biological features make these implants particularly attractive for minimal invasive treatment, the main goal of this paper is to evaluate the I-125 seed time and dose reached to brain glioma tumors of different sizes for treatment using Monte Carlo modeling. Methods: In this paper, Monte Carlo simulation has been applied by the Gate code with 20 (MBq) activity for an iodine seed design for low-grade glioma tumors treatment. Dosimetry features of this source were defined by the updated TG-43U1 recommendations. The absorbed dose distribution around the seed was calculated using the Gate code in liquid water. Result: The ideal condition for brachytherapy is for tumors smaller than 4 cm. With a larger tumor size, the absorption dose at the border of tumor and healthy tissue will be decreased and the implantation time for seeds will increase. Conclusion: Placing an iodine-125 source inside the tumor is not sufficient because of the non-uniform dose distribution in the tumor and the length of treatment time. Using four iodine-125 sources eliminates the tumor, and also, a uniform dose distribution is created in the tumor and the implantation time will be reduced, respectively.

Medical Treatment of Pediatric Low-Grade Glioma.

Low-grade glioma (LGG) is the most common brain tumor in children and has excellent long-term survival. With an excellent survival rate, the choice of treatment involves careful consideration of minimizing late toxicity from surgery, radiation, and chemotherapy. Surgery, radiation therapy, and chemotherapy can be used as monotherapy or in combination, providing different therapeutic ratios and complications. As a result, establishing the selection of ideal therapies has been a controversial area, presenting challenges. Recent advances in understanding molecular characteristics of pediatric LGG affect classification and treatment approaches. This review aims to overview recent developments in medical treatment in pediatric LGG.

Identification of Autophagy-Related Prognostic Signature and Analysis of Immune Cell Infiltration in Low-Grade Gliomas.

Autophagy plays an important role in cancer. Many studies have demonstrated that autophagy-related genes (ARGs) can act as a prognostic signature for some cancers, but little has been known in low-grade gliomas (LGG). In our study, we aimed to establish a prognostical model based on ARGs and find prognostic risk-related key genes in LGG. In the present study, a prognostic signature was constructed based on a total of 8 ARGs (MAPK8IP1, EEF2, GRID2, BIRC5, DLC1, NAMPT, GRID1, and TP73). It was revealed that the higher the risk score, the worse was the prognosis. Time-dependent ROC analysis showed that the risk score could precisely predict the prognosis of LGG patients. Additionally, four key genes (TGFβ2, SERPING1, SERPINE1, and TIMP1) were identified and found significantly associated with OS of LGG patients. Besides, they were also discovered to be strongly related to six types of immune cells which infiltrated in LGG tumor. Taken together, the present study demonstrated the promising potential of the ARG risk score formula as an independent factor for LGG prediction. It also provided the autophagy-related signature of prognosis and potential therapeutic targets for the treatment of LGG.

Risk of secondary neoplasms after external-beam radiation therapy treatment of pediatric low-grade gliomas: a SEER analysis, 1973-2015.

Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG. A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients. In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010). Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.

Alcohol-abuse drug disulfiram targets pediatric glioma via MLL degradation

Pediatric gliomas comprise a broad range of brain tumors derived from glial cells. While high-grade gliomas are often resistant to therapy and associated with a poor outcome, children with low-grade gliomas face a better prognosis. However, the treatment of low-grade gliomas is often associated with severe long-term adverse effects. This shows that there is a strong need for improved treatment approaches. Here, we highlight the potential for repurposing disulfiram to treat pediatric gliomas. Disulfiram is a drug used to support the treatment of chronic alcoholism and was found to be effective against diverse cancer types in preclinical studies. Our results show that disulfiram efficiently kills pediatric glioma cell lines as well as patient-derived glioma stem cells. We propose a novel mechanism of action to explain disulfiram’s anti-oncogenic activities by providing evidence that disulfiram induces the degradation of the oncoprotein MLL. Our results further reveal that disulfiram treatment and MLL downregulation induce similar responses at the level of histone modifications and gene expression, further strengthening that MLL is a key target of the drug and explaining its anti-oncogenic properties.

Dual-Knockout of Mutant Isocitrate Dehydrogenase 1 and 2 Subtypes Towards Glioma Therapy: Structural Mechanistic Insights on the Role of Vorasidenib.

