RADT-20. SINGLE INSTITUTION REVIEW OF LARGE VOLUME HIGH GRADE GLIOMA PATIENTS TREATED WITH RADIOTHERAPY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi45-vi45
Author(s):  
Vishal Manik ◽  
Angela Swampillai ◽  
Omar Al-Salihi ◽  
Kazumi Chia ◽  
Lucy Brazil
Keyword(s):  
Large Volume ◽  
Brain Volume ◽  
Collaborative Study ◽  
High Grade Glioma ◽  
Study Data ◽  
Molecular Profile ◽  
Normal Brain ◽  
High Grade ◽  
Total Brain Volume ◽  
Dose Volume

Abstract AIM Not uncommonly, we come across significantly large high grade glioma cases (HGGs). With standard delineation protocols, we end up irradiating a large volume of normal brain. Emami & QUANTEC data define normal brain tolerance doses, however they are often of limited use in clinic practice. Thus, we reviewed our patients with significant tumor volumes to derive a safe dose/ volume level for brain. METHODOLOGY Patients with HGGs over the last 3 years were extracted from Mosaiq™ information system. The output was sorted with respect to clinical target volumes from lowest to highest. The top 25 percentile i.e. patients with a CTV of > 412cc (n=53) were identified for this study. Data was collected with respect to clinical, tumor characteristics and radiotherapy parameters. RESULTS Median age of population was 53 and majority (n=38) were males. Nine patients had multi-focal tumors while six had bilateral extension. Majority of the study group had Glioblastoma Multiforme (n=44), whereas 6 had Grade 3 tumors. Most of the patients could only have a biopsy (n=27). Molecular profile showed 42 were Isocitrate-Dehydrogenase negative and 26 were unmethylated tumors. Stupp’s & Perry’s regimen were the commonly used protocols, however patients (n=7) with significant volumes near critical structures were treated with doses in the range of 50.4 – 55Gy in 30 fractions. The CTV volumes in the population ranged from 412 – 1223 cc while total brain volume range was 1112 – 1667 cc. Median of 43.5% of brain volume was covered in the PTV, while median of 5% of brain volume outside the PTV was treated to BED2 of 100Gy. Median survival was 12.4 months. CONCLUSION Our study shows reasonable tolerance of radiotherapy doses of > 50 Gy to larger volumes of brain. We propose a multi-center collaborative study to derive a new standardized dose volume tolerance.

PATH-41. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG WITH FGFR3-TACC3 FUSION MIMICKING HIGH-GRADE GLIOMA: CASE REPORT AND SERIES OF HIGH-GRADE CORRELATES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi124-vi124
Author(s):  
Danielle Golub ◽  
Peter C Pan ◽  
Benjamin Liechty ◽  
Cheyanne Slocum ◽  
Tejus Bale ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Grade Glioma ◽  
Proliferation Index ◽  
Molecular Profile ◽  
Low Grade ◽  
High Grade ◽  
Molecular Features ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Abstract BACKGROUND Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently-described entity that can occasionally histologically and molecularly mimic high-grade glioma. The histologic and molecular features that predict aggressive behavior in FGFR3-TACC3 altered tumors are unclear. CASES We present a rare case of an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of high-grade glioma and analyze common molecular features between this case and a series of high-grade gliomas. After total resection, pathology of the case patient revealed predominantly low-grade cytomorphology, abundant microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34 immunoreactive and harbored both an FGFR3-TACC3 fusion and a TERT promoter mutation. Based on the overall histologic and molecular profile, a diagnosis of PLNTY was favored. The patient was thereafter observed without adjuvant therapy with no evidence of progression at 15-month follow-up. In contrast, a series of eight adult patients with glioblastomas harboring FGFR3-TACC3 fusions and correspondingly aggressive clinical courses are also presented. Common molecular findings included IDH-wildtype status, absence of 1p19q codeletion, and CDKN2A loss. TERT promoter mutations and lack of MGMT promoter methylation were also frequently observed. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival. CONCLUSIONS PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.