Recently, Vorasidenib (AG-881) has been reported as a therapeutic alternative that exerts potent dual inhibitory activity against mIDH1/2 towards the treatment of low-grade glioma. However, structural and dynamic events associated with its dual inhibition mechanism remain unclear. As such, we employ integrative computer-assisted atomistic techniques to provide thorough structural and dynamic insights. Our analysis proved that the dual-targeting ability of AG-881 is mediated by Val255/Val294 within the binding pockets of both mIDH1 and mIDH2 which are shown to elicit a strong intermolecular interaction, thus favoring binding affinity. The structural orientations of AG-881 within the respective hydrophobic pockets allowed favorable interactions with binding site residues which accounted for its high binding free energy of -28.69 kcal/mol and -19.89 kcal/mol towards mIDH1 and mIDH2, respectively. Interestingly, upon binding, AG-881 was found to trigger systemic alterations of mIDH1 and mIDH2 characterized by restricted residue flexibility and a reduction in exposure of residues to the solvent surface area. As a result of these structural alterations, crucial interactions of the mutant enzymes were inhibited, a phenomenon that results in a suppression of the production of oncogenic stimulator 2-HG. Findings therefore provide thorough structural and dynamic insights associated with the dual inhibitory activity of AG-881 towards glioma therapy.

Identification and validation of a novel eight mutant-derived long non-coding RNAs signature as a prognostic biomarker for genome instability in low-grade glioma.

Long non-coding RNAs (lncRNAs) comprise an integral part of the eukaryotic transcriptome. Alongside proteins, lncRNAs modulate lncRNA-based gene signatures of unstable transcripts, play a crucial role as antisense lncRNAs to control intracellular homeostasis and are implicated in tumorigenesis. However, the role of genomic instability-associated lncRNAs in low-grade gliomas (LGG) has not been fully explored. In this study, lncRNAs expression and somatic mutation profiles in low-grade glioma genome were used to identify eight novel mutant-derived genomic instability-associated lncRNAs including H19, FLG-AS1, AC091932.1, AC064875.1, AL138767.3, AC010273.2, AC131097.4 and ISX-AS1. Patients from the LGG gene mutagenome atlas were grouped into training and validation sets to test the performance of the signature. The genomic instability-associated lncRNAs signature (GILncSig) was then validated using multiple external cohorts. A total of 59 novel genomic instability-associated lncRNAs in LGG were used for least absolute shrinkage and selection operator (Lasso), single and multifactor Cox regression analysis using the training set. Furthermore, the independent predictive role of risk features in the training and validation sets were evaluated through survival analysis, receiver operating feature analysis and construction of a nomogram. Patients with IDH1 mutation status were grouped into two different risk groups based on the GILncSig score. The low-risk group showed a relatively higher rate of IDH1 mutations compared with patients in the high-risk group. Furthermore, patients in the low-risk group had better prognosis compared with patients in the high-risk group. In summary, this study reports a reliable prognostic prediction signature and provides a basis for further investigation of the role of lncRNAs on genomic instability. In addition, lncRNAs in the signature can be used as new targets for treatment of LGG.

Construction of a SUMOylation regulator-based prognostic model in low-grade glioma.

Low‐grade glioma (LGG) is an intracranial malignant tumour that mainly originates from astrocytes and oligodendrocytes. SUMOylation is one of the post‐translational modifications but studies of SUMOylation in LGG is quite limited. Transcriptome data, single nucleotide variant (SNV) data and clinical data of LGG were derived from public databases. The differences between the expression of SUMOylation regulators in LGG and normal brain tissue were analysed. Cox regression was used to construct a prognostic model in the training cohort. Kaplan‐Meier survival curves and ROC curves were plotted in the training and the validation cohort to evaluate the effectiveness of the prognostic model. GO and KEGG analyses were applied to preliminarily analyse the biological functions. Compared with normal brain tissue, SENP1 and SENP7 were up‐regulated and SENP5 was down‐regulated in LGG. SUMOylation regulators may be involved in functions such as mRNA splicing, DNA replication, ATPase activity and spliceosome. One prognostic model was established based on the 4 SUMOylation regulator‐related signatures (RFWD3, MPHOSPH9, WRN and NUP155), which had a good predictive ability for overall survival. This study is expected to provide targets for the diagnosis and treatment of low‐grade glioma.