scholarly journals HGG-39. ALTERNATIVE SPLICING OF NEUROFIBROMIN 1 IS ASSOCIATED WITH ELEVATED MAPK ACTIVITY AND POOR PROGNOSIS IN HIGH-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i25-i25
Author(s):  
Robert Siddaway ◽  
Scott Milos ◽  
Arun Vadivel ◽  
Tara Dobson ◽  
Jyothishmathi Swaminathan ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Mapk Pathway ◽  
High Grade Glioma ◽  
Mapk Signaling ◽  
Normal Brain ◽  
High Grade ◽  
Driver Genes ◽  
Cancer Driver ◽  
Mapk Activity ◽  
Neurofibromin 1

Abstract Despite a good understanding of the coding mutations underlying high-grade gliomas (HGG), their prognosis remains poor. We sought to characterize their transcriptional alterations and how this contributes to pathogenesis. We analyzed a large cohort of pediatric HGG (pHGG) by DNA sequencing (n=79) and RNA-Seq (n=63 plus normal brain, n=20), finding spliceosome mutations that are associated with increased splicing burden. High levels of alternative splicing were found in known cancer driver genes, with enrichment for chromatin regulators (including the SWI/SNF and NuRD complexes) and the RAS/MAPK pathway, in particular neurofibromin 1 (NF1). Both pediatric and adult HGG preferentially expressed NF1-II, a less active RAS GTPase, resulting in increased RAS/MAPK activity resulting from inclusion of exon23a into the GAP-related domain of NF1. In IDH wild-type, adult HGG, NF1-II was associated with reduced survival independently from RAS/MAPK pathway mutations. NF1 exon23a splicing was regulated by REST-mediated suppression of splicing factors controlling its inclusion. Together, our results identify a novel mechanism by which HGG can activate RAS/MAPK signaling and other oncogenic pathways to promote tumorigenesis independently from direct mutations.

scholarly journals RTHP-14. PSEUDOPROGRESSION IN HIGH GRADE GLIOMA PATIENTS AFTER PROTON OR PHOTON THERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi213-vi213
Author(s):  
Vonetta Williams ◽  
Lia Halasz ◽  
Jason Rockhill ◽  
James Fink
Keyword(s):  
Mr Imaging ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
High Dose ◽  
High Grade ◽  
Proton Group ◽  
Kaplan Meier ◽  
Dose Volume ◽  
Biological Effectiveness ◽  
Grade Iii

Abstract Pseudoprogression is defined as the appearance of false progression on MR imaging following radiation therapy. Proton therapy is thought to have increased relative biological effectiveness-the ratio of the doses required by two types of radiation to cause the same level of effect-near the edges of the high dose volume. This could lead to different rates of pseudoprogression for protons compared to photons. In our IRB approved study, a board-certified neuroradiologist reviewed serial imaging of 74 patients (photons: n=37, protons: n=37) treated from 2013–2018 with either proton or photon radiotherapy to 59.4–60 Gy in 30–33 fractions and temozolomide for high grade glioma. MR imaging was performed 1 month after completion of treatment and then every 3 months. True progression was scored based on updated RANO criteria. Pseudoprogression was determined if imaging improved without change in therapy. Cumulative incidences of these outcomes and survival were calculated utilizing Kaplan-Meier analyses. Patient and treatment factors were analyzed for their association with incidence of pseudoprogression. Median follow-up for alive patients in the proton and photon groups were 15 and 29 months, respectively. Median age was 49 years in the proton group and 54 years in the photon group (p=0.17). Among proton patients, 14 had grade III glioma and 23 had grade IV glioblastoma. Among photon patients, 1 had grade III glioma. Median survival was 23 and 35 months for the proton and photon groups, respectively (p=0.57). The cumulative incidence of pseudoprogression was 14.4% and 10.4% at 12 months for the proton and photon groups, respectively (p=0.53). Grade, extent of resection, age, and IDH status, were not significantly associated with development of pseudoprogression. MGMT methylated tumors showed a trend toward association with pseudoprogression compared to unmethylated tumors (p=0.058). We concluded that the incidence of pseudoprogression is similar regardless of whether proton or photon therapy was utilized.