Current Salvage Treatment Strategies for Younger Children (

Pediatric low-grade gliomas (LGGs) are the most common brain tumors in children. Treatment of pediatric LGG can often be challenging, particularly when not resectable and refractory or recurrent following standard chemotherapy regimens. There is no current accepted standard of care salvage regimen for progressive LGG after the failure of first-line chemotherapy. A web-based survey was distributed to pediatric cancer centers throughout North America to inquire regarding institutional preferences of salvage treatment strategies after initial chemotherapy for LGG in children less than 10 years of age, as well as molecular testing preferences. Highlights from the survey results were as follows: vincristine/carboplatin (VC) and vinblastine (VBL) were the top 2 preferred salvage regimens for non-BRAF-altered pediatric LGG. BRAF and MEK inhibitors were the most preferred salvage regimens for BRAF V600e-mutated and BRAF fusion-positive pediatric LGG, respectively. VC ranked second. As high as 47.8% of North American centers would use conformal radiation for younger children with non-neurofibromatosis type 1 LGG after failing 2 to 3 chemotherapy regimens. Overall, 87% (87%) of North American institutions obtain some type of routine molecular testing for non-neurofibromatosis type 1-associated pediatric LGG cases. Less than 60% of centers obtain routine H3 K27M molecular testing for pediatric LGG with a midline location.

OSlgg: An Online Prognostic Biomarker Analysis Tool for Low-Grade Glioma.

Glioma is the most frequent primary brain tumor that causes high mortality and morbidity with poor prognosis. There are four grades of gliomas, I to IV, among which grade II and III are low-grade glioma (LGG). Although less aggressive, LGG almost universally progresses to high-grade glioma and eventual causes death if lacking of intervention. Current LGG treatment mainly depends on surgical resection followed by radiotherapy and chemotherapy, but the survival rates of LGG patients are low. Therefore, it is necessary to use prognostic biomarkers to classify patients into subgroups with different risks and guide clinical managements. Using gene expression profiling and long-term follow-up data, we established an Online consensus Survival analysis tool for LGG named OSlgg. OSlgg is comprised of 720 LGG cases from two independent cohorts. To evaluate the prognostic potency of genes, OSlgg employs the Kaplan-Meier plot with hazard ratio and p value to assess the prognostic significance of genes of interest. The reliability of OSlgg was verified by analyzing 86 previously published prognostic biomarkers of LGG. Using OSlgg, we discovered two novel potential prognostic biomarkers (CD302 and FABP5) of LGG, and patients with the elevated expression of either CD302 or FABP5 present the unfavorable survival outcome. These two genes may be novel risk predictors for LGG patients after further validation. OSlgg is public and free to the users at http://bioinfo.henu.edu.cn/LGG/LGGList.jsp.

A three-lncRNA signature predicts clinical outcomes in low-grade glioma patients after radiotherapy.

Although radiation therapy (RT) plays a critical role in the treatment of low-grade glioma (LGG), many patients suffer from adverse effects without experiencing survival benefits. In various carcinomas, long non-coding RNAs (lncRNAs) contribute to pathogenic processes, including tumorigenesis, metastasis, chemoresistance, and radioresistance. Currently, the role of lncRNAs in the radiosensitivity of LGG is largely unknown. Here, we downloaded clinical data for 167 LGG patients from The Cancer Genome Atlas database and divided them between radiosensitive and radioresistant groups based on their clinical outcomes after receiving radiotherapy. We identified 37 lncRNAs that were differentially expressed (DElncRNAs) between the groups. Functional enrichment analysis revealed that their potential target mRNAs were mainly enriched in the PI3K-Akt and MAPK signaling pathways and in DNA damage response. Kaplan-Meier survival analysis revealed that increased expression of six lncRNAs was significantly associated with radiosensitivity. We then developed a risk signature based on three of the DElncRNAs that served as an independent biomarker for predicting LGG patient outcomes after radiotherapy. In vitro experiments further validated the biological function of these lncRNAs on low-grade glioma radiation response.

High Levels of HIST1H2BK in Low-Grade Glioma Predicts Poor Prognosis: A Study Using CGGA and TCGA Data.

A number of biomarkers have been identified for various cancers. However, biomarkers associated with glioma remain largely to be explored. In the current study, we investigated the relationship between the expression and prognostic value of the HIST1H2BK gene in glioma. Sequential data filtering (survival analysis, independent prognostic analysis, ROC curve analysis, and clinical correlation analysis) was performed, which resulted in identification of the association between the HIST1H2BK gene and glioma. Then, the HIST1H2BK gene was analyzed using bioinformatics (Kaplan–Meier survival analysis, univariate Cox analysis, multivariate Cox analysis, and ROC curve analysis). The results showed that low expression of HIST1H2BK was associated with better prognosis, and high expression of HIST1H2BK was associated with poor prognosis. In addition, HIST1H2BK was an independent prognostic indicator for patients with glioma. We also evaluated the association between HIST1H2BK and clinical characteristics. Furthermore, gene set enrichment analysis (GSEA) and analysis of immune infiltration were performed. The results showed that HIST1H2BK was associated with intensity of immune infiltration in glioma. Finally, co-expression analysis was performed. The results showed that HIST1H2BK was positively correlated with HIST1H2AG, HIST2H2AA4, HIST1H2BJ, HIST2H2BE, and HIST1H2AC, and negatively correlated with PDZD4, CRY2, GABBR1, rp5-1119a7.17, and KCNJ11. This study showed that upregulation of HIST1H2BK in low-grade glioma (LGG) tissue was an indicator of poor prognosis. Moreover, this study demonstrated that HIST1H2BK may be a promising biomarker for the treatment of LGG.

Italian consensus and recommendations on diagnosis and treatment of low-grade gliomas. An intersociety (SINch/AINO/SIN) document.

In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.

MGMT promoter methylation level in newly diagnosed low-grade glioma is a predictor of hypermutation at recurrence

Emerging data suggest that a subset of patients with diffuse isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG) who receive adjuvant temozolomide (TMZ) recur with hypermutation in association with malignant progression to higher-grade tumors. It is currently unclear why some TMZ-treated LGG patients recur with hypermutation while others do not. MGMT encodes O6-methylguanine-DNA methyltransferase, a DNA repair protein that removes cytotoxic and potentially mutagenic lesions induced by TMZ. Here, we hypothesize that epigenetic silencing of MGMT by promoter methylation facilitates TMZ-induced mutagenesis in LGG patients and contributes to development of hypermutation at recurrence. We utilize a quantitative deep sequencing assay to characterize MGMT promoter methylation in 109 surgical tissue specimens from initial tumors and post-treatment recurrences of 37 TMZ-treated LGG patients. We utilize methylation arrays to validate our sequencing assay, RNA sequencing to assess the relationship between methylation and gene expression, and exome sequencing to determine hypermutation status. Methylation level at the MGMT promoter is significantly higher in initial tumors of patients that develop hypermutation at recurrence relative to initial tumors of patients that do not (45.7% vs 34.8%, P = 0.027). Methylation level in initial tumors can predict hypermutation at recurrence in univariate models and multivariate models that incorporate patient age and molecular subtype. These findings reveal a mechanistic basis for observed differences in patient susceptibility to TMZ-driven hypermutation. Furthermore, they establish MGMT promoter methylation level as a potential biomarker to inform clinical management of LGG patients, including monitoring and treatment decisions, by predicting risk of hypermutation at recurrence.

Cyclovirobuxine D inhibits cell proliferation and migration and induces apoptosis in human glioblastoma multiforme and low‑grade glioma.

Gliomas are the most common neoplasm of the human central nervous system. Glioblastoma multiforme (GBM) is one of the most serious types of gliomas. Although considerable progress has been made in the development of cancer therapeutic agents, several antineoplastic drugs fail to penetrate the blood-brain barrier (BBB), resulting in a low survival rate of glioma patients. Recent studies have revealed that the traditional Chinese medicine Buxus microphylla contains the main active component Cyclovirobuxine D (CVB-D), which can cross the BBB with a novel delivery system. However, it remains unclear whether CVB-D exerts anticancer effects against GBM and low-grade glioma (LGG). The aim of the present study was to explore the feasibility of CVB-D as a new effective agent in the treatment of GBM and LGG. The ability of CVB-D to inhibit GBM and LGG cell proliferation was detected by CCK8 assay. Flow cytometry was used to detect cell cycle progression and apoptosis induction by Annexin V-FITC/PI assay. The expression levels of the apoptosis-associated proteins, namely cleaved caspase-3 and Bax/Bcl-2, were detected by western blot analysis. The mitochondrial membrane potential (ΔΨm) was detected by Rh123 dyed fluorescence micrograph. Hoechst staining was used to observe the morphological characteristics of the apoptotic cells. The scratch test was used to evaluate the migration of GBM and LGG cells. The results indicated that CVB-D reduced cell viability of T98G and Hs683 cells. Flow cytometry demonstrated that CVB-D-treated cells were arrested at the S phase of their cell cycle. The expression levels of the apoptosis-associated proteins were increased in CVB-D-treated cells. Rh123 and Hoechst staining indicated morphological changes and mitochondrial membrane potential changes of the cells undergoing apoptosis. The data confirmed that CVB-D inhibited cell proliferation by arresting the cell cycle of GBM and LLG cells and that it promoted the induction of cell apoptosis by altering the mitochondrial membrane potential. The findings of the present study indicate the potential value of CVB-D in the treatment of glioma.