scholarly journals Dynamics of circulating hypoxia-mediated miRNAs and tumor response in patients with high-grade glioma treated with bevacizumab

2016 ◽  
Vol 125 (4) ◽  
pp. 1008-1015 ◽  
Author(s):  
Tali Siegal ◽  
Hanna Charbit ◽  
Iddo Paldor ◽  
Bracha Zelikovitch ◽  
Tamar Canello ◽  
...  
Keyword(s):  
Tumor Response ◽  
High Grade Glioma ◽  
Response Assessment ◽  
High Rate ◽  
Normal Brain ◽  
High Grade ◽  
Serum Samples ◽  
Antiangiogenic Effect ◽  
Bevacizumab Treatment ◽  
Fluid Attenuated Inversion Recovery

OBJECTIVE Bevacizumab is an antiangiogenic agent under investigation for use in patients with high-grade glioma. It produces a high rate of radiological response; however, this response should be interpreted with caution because it may reflect normalization of the tumor vasculature and not necessarily a true antitumor effect. The authors previously demonstrated that 4 hypoxia-mediated microRNAs (miRNA)—miR-210, miR-21, miR-10b, and miR-196b—are upregulated in glioma as compared with normal brain tissue. The authors hypothesized that the regulation and expression of these miRNAs would be altered in response to bevacizumab treatment. The object of this study was to perform longitudinal monitoring of circulating miRNA levels in patients undergoing bevacizumab treatment and to correlate it with tumor response. METHODS A total of 120 serum samples from 28 patients with high-grade glioma were prospectively collected prior to bevacizumab (n = 15) or temozolomide (TMZ; n = 13) treatment and then longitudinally during treatment. Quantification of the 4 miRNAs was evaluated by real-time polymerase chain reaction using total RNA extracted from the serum. At each time point, tumor response was assessed by Response Assessment in Neuro-Oncology criteria and by performing MRI using fluid attenuated inversion recovery (FLAIR) and contrast-enhanced images. RESULTS As compared with pretreatment levels, high levels of miR-10b and miR-21 were observed in the majority of patients throughout the bevacizumab treatment period. miR-10b and miR-21 levels correlated negatively and significantly with changes in enhancing tumor diameters (r = −0.648, p < 0.0001) in the bevacizumab group but not in the TMZ group. FLAIR images and the RANO assessment did not correlate with the sum quantification of these miRNAs in either group. CONCLUSIONS Circulating levels of miR-10b and miR-21 probably reflect the antiangiogenic effect of therapy, but their role as biomarkers for tumor response remains uncertain and requires further investigation.

scholarly journals Large volume re-irradiation with bevacizumab is a feasible salvage option for patients with refractory high-grade glioma

2014 ◽  
Vol 2 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Michael Back ◽  
Cecelia E. Gzell ◽  
Marina Kastelan ◽  
Linxin Guo ◽  
Helen R. Wheeler
Keyword(s):  
Median Survival ◽  
Large Volume ◽  
Small Volume ◽  
Tumor Volume ◽  
High Grade Glioma ◽  
Target Volume ◽  
Tumor Diameter ◽  
High Grade ◽  
Kaplan Meier ◽  
Maximum Tumor Diameter