Improved Tumor Control and Absence of Late Neurotoxicity using Alpha (213Bi) as Compared to Beta (90Y) labelled-DOTA-Substance P for the Treatment of Low Grade Gliomas

Improved Tumor Control and Absence of Late Neurotoxicity using Alpha (213Bi) as Compared to Beta (90Y) labelled-DOTA-Substance P for the Treatment of Low Grade Gliomas

PDTC-17. A RETROSPECTIVE STUDY OF RECOMBINANT HUMAN ENDOSTATIN COMBINED WITH CARBOPLATIN AND VINCRISTINE FOR PEDIATRIC LOW-GRADE GLIOMAS

Abstract OBJECTIVE To analyze the response and toxicity of recombinant human endostatin (rh-ES) combined with carboplatin and vincristine (CV) chemotherapy regimen for pediatric low-grade gliomas (LGGs). METHODS Retrospectively reviewed the clinical data of the patients who were received rh-ES with CV chemotherapy regimen at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University from October 2014 to October 2018. Carboplatin was administrated at a dose of 200~300 mg/m2 and the vincristine dose was 1.5 mg/m2 (maximum dose: 2 mg). Rh-ES was administrated 15 mg/d, daily for 14 days of each 28-day treatment cycle. RESULTS 26 patients were enrolled. By the time of the last follow-up, 14 patients had completed the treatment and 6 were still in treatment. Of the 26 patients, 14 had partial response (PR), 12 had stable disease (SD), and the objective response rate (ORR) was 53.8%. Of the 14 patients who completed all the treatment, 10 achieved PR, 4 got SD, and the ORR was 71.4%. The median time interval to response was 3.3 months (range 2–12.6 months). The main adverse reactions were myelosuppression and allergy to carboplatin. Three patients were terminated in the consolidation phase due to adverse reactions. CONCLUSIONS The rh-ES combined with CV regimen is effective in the treatment of pediatric LGGs and had a rapid time interval to response, which is conducive to the rapid relief of brain stem or visual function damage.

NCOG-11. NEUROPSYCHOLOGICAL OUTCOMES FOLLOWING AWAKE CRANIOTOMY FOR LOW GRADE GLIOMA

Abstract BACKGROUND Awake craniotomy is an established treatment for tumours in eloquent brain regions. It aims to achieve maximal resection without significant neurological and functional morbidity. There is an emerging evidence base about the neuropsychological outcomes following awake craniotomy for low grade gliomas (LGGs) with inconsistent findings potentially reflective of methodological confounders such as the inclusion of mixed tumour types and the use of varied neurocognitive measures and timescales for repeat testing. We describe detailed neuropsychological outcomes for a cohort of patients following awake craniotomy for LGGs. METHOD Data were collected from patients undergoing first-time awake resection of presumed LGGs at Leeds Teaching Hospitals, UK between 2010 and 2018. Patients were included if they consented to and completed the full battery of pre- and postoperative neuropsychological testing. Neuropsychometric testing involved assessment of general intellectual functioning, language, memory, executive functioning, perception, processing speed and mood. Data were analysed using paired-samples t-test or Wilcoxon signed-rank test with Bonferroni correction for multiple statistical comparisons. RESULTS Twenty-two patients undergoing awake craniotomy for presumed supratentorial LGG (13 left hemisphere, 9 right hemisphere; mean age 35 years) met the above inclusion criteria. Tumour location was heterogenous (11 insular, 9 frontal, 1 temporal, 1 parietal). Histopathology confirmed WHO Grade II diffuse astrocytoma (n=11), WHO Grade II oligodendroglioma (n=10) and WHO Grade III anaplastic oligodendroglioma (n=1). No statistical differences in neurocognitive test scores were found pre- and post-neurosurgery (mean follow-up was 61 weeks). Other outcomes including extent of resection and reliable change statistics for neurocognitive tests and measures of mood were also analysed. CONCLUSION No significant change in neurocognitive functioning was found in patients following recovery from awake craniotomy for LGG. Our findings suggest that awake craniotomy is a safe treatment for LGG and that neuropsychological input is an important part of the treatment pathway for patients with LGG.

NIMG-31. BRAIN CONNECTIVITY PATTERNS CHARACTERIZE COGNITIVE IMPAIRMENT IN LONG-TERM SURVIVORS OF LOW-GRADE GLIOMA (LGG) USING RESTING-STATE FUNCTIONAL MRI (rs-fMRI)

Abstract Advanced multimodality treatments that have led to longer survival rates for patients with low-grade gliomas (LGGs) have also resulted in significant changes in cognition and quality of life (QoL). These changes remain poorly understood, largely due to the lack of multifactorial and in-depth studies on cognitive impairment in patients with LGG. Resting-state functional MRI (rs-fMRI) has been widely used as a reliable imaging biomarker to evaluate the treatment outcome by characterizing the cerebral networking alteration associated with a patient’s neurological status. In this preliminary report of an active study, we investigated the cognitive function and cerebral networking connectivity via rs-fMRI in survivors who had completed treatment for LGG within the past 10 years. Survivors were administered a battery of standardized neuropsychological tests. Of the 20 participants enrolled to date (mean age 43 ± 11), 10 participants were categorized as cognitively impaired based on the International Cognition and Cancer Task Force (ICCTF) guidelines, with recommended adjustments considering the number of tests in the battery. Compared to cognitively unimpaired participants, functional connectivity in cognitively impaired patients was lower between memory, visuospatial processing, and primary sensorimotor regions. These preliminary observations suggest there is a potential link between overall cognitive impairment and functional connectivity of various networks as measured using resting-state fMRI.

Low-dose cisplatin combined with etoposide in the treatment of low-grade glioma in the sellar region of children with diencephalic syndrome: A report of four cases

Objective To investigate the therapeutic effect of low-dose cisplatin combined with etoposide on low-grade glioma in the sellar region of children with diencephalic syndrome. Methods The clinical characteristics, treatment and outcomes of 4 children with diencephalic syndrome secondary to low-grade glioma in the sellar region were retrospectively analyzed who were admitted to Department of Neurosurgery, Children's Hospital of Fudan University from January 2015 to December 2017. Of 4 cases, 2 were females and 2 were males. The range of age was 6 months to 34 months, with the median age of 16 months. One case with severe hydrocephalus was treated with ventriculoperitoneal shunt surgery. Surgical biopsy or resection was not performed in this series. Low doses of cisplatin (1 mg·kg-1·d-1 d0-d2) and etoposide (5 mg·kg-1·d-1, d0-d2) were used for 10 cycles of chemotherapy to observe the clinical effect. Results All cases successfully completed chemotherapy and no obvious side effects of chemotherapy were reported. Follow-up post chemotherapy lasted for 6 to 20 months (with the median duration of 12 months). The clinical symptoms were better than before and the weight was about 29.3%-50.0% higher than before. The starting time to gain weight was 3 to 12 months after the initiation of chemotherapy (with the median duration of 7 months). There was no progress in the review of cranial MRI saddle area in 2 cases, tumor reduction in 1, substance decrease in 1, disappearance of cisterna ambiens lesion in 1 and disappearance of the fourth ventricular lesion in 1. There was no significant change in hormone level compared with conditions prior to chemotherapy. One case gained weight at 1 year post chemotherapy and presented good clinical performance. Partial resection of tumor was performed. Its final pathological result was pilocytic astrocytoma (WHO Ⅰ) and further radiotherapy was administered. Conclusions The chemotherapy regimen of low-dose cisplatin combined with etoposide seems to have a good effect which was to improve the clinical symptoms and postpone the tumor progression of children with diencephalic syndrome secondary to low-grade gliomas in the sellar region. Key words: Glioma; Child; Cisplatin; Etoposide; Diencephalic syndrome; Sellar region; Low-grade