AbstractBackgroundClinical studies of re-irradiation (ReRT) for relapsed high-grade glioma (HGG) have generally reported the use of small volume ReRT techniques such as stereotactic radiosurgery in selected patients with isolated focal relapse. This study reports the outcome with large-volume ReRT to manage the more common mescenario of extensive diffuse relapse of HGG.MethodsAll HGG patients managed with an overlapping second course of radiation therapy (RT) for refractory progression of HGG between October 2009 and April 2013 were included. ReRT was initially used with bevacizumab (BEV), then used when disease was refractory to BEV, and finally used upfront with BEV-naïve patients. Tumor volume (GTV) and specific RT dosimetry factors, including the target volume treated (PTV), and cumulative RT dose maximum (Dmax), were analyzed. Median survival post ReRT was calculated using the Kaplan-Meier method and SPPS v19 software.ResultsEighteen HGG participants with refractory, bulky contrast-enhancing disease received ReRT. Thirteen participants had a maximum tumor diameter &gt;5 cm, and median GTV was 54 cm3. Seven participants had BEV-refractory disease, and 8 participants were BEV naïve. ReRT dose was 35–40 Gy in 15 fractions; median PTV was 133 cm3, and median Dmax was 98.2 Gy. Median survival post ReRT for all participants was 8 months (95%CI, 5.8–10.2 months); with 10 months and 3 months for the BEV-naïve and BEV-refractory participants, respectively (P = .024). Two early participants, who were managed without BEV, were later salvaged with BEV, including one who required craniotomy for radiation necrosis at 6 weeks post RT. No other significant morbidity was reported.ConclusionReRT combined with BEV is a feasible salvage treatment option for diffuse refractory HGG.

scholarly journals The role of large volume re-irradiation with Bevacizumab in chemorefractory high grade glioma

2020 ◽  
Vol 22 ◽  
pp. 33-39
Author(s):  
Joseph Chan ◽  
Dasantha Jayamanne ◽  
Helen Wheeler ◽  
Mustafa Khasraw ◽  
Matthew Wong ◽  
...  
Keyword(s):  
Large Volume ◽  
High Grade Glioma ◽  
High Grade

scholarly journals [ 18F]-FDHT PET/CT as a Tool for Imaging Androgen Receptor Expression in High-Grade Glioma

2021 ◽  
Author(s):  
Marina Orevi ◽  
Ofer Shamni ◽  
Nomi Zalcman ◽  
Alexandre Chicheportiche ◽  
Anat Mordechai ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Protein Expression ◽  
Pearson Correlation ◽  
High Grade Glioma ◽  
Receptor Expression ◽  
Normal Brain ◽  
High Grade ◽  
Pet Tracer ◽  
Standardized Uptake Values ◽  
Pet Ct

Abstract Background Glioblastoma (GBM) is associated with poor overall survival. Recently, we showed that androgen receptor (AR) protein is overexpressed in 56% of GBM specimens and AR antagonists induced dose-dependent death in several GBM cell lines and significantly reduced tumor growth and prolonged the lifespan of mice implanted with human GBM. 16β-18F-fluoro-5α-dihydrotestosterone ([18F]-FDHT) is a PET tracer used to detect AR expression in prostate and breast cancers. This study was aimed at exploring the ability of [18F]-FDHT-PET to detect AR expression in high-grade gliomas. Methods Twelve patients with suspected high-grade glioma underwent a regular workup and additional dynamic and static [ 18 F]-FDHT-PET/CT. Visual and quantitative analyses of [ 18 F]-FDHT kinetics in the tumor and normal brain were performed. Mean and maximum (max) standardized uptake values (SUVs) were determined in selected volumes of interest. The patients had surgery or biopsy after PET/CT. AR protein was analyzed in the tumor samples by western blot. Fold change in AR expression was calculated by densitometry analysis. Correlation between imaging and AR protein samples was determined. Results In six of the 12 patients, [ 18 F]-FDHT uptake was significantly higher in the tumor than in the normal brain. These patients also had increased AR protein expression within the tumor. Pearson correlation coefficient analysis for the tumor-to-control normal brain uptake ratio in terms of SUVmean versus AR protein expression, was positive and significant (R = 0.84; p = 0.002). Conclusion [ 18 F]-FDHT-PET/CT could identify increased AR expression in high-grade glioma.

